Aperio Technologies, Inc., (Aperio), a global leader in digital pathology for the healthcare and life sciences industry, is pleased to announce the launch of a digital pathology solution for Immunohistochemistry (IHC) designed specifically for the clinical market. Aperio's digital IHC solution is the only commercially available FDA-cleared system allowing pathologists to run quantitative IHC image analysis while reading slides on a computer monitor.
A digital IHC system significantly streamlines clinical workflow. By using a single system to read digital IHC slides, perform quantitative image analysis, and create professional reports, pathologists can provide faster turn-around times, more informed decision-making, and accurate and consistent test results.
Eric F. Glassy, MD, medical director at Pathology Inc., stated, "After switching to Aperio's digital IHC solution from a different computer-assisted technology, we immediately experienced improved efficiency. More importantly, the interpretation algorithms offer far more control and accuracy, and the reporting capability is superior. We especially appreciate the ability to link thumb nail images on the PDF file to the actual whole slide images. The power and flexibility are simply remarkable."
The digital IHC system includes FDA-cleared algorithms for HER2, ER and PR stained breast specimens for diagnosing digital slides for clinical use in pathology. In addition, the system comes with a suite of image analysis algorithms that can be tuned for different tissue types (e.g. breast, colon, prostate), stains (e.g. HER2, ER, PR, Ki-67, P53, EGFR), reagents (e.g. Dako, Ventana) or to correlate algorithm results with other test methods (e.g. FISH, CISH).
"An integrated system is key to providing an efficient workflow for pathologists, and a major advantage over add-on image analysis systems," said Dirk Soenksen, CEO of Aperio. "Pathologists can now use Aperio's sophisticated cell-based image analysis capabilities with the click of a button while reading a slide."
Aperio's versatile digital pathology platform allows laboratories and pathologists to adopt digital pathology in applications like IHC and then expand the utility of the system to many other digital pathology services such as secondary consultations, tumor boards, quality assurance programs, and proficiency testing and training.
Source
Aperio
вторник, 28 июня 2011 г.
суббота, 25 июня 2011 г.
New Way To Get Physical In The Fight Against Cancer
Conventional biological wisdom holds that living cells interact with their environment through an elaborate network of chemical signals. As a result many therapies for the treatment of cancer and other diseases in which cell behavior goes awry focus on drugs that block or disrupt harmful chemical signals. Now, a new road for future therapies may have been opened with scientific evidence for a never seen before way in which cells can also sense and respond to physical forces.
A team of researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley has shown that the biochemical activity of a cellular protein system, which plays a key role in cancer metastasis, can be altered by the application of a direct physical force. This discovery sheds important new light on how the protein signaling complex known as EphA2/ephrin-A1 contributes to the initiation, growth and progression of cancerous cells, and also suggests how the activity of cancer cells can be affected by surrounding tissue.
"This first evidence that the EphA2/ephrin-A1 receptor-ligand complex, which was previously thought to be strictly a chemical sensor, can actually sense mechanical properties as well," says chemist Jay Groves, who led this research. "This coupling of mechanical and chemical signaling, which could never have been seen with classical biological methods, helps explain some of the biological mysteries concerning the onset and progression of cancer."
Groves holds a joint appointment with Berkeley Lab's Physical Biosciences Division and UC Berkeley's Chemistry Department. He is also a Howard Hughes Medical Institute (HHMI) investigator. With members of his research group Khalid Salaita and Pradeep Nair, plus Rebecca Petit, he has co-authored a paper on this research that was published in the March 12, 2010 issue of the journal Science. The paper is titled, "Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2." Other co-authors were Joe Gray, Richard Neve and Debopriya Das of Berkeley Lab's Life Sciences Division.
Cancer and EphA2/ephrin-A1
The term "metastasis" comes from the Greek word for "displacement," and it is used to describe the process whereby cancer cells detach from a tumor, enter the bloodstream and spread to other tissues throughout the body. For example, cancerous breast cells can spread to a lung and form a new breast cancer tumor there. Central to metastasis is the EphA2/ephrin-A1 receptor-ligand complex.
EphA2 is a member of the receptor tyrosine kinase (RTK) family of enzymes that are key regulators of cellular processes. The over-expression of EphA2 has been linked to a number of human cancers, including melanoma, lung, colon and prostate, but is especially prominent in breast cancer. Some 40-percent of all breast cancer patients show an over-abundance of EphA2, with the highest levels found in the most aggressive cancer cells. Ephrin-A1 is a signaling protein that is tethered to the surface of a cell's outer membrane. It binds to EphA2 in a neighboring cell like a key fitted into a lock. When ephrin-A1 binds with EphA2, the newly bound complexes become activated and gather in a cluster.
"The host cell will then literally give the clusters a distinctive tug, applying a force that pulls the clusters across the surface of the cell to a centralized location," Grove says. "What we found is that by applying an opposing force, we could alter the cell's biochemical activity. When we applied a big opposing force we were able to convert highly invasive cells into well-behaved cells. This shows that in addition to chemically sensing the presence of ephrin-A1, the cells also sense the mechanical properties of the local environment in which ephrin-A1 is displayed."
Spatial Mutation
Observations have indicated that mammalian cells are sensitive to the physical aspects of their environment, such as the texture or geometry of the surrounding tissue. However, evidence that physical forces impact freely-moving signaling molecules (as opposed to focal adhesion molecules) in the membranes of cells has been lacking because the cell membrane is an environment that has always been difficult to characterize and manipulate. Groves and his research group have found a way to overcome this obstacle with the development of unique synthetic membranes constructed out of lipids and assembled onto a substrate of solid silica that enables them to directly control cellular signaling activities.
"We call this approach the 'spatial mutation' strategy because molecules in a cell can be spatially re-arranged without altering the cell in any other way," Groves says. "We first used this strategy in 2005 to study T cell signaling in the immune system."
In this latest study, Groves and his colleagues worked with mammary epithelial cells from a library of 26 model human breast cancer cell lines that have been well-characterized by co-author Gray and his research groups at Berkeley Lab and UC San Francisco.
Says co-author Nair, "Gray's research has demonstrated that this library substantially reproduces the genomic abnormalities and drug responsiveness of primary breast cancer tumor cells from patients, and constitutes the most comprehensive system for the study of the various aberrations responsible for human breast cancer."
To test the sensitivity of the EphA2/ephrin-A1 signaling complex to mechanical forces, Groves and his group patterned their silica substrates with chromium metal lines that were 10 nanometers in height and 100 nanometers wide. These metal lines acted as diffusion barriers that impeded the lateral mobility of the EphA2/ephrin-A1 complexes in the synthetic membrane. The movement and spatial organization of the complexes were subsequently tracked through a combination of Total Internal Reflection Fluorescence (TIRF), reflection interference and epifluorescence imaging techniques.
"Without the barriers, the clusters of EphA2/ephrin-A1 signaling complexes were transported to the center of the cell-supported membrane junction, but with the barriers in place, there was an accumulation of clusters at the barrier boundaries," Groves says. "This resulted in a spatial reorganization that altered the cell's biochemical behavior."
Quantitative analysis of these changes to the spatial organization of the EphA2/ephrin-A1 signaling complexes across the library of breast cancer cell lines revealed a strong correlation with the potential for metastasis. Since the patterned metal lines in the silica substrate are analogous to the stiffness, texture and other elastic and mechanical properties of tissue, as well as to internal structures within the cell membrane, the results of this study point to intriguing new possibilities for breast and other cancer therapies.
"It's possible that the force-sensing process itself could provide a target for therapeutic intervention," says Groves. "We're also excited about finding targets for which there may be drugs that have already been developed but are now being used to treat diseases other than cancer. Given the sensitivity to mechanical forces displayed by the EphA2/ephrin-A1 signaling complexes, it is possible these existing drugs could be redirected to the treatment of cancer."
This research was carried out under a grant from the Bay Area Physical Sciences-Oncology Center, which is funded by the National Cancer Institute to enable the tools and insights of the physical sciences to be applied to the investigation of cancer's underlying mechanisms. This center is under the direction of Jan Liphardt, a biophysicist who also holds joint appointments with Berkeley Lab and UC Berkeley.
Source:
Lynn Yarris
DOE/Lawrence Berkeley National Laboratory
A team of researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley has shown that the biochemical activity of a cellular protein system, which plays a key role in cancer metastasis, can be altered by the application of a direct physical force. This discovery sheds important new light on how the protein signaling complex known as EphA2/ephrin-A1 contributes to the initiation, growth and progression of cancerous cells, and also suggests how the activity of cancer cells can be affected by surrounding tissue.
"This first evidence that the EphA2/ephrin-A1 receptor-ligand complex, which was previously thought to be strictly a chemical sensor, can actually sense mechanical properties as well," says chemist Jay Groves, who led this research. "This coupling of mechanical and chemical signaling, which could never have been seen with classical biological methods, helps explain some of the biological mysteries concerning the onset and progression of cancer."
Groves holds a joint appointment with Berkeley Lab's Physical Biosciences Division and UC Berkeley's Chemistry Department. He is also a Howard Hughes Medical Institute (HHMI) investigator. With members of his research group Khalid Salaita and Pradeep Nair, plus Rebecca Petit, he has co-authored a paper on this research that was published in the March 12, 2010 issue of the journal Science. The paper is titled, "Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2." Other co-authors were Joe Gray, Richard Neve and Debopriya Das of Berkeley Lab's Life Sciences Division.
Cancer and EphA2/ephrin-A1
The term "metastasis" comes from the Greek word for "displacement," and it is used to describe the process whereby cancer cells detach from a tumor, enter the bloodstream and spread to other tissues throughout the body. For example, cancerous breast cells can spread to a lung and form a new breast cancer tumor there. Central to metastasis is the EphA2/ephrin-A1 receptor-ligand complex.
EphA2 is a member of the receptor tyrosine kinase (RTK) family of enzymes that are key regulators of cellular processes. The over-expression of EphA2 has been linked to a number of human cancers, including melanoma, lung, colon and prostate, but is especially prominent in breast cancer. Some 40-percent of all breast cancer patients show an over-abundance of EphA2, with the highest levels found in the most aggressive cancer cells. Ephrin-A1 is a signaling protein that is tethered to the surface of a cell's outer membrane. It binds to EphA2 in a neighboring cell like a key fitted into a lock. When ephrin-A1 binds with EphA2, the newly bound complexes become activated and gather in a cluster.
"The host cell will then literally give the clusters a distinctive tug, applying a force that pulls the clusters across the surface of the cell to a centralized location," Grove says. "What we found is that by applying an opposing force, we could alter the cell's biochemical activity. When we applied a big opposing force we were able to convert highly invasive cells into well-behaved cells. This shows that in addition to chemically sensing the presence of ephrin-A1, the cells also sense the mechanical properties of the local environment in which ephrin-A1 is displayed."
Spatial Mutation
Observations have indicated that mammalian cells are sensitive to the physical aspects of their environment, such as the texture or geometry of the surrounding tissue. However, evidence that physical forces impact freely-moving signaling molecules (as opposed to focal adhesion molecules) in the membranes of cells has been lacking because the cell membrane is an environment that has always been difficult to characterize and manipulate. Groves and his research group have found a way to overcome this obstacle with the development of unique synthetic membranes constructed out of lipids and assembled onto a substrate of solid silica that enables them to directly control cellular signaling activities.
"We call this approach the 'spatial mutation' strategy because molecules in a cell can be spatially re-arranged without altering the cell in any other way," Groves says. "We first used this strategy in 2005 to study T cell signaling in the immune system."
In this latest study, Groves and his colleagues worked with mammary epithelial cells from a library of 26 model human breast cancer cell lines that have been well-characterized by co-author Gray and his research groups at Berkeley Lab and UC San Francisco.
Says co-author Nair, "Gray's research has demonstrated that this library substantially reproduces the genomic abnormalities and drug responsiveness of primary breast cancer tumor cells from patients, and constitutes the most comprehensive system for the study of the various aberrations responsible for human breast cancer."
To test the sensitivity of the EphA2/ephrin-A1 signaling complex to mechanical forces, Groves and his group patterned their silica substrates with chromium metal lines that were 10 nanometers in height and 100 nanometers wide. These metal lines acted as diffusion barriers that impeded the lateral mobility of the EphA2/ephrin-A1 complexes in the synthetic membrane. The movement and spatial organization of the complexes were subsequently tracked through a combination of Total Internal Reflection Fluorescence (TIRF), reflection interference and epifluorescence imaging techniques.
"Without the barriers, the clusters of EphA2/ephrin-A1 signaling complexes were transported to the center of the cell-supported membrane junction, but with the barriers in place, there was an accumulation of clusters at the barrier boundaries," Groves says. "This resulted in a spatial reorganization that altered the cell's biochemical behavior."
Quantitative analysis of these changes to the spatial organization of the EphA2/ephrin-A1 signaling complexes across the library of breast cancer cell lines revealed a strong correlation with the potential for metastasis. Since the patterned metal lines in the silica substrate are analogous to the stiffness, texture and other elastic and mechanical properties of tissue, as well as to internal structures within the cell membrane, the results of this study point to intriguing new possibilities for breast and other cancer therapies.
"It's possible that the force-sensing process itself could provide a target for therapeutic intervention," says Groves. "We're also excited about finding targets for which there may be drugs that have already been developed but are now being used to treat diseases other than cancer. Given the sensitivity to mechanical forces displayed by the EphA2/ephrin-A1 signaling complexes, it is possible these existing drugs could be redirected to the treatment of cancer."
This research was carried out under a grant from the Bay Area Physical Sciences-Oncology Center, which is funded by the National Cancer Institute to enable the tools and insights of the physical sciences to be applied to the investigation of cancer's underlying mechanisms. This center is under the direction of Jan Liphardt, a biophysicist who also holds joint appointments with Berkeley Lab and UC Berkeley.
Source:
Lynn Yarris
DOE/Lawrence Berkeley National Laboratory
среда, 22 июня 2011 г.
Bernard Fisher Receives AACR Lifetime Achievement Award For Contributions Towards Breast Cancer Care
Bernard Fisher, M.D., the renowned clinical cancer researcher whose career has been dedicated toward improving survival as well as quality of life for women with breast cancer, will receive the American Association for Cancer Research Award for Lifetime Achievement in Cancer Research.
The award will be presented April 2 during ceremonies at AACR's 97th Annual Meeting in Washington, D.C.
Dr. Fisher 's early work on tumor metastasis paved the way for later hypotheses about the spread of this disease. He used clinical trials to confirm that patterns of tumor spread are not solely dictated by anatomical considerations, but are also influenced by intrinsic factors in the tumor cells and the organs they invade.
Dr. Fisher's systematic clinical trials changed the way physicians manage patients with breast cancer. Together with a consortium of colleagues, he evaluated the effect of radical surgical procedures for breast cancer and found that radical mastectomy was no more effective than total mastectomy. Further investigations revealed that a combination of lumpectomy and radiation therapy was equally effective as total mastectomy.
Dr. Fisher and his colleagues also were instrumental in defining the effectiveness of adjuvant chemotherapy and hormonal therapy with the synthetic estrogen tamoxifen in treating breast cancer as a systemic disease. His studies revealed that tamoxifen substantially reduces the incidence of breast cancer in high-risk women when taken as a preventative measure.
"Dr. Fisher's important work not only helped those who fight the disease, but has also helped prevent breast cancer in women who are at high risk," said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. "We are honored to recognize Dr. Fisher's exemplary contributions to the field of breast cancer research and improvement in the quality of life for women who struggle with this disease."
Dr. Fisher is a 1943 graduate of the University of Pittsburgh School of Medicine, where he spent the majority of his career. From 1950 through 1952, he was a fellow in experimental surgery at the University of Pennsylvania, and, in 1955, he served as a research fellow at the London-Post-Graduate Medical School. In 1959, Dr. Fisher became professor of surgery at the University of Pittsburgh, and, in 1986, was appointed Distinguished Service Professor of Surgery at the university. Dr. Fisher co-founded the National Surgical Adjuvant Breast and Bowel Project, a research consortium which he chaired from 1967 to 1994. In his role as past chairman and scientific director of that Pittsburgh-based research consortium, Dr. Fisher and his colleagues contributed research that set a new course not only for the treatment of breast cancer but for other types of cancer as well.
Dr. Fisher's previous honors and awards include the Albert Lasker Clinical Medical Research Award, the General Motors Cancer Research Foundation's Kettering Prize, the Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research, the American Cancer Society Medal of Honor, and the AACR-Joseph H. Burchenal Clinical Research Award.
The AACR Award for Lifetime Achievement in Cancer Research was established and first presented in 2004 to honor individuals who have made significant fundamental contributions to cancer researcher either through a single scientific discovery or a body of work. These contributions, whether they have been in research, leadership, or mentorship, must have had a lasting impact on the cancer field and must have demonstrated a lifetime commitment to understanding, controlling or curing cancer, and the improvement of the human condition for those who have the disease.
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 60 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 16,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.
Contact: Russell Vanderboom, Ph.D.
vanderboomaacr
American Association for Cancer Research
The award will be presented April 2 during ceremonies at AACR's 97th Annual Meeting in Washington, D.C.
Dr. Fisher 's early work on tumor metastasis paved the way for later hypotheses about the spread of this disease. He used clinical trials to confirm that patterns of tumor spread are not solely dictated by anatomical considerations, but are also influenced by intrinsic factors in the tumor cells and the organs they invade.
Dr. Fisher's systematic clinical trials changed the way physicians manage patients with breast cancer. Together with a consortium of colleagues, he evaluated the effect of radical surgical procedures for breast cancer and found that radical mastectomy was no more effective than total mastectomy. Further investigations revealed that a combination of lumpectomy and radiation therapy was equally effective as total mastectomy.
Dr. Fisher and his colleagues also were instrumental in defining the effectiveness of adjuvant chemotherapy and hormonal therapy with the synthetic estrogen tamoxifen in treating breast cancer as a systemic disease. His studies revealed that tamoxifen substantially reduces the incidence of breast cancer in high-risk women when taken as a preventative measure.
"Dr. Fisher's important work not only helped those who fight the disease, but has also helped prevent breast cancer in women who are at high risk," said Margaret Foti, Ph.D., M.D. (h.c.), chief executive officer of the AACR. "We are honored to recognize Dr. Fisher's exemplary contributions to the field of breast cancer research and improvement in the quality of life for women who struggle with this disease."
Dr. Fisher is a 1943 graduate of the University of Pittsburgh School of Medicine, where he spent the majority of his career. From 1950 through 1952, he was a fellow in experimental surgery at the University of Pennsylvania, and, in 1955, he served as a research fellow at the London-Post-Graduate Medical School. In 1959, Dr. Fisher became professor of surgery at the University of Pittsburgh, and, in 1986, was appointed Distinguished Service Professor of Surgery at the university. Dr. Fisher co-founded the National Surgical Adjuvant Breast and Bowel Project, a research consortium which he chaired from 1967 to 1994. In his role as past chairman and scientific director of that Pittsburgh-based research consortium, Dr. Fisher and his colleagues contributed research that set a new course not only for the treatment of breast cancer but for other types of cancer as well.
Dr. Fisher's previous honors and awards include the Albert Lasker Clinical Medical Research Award, the General Motors Cancer Research Foundation's Kettering Prize, the Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research, the American Cancer Society Medal of Honor, and the AACR-Joseph H. Burchenal Clinical Research Award.
The AACR Award for Lifetime Achievement in Cancer Research was established and first presented in 2004 to honor individuals who have made significant fundamental contributions to cancer researcher either through a single scientific discovery or a body of work. These contributions, whether they have been in research, leadership, or mentorship, must have had a lasting impact on the cancer field and must have demonstrated a lifetime commitment to understanding, controlling or curing cancer, and the improvement of the human condition for those who have the disease.
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 24,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 60 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 16,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.
Contact: Russell Vanderboom, Ph.D.
vanderboomaacr
American Association for Cancer Research
воскресенье, 19 июня 2011 г.
Red Meat Linked To Breast Cancer
Eating red meat increases a woman's chance of developing breast cancer, according to new research from the University of Leeds.
The findings are most striking for post-menopausal women those with the highest intake of red meat, the equivalent to one portion a day (more than 57 grams) - run a 56 per cent greater risk of breast cancer than those who eat none. Women who eat the most processed meat, such as bacon, sausages, ham or pies, run a 64 per cent greater risk of breast cancer than those who eat none.
Researchers at the University's Centre for Epidemiology and Biostatistics have been tracking the eating habits and health of more than 35,000 women for the past seven years, and their latest findings are published in the British Journal of Cancer. Earlier findings, widely reported in January, showed that pre-menopausal women who have the greatest intake of fibre have cut their risk of breast cancer in half.
LEEDS UNIVERSITY
Leeds
LS2 9JT
leeds.ac.uk
The findings are most striking for post-menopausal women those with the highest intake of red meat, the equivalent to one portion a day (more than 57 grams) - run a 56 per cent greater risk of breast cancer than those who eat none. Women who eat the most processed meat, such as bacon, sausages, ham or pies, run a 64 per cent greater risk of breast cancer than those who eat none.
Researchers at the University's Centre for Epidemiology and Biostatistics have been tracking the eating habits and health of more than 35,000 women for the past seven years, and their latest findings are published in the British Journal of Cancer. Earlier findings, widely reported in January, showed that pre-menopausal women who have the greatest intake of fibre have cut their risk of breast cancer in half.
LEEDS UNIVERSITY
Leeds
LS2 9JT
leeds.ac.uk
четверг, 16 июня 2011 г.
Breast-Lesion Biopsies May Be Reduced By New Statistical Model
A new method of characterizing breast lesions found during an MRI exam could result in fewer biopsies of benign tumors with the benefits of reduced pain and expense for patients and providers, according to a paper that was presented Nov. 30 at the annual meeting of the Radiological Society of North America (RSNA).
Wendy DeMartini, M.D., and colleagues in the breast imaging department at the Seattle Cancer Care Alliance developed a preliminary statistical model that breast radiologists could use eventually when deciding whether a lesion found on breast MRI is likely to be malignant or benign. Their retrospective review of almost 2,600 breast MRI exams performed during a four-year period at the SCCA found three crucial patient and lesion characteristics that, when used in combination, could predict the likelihood of malignancy, including identifying some lesions with probabilities of cancer close to zero.
Such a model, if confirmed by more research, could be beneficial because MRI exams are so sensitive that they reveal cancerous and non-cancerous lesions that often look alike and behave similarly when contrast dye is injected into the patient. Biopsy is often necessary to determine whether a lesion is cancerous. Statistical models may improve the ability to distinguish between such lesions and avoid unnecessary biopsies.
The researchers looked at several patient and lesion characteristics that radiologists take into account now when deciding whether a biopsy is required for diagnosis. They found three categories of characteristics that, when taken together, were the best at predicting malignancy. These were the reason that the women was having a breast MRI, the size of the lesion, and the lesion enhancement pattern from the the MRI contrast dye.
Lesions found in women undergoing MRI to look for additional malignancy after new breast cancer diagnosis, lesions that were found to be larger than one centimeter, and those whose enhancement quickly faded (called washout) were the most likely to be malignant, according to DeMartini, who is an assistant professor in the University of Washington School of Medicine.
In contrast, breast lesions found in women being screened because they are considered to be at high risk for developing cancer, that were found to be small lesions and increased their enhancement over time were very likely to benign.
"If the lesions had those three characteristics, the likelihood of malignancy was 1 percent," said DeMartini. "This is so close to zeros that rather than doing a biopsy we could instead follow the patient by doing another MRI in a few months, or we may not need to do any additional testing."
DeMartini cautioned that more research is needed before this statistical model can be validated for use as standard practice.
"This is a preliminary model. Future work will look at additional patient and lesion features and in the longer term we need to examine lesions from multiple practice sites," she said. "Our goal is to identify a group of lesions that we currently recommend for additional tests where the likelihood of cancer is so low that we can safely avoid additional testing."
About Seattle Cancer Care Alliance
Seattle Cancer Care Alliance, established in 1998, unites the adult and pediatric cancer-care services of Fred Hutchinson Cancer Research Center, UW Medicine and Children's Hospital and Regional Medical Center. A major focus of SCCA is to speed the transfer of new diagnostic and treatment techniques from the research setting to the patient bedside while providing premier, patient-focused cancer care. Patients who come to SCCA receive the latest research-based cancer therapies as well as cutting-edge treatments for a number of non-malignant diseases under development by its partner organizations. SCCA has three clinical-care sites: an outpatient clinic on the Fred Hutchinson campus, a pediatric-inpatient unit at Children's and an adult-inpatient unit at UW Medical Center. For more information about SCCA, visit seattlecca.
Source: Dean Forbes
Fred Hutchinson Cancer Research Center
Wendy DeMartini, M.D., and colleagues in the breast imaging department at the Seattle Cancer Care Alliance developed a preliminary statistical model that breast radiologists could use eventually when deciding whether a lesion found on breast MRI is likely to be malignant or benign. Their retrospective review of almost 2,600 breast MRI exams performed during a four-year period at the SCCA found three crucial patient and lesion characteristics that, when used in combination, could predict the likelihood of malignancy, including identifying some lesions with probabilities of cancer close to zero.
Such a model, if confirmed by more research, could be beneficial because MRI exams are so sensitive that they reveal cancerous and non-cancerous lesions that often look alike and behave similarly when contrast dye is injected into the patient. Biopsy is often necessary to determine whether a lesion is cancerous. Statistical models may improve the ability to distinguish between such lesions and avoid unnecessary biopsies.
The researchers looked at several patient and lesion characteristics that radiologists take into account now when deciding whether a biopsy is required for diagnosis. They found three categories of characteristics that, when taken together, were the best at predicting malignancy. These were the reason that the women was having a breast MRI, the size of the lesion, and the lesion enhancement pattern from the the MRI contrast dye.
Lesions found in women undergoing MRI to look for additional malignancy after new breast cancer diagnosis, lesions that were found to be larger than one centimeter, and those whose enhancement quickly faded (called washout) were the most likely to be malignant, according to DeMartini, who is an assistant professor in the University of Washington School of Medicine.
In contrast, breast lesions found in women being screened because they are considered to be at high risk for developing cancer, that were found to be small lesions and increased their enhancement over time were very likely to benign.
"If the lesions had those three characteristics, the likelihood of malignancy was 1 percent," said DeMartini. "This is so close to zeros that rather than doing a biopsy we could instead follow the patient by doing another MRI in a few months, or we may not need to do any additional testing."
DeMartini cautioned that more research is needed before this statistical model can be validated for use as standard practice.
"This is a preliminary model. Future work will look at additional patient and lesion features and in the longer term we need to examine lesions from multiple practice sites," she said. "Our goal is to identify a group of lesions that we currently recommend for additional tests where the likelihood of cancer is so low that we can safely avoid additional testing."
About Seattle Cancer Care Alliance
Seattle Cancer Care Alliance, established in 1998, unites the adult and pediatric cancer-care services of Fred Hutchinson Cancer Research Center, UW Medicine and Children's Hospital and Regional Medical Center. A major focus of SCCA is to speed the transfer of new diagnostic and treatment techniques from the research setting to the patient bedside while providing premier, patient-focused cancer care. Patients who come to SCCA receive the latest research-based cancer therapies as well as cutting-edge treatments for a number of non-malignant diseases under development by its partner organizations. SCCA has three clinical-care sites: an outpatient clinic on the Fred Hutchinson campus, a pediatric-inpatient unit at Children's and an adult-inpatient unit at UW Medical Center. For more information about SCCA, visit seattlecca.
Source: Dean Forbes
Fred Hutchinson Cancer Research Center
понедельник, 13 июня 2011 г.
High levels of daily stress may lower risk of breast cancer
High levels of daily stress appear to result in a lower risk of developing breast cancer for the first time, says a study in this week's BMJ.
But high stress may put women at risk of other serious illnesses warn the researchers, a team from Denmark.
The findings follow an eighteen year study of over 6,500 women in Copenhagen. At the start of the study researchers asked the women what levels of stress they experienced routinely in their lives, and classified the results into low, medium and high levels. Stress was defined as tension, nervousness, impatience, anxiety, or sleeplessness. (Stress levels were not measured throughout the study.) In calculating the effects of stress, researchers also adjusted the results for other factors, such as whether they had children or whether they were menopausal, which would have an influence on developing breast cancer. They did not account for risk factors such as family history of the disease however.
Of the 251 women diagnosed with first-time breast cancer over the study period, researchers found that women reporting high levels of stress were 40% less likely to develop breast cancer than women reporting low levels of stress.
The study further found that, for every increased level of stress on a six-level scale, women were 8% less likely to develop breast cancer.
One explanation for the findings may be that sustained levels of high stress may affect oestrogen levels - which, over time, may have an influence on developing breast cancer. But this theory has not been tested, and research in this area so far has mainly been restricted to animals, caution the authors.
Despite the findings, the authors warn that stress-induced changes in hormonal balances are not a healthy response, and continued stress may play a damaging part in other illnesses - particularly heart disease.
Self reported stress and risk of breast cancer: prospective cohort study BMJ Volume 331, pp548-50
Emma Dickinson
edickinsonbmj
44-20-7383-6529
BMJ-British Medical Journal
bmj
But high stress may put women at risk of other serious illnesses warn the researchers, a team from Denmark.
The findings follow an eighteen year study of over 6,500 women in Copenhagen. At the start of the study researchers asked the women what levels of stress they experienced routinely in their lives, and classified the results into low, medium and high levels. Stress was defined as tension, nervousness, impatience, anxiety, or sleeplessness. (Stress levels were not measured throughout the study.) In calculating the effects of stress, researchers also adjusted the results for other factors, such as whether they had children or whether they were menopausal, which would have an influence on developing breast cancer. They did not account for risk factors such as family history of the disease however.
Of the 251 women diagnosed with first-time breast cancer over the study period, researchers found that women reporting high levels of stress were 40% less likely to develop breast cancer than women reporting low levels of stress.
The study further found that, for every increased level of stress on a six-level scale, women were 8% less likely to develop breast cancer.
One explanation for the findings may be that sustained levels of high stress may affect oestrogen levels - which, over time, may have an influence on developing breast cancer. But this theory has not been tested, and research in this area so far has mainly been restricted to animals, caution the authors.
Despite the findings, the authors warn that stress-induced changes in hormonal balances are not a healthy response, and continued stress may play a damaging part in other illnesses - particularly heart disease.
Self reported stress and risk of breast cancer: prospective cohort study BMJ Volume 331, pp548-50
Emma Dickinson
edickinsonbmj
44-20-7383-6529
BMJ-British Medical Journal
bmj
воскресенье, 12 июня 2011 г.
Fenretinide Cuts The Risk Of Second Breast Cancers In Young Women, Italian Researchers Find
A 15-year follow-up of women in a breast cancer trial has found that fenretinide[1] - a drug related to vitamin A - significantly cuts the risk of a second breast cancer among younger patients.
The Italian research team reporting the findings on-line (Thursday 4 May) in Annals of Oncology[2], are sufficiently convinced of the drug's protective potential to call for a trial to test its use as a preventive in pre-menopausal healthy women at high risk of the disease. They are now seeking international partners and funding for such a trial.
The women in the long-term follow-up comprised a sub-group of 1,700 - 60% of the patients in a 10-centre trial lead by Professor Umberto Veronesi and co-ordinated by Milan's Istituto Nazionale Tumori when he was its director. The study, which began in 1987, randomised more than 2,800 women to receive 200 mg fenretinide daily for five years or no extra treatment after surgery for early-stage breast cancer.
The new analysis, also lead by Professor Veronesi, who is now Director of the European Institute of Oncology in Milan, followed the 1,739 patients who had been recruited by the Istituto Nazionale Tumori centre, investigating whether these patients developed a second cancer either in the treated breast or the other breast.
Co-author Dr Andrea Decensi, Director of the Department of Medical Oncology at the Galliera Hospital in Genoa, said: "We followed these patients for between 12 and 16 years and we found 168 second breast cancers in the fenretinide arm and 190 in the control arm. In post-menopausal women there were actually more cancers in the fenretinide arm than among the controls (85 as against 64). But, among pre-menopausal women there were only 83 second cancers in the fenretinide group compared with 126 in the control group.
Dr Decensi said that overall, this meant a 17% reduction in second cancers among the fenretinide group, which was of borderline statistical significance. But, there were four really strong messages within that overall finding:
* fenretinide had different effects on post-menopausal and pre-menopausal women and the increase in second breast cancers among post-menopausal women in the fenretinide arm meant it should not be given to that age group;
* it produced a statistically significant 38% reduction in second breast cancers in pre-menopausal women and halved the risk in women under 40;
* the protection in pre-menopausal women still persisted at 15 years follow-up even though the drug was given for only five years;
* the drug was effective in pre-menopausal women against both oestrogen receptor positive and oestrogen receptor negative breast cancer
Professor Veronesi said that fenretinide appeared to work by re-imposing order on breast cells that were in the process of becoming disorganised and growing out of control and also by forcing those that were in danger of becoming immortal to undergo normal cell death (apoptosis).
He said that the study had the limitation of being a retrospective sub-group analysis, so it needed to be updated and confirmed by results for the other 40% of patients, which they planned to do if funds became available.
"This sub-group analysis had not been foreseen when the original study was planned, so our findings are therefore hypothesis generating. It means that we are not in a position to make clinical recommendations from these data alone, but that this evidence provides a rationale for a new trial in young women at high risk of breast cancer. However, the magnitude of the effect, and the finding that the younger the woman the greater was the benefit, is so striking that we believe it is likely to be real."
The researchers also want studies to discover exactly how the drug works because the biological mechanisms are still unclear, especially the reasons why it works differently in younger or older women. They suggest that fenretinide may enhance the protective or damaging effects of hormones in different ways according to the stage of breast gland development in women.
Said Dr Decensi: "Its differential effect recalls the effect of first full term pregnancy on breast cancer risk, which is protective at a young age and deleterious at an older age."
He said the team wanted to initiate a prevention trial in young high-risk women, which would also look at the drug's potential for preventing ovarian cancer where there was some existing evidence that it may also be effective. They hoped that it might be possible to undertake it as a multi-centre international Europe/USA collaboration.
Professor Guiseppe De Palo from the Istituto Nazionale, who co-ordinated the study, explained that women carrying the BRCA-1 and 2 'breast cancer' genes, which also confer a higher risk of ovarian cancer, would be ideal candidates for a prevention trial. The drug had few side effects although there were still concerns that it could be harmful to unborn babies, which meant young women taking part must use reliable contraception.
"Fenretinide is something of a Cinderella drug," he said. "Like other retinoids it is tricky to manufacture because it is difficult to maintain the stability of the formulation and there are problems of pharmacological interactions. So, the pharmaceutical industry was reluctant to risk investing in its long-term clinical research, especially given that the patent would run out and tamoxifen was already on the market for treatment and had more efficacy data from large international trials."
Dr Decensi added that a preventive trial of fenretinide would be a clear example of the importance of health-care provider and community support for not-for-profit academic clinical research with older compounds. These were often safer than new agents for which long-term safety - a crucial issue in prevention - was still unknown.
[1] Fenretinide: A synthetic retinoid - analogue of retinol (vitamin A), which binds to and activates retinoic acid receptors, inducing cell differentiation and cell death in some tumour types. It also inhibits tumour growth by modulating the growth factors associated with blood vessel development.
[2] Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer. Annals of Oncology. doi"10.1093/annonc/mdl047.
A PDF of the research paper is available on request.
Please acknowledge Annals of Oncology as a source in any reports.
Annals of Oncology is the monthly journal of the European Society for Medical Oncology.
Annals of Oncology website: annonc.oxfordjournals/
Contact: Margaret Willson
European Society for Medical Oncology
The Italian research team reporting the findings on-line (Thursday 4 May) in Annals of Oncology[2], are sufficiently convinced of the drug's protective potential to call for a trial to test its use as a preventive in pre-menopausal healthy women at high risk of the disease. They are now seeking international partners and funding for such a trial.
The women in the long-term follow-up comprised a sub-group of 1,700 - 60% of the patients in a 10-centre trial lead by Professor Umberto Veronesi and co-ordinated by Milan's Istituto Nazionale Tumori when he was its director. The study, which began in 1987, randomised more than 2,800 women to receive 200 mg fenretinide daily for five years or no extra treatment after surgery for early-stage breast cancer.
The new analysis, also lead by Professor Veronesi, who is now Director of the European Institute of Oncology in Milan, followed the 1,739 patients who had been recruited by the Istituto Nazionale Tumori centre, investigating whether these patients developed a second cancer either in the treated breast or the other breast.
Co-author Dr Andrea Decensi, Director of the Department of Medical Oncology at the Galliera Hospital in Genoa, said: "We followed these patients for between 12 and 16 years and we found 168 second breast cancers in the fenretinide arm and 190 in the control arm. In post-menopausal women there were actually more cancers in the fenretinide arm than among the controls (85 as against 64). But, among pre-menopausal women there were only 83 second cancers in the fenretinide group compared with 126 in the control group.
Dr Decensi said that overall, this meant a 17% reduction in second cancers among the fenretinide group, which was of borderline statistical significance. But, there were four really strong messages within that overall finding:
* fenretinide had different effects on post-menopausal and pre-menopausal women and the increase in second breast cancers among post-menopausal women in the fenretinide arm meant it should not be given to that age group;
* it produced a statistically significant 38% reduction in second breast cancers in pre-menopausal women and halved the risk in women under 40;
* the protection in pre-menopausal women still persisted at 15 years follow-up even though the drug was given for only five years;
* the drug was effective in pre-menopausal women against both oestrogen receptor positive and oestrogen receptor negative breast cancer
Professor Veronesi said that fenretinide appeared to work by re-imposing order on breast cells that were in the process of becoming disorganised and growing out of control and also by forcing those that were in danger of becoming immortal to undergo normal cell death (apoptosis).
He said that the study had the limitation of being a retrospective sub-group analysis, so it needed to be updated and confirmed by results for the other 40% of patients, which they planned to do if funds became available.
"This sub-group analysis had not been foreseen when the original study was planned, so our findings are therefore hypothesis generating. It means that we are not in a position to make clinical recommendations from these data alone, but that this evidence provides a rationale for a new trial in young women at high risk of breast cancer. However, the magnitude of the effect, and the finding that the younger the woman the greater was the benefit, is so striking that we believe it is likely to be real."
The researchers also want studies to discover exactly how the drug works because the biological mechanisms are still unclear, especially the reasons why it works differently in younger or older women. They suggest that fenretinide may enhance the protective or damaging effects of hormones in different ways according to the stage of breast gland development in women.
Said Dr Decensi: "Its differential effect recalls the effect of first full term pregnancy on breast cancer risk, which is protective at a young age and deleterious at an older age."
He said the team wanted to initiate a prevention trial in young high-risk women, which would also look at the drug's potential for preventing ovarian cancer where there was some existing evidence that it may also be effective. They hoped that it might be possible to undertake it as a multi-centre international Europe/USA collaboration.
Professor Guiseppe De Palo from the Istituto Nazionale, who co-ordinated the study, explained that women carrying the BRCA-1 and 2 'breast cancer' genes, which also confer a higher risk of ovarian cancer, would be ideal candidates for a prevention trial. The drug had few side effects although there were still concerns that it could be harmful to unborn babies, which meant young women taking part must use reliable contraception.
"Fenretinide is something of a Cinderella drug," he said. "Like other retinoids it is tricky to manufacture because it is difficult to maintain the stability of the formulation and there are problems of pharmacological interactions. So, the pharmaceutical industry was reluctant to risk investing in its long-term clinical research, especially given that the patent would run out and tamoxifen was already on the market for treatment and had more efficacy data from large international trials."
Dr Decensi added that a preventive trial of fenretinide would be a clear example of the importance of health-care provider and community support for not-for-profit academic clinical research with older compounds. These were often safer than new agents for which long-term safety - a crucial issue in prevention - was still unknown.
[1] Fenretinide: A synthetic retinoid - analogue of retinol (vitamin A), which binds to and activates retinoic acid receptors, inducing cell differentiation and cell death in some tumour types. It also inhibits tumour growth by modulating the growth factors associated with blood vessel development.
[2] Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer. Annals of Oncology. doi"10.1093/annonc/mdl047.
A PDF of the research paper is available on request.
Please acknowledge Annals of Oncology as a source in any reports.
Annals of Oncology is the monthly journal of the European Society for Medical Oncology.
Annals of Oncology website: annonc.oxfordjournals/
Contact: Margaret Willson
European Society for Medical Oncology
суббота, 11 июня 2011 г.
CuraGen Updates CR011-vcMMAE Data At ASCO
CuraGen Corporation (Nasdaq: CRGN) reported three data presentations from its ongoing clinical trials of CR011-vcMMAE, an antibody-drug conjugate that targets GPNMB, in patients with advanced breast cancer and melanoma at the 2009 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Orlando, Florida.
The Phase I/II study of CR011-vcMMAE administered intravenously once every three weeks in patients with advanced breast cancer began with a bridging phase to confirm the maximum tolerated dose and has expanded into a Phase II open-label, multi-center study. The study is designed to assess efficacy with an endpoint of progression-free rate at 12 weeks. The principal investigator is Dr. Linda Vahdat, Medical Director of the Breast Cancer Research Program and Associate Professor of Clinical Medicine, NewYork-Presbyterian Hospital/Weill Cornell.
Preliminary data were presented on 18 evaluable patients treated at doses of 1.0 - 1.88mg/kg from the Phase I portion and the initial portion of the Phase II study. Selection for enrollment was not based on expression of GPNMB in patients' tumors. The median number of prior chemotherapy regimens for metastatic disease was 4 (range 2-11). Triple negative disease (ER/PR/Her-2 negative) was present in 44% of patients. Partial responses were seen in 3 patients (1 confirmed), including a patient with triple negative disease. Fifty percent (50%) of patients showed tumor shrinkage. Toxicities were similar to those observed in previous studies with CR011-vcMMAE; the most common adverse events were rash, alopecia, and fatigue. Twelve patients have now been enrolled in the Phase II portion of the study at a dose of 1.88mg/kg given once every three weeks, with total Phase II enrollment planned for up to 25 patients.
"We are very encouraged by the early evidence of activity demonstrated in this trial and look forward to presenting additional data on the Phase II study in the second half of the year," commented Dr. Ronit Simantov, Chief Medical Officer of CuraGen. "The emerging role of GPNMB, which is present in 25-40% of breast cancer patients, combined with our clinical activity, suggests that GPNMB may be an important new target in breast cancer."
Also at ASCO, data from a Phase II trial of CR011-vcMMAE in patients with advanced melanoma were presented at a poster discussion session. Thirty-six patients were enrolled into this Phase II open-label, multi-center trial that evaluated the efficacy and safety of CR011-vcMMAE 1.88 mg/kg administered intravenously once every three weeks. Eligible patients had progressive disease at trial entry and may have received one prior cytotoxic regimen and any number of prior immunotherapies. Of the patients enrolled, 94% had Stage IV disease of which two-thirds were classified as M1c, the poorest risk group.
The study successfully met its primary activity endpoint, with 5 objective responses (1 unconfirmed) observed in 34 evaluable patients, and median duration of response of 5.3 months. The median overall progression-free survival (PFS) was 4.4 months. Tumor shrinkage was observed in 58% of patients, and 20 patients had best response of stable disease. Dermatologic adverse events consisting of rash, alopecia, and pruritus were the most common toxicities in this study. Other adverse events included fatigue, diarrhea, anorexia and nausea. Grade 3 or 4 neutropenia was observed in 5 patients. The absence of rash in the first cycle of treatment predicted a worse PFS. Additionally, in a subset of patients with tumor biopsies, high levels of tumor expression of GPNMB appeared to correlate with favorable outcome.
"These Phase II results show evidence of activity in patients with advanced melanoma that compares favorably to activity seen with other currently used treatments for these patients, who are in need of additional options," commented Dr. Simantov.
In addition, data from the ongoing assessment of more frequent dosing of CR011-vcMMAE in 28 patients with advanced melanoma were presented at ASCO. Thus far, a dose of 1.0 mg/kg given once every week has been identified as the maximum tolerated dose in a weekly schedule, and a dose of 1.5mg/kg is currently being explored in the two out of three week schedule. Although median duration of follow-up is only 6 weeks, objective responses have thus far been observed in 3 of 11 evaluable patients treated with weekly CR011-vcMMAE (1 confirmed) and 1 confirmed response in 8 evaluable patients treated with CR011-vcMMAE two out of every three weeks.
"This study has confirmed that CR011 is active and that more total drug can be safely given with more frequent dosing," stated Dr. Simantov. "The expansion phase of the study will be used to generate a better estimate of the response rate with these schedules to compare to the once every three week schedule."
"The results presented at ASCO are important because they expand the activity of CR011 into patients with metastatic breast cancer and open this area up as an important development opportunity in addition to the opportunity in patients with metastatic melanoma," commented Dr. Timothy Shannon, President and Chief Executive Officer of CuraGen. "The remainder of these studies will be used to better understand the breast cancer opportunity and to understand how dose, schedule and the use of biomarkers such as the presence of GPNMB and rash might be used to enhance activity in further development."
About CR011-vcMMAE
CR011-vcMMAE is an antibody-drug conjugate (ADC) being developed by CuraGen that consists of a fully-human monoclonal antibody, CR011, linked to a potent cell-killing drug, monomethyl-auristatin E (MMAE). The ADC technology, comprised of MMAE and a stable linker system for attaching it to CR011, was licensed from Seattle Genetics, Inc. The ADC is designed to be stable in the bloodstream. Following intravenous administration, CR011-vcMMAE targets and binds to GPNMB, a specific protein that is predominantly expressed on the surface of cancer cells, including melanoma, breast cancer and gliomas. Upon internalization into the targeted cell, CR011-vcMMAE is designed to release MMAE from CR011 to produce a cell-killing effect. CR011-vcMMAE is currently in two Phase II trials assessing the safety and efficacy in the treatment of melanoma and for the treatment of metastatic breast cancer, and in a Phase I trial to evaluate the safety and activity of alternate dosing schedules.
About Melanoma
According to the American Cancer Society, it is expected that approximately 60,000 new cases of melanoma will be diagnosed, including nearly 11,000 patients diagnosed with Stage III or Stage IV disease, and an estimated 8,000 people in the U.S. will die of the disease during 2009. The prognosis for patients with advanced melanoma is poor, and studies have shown that the median survival is less than nine months.
About Breast Cancer
Breast cancer is the most common cancer in women and a leading cause of death in the United States. According to the American Cancer Society, more than 180,000 women will be diagnosed with invasive breast cancer in 2009 with more than 40,000 deaths attributed to this disease. Despite recent advances in therapy, the median survival of patients with metastatic breast cancer is 2 to 3 years, while patients with "triple-negative" or "basal-like" breast cancer have limited treatment options and poorer outcomes. Therefore, a significant unmet need remains for novel therapeutic approaches for patients with locally advanced and metastatic breast cancer who have failed other therapies.
About CuraGen
CuraGen Corporation (Nasdaq: CRGN) is a clinical-stage biopharmaceutical company developing promising approaches for the treatment of cancer. CuraGen Corporation is headquartered in Branford, Connecticut.
Forward Looking Statements
Statements in this press release regarding management's future expectations, beliefs, intentions, goals, strategies, plans or prospects, including statements relating to CuraGen's development program for CR011-vcMMAE, including CuraGen's ability to advance CR011-vcMMAE through Phase II clinical trials for melanoma and metastatic breast cancer, to explore additional doses and schedules of this antibody-drug conjugate, and to explore the potential of CR011-vcMMAE in a patient population in need of new therapies may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by terminology such as "anticipate," "believe," "could," "could increase the likelihood," "estimate," "expect," "intend," "is planned," "may," "should," "will," "will enable," "would be expected," "look forward," "may provide," "would" or similar terms, variations of such terms or the negative of those terms. Such forward-looking statements involve known and unknown risks, uncertainties and other factors including the risk that any one or more of CuraGen's drug development programs will not proceed as planned for technical, scientific or commercial reasons or due to patient enrollment issues or based on new information from nonclinical or clinical studies or from other sources, the success of competing products and technologies, CuraGen's stage of development as a biopharmaceutical company, government regulation and healthcare reform, technological uncertainty and product development risks, product liability exposure, uncertainty of additional funding, CuraGen's history of incurring losses and the uncertainty of achieving profitability, reliance on research collaborations and strategic alliances, competition, patent infringement claims against CuraGen's products, processes and technologies, CuraGen's ability to protect its patents and proprietary rights and uncertainties relating to commercialization rights, as well as those risks, uncertainties and factors referred to in CuraGen's Quarterly Report on Form 10-Q for the period ended March 31, 2009 filed with the Securities and Exchange Commission under the section "Risk Factors," as well as other documents that may be filed by CuraGen from time to time with the Securities and Exchange Commission. As a result of such risks, uncertainties and factors, CuraGen's actual results may differ materially from any future results, performance or achievements discussed in or implied by the forward-looking statements contained herein. CuraGen is providing the information in this press release as of this date and assumes no obligations to update the information included in this press release or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Source: CuraGen Corporation
The Phase I/II study of CR011-vcMMAE administered intravenously once every three weeks in patients with advanced breast cancer began with a bridging phase to confirm the maximum tolerated dose and has expanded into a Phase II open-label, multi-center study. The study is designed to assess efficacy with an endpoint of progression-free rate at 12 weeks. The principal investigator is Dr. Linda Vahdat, Medical Director of the Breast Cancer Research Program and Associate Professor of Clinical Medicine, NewYork-Presbyterian Hospital/Weill Cornell.
Preliminary data were presented on 18 evaluable patients treated at doses of 1.0 - 1.88mg/kg from the Phase I portion and the initial portion of the Phase II study. Selection for enrollment was not based on expression of GPNMB in patients' tumors. The median number of prior chemotherapy regimens for metastatic disease was 4 (range 2-11). Triple negative disease (ER/PR/Her-2 negative) was present in 44% of patients. Partial responses were seen in 3 patients (1 confirmed), including a patient with triple negative disease. Fifty percent (50%) of patients showed tumor shrinkage. Toxicities were similar to those observed in previous studies with CR011-vcMMAE; the most common adverse events were rash, alopecia, and fatigue. Twelve patients have now been enrolled in the Phase II portion of the study at a dose of 1.88mg/kg given once every three weeks, with total Phase II enrollment planned for up to 25 patients.
"We are very encouraged by the early evidence of activity demonstrated in this trial and look forward to presenting additional data on the Phase II study in the second half of the year," commented Dr. Ronit Simantov, Chief Medical Officer of CuraGen. "The emerging role of GPNMB, which is present in 25-40% of breast cancer patients, combined with our clinical activity, suggests that GPNMB may be an important new target in breast cancer."
Also at ASCO, data from a Phase II trial of CR011-vcMMAE in patients with advanced melanoma were presented at a poster discussion session. Thirty-six patients were enrolled into this Phase II open-label, multi-center trial that evaluated the efficacy and safety of CR011-vcMMAE 1.88 mg/kg administered intravenously once every three weeks. Eligible patients had progressive disease at trial entry and may have received one prior cytotoxic regimen and any number of prior immunotherapies. Of the patients enrolled, 94% had Stage IV disease of which two-thirds were classified as M1c, the poorest risk group.
The study successfully met its primary activity endpoint, with 5 objective responses (1 unconfirmed) observed in 34 evaluable patients, and median duration of response of 5.3 months. The median overall progression-free survival (PFS) was 4.4 months. Tumor shrinkage was observed in 58% of patients, and 20 patients had best response of stable disease. Dermatologic adverse events consisting of rash, alopecia, and pruritus were the most common toxicities in this study. Other adverse events included fatigue, diarrhea, anorexia and nausea. Grade 3 or 4 neutropenia was observed in 5 patients. The absence of rash in the first cycle of treatment predicted a worse PFS. Additionally, in a subset of patients with tumor biopsies, high levels of tumor expression of GPNMB appeared to correlate with favorable outcome.
"These Phase II results show evidence of activity in patients with advanced melanoma that compares favorably to activity seen with other currently used treatments for these patients, who are in need of additional options," commented Dr. Simantov.
In addition, data from the ongoing assessment of more frequent dosing of CR011-vcMMAE in 28 patients with advanced melanoma were presented at ASCO. Thus far, a dose of 1.0 mg/kg given once every week has been identified as the maximum tolerated dose in a weekly schedule, and a dose of 1.5mg/kg is currently being explored in the two out of three week schedule. Although median duration of follow-up is only 6 weeks, objective responses have thus far been observed in 3 of 11 evaluable patients treated with weekly CR011-vcMMAE (1 confirmed) and 1 confirmed response in 8 evaluable patients treated with CR011-vcMMAE two out of every three weeks.
"This study has confirmed that CR011 is active and that more total drug can be safely given with more frequent dosing," stated Dr. Simantov. "The expansion phase of the study will be used to generate a better estimate of the response rate with these schedules to compare to the once every three week schedule."
"The results presented at ASCO are important because they expand the activity of CR011 into patients with metastatic breast cancer and open this area up as an important development opportunity in addition to the opportunity in patients with metastatic melanoma," commented Dr. Timothy Shannon, President and Chief Executive Officer of CuraGen. "The remainder of these studies will be used to better understand the breast cancer opportunity and to understand how dose, schedule and the use of biomarkers such as the presence of GPNMB and rash might be used to enhance activity in further development."
About CR011-vcMMAE
CR011-vcMMAE is an antibody-drug conjugate (ADC) being developed by CuraGen that consists of a fully-human monoclonal antibody, CR011, linked to a potent cell-killing drug, monomethyl-auristatin E (MMAE). The ADC technology, comprised of MMAE and a stable linker system for attaching it to CR011, was licensed from Seattle Genetics, Inc. The ADC is designed to be stable in the bloodstream. Following intravenous administration, CR011-vcMMAE targets and binds to GPNMB, a specific protein that is predominantly expressed on the surface of cancer cells, including melanoma, breast cancer and gliomas. Upon internalization into the targeted cell, CR011-vcMMAE is designed to release MMAE from CR011 to produce a cell-killing effect. CR011-vcMMAE is currently in two Phase II trials assessing the safety and efficacy in the treatment of melanoma and for the treatment of metastatic breast cancer, and in a Phase I trial to evaluate the safety and activity of alternate dosing schedules.
About Melanoma
According to the American Cancer Society, it is expected that approximately 60,000 new cases of melanoma will be diagnosed, including nearly 11,000 patients diagnosed with Stage III or Stage IV disease, and an estimated 8,000 people in the U.S. will die of the disease during 2009. The prognosis for patients with advanced melanoma is poor, and studies have shown that the median survival is less than nine months.
About Breast Cancer
Breast cancer is the most common cancer in women and a leading cause of death in the United States. According to the American Cancer Society, more than 180,000 women will be diagnosed with invasive breast cancer in 2009 with more than 40,000 deaths attributed to this disease. Despite recent advances in therapy, the median survival of patients with metastatic breast cancer is 2 to 3 years, while patients with "triple-negative" or "basal-like" breast cancer have limited treatment options and poorer outcomes. Therefore, a significant unmet need remains for novel therapeutic approaches for patients with locally advanced and metastatic breast cancer who have failed other therapies.
About CuraGen
CuraGen Corporation (Nasdaq: CRGN) is a clinical-stage biopharmaceutical company developing promising approaches for the treatment of cancer. CuraGen Corporation is headquartered in Branford, Connecticut.
Forward Looking Statements
Statements in this press release regarding management's future expectations, beliefs, intentions, goals, strategies, plans or prospects, including statements relating to CuraGen's development program for CR011-vcMMAE, including CuraGen's ability to advance CR011-vcMMAE through Phase II clinical trials for melanoma and metastatic breast cancer, to explore additional doses and schedules of this antibody-drug conjugate, and to explore the potential of CR011-vcMMAE in a patient population in need of new therapies may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by terminology such as "anticipate," "believe," "could," "could increase the likelihood," "estimate," "expect," "intend," "is planned," "may," "should," "will," "will enable," "would be expected," "look forward," "may provide," "would" or similar terms, variations of such terms or the negative of those terms. Such forward-looking statements involve known and unknown risks, uncertainties and other factors including the risk that any one or more of CuraGen's drug development programs will not proceed as planned for technical, scientific or commercial reasons or due to patient enrollment issues or based on new information from nonclinical or clinical studies or from other sources, the success of competing products and technologies, CuraGen's stage of development as a biopharmaceutical company, government regulation and healthcare reform, technological uncertainty and product development risks, product liability exposure, uncertainty of additional funding, CuraGen's history of incurring losses and the uncertainty of achieving profitability, reliance on research collaborations and strategic alliances, competition, patent infringement claims against CuraGen's products, processes and technologies, CuraGen's ability to protect its patents and proprietary rights and uncertainties relating to commercialization rights, as well as those risks, uncertainties and factors referred to in CuraGen's Quarterly Report on Form 10-Q for the period ended March 31, 2009 filed with the Securities and Exchange Commission under the section "Risk Factors," as well as other documents that may be filed by CuraGen from time to time with the Securities and Exchange Commission. As a result of such risks, uncertainties and factors, CuraGen's actual results may differ materially from any future results, performance or achievements discussed in or implied by the forward-looking statements contained herein. CuraGen is providing the information in this press release as of this date and assumes no obligations to update the information included in this press release or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Source: CuraGen Corporation
пятница, 10 июня 2011 г.
Circulating Tumor Cells Are A Reliable Predictor Of Treatment Response In Metastatic Breast Cancer
With the goal of tailoring cancer treatment for each individual, researchers at Georgetown University Medical Center have presented a study suggesting a simple blood test can help doctors more reliably assess treatment efficacy for patients with metastatic breast cancer.
"It can take several weeks and sometimes months to determine if a particular cancer treatment is working because it can take that long to observe any significant radiographic changes in tumor size or appearance," says Minetta Liu, M.D., of Georgetown's Lombardi Comprehensive Cancer Center. "Right now, we have to rely on radiology studies such as CT scans, ultrasound, and the like to determine whether or not there is disease progression. With this new blood test, we have another reliable tool that may allow us to determine much sooner if a therapy is ineffective so that we can change therapy earlier and potentially make more significant improvements in survival."
Using the FDA-approved CellSearch™ technology, researchers measured the number of circulating tumor cells (CTC) in blood collected from women with metastatic breast cancer. About one tablespoon of blood was collected every three to four weeks. The number of CTCs was correlated with disease response or progression as determined by standard radiology studies performed every 9-12 weeks. The women in the study received various treatments including chemotherapy, endocrine therapy, and combination therapy with a biologic agent.
A CTC count of five was used as the threshold, based on previous studies. There was a highly significant difference in the distribution of progression between two groups of patients defined by their CTC result. Seventy-one percent of patients who had a CTC greater than or equal to five had disease progression, and 66 percent of patients with a CTC count of less than five did not.
"A CTC count of five or greater at the time of restaging was associated with a 5.32 fold increase in a patient's chance of having disease progression compared to CTC counts of less than five," explains Liu. "CTC assessments should be used as a surrogate marker for treatment efficacy and disease responsiveness. Changes in CTC results from less than five to greater than or equal to five over time may herald disease progression."
Liu adds that the CTC assay is a more reliable means of assessing treatment response than the traditional tumor markers currently in use.
"We have a follow-up study underway that evaluates CTC results within the framework of a randomized clinical trial to eliminate potential variability from the treatment administered, "says Liu, the national principal investigator of the new trial. Liu and her colleagues believe a study with the same therapies would offer even stronger evidence for routine use of CTC in patients with metastatic breast cancer.
"We have many treatment options for advanced breast cancer. The key is to find the most effective therapy for each patient. It shouldn't take months to figure that out," she concludes.
The study was funded by Veridex, LLC, makers of CellSearch. Liu reports receiving limited compensation for research-related speaking engagements on behalf of Veridex.
Liu's preliminary results have been released online in advance of the American Society of Clinical Oncology annual meeting. The complete data will be presented during the poster discussion of this study at the annual meeting place in Chicago May 30-June 3.
About Lombardi Comprehensive Cancer Center
The Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Lombardi is one of only 39 comprehensive cancer centers in the nation, as designated by the National Cancer Institute, and the only one in the Washington, DC, area. For more information, go to lombardi.georgetown/.
About Georgetown University Medical Center
Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through our partnership with MedStar Health). Our mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, the world-renowned Lombardi Comprehensive Cancer Center and the Biomedical Graduate Research Organization (BGRO), home to 60 percent of the university's sponsored research funding.
Source: Karen Mallet
Georgetown University Medical Center
"It can take several weeks and sometimes months to determine if a particular cancer treatment is working because it can take that long to observe any significant radiographic changes in tumor size or appearance," says Minetta Liu, M.D., of Georgetown's Lombardi Comprehensive Cancer Center. "Right now, we have to rely on radiology studies such as CT scans, ultrasound, and the like to determine whether or not there is disease progression. With this new blood test, we have another reliable tool that may allow us to determine much sooner if a therapy is ineffective so that we can change therapy earlier and potentially make more significant improvements in survival."
Using the FDA-approved CellSearch™ technology, researchers measured the number of circulating tumor cells (CTC) in blood collected from women with metastatic breast cancer. About one tablespoon of blood was collected every three to four weeks. The number of CTCs was correlated with disease response or progression as determined by standard radiology studies performed every 9-12 weeks. The women in the study received various treatments including chemotherapy, endocrine therapy, and combination therapy with a biologic agent.
A CTC count of five was used as the threshold, based on previous studies. There was a highly significant difference in the distribution of progression between two groups of patients defined by their CTC result. Seventy-one percent of patients who had a CTC greater than or equal to five had disease progression, and 66 percent of patients with a CTC count of less than five did not.
"A CTC count of five or greater at the time of restaging was associated with a 5.32 fold increase in a patient's chance of having disease progression compared to CTC counts of less than five," explains Liu. "CTC assessments should be used as a surrogate marker for treatment efficacy and disease responsiveness. Changes in CTC results from less than five to greater than or equal to five over time may herald disease progression."
Liu adds that the CTC assay is a more reliable means of assessing treatment response than the traditional tumor markers currently in use.
"We have a follow-up study underway that evaluates CTC results within the framework of a randomized clinical trial to eliminate potential variability from the treatment administered, "says Liu, the national principal investigator of the new trial. Liu and her colleagues believe a study with the same therapies would offer even stronger evidence for routine use of CTC in patients with metastatic breast cancer.
"We have many treatment options for advanced breast cancer. The key is to find the most effective therapy for each patient. It shouldn't take months to figure that out," she concludes.
The study was funded by Veridex, LLC, makers of CellSearch. Liu reports receiving limited compensation for research-related speaking engagements on behalf of Veridex.
Liu's preliminary results have been released online in advance of the American Society of Clinical Oncology annual meeting. The complete data will be presented during the poster discussion of this study at the annual meeting place in Chicago May 30-June 3.
About Lombardi Comprehensive Cancer Center
The Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Lombardi is one of only 39 comprehensive cancer centers in the nation, as designated by the National Cancer Institute, and the only one in the Washington, DC, area. For more information, go to lombardi.georgetown/.
About Georgetown University Medical Center
Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through our partnership with MedStar Health). Our mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, the world-renowned Lombardi Comprehensive Cancer Center and the Biomedical Graduate Research Organization (BGRO), home to 60 percent of the university's sponsored research funding.
Source: Karen Mallet
Georgetown University Medical Center
New Breast Cancer Survival Data From The Intergroup Exemestane Study (IES) Published In The Lancet Today
New data from the Intergroup Exemestane Study (IES),
published in the Lancet today show that, 2 to 3 years after the end of their treatment,
postmenopausal women with oestrogen sensitive early breast cancer who switched to
exemestane (AROMASIN™) after 2 to 3 years of tamoxifen are 15% - 17% more likely to
be alive, compared to patients who remained on tamoxifen for the full five years of therapy.
These data also demonstrated that patients who switched to exemestane are 25% less
likely to have their cancer return than patients who continued on tamoxifen.1
Lead Investigator Professor Charles Coombes, Director of Cancer Medicine, Imperial
College, London explained: "Exemestane, when given after 2-3 years tamoxifen, reduces
the risk of dying by an additional 15-17% in women with endocrine (hormone) responsive
breast cancer, which accounts for 80-85% of all cases in postmenopausal patients. Since
tamoxifen reduces the risk of dying by 31%, by sequencing, we have shown that the
benefit is to nearly half the risk of dying when compared with no endocrine treatment."
The Lancet publication reinforces the strength of the exemestane data and follows NICE's
Final Appraisal Determination (FAD) on hormonal therapies for the adjuvant treatment of
early oestrogen-receptor-positive breast cancer. Exemestane is the only treatment option
recommended by NICE as an alternative to continued tamoxifen for women who have
already received 2-3 years of initial adjuvant tamoxifen therapy.2
It is estimated that 31,000 postmenopausal women are diagnosed with breast cancer
every year in the UK.2 Exemestane works in postmenopausal women where the hormone
oestrogen promotes tumour growth, which occurs in over two thirds of cases.3 Tamoxifen
blocks the effects of oestrogen on cancer cells, whereas exemestane inhibits the body's
production of oestrogen, stopping the supply of oestrogen to the cancer cells.
"Exemestane is now available in the UK to the thousands of postmenopausal women who
have been and will be diagnosed with oestrogen sensitive breast cancer," said Dr Mary
McCormack, Consultant Clinical Oncologist, University College London Hospital. "It is
important that women with the disease who have received tamoxifen for two to three
years, are fully informed of the potential benefits of switching therapy," she continued.
AROMASIN (exemestane) indication
AROMASIN (exemestane) is indicated for the adjuvant treatment of postmenopausal women with
oestrogen receptor positive invasive early breast cancer, following 2 -3 years of initial adjuvant
tamoxifen therapy. It has been licensed for the treatment of advanced breast cancer in patients that
have progressed on anti-oestrogen therapy since 1999.
About the Intergroup Exemestane Study (IES)1
• The IES is a randomised phase III double-blind study in postmenopausal women with
oestrogen sensitive early breast cancer. The study was designed to test whether, switching to
exemestane after 2-3 years of tamoxifen was more effective than continuing tamoxifen therapy
for the remainder of the five years of treatment
• The study enrolled 4,742 patients from 37 countries and 20 co-operative groups
-- Exemestane group = 2,362 patients
-- Tamoxifen group = 2,380 patients
• Average time on tamoxifen prior to switching to exemestane: 28 months
-- Median follow-up of updated efficacy analysis: 55.7 months
• Compared to continuing tamoxifen therapy, switching to exemestane after 2-3 years of
tamoxifen in postmenopausal women with early breast cancer fuelled by oestrogen has been
shown to:
-- improve disease free survival by 24 percent
-- reduce the risk of the breast cancer coming back by 24 percent
-- reduce the risk of cancer occurring in the other breast by 43 percent
• Aromasin® was generally well tolerated across all studies and in the clinical studies, conducted
with Aromasin®, undesirable effects were usually mild to moderate. The withdrawal rate due to
adverse events in studies was 6.3% in patients with early breast cancer receiving adjuvant
treatment with Aromasin® following initial adjuvant tamoxifen therapy.
- The most commonly reported adverse reactions were hot flushes (22%), arthralgia (17%)
and fatigue (17%).
- Fractures occurred in 277 patients; 162 (7%) exemestane-treated patients and 115 (4.9%)
tamoxifen-treated patients (p=0.003). Hip, spine and wrist fracture rates were low. During
adjuvant treatment with Aromasin®, women with osteoporosis or at risk of osteoporosis
should have their bone mineral density formally assessed by bone densitometry at the
commencement of treatment.
- Most adverse reactions can be attributed to the normal pharmacological consequences of
oestrogen deprivation (e.g. hot flushes).
• Lead investigator:
Professor Charles Coombes
Head of Department, Cancer Medicine - Imperial College School of Medicine
Breast cancer facts4
• Breast cancer is the most common cancer in women, around 42,000 women are diagnosed
each year in the UK
• The strongest risk factor for breast cancer is age: the older the woman the higher the risk
• Most cases (around 80%) of breast cancer occur in postmenopausal women - approximately
8,000 women were diagnosed before their menopause in the UK in 2000
Pfizer Oncology
Pfizer is a research-based global pharmaceutical company that discovers, develops, manufactures
and markets leading prescription medicines for humans and animals, and many of the world's bestknown
brands. In 2003, Pfizer acquired Pharmacia, bringing together two of the world's fastest
growing and most innovative companies to become the largest pharmaceutical company in the
world. The combination expanded Pfizer's global pharmaceutical leadership, broadened its product
base and bolstered its research and development capacity. Currently, Pfizer employs over 100,000
people in over 60 countries, has sales in more than 150 countries. pfizeroncology
References
1 Coombes RC, Kilburn LS, Snowdon CF, on behalf of the Intergroup Exemestane Study. Survival
and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup
Exemestane Study): a randomised controlled trial. Lancet 2007; published online Feb
13.DOI:10.1016/S0140-6736(07)60200-1.
2 National Institute of Clinical Excellence, Final Appraisal Determination. Hormonal therapies for the
adjuvant treatment of early oestrogen-receptor-positive breast cancer: nice.uk
Accessed August 2006
3 Health-cares. Hormone therapy for breast cancer, Available
here. Accessed August 2006
4 Breast Cancer Care. Statistics and facts about breast cancer, Available
here. Accessed August 2006
View drug information on Aromasin Tablets.
published in the Lancet today show that, 2 to 3 years after the end of their treatment,
postmenopausal women with oestrogen sensitive early breast cancer who switched to
exemestane (AROMASIN™) after 2 to 3 years of tamoxifen are 15% - 17% more likely to
be alive, compared to patients who remained on tamoxifen for the full five years of therapy.
These data also demonstrated that patients who switched to exemestane are 25% less
likely to have their cancer return than patients who continued on tamoxifen.1
Lead Investigator Professor Charles Coombes, Director of Cancer Medicine, Imperial
College, London explained: "Exemestane, when given after 2-3 years tamoxifen, reduces
the risk of dying by an additional 15-17% in women with endocrine (hormone) responsive
breast cancer, which accounts for 80-85% of all cases in postmenopausal patients. Since
tamoxifen reduces the risk of dying by 31%, by sequencing, we have shown that the
benefit is to nearly half the risk of dying when compared with no endocrine treatment."
The Lancet publication reinforces the strength of the exemestane data and follows NICE's
Final Appraisal Determination (FAD) on hormonal therapies for the adjuvant treatment of
early oestrogen-receptor-positive breast cancer. Exemestane is the only treatment option
recommended by NICE as an alternative to continued tamoxifen for women who have
already received 2-3 years of initial adjuvant tamoxifen therapy.2
It is estimated that 31,000 postmenopausal women are diagnosed with breast cancer
every year in the UK.2 Exemestane works in postmenopausal women where the hormone
oestrogen promotes tumour growth, which occurs in over two thirds of cases.3 Tamoxifen
blocks the effects of oestrogen on cancer cells, whereas exemestane inhibits the body's
production of oestrogen, stopping the supply of oestrogen to the cancer cells.
"Exemestane is now available in the UK to the thousands of postmenopausal women who
have been and will be diagnosed with oestrogen sensitive breast cancer," said Dr Mary
McCormack, Consultant Clinical Oncologist, University College London Hospital. "It is
important that women with the disease who have received tamoxifen for two to three
years, are fully informed of the potential benefits of switching therapy," she continued.
AROMASIN (exemestane) indication
AROMASIN (exemestane) is indicated for the adjuvant treatment of postmenopausal women with
oestrogen receptor positive invasive early breast cancer, following 2 -3 years of initial adjuvant
tamoxifen therapy. It has been licensed for the treatment of advanced breast cancer in patients that
have progressed on anti-oestrogen therapy since 1999.
About the Intergroup Exemestane Study (IES)1
• The IES is a randomised phase III double-blind study in postmenopausal women with
oestrogen sensitive early breast cancer. The study was designed to test whether, switching to
exemestane after 2-3 years of tamoxifen was more effective than continuing tamoxifen therapy
for the remainder of the five years of treatment
• The study enrolled 4,742 patients from 37 countries and 20 co-operative groups
-- Exemestane group = 2,362 patients
-- Tamoxifen group = 2,380 patients
• Average time on tamoxifen prior to switching to exemestane: 28 months
-- Median follow-up of updated efficacy analysis: 55.7 months
• Compared to continuing tamoxifen therapy, switching to exemestane after 2-3 years of
tamoxifen in postmenopausal women with early breast cancer fuelled by oestrogen has been
shown to:
-- improve disease free survival by 24 percent
-- reduce the risk of the breast cancer coming back by 24 percent
-- reduce the risk of cancer occurring in the other breast by 43 percent
• Aromasin® was generally well tolerated across all studies and in the clinical studies, conducted
with Aromasin®, undesirable effects were usually mild to moderate. The withdrawal rate due to
adverse events in studies was 6.3% in patients with early breast cancer receiving adjuvant
treatment with Aromasin® following initial adjuvant tamoxifen therapy.
- The most commonly reported adverse reactions were hot flushes (22%), arthralgia (17%)
and fatigue (17%).
- Fractures occurred in 277 patients; 162 (7%) exemestane-treated patients and 115 (4.9%)
tamoxifen-treated patients (p=0.003). Hip, spine and wrist fracture rates were low. During
adjuvant treatment with Aromasin®, women with osteoporosis or at risk of osteoporosis
should have their bone mineral density formally assessed by bone densitometry at the
commencement of treatment.
- Most adverse reactions can be attributed to the normal pharmacological consequences of
oestrogen deprivation (e.g. hot flushes).
• Lead investigator:
Professor Charles Coombes
Head of Department, Cancer Medicine - Imperial College School of Medicine
Breast cancer facts4
• Breast cancer is the most common cancer in women, around 42,000 women are diagnosed
each year in the UK
• The strongest risk factor for breast cancer is age: the older the woman the higher the risk
• Most cases (around 80%) of breast cancer occur in postmenopausal women - approximately
8,000 women were diagnosed before their menopause in the UK in 2000
Pfizer Oncology
Pfizer is a research-based global pharmaceutical company that discovers, develops, manufactures
and markets leading prescription medicines for humans and animals, and many of the world's bestknown
brands. In 2003, Pfizer acquired Pharmacia, bringing together two of the world's fastest
growing and most innovative companies to become the largest pharmaceutical company in the
world. The combination expanded Pfizer's global pharmaceutical leadership, broadened its product
base and bolstered its research and development capacity. Currently, Pfizer employs over 100,000
people in over 60 countries, has sales in more than 150 countries. pfizeroncology
References
1 Coombes RC, Kilburn LS, Snowdon CF, on behalf of the Intergroup Exemestane Study. Survival
and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup
Exemestane Study): a randomised controlled trial. Lancet 2007; published online Feb
13.DOI:10.1016/S0140-6736(07)60200-1.
2 National Institute of Clinical Excellence, Final Appraisal Determination. Hormonal therapies for the
adjuvant treatment of early oestrogen-receptor-positive breast cancer: nice.uk
Accessed August 2006
3 Health-cares. Hormone therapy for breast cancer, Available
here. Accessed August 2006
4 Breast Cancer Care. Statistics and facts about breast cancer, Available
here. Accessed August 2006
View drug information on Aromasin Tablets.
четверг, 9 июня 2011 г.
New Breast Cancer Clinical Data Accepted For Presentation At San Antonio Breast Cancer Symposium
Predictive medicine company
PreMD Inc. (TSX: PMD; Amex: PME) announced that an abstract entitled,
'Galactose oxidase Schiff's reactivity is higher in nipple aspirate fluid
from cancerous breasts than from healthy patients' has been accepted for
presentation at the 30th Annual San Antonio Breast Cancer Symposium
(SABCS). The SABCS is a leading international symposium for physicians and
healthcare researchers involved in breast cancer research.
"We are extremely pleased and honored that this abstract has been
accepted for presentation at this influential symposium," said Brent
Norton, president and chief executive officer of PreMD Inc. "This study
provides valuable clinical insight as to how women with unilateral breast
cancer may benefit from testing with galactose oxidase Schiff's (GOS)
reactivity. This presentation further strengthens our clinical data and our
entire cancer franchise, which we are progressively developing."
GOS reactivity is significantly different between nipple aspirate fluid
(NAF) taken from cancerous versus non-cancerous breasts of women with
unilateral breast cancer. This study extends these findings and evaluates
GOS reactivity in healthy control patients.
The lead author on the study is Dr. Anees B. Chagpar from the
University of Louisville. The San Antonio Breast Cancer Symposium takes
place on December 13-16, 2007, in San Antonio, Texas.
About PreMD Inc.
PreMD Inc. is a leader in predictive medicine, dedicated to developing
rapid, non-invasive tests for the early detection of life-threatening
diseases. PreMD's cardiovascular products are branded as PREVU(x) Skin
Cholesterol Test, to be marketed and distributed by AstraZeneca. The
company's cancer tests include ColorectAlert(TM), LungAlert(TM) and a
breast cancer test. PreMD's head office is located in Toronto, Ontario and
its research and product development facility is at McMaster University in
Hamilton, Ontario. For further information, please visit premdinc.
For more information about PREVU(x), please visit prevu.
This press release contains forward-looking statements. These
statements involve known and unknown risks and uncertainties, which could
cause the Company's actual results to differ materially from those in the
forward-looking statements. Such risks and uncertainties include, among
others, the success of a plan for regaining compliance with certain
continued listing standards of the American Stock Exchange, successful
development or marketing of the Company's products, the competitiveness of
the Company's products if successfully commercialized, the lack of
operating profit and availability of funds and resources to pursue R&D
projects, the successful and timely completion of clinical studies, product
liability, reliance on third-party manufacturers, the ability of the
Company to take advantage of business opportunities, uncertainties related
to the regulatory process, and general changes in economic conditions.
In addition, while the Company routinely obtains patents for its
products and technology, the protection offered by the Company's patents
and patent applications may be challenged, invalidated or circumvented by
our competitors and there can be no guarantee of our ability to obtain or
maintain patent protection for our products or product candidates.
Investors should consult the Company's quarterly and annual filings
with the Canadian and U.S. securities commissions for additional
information on risks and uncertainties relating to the forward-looking
statements. Investors are cautioned not to rely on these forward-looking
statements. PreMD is providing this information as of the date of this
press release and does not undertake any obligation to update any
forward-looking statements contained in this press release as a result of
new information, future events or otherwise.
(x) Trademark
PreMD Inc.
premdinc
PreMD Inc. (TSX: PMD; Amex: PME) announced that an abstract entitled,
'Galactose oxidase Schiff's reactivity is higher in nipple aspirate fluid
from cancerous breasts than from healthy patients' has been accepted for
presentation at the 30th Annual San Antonio Breast Cancer Symposium
(SABCS). The SABCS is a leading international symposium for physicians and
healthcare researchers involved in breast cancer research.
"We are extremely pleased and honored that this abstract has been
accepted for presentation at this influential symposium," said Brent
Norton, president and chief executive officer of PreMD Inc. "This study
provides valuable clinical insight as to how women with unilateral breast
cancer may benefit from testing with galactose oxidase Schiff's (GOS)
reactivity. This presentation further strengthens our clinical data and our
entire cancer franchise, which we are progressively developing."
GOS reactivity is significantly different between nipple aspirate fluid
(NAF) taken from cancerous versus non-cancerous breasts of women with
unilateral breast cancer. This study extends these findings and evaluates
GOS reactivity in healthy control patients.
The lead author on the study is Dr. Anees B. Chagpar from the
University of Louisville. The San Antonio Breast Cancer Symposium takes
place on December 13-16, 2007, in San Antonio, Texas.
About PreMD Inc.
PreMD Inc. is a leader in predictive medicine, dedicated to developing
rapid, non-invasive tests for the early detection of life-threatening
diseases. PreMD's cardiovascular products are branded as PREVU(x) Skin
Cholesterol Test, to be marketed and distributed by AstraZeneca. The
company's cancer tests include ColorectAlert(TM), LungAlert(TM) and a
breast cancer test. PreMD's head office is located in Toronto, Ontario and
its research and product development facility is at McMaster University in
Hamilton, Ontario. For further information, please visit premdinc.
For more information about PREVU(x), please visit prevu.
This press release contains forward-looking statements. These
statements involve known and unknown risks and uncertainties, which could
cause the Company's actual results to differ materially from those in the
forward-looking statements. Such risks and uncertainties include, among
others, the success of a plan for regaining compliance with certain
continued listing standards of the American Stock Exchange, successful
development or marketing of the Company's products, the competitiveness of
the Company's products if successfully commercialized, the lack of
operating profit and availability of funds and resources to pursue R&D
projects, the successful and timely completion of clinical studies, product
liability, reliance on third-party manufacturers, the ability of the
Company to take advantage of business opportunities, uncertainties related
to the regulatory process, and general changes in economic conditions.
In addition, while the Company routinely obtains patents for its
products and technology, the protection offered by the Company's patents
and patent applications may be challenged, invalidated or circumvented by
our competitors and there can be no guarantee of our ability to obtain or
maintain patent protection for our products or product candidates.
Investors should consult the Company's quarterly and annual filings
with the Canadian and U.S. securities commissions for additional
information on risks and uncertainties relating to the forward-looking
statements. Investors are cautioned not to rely on these forward-looking
statements. PreMD is providing this information as of the date of this
press release and does not undertake any obligation to update any
forward-looking statements contained in this press release as a result of
new information, future events or otherwise.
(x) Trademark
PreMD Inc.
premdinc
среда, 8 июня 2011 г.
Xgeva (denosumab), To Protect Bones Of Patients With Advanced Cancer Approved By FDA
Patients with cancer that has metastasized (spread) may benefit from treatment with Xgeva (denosumab), which has been approved by the FDA (Food and Drug Administration) today. Specifically, Xgeva is designed to protect against skeletal-related events in advanced cancer patients who have bone damage - bone metastasis. Examples of skeletal-related events are bone fractures linked to cancer, and bone pain that requires radiation therapy or surgery.
Human TANKL is a protein involved in the destruction of the bones in patients with cancer. Xgeva, a monoclonal antibody, tagets human RANKL. Zometa (zoledronic acid) and Aredia (pamidronate disodium), two other medications, also have similar indications.
Patients with multiple myeloma or other blood cancers should not be given Xgeva, the FDA informs.
Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, said:
"Bone metastases represent a major cause of pain and suffering in patients with cancer and can affect a patient's quality of life. Xgeva has a different mechanism of action than currently approved drugs aimed at reducing bone complications from cancer."
Bone metastasis is the spread of cancer to the bones.
Three randomized, double-blind clinical trials involving 5,723 participants which compared Xgeva with Zometa for safety and effectiveness confirmed those primary endpoints - in other words, the drug was found to be safe and effective. One of the studies was with breast cancer patients, another with prostate cancer, and the other involved patients with several different types of cancers.
The studies aimed to measure how long it took for a fracture or cord compression to occur, as well as length of time before radiation or surgery to treat bone pain was required.
Xgeva was found to be better than Zometa in delaying skeletal related events (SREs) in breast and prostate cancer patients. Among the prostate cancer participants on Xgeva, the average time was 21 months, compared to 16 months for those on Zometa.
Breast cancer patients on Zometa have taken an average of 26 to experience an SRE. The length of time for those on Xgeva has not been reached yet, the FDA wrote today.
Among those with other cancers (other solid tumors), there was no significant difference in time to develop an SRE between the two drugs. Most of the patients with other cancers had non-small cell lung cancer, kidney cancer, small cell lung cancer, and multiple myeloma.
The most serious adverse events linked to Xgeva use were hypocalcemia (low calcium blood levels) and osteonecrosis of the jaw.
Denosumab, under the brand name Prolia, was approved in June this year for postmenopausal females who were at higher risk of developing bone fractures. Xgeva is given at a higher dose for cancer patients than Prolia is to post-menopausal women, and also more frequently. Xgeva's profile for patients with cancer and bone metastases is different from Prolia's.
Kevin Sharer, chairman and chief executive officer of Amgen, the marketers of Xgeva, said:
"Today's approval of XGEVA illustrates what is possible when scientific innovation, commitment and investment come together to advance medicine. A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating. We are pleased to offer this new advance to patients and their healthcare providers."
David H. Henry, M.D., clinical professor of medicine, and vice chair, Department of Medicine, Pennsylvania Hospital, University of Pennsylvania Healthcare System, said:
"As many as 3 out of 4 patients with advanced prostate, lung, and breast cancer will experience spread to their bones. Despite the availability of current treatments, a significant proportion of these patients still experience bone complications or are not candidates for existing treatment. Based on the compelling science and robust clinical evidence seen with XGEVA, I expect this new option to quickly become a mainstay of cancer care and to play an important role in reducing the incidence of debilitating bone complications in patients with advanced cancer."
Bone metastases are estimated to cost the US economy approximately $12 billion each year. Cancer patients who have an SRE linked to bone metastases subsequently incur much higher medical costs, compared to similar patients who don't. A patient who does have an SRE has a much higher risk of eventually having another one.
Sources: FDA, Amgen
Written by
View drug information on Aredia; Prolia; Xgeva.
Human TANKL is a protein involved in the destruction of the bones in patients with cancer. Xgeva, a monoclonal antibody, tagets human RANKL. Zometa (zoledronic acid) and Aredia (pamidronate disodium), two other medications, also have similar indications.
Patients with multiple myeloma or other blood cancers should not be given Xgeva, the FDA informs.
Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, said:
"Bone metastases represent a major cause of pain and suffering in patients with cancer and can affect a patient's quality of life. Xgeva has a different mechanism of action than currently approved drugs aimed at reducing bone complications from cancer."
Bone metastasis is the spread of cancer to the bones.
Three randomized, double-blind clinical trials involving 5,723 participants which compared Xgeva with Zometa for safety and effectiveness confirmed those primary endpoints - in other words, the drug was found to be safe and effective. One of the studies was with breast cancer patients, another with prostate cancer, and the other involved patients with several different types of cancers.
The studies aimed to measure how long it took for a fracture or cord compression to occur, as well as length of time before radiation or surgery to treat bone pain was required.
Xgeva was found to be better than Zometa in delaying skeletal related events (SREs) in breast and prostate cancer patients. Among the prostate cancer participants on Xgeva, the average time was 21 months, compared to 16 months for those on Zometa.
Breast cancer patients on Zometa have taken an average of 26 to experience an SRE. The length of time for those on Xgeva has not been reached yet, the FDA wrote today.
Among those with other cancers (other solid tumors), there was no significant difference in time to develop an SRE between the two drugs. Most of the patients with other cancers had non-small cell lung cancer, kidney cancer, small cell lung cancer, and multiple myeloma.
The most serious adverse events linked to Xgeva use were hypocalcemia (low calcium blood levels) and osteonecrosis of the jaw.
Denosumab, under the brand name Prolia, was approved in June this year for postmenopausal females who were at higher risk of developing bone fractures. Xgeva is given at a higher dose for cancer patients than Prolia is to post-menopausal women, and also more frequently. Xgeva's profile for patients with cancer and bone metastases is different from Prolia's.
Kevin Sharer, chairman and chief executive officer of Amgen, the marketers of Xgeva, said:
"Today's approval of XGEVA illustrates what is possible when scientific innovation, commitment and investment come together to advance medicine. A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating. We are pleased to offer this new advance to patients and their healthcare providers."
David H. Henry, M.D., clinical professor of medicine, and vice chair, Department of Medicine, Pennsylvania Hospital, University of Pennsylvania Healthcare System, said:
"As many as 3 out of 4 patients with advanced prostate, lung, and breast cancer will experience spread to their bones. Despite the availability of current treatments, a significant proportion of these patients still experience bone complications or are not candidates for existing treatment. Based on the compelling science and robust clinical evidence seen with XGEVA, I expect this new option to quickly become a mainstay of cancer care and to play an important role in reducing the incidence of debilitating bone complications in patients with advanced cancer."
Bone metastases are estimated to cost the US economy approximately $12 billion each year. Cancer patients who have an SRE linked to bone metastases subsequently incur much higher medical costs, compared to similar patients who don't. A patient who does have an SRE has a much higher risk of eventually having another one.
Sources: FDA, Amgen
Written by
View drug information on Aredia; Prolia; Xgeva.
вторник, 7 июня 2011 г.
Mammography Utilization In The United States Decreases: A State-Level Look
Nearly two thirds of the states in the US saw a small decrease in mammography utilization between the years 2000 and 2006, according to a study performed at the Centers for Disease Control and Prevention (CDC) in Atlanta, GA.
Data showed that although mammography use in 17 states including Minnesota, Tennessee, Georgia and Alabama had increased slightly between 2002 and 2006, mammography use in 34 states and the District of Columbia including Utah, South Carolina, New Mexico and Delaware had a slight decrease. The decrease in utilization ranged from -0.3% to -5.3%. The CDC also reviewed incidence rates and found that between 2000 and 2004 all but one state (Tennessee) had a decrease in breast cancer incidence rates. There was no clear pattern among the states though in regards to region, average age, average income or population density.
"The Government Accountability Office reported that there was a 6% decrease in mammography facilities use across the US, but despite their report there is a growing concern that this rate in low resource areas could be higher," said Jacqueline Miller, MD, lead author of the study. "Women in these areas may not have a convenient place to go. Also, reports have shown that insurance co-pays were related to women not getting their mammogram and we know that some insurance companies have increased their co-pay requirements. When there are more out of pocket costs, women start weighing the costs of screening against other competing factors," said Dr. Miller.
"Monitoring breast cancer screening practices and breast cancer incidence trends at the state-level may enable us to catch changes early. If we start to see that screening rates are going down, we can work to identify where and who interventions need to be targeted," said Dr. Miller. "In doing so, we can decrease invasive breast cancer incidences and breast cancer mortalities," she said.
"We need to do more to get the word out to women and healthcare providers about the importance of mammography. At the state-level, we hope to get the word out in different avenues to reach different audiences," said Dr. Miller.
This study appears in the February issue of the American Journal of Roentgenology.
Click here for abstract
About ARRS
The American Roentgen Ray Society (ARRS) was founded in 1900 and is the oldest radiology society in the United States. Its monthly journal, the American Journal of Roentgenology, began publication in 1906. Radiologists from all over the world attend the ARRS annual meeting to participate in instructional courses, scientific paper presentations and scientific and commercial exhibits related to the field of radiology. The Society is named after the first Nobel Laureate in Physics, Wilhelm Röentgen, who discovered the x-ray in 1895.
American Roentgen Ray Society
Data showed that although mammography use in 17 states including Minnesota, Tennessee, Georgia and Alabama had increased slightly between 2002 and 2006, mammography use in 34 states and the District of Columbia including Utah, South Carolina, New Mexico and Delaware had a slight decrease. The decrease in utilization ranged from -0.3% to -5.3%. The CDC also reviewed incidence rates and found that between 2000 and 2004 all but one state (Tennessee) had a decrease in breast cancer incidence rates. There was no clear pattern among the states though in regards to region, average age, average income or population density.
"The Government Accountability Office reported that there was a 6% decrease in mammography facilities use across the US, but despite their report there is a growing concern that this rate in low resource areas could be higher," said Jacqueline Miller, MD, lead author of the study. "Women in these areas may not have a convenient place to go. Also, reports have shown that insurance co-pays were related to women not getting their mammogram and we know that some insurance companies have increased their co-pay requirements. When there are more out of pocket costs, women start weighing the costs of screening against other competing factors," said Dr. Miller.
"Monitoring breast cancer screening practices and breast cancer incidence trends at the state-level may enable us to catch changes early. If we start to see that screening rates are going down, we can work to identify where and who interventions need to be targeted," said Dr. Miller. "In doing so, we can decrease invasive breast cancer incidences and breast cancer mortalities," she said.
"We need to do more to get the word out to women and healthcare providers about the importance of mammography. At the state-level, we hope to get the word out in different avenues to reach different audiences," said Dr. Miller.
This study appears in the February issue of the American Journal of Roentgenology.
Click here for abstract
About ARRS
The American Roentgen Ray Society (ARRS) was founded in 1900 and is the oldest radiology society in the United States. Its monthly journal, the American Journal of Roentgenology, began publication in 1906. Radiologists from all over the world attend the ARRS annual meeting to participate in instructional courses, scientific paper presentations and scientific and commercial exhibits related to the field of radiology. The Society is named after the first Nobel Laureate in Physics, Wilhelm Röentgen, who discovered the x-ray in 1895.
American Roentgen Ray Society
The Importance Of Healthy Living Reinforced By 'First Sister' Study Results
Women who maintain a healthy weight and who have lower perceived stress may be less likely to have chromosome changes associated with aging than obese and stressed women, according to a pilot study that was part of the Sister Study. The long-term Sister Study is looking at the environmental and genetic characteristics of women whose sister had breast cancer to identify factors associated with developing breast cancer. This early pilot used baseline questionnaires and samples provided by participants when they joined the Sister Study.
Two recent papers published in Cancer Epidemiology Biomarkers and Prevention looked at the length of telomeres, or the repeating DNA sequences that cap the ends of a person's chromosomes. Telomere length is one of the many measures being looked at in the Sister Study. Telomeres protect the ends of chromosomes and buffer them against the loss of important genes during cell replication. Over the course of an individual's lifetime, telomeres shorten, gradually becoming so short that they can trigger cell death. The papers show that factors such as obesity and perceived stress may shorten telomeres and accelerate the aging process.
"Together these two studies reinforce the need to start a healthy lifestyle early and maintain it," said Linda Birnbaum, Ph.D., the director of the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health. The researchers who published these papers are from the NIEHS which sponsors the Sister Study.
The papers are the first findings coming out of the Sister Study. The Sister Study is just completing its enrollment of 50,000 women aged 35-74 to prospectively study risk factors for breast cancer. "We anticipate a wealth of information to come out of the Sister Study," said Dale Sandler, Ph.D., chief of the Epidemiology Branch at NIEHS and principal investigator of the Sister Study. "Not only do we hope to find out more about the environmental and genetic factors that might lead to breast cancer, we also want to learn more about how factors such as stress, diet and exercise might impact cancer and other disease risks."
One of the studies published this week found that women who were obese for a long time had reduced telomere length. The researchers looked at the relationship between various measures of current and past body size and telomere length in 647 women enrolled in the Sister Study. They found that women who had an overweight or obese body mass index (BMI) before or during their 30s, and maintained that status since those years, had shorter telomeres than those who became overweight or obese after their 30s. "This suggests that duration of obesity may be more important than weight change per se, although other measures of overweight and obesity were also important," said Sangmi Kim, Ph.D., epidemiologist and lead author on the paper. "Our results support the hypothesis that obesity accelerates the aging process," said Kim.
The other paper published in February looked at the association between telomere length and the perceived stress levels of 647 women enrolled in the Sister Study, and found that similar to the obesity finding, stress can also impact telomere length. The researchers extracted DNA from blood drawn during initial enrollment to estimate telomere length, and measured levels of stress hormones in urine samples the women provided. Additionally, the researchers used a standardized scale to characterize levels of perceived stress based on answers to questions about how stressful participants perceived their life situations. In general, the researchers report that women in the Sister Study typically reported low levels of perceived stress.
"Even so, women who reported above-average stress had somewhat shorter telomeres, but the difference in telomere length was most striking when we looked at the relationship between perceived stress and telomere length among women with the highest levels of stress hormones," said Christine Parks, Ph.D., an NIEHS epidemiologist and lead author on the paper. "Among women with both higher perceived stress and elevated levels of the stress hormone epinephrine, the difference in telomere length was equivalent to or greater than the effects of being obese, smoking or 10 years of aging."
The researchers also found that the effects of stress may be stronger in older women. They found that among women 55 years and older, those with higher perceived stress had 5 percent shorter telomeres than women with low stress levels. "More research is needed to determine if the shortening of telomeres in these women is related to aging or hormonal differences in the stress response, or simply represents the accumulated effects of stress across the lifespan," said Parks.
"These papers remind us that there are things people can do to modify their behavior and live healthier lives, such as maintain a healthy weight and cultivate healthy responses to stress," said Birnbaum.
Notes:
The NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit our website at niehs.nih.
The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.
References:
Kim S, Parks CG, DeRoo LA., Chen, H, Taylor JA, Cawthon RM, Sandler DP. Obesity and Weight Gain in Adulthood and Telomere Length. Cancer Epidemiology Biomarkers & Prevention 2009;18(3):816-20 March 2009.
Parks CG, Miller DB, McCanlies EC, Cawthon RM, Andrew ME, DeRoo LA, Sandler, DP. Telomere Length, Current Perceived Stress, and Urinary Stress Hormones in Women. Cancer Epidemiology Biomarkers & Prevention 2009; 18(2): 551-560. February 2009.
Source: Robin Mackar
NIH/National Institute of Environmental Health Sciences
Two recent papers published in Cancer Epidemiology Biomarkers and Prevention looked at the length of telomeres, or the repeating DNA sequences that cap the ends of a person's chromosomes. Telomere length is one of the many measures being looked at in the Sister Study. Telomeres protect the ends of chromosomes and buffer them against the loss of important genes during cell replication. Over the course of an individual's lifetime, telomeres shorten, gradually becoming so short that they can trigger cell death. The papers show that factors such as obesity and perceived stress may shorten telomeres and accelerate the aging process.
"Together these two studies reinforce the need to start a healthy lifestyle early and maintain it," said Linda Birnbaum, Ph.D., the director of the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health. The researchers who published these papers are from the NIEHS which sponsors the Sister Study.
The papers are the first findings coming out of the Sister Study. The Sister Study is just completing its enrollment of 50,000 women aged 35-74 to prospectively study risk factors for breast cancer. "We anticipate a wealth of information to come out of the Sister Study," said Dale Sandler, Ph.D., chief of the Epidemiology Branch at NIEHS and principal investigator of the Sister Study. "Not only do we hope to find out more about the environmental and genetic factors that might lead to breast cancer, we also want to learn more about how factors such as stress, diet and exercise might impact cancer and other disease risks."
One of the studies published this week found that women who were obese for a long time had reduced telomere length. The researchers looked at the relationship between various measures of current and past body size and telomere length in 647 women enrolled in the Sister Study. They found that women who had an overweight or obese body mass index (BMI) before or during their 30s, and maintained that status since those years, had shorter telomeres than those who became overweight or obese after their 30s. "This suggests that duration of obesity may be more important than weight change per se, although other measures of overweight and obesity were also important," said Sangmi Kim, Ph.D., epidemiologist and lead author on the paper. "Our results support the hypothesis that obesity accelerates the aging process," said Kim.
The other paper published in February looked at the association between telomere length and the perceived stress levels of 647 women enrolled in the Sister Study, and found that similar to the obesity finding, stress can also impact telomere length. The researchers extracted DNA from blood drawn during initial enrollment to estimate telomere length, and measured levels of stress hormones in urine samples the women provided. Additionally, the researchers used a standardized scale to characterize levels of perceived stress based on answers to questions about how stressful participants perceived their life situations. In general, the researchers report that women in the Sister Study typically reported low levels of perceived stress.
"Even so, women who reported above-average stress had somewhat shorter telomeres, but the difference in telomere length was most striking when we looked at the relationship between perceived stress and telomere length among women with the highest levels of stress hormones," said Christine Parks, Ph.D., an NIEHS epidemiologist and lead author on the paper. "Among women with both higher perceived stress and elevated levels of the stress hormone epinephrine, the difference in telomere length was equivalent to or greater than the effects of being obese, smoking or 10 years of aging."
The researchers also found that the effects of stress may be stronger in older women. They found that among women 55 years and older, those with higher perceived stress had 5 percent shorter telomeres than women with low stress levels. "More research is needed to determine if the shortening of telomeres in these women is related to aging or hormonal differences in the stress response, or simply represents the accumulated effects of stress across the lifespan," said Parks.
"These papers remind us that there are things people can do to modify their behavior and live healthier lives, such as maintain a healthy weight and cultivate healthy responses to stress," said Birnbaum.
Notes:
The NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit our website at niehs.nih.
The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.
References:
Kim S, Parks CG, DeRoo LA., Chen, H, Taylor JA, Cawthon RM, Sandler DP. Obesity and Weight Gain in Adulthood and Telomere Length. Cancer Epidemiology Biomarkers & Prevention 2009;18(3):816-20 March 2009.
Parks CG, Miller DB, McCanlies EC, Cawthon RM, Andrew ME, DeRoo LA, Sandler, DP. Telomere Length, Current Perceived Stress, and Urinary Stress Hormones in Women. Cancer Epidemiology Biomarkers & Prevention 2009; 18(2): 551-560. February 2009.
Source: Robin Mackar
NIH/National Institute of Environmental Health Sciences
понедельник, 6 июня 2011 г.
Genome Update Defines Landscape Of Breast And Colon Cancers
One year after completing the first large-scale report sequencing breast and colon cancer genes, Johns Hopkins Kimmel Cancer Center scientists have studied the vast majority of protein coding genes which now suggest a landscape dominated by genes that each are mutated in relatively few cancers.
Their report, published online in the October 11 issue of Science Express, indicates that while little is known about these less-commonly mutated genes, they can be grouped into clusters according to their pathways.
"There are gene 'mountains' represented by those that are frequently altered and have been the focus of cancer research for years, in part because they were the only genes known to contribute to cancer," says Bert Vogelstein, M.D., an investigator at the Howard Hughes Medical Institute and co-director of the Ludwig Center at Johns Hopkins. "Now, we can see the whole picture, and it is clear that lower peaks or gene 'hills' are the predominant feature."
In a systematic search of 18,191 genes representing more than 90 percent of the protein-coding genes in the human genome -- about 5,000 more than in the first screen -- the Johns Hopkins scientists found that most cancer-causing gene mutations are quite diverse and can vary from person to person. They found that an average 77 genes are mutated in an individual colon cancer and 81 in breast cancer. Of these, about 15 are likely to contribute to a cancer's key characteristics, and most of these genes may be different for each patient.
"Fifteen years ago, we said the p53 gene was the most commonly mutated gene in cancer. It's amazing that this is still true," says Kenneth W. Kinzler, Ph.D., professor of oncology at Hopkins' Kimmel Cancer Center.
With no more higher-frequency mutations on the horizon, the investigators say that "personalized medicines" may now focus on the more complicated pathways that link these less-commonly mutated genes.
As an example, the Hopkins team charted the path of nine genes less frequently mutated in breast or colon cancers. Each of the genes' protein products interacted with an average of 25 other proteins, encoded by separate genes also found to be mutated in the cancers. It suggests that these genes converge in similar pathways. "The hard part used to be finding these mutant genes, now the challenge will be to link them to specific pathways and understand their function," says Victor Velculescu, M.D., Ph.D., associate professor of oncology at the Johns Hopkins Kimmel Cancer Center.
The scientists say that directing therapies at common pathways that are linked by both prevalent and rare gene mutations is a better approach than aiming treatments at specific genes. They also note that personalized cancer genomics paves the way for tailored therapies and diagnostics focusing on the alterations identified in a particular patient's cancer. Many of the mutations identified by scientists could be important in developing individualized cancer vaccines and monitoring patients for early recurrence of their disease.
For the study, the scientists screened the same set of tissue samples that were used for their first genome draft 11 each of breast and colorectal cancers, removed from patients after surgery. Then, they evaluated all mutated genes in a second group of 24 samples from each cancer, and a subset of the most promising mutations were studied in a further 96 colorectal cancers. They compared the genetic sequence of these tumors with that of normal tissue samples from the same patients using computer software that matches up gene codes in cancer and normal cells.
Within each cell, chemicals called nucleotides pair up to form the rungs of a DNA ladder that carry genetic instructions guiding everything from cell-to-cell contact to eye color. Changes in the nucleotide arrangement can create errors in the proteins made from the DNA. Buildup of damaged proteins can turn a normal cell into a cancerous one.
Laura Wood, a postdoctoral fellow at Hopkins' Kimmel Cancer Center says that these results can help to direct the global race to map additional cancer genomes. For other cancers, she says scientists should expect to find a similar genetic landscape - "few mountains surrounded by many hills."
Funding for this study was provided by The Virginia and D.K. Ludwig Fund for Cancer Research, the Department of Defense, Pew Charitable Trusts, The Palmetto Health Foundation, The Maryland Cigarette Restitution Fund, the State of Ohio Biomedical Research and Technology Transfer Commission, the Clayton Fund, the Blaustein Foundation, the National Colorectal Cancer Research Alliance, the Strang Cancer Prevention Center, the Division of Cancer Prevention of the National Cancer Institute, the Avon Foundation, the Flight Attendant Medical Research Institute, the V Foundation for Cancer Research, and the Summer Running Fund.
Additional research participants include D. William Parsons, Sian Jones, Jimmy Lin, Tobias Sjoblom, Rebecca Leary, Dong Shen, Simina M. Boca, Thomas Barber, Janine Ptak, Natalie Silliman, Steve Szabo, Saraswati Sukumar, Ben Ho Park, Nickolas Papadopoulos, and Giovanni Parmigiani from Johns Hopkins; Zoltan Dezso, Vadim Ustyanksky, Tatiana Nikolskaha, and Yuri Nicolsky from GeneGo Inc. and the Vavilov Institute of General Genetics, Moscow, Russia; Rachel Karchin and Paul Wilson from the Department of Biomedical Engineering at The Johns Hopkins University; Joshua S. Kaminker and Zemin Zhang from Genentech; Randal Croshaw and Phillip Buckhaults from the University of South Carolina; Joseph Willis and Dawn Dawson and Sanford Markowitz from Case Western Reserve University; Michail Shipitsin and Kornelia Polyak from the Dana Farber Cancer Institute, James K.V. Willson from the University of Texas Southwestern Medical Center; Charit L. Pathiyagoda, P.V. Krishna Pant, and Dennis G. Ballinger from Perlegen Sciences; Andrew B. Sparks from Complete Genomics Inc.; James Hartigan, Douglas R. Smith, and Erick Suh from Agencourt Bioscience Corporation.
Johns Hopkins Medicine
901 S. Bond St., Ste 550
Baltimore, MD 21231
United States
hopkinsmedicine
Their report, published online in the October 11 issue of Science Express, indicates that while little is known about these less-commonly mutated genes, they can be grouped into clusters according to their pathways.
"There are gene 'mountains' represented by those that are frequently altered and have been the focus of cancer research for years, in part because they were the only genes known to contribute to cancer," says Bert Vogelstein, M.D., an investigator at the Howard Hughes Medical Institute and co-director of the Ludwig Center at Johns Hopkins. "Now, we can see the whole picture, and it is clear that lower peaks or gene 'hills' are the predominant feature."
In a systematic search of 18,191 genes representing more than 90 percent of the protein-coding genes in the human genome -- about 5,000 more than in the first screen -- the Johns Hopkins scientists found that most cancer-causing gene mutations are quite diverse and can vary from person to person. They found that an average 77 genes are mutated in an individual colon cancer and 81 in breast cancer. Of these, about 15 are likely to contribute to a cancer's key characteristics, and most of these genes may be different for each patient.
"Fifteen years ago, we said the p53 gene was the most commonly mutated gene in cancer. It's amazing that this is still true," says Kenneth W. Kinzler, Ph.D., professor of oncology at Hopkins' Kimmel Cancer Center.
With no more higher-frequency mutations on the horizon, the investigators say that "personalized medicines" may now focus on the more complicated pathways that link these less-commonly mutated genes.
As an example, the Hopkins team charted the path of nine genes less frequently mutated in breast or colon cancers. Each of the genes' protein products interacted with an average of 25 other proteins, encoded by separate genes also found to be mutated in the cancers. It suggests that these genes converge in similar pathways. "The hard part used to be finding these mutant genes, now the challenge will be to link them to specific pathways and understand their function," says Victor Velculescu, M.D., Ph.D., associate professor of oncology at the Johns Hopkins Kimmel Cancer Center.
The scientists say that directing therapies at common pathways that are linked by both prevalent and rare gene mutations is a better approach than aiming treatments at specific genes. They also note that personalized cancer genomics paves the way for tailored therapies and diagnostics focusing on the alterations identified in a particular patient's cancer. Many of the mutations identified by scientists could be important in developing individualized cancer vaccines and monitoring patients for early recurrence of their disease.
For the study, the scientists screened the same set of tissue samples that were used for their first genome draft 11 each of breast and colorectal cancers, removed from patients after surgery. Then, they evaluated all mutated genes in a second group of 24 samples from each cancer, and a subset of the most promising mutations were studied in a further 96 colorectal cancers. They compared the genetic sequence of these tumors with that of normal tissue samples from the same patients using computer software that matches up gene codes in cancer and normal cells.
Within each cell, chemicals called nucleotides pair up to form the rungs of a DNA ladder that carry genetic instructions guiding everything from cell-to-cell contact to eye color. Changes in the nucleotide arrangement can create errors in the proteins made from the DNA. Buildup of damaged proteins can turn a normal cell into a cancerous one.
Laura Wood, a postdoctoral fellow at Hopkins' Kimmel Cancer Center says that these results can help to direct the global race to map additional cancer genomes. For other cancers, she says scientists should expect to find a similar genetic landscape - "few mountains surrounded by many hills."
Funding for this study was provided by The Virginia and D.K. Ludwig Fund for Cancer Research, the Department of Defense, Pew Charitable Trusts, The Palmetto Health Foundation, The Maryland Cigarette Restitution Fund, the State of Ohio Biomedical Research and Technology Transfer Commission, the Clayton Fund, the Blaustein Foundation, the National Colorectal Cancer Research Alliance, the Strang Cancer Prevention Center, the Division of Cancer Prevention of the National Cancer Institute, the Avon Foundation, the Flight Attendant Medical Research Institute, the V Foundation for Cancer Research, and the Summer Running Fund.
Additional research participants include D. William Parsons, Sian Jones, Jimmy Lin, Tobias Sjoblom, Rebecca Leary, Dong Shen, Simina M. Boca, Thomas Barber, Janine Ptak, Natalie Silliman, Steve Szabo, Saraswati Sukumar, Ben Ho Park, Nickolas Papadopoulos, and Giovanni Parmigiani from Johns Hopkins; Zoltan Dezso, Vadim Ustyanksky, Tatiana Nikolskaha, and Yuri Nicolsky from GeneGo Inc. and the Vavilov Institute of General Genetics, Moscow, Russia; Rachel Karchin and Paul Wilson from the Department of Biomedical Engineering at The Johns Hopkins University; Joshua S. Kaminker and Zemin Zhang from Genentech; Randal Croshaw and Phillip Buckhaults from the University of South Carolina; Joseph Willis and Dawn Dawson and Sanford Markowitz from Case Western Reserve University; Michail Shipitsin and Kornelia Polyak from the Dana Farber Cancer Institute, James K.V. Willson from the University of Texas Southwestern Medical Center; Charit L. Pathiyagoda, P.V. Krishna Pant, and Dennis G. Ballinger from Perlegen Sciences; Andrew B. Sparks from Complete Genomics Inc.; James Hartigan, Douglas R. Smith, and Erick Suh from Agencourt Bioscience Corporation.
Johns Hopkins Medicine
901 S. Bond St., Ste 550
Baltimore, MD 21231
United States
hopkinsmedicine
воскресенье, 5 июня 2011 г.
Improving breast-cancer diagnostic tools
As much as patients would like for the word "doctor" to mean "all-knowing," unfortunately, this will never be the case. Human fallibility on the part of medical professionals sometimes leads to devastating misdiagnoses that can result in additional suffering, or even death, for their patients.
But there is hope for better, more accurate medical diagnoses through the development of new technologies, and one Florida State University researcher is putting her engineering knowledge to work to develop tools for more accurately diagnosing breast cancer.
Anke Meyer-Baese is an assistant professor of electrical and computer engineering at the Florida A&M University-FSU College of Engineering. Her work focuses on electrical and computer engineering, with a specialization in methods of artificial intelligence that can be applied to medical imaging.
Meyer-Baese recently became the first College of Engineering faculty member to receive a National Institutes of Health Career Award, which comes with $695,000 in research funding. With the money, she will lead a five-year project to give doctors a new tool to better diagnose breast cancer. The aggressive disease claims the lives of more than 40,000 American women each year -- so a diagnostic tool that will allow patients to begin a course of treatment as early as possible is urgently needed.
Meyer-Baese hopes to utilize magnetic resonance imaging (MRI) -- which holds promise in better detection of hard-to-find cases of breast cancer -- to provide doctors with the more critical eyes of a computer. Despite the incredible potential of MRI technology, which cranks out at least 200 scans for a single patient, the sheer volume of images can be daunting for human eyes to evaluate.
Meyer-Baese is developing computer software to mimic the way a radiologist analyzes all of that information -- and to do it better and faster.
"The outcome of the proposed research is expected to have substantial implications in health care by contributing to the improved diagnosis of indeterminate breast lesions by non-invasive imaging," Meyer-Baese said. "We will deliver a flexible and reusable software system in MR mammography."
Meyer-Baese said she was "thrilled" to hear that she had been chosen for an NIH Career Award.
"I was very excited, because I can do research in advancing breast cancer research, train students in biomedical engineering and promote interdisciplinary research at FSU," she said.
For more stories about FSU, visit our news site at fsu
Anke Meyer-Baese
ambeng.fsu
Florida State University
fsu
But there is hope for better, more accurate medical diagnoses through the development of new technologies, and one Florida State University researcher is putting her engineering knowledge to work to develop tools for more accurately diagnosing breast cancer.
Anke Meyer-Baese is an assistant professor of electrical and computer engineering at the Florida A&M University-FSU College of Engineering. Her work focuses on electrical and computer engineering, with a specialization in methods of artificial intelligence that can be applied to medical imaging.
Meyer-Baese recently became the first College of Engineering faculty member to receive a National Institutes of Health Career Award, which comes with $695,000 in research funding. With the money, she will lead a five-year project to give doctors a new tool to better diagnose breast cancer. The aggressive disease claims the lives of more than 40,000 American women each year -- so a diagnostic tool that will allow patients to begin a course of treatment as early as possible is urgently needed.
Meyer-Baese hopes to utilize magnetic resonance imaging (MRI) -- which holds promise in better detection of hard-to-find cases of breast cancer -- to provide doctors with the more critical eyes of a computer. Despite the incredible potential of MRI technology, which cranks out at least 200 scans for a single patient, the sheer volume of images can be daunting for human eyes to evaluate.
Meyer-Baese is developing computer software to mimic the way a radiologist analyzes all of that information -- and to do it better and faster.
"The outcome of the proposed research is expected to have substantial implications in health care by contributing to the improved diagnosis of indeterminate breast lesions by non-invasive imaging," Meyer-Baese said. "We will deliver a flexible and reusable software system in MR mammography."
Meyer-Baese said she was "thrilled" to hear that she had been chosen for an NIH Career Award.
"I was very excited, because I can do research in advancing breast cancer research, train students in biomedical engineering and promote interdisciplinary research at FSU," she said.
For more stories about FSU, visit our news site at fsu
Anke Meyer-Baese
ambeng.fsu
Florida State University
fsu
суббота, 4 июня 2011 г.
Avastin Plus Commonly Used Chemotherapies Improved Progression-Free Survival (PFS) In Women With Previously Treated Advanced Breast Cancer
Genentech, Inc., a wholly-owned member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that a Phase III study (RIBBON 2) of Avastin® (bevacizumab) in combination with chemotherapy increased the time women with metastatic HER2-negative breast cancer whose initial chemotherapy had stopped working lived without the disease worsening (progression-free survival or PFS), compared to chemotherapy alone. The doctors treating the women in the study chose the type of chemotherapy used in combination with Avastin and the chemotherapies were assessed together in the primary endpoint analysis. Adverse events were consistent with those previously reported for Avastin, and no new Avastin safety signals were observed in the study. Data from the study will be submitted for presentation at a future medical meeting.
"Advanced breast cancer is aggressive and nearly all women will need additional treatment when initial chemotherapy stops working," said Hal Barron, M.D., executive vice president, Global Development and chief medical officer. "We have learned for the first time that Avastin given in the second-line with standard chemotherapies helped women live longer without the disease worsening and look forward to discussing these new data with the FDA."
Avastin, in combination with paclitaxel, was approved for first-line treatment of advanced HER2-negative breast cancer in February 2008 under the U.S. Food and Drug Administration's (FDA) accelerated approval program, which allows provisional approval of medicines for cancer or other life-threatening diseases. Avastin, in combination with paclitaxel, is indicated for the treatment of patients who have not received chemotherapy for advanced HER2-negative breast cancer. The effectiveness of Avastin in metastatic breast cancer is based on an improvement in PFS. Avastin is not indicated for patients with breast cancer that has progressed following anthracycline and taxane chemotherapy administered for metastatic disease. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Avastin in breast cancer.
A full review of data from the previously announced RIBBON 1 and AVADO studies is required for the accelerated approval of Avastin for the treatment of patients who have not received chemotherapy for advanced HER2-negative breast cancer (first-line treatment) to be converted into a full approval. Results from these trials will be submitted to the FDA later this year. Genentech is committed to understanding the potential role of Avastin in breast cancer and will submit data from the new study (RIBBON 2) of Avastin in the second-line to the FDA. Additionally, the data from two other ongoing randomized Phase III trials in the first-line setting will also be submitted to the FDA when available.
About RIBBON 2 (AVF3693g)
RIBBON 2 is an international, multicenter, randomized, double-blind, placebo-controlled clinical study that enrolled 684 patients with metastatic HER2-negative breast cancer who had previously received chemotherapy for their metastatic disease. The trial evaluated the addition of either Avastin or placebo to an investigator's choice of chemotherapy. The following chemotherapy regimens were used in the study:
- Taxanes: paclitaxel, protein-bound paclitaxel or docetaxel
- Gemcitabine
- Capecitabine
- Vinorelbine
In the study, PFS was defined as the time from randomization to disease progression or death as assessed by the treating physicians in the study. Secondary endpoints included objective response rate, duration of response, one-year survival rate, overall survival, PFS assessment by chemotherapy type and safety.
About Avastin
Avastin is a biologic antibody designed to specifically bind to a protein called vascular endothelial growth factor (VEGF) that plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. Avastin interferes with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. Avastin does not bind to receptors on normal or cancer cells. The tumor blood supply is thought to be critical to a tumor's ability to grow and spread in the body (metastasize). For more information about angiogenesis, visit gene.
Avastin was the first anti-angiogenesis therapy approved by the FDA and is approved for the treatment of five tumor types. Avastin is indicated for the first- and second-line treatment of metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy; for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel; for the treatment of metastatic renal cell carcinoma in combination with interferon alfa; for previously untreated, metastatic HER2-negative breast cancer in combination with paclitaxel; and for glioblastoma that has progressed following prior therapy.
The effectiveness of Avastin in metastatic breast cancer is based on an improvement in PFS. Avastin is not indicated for patients with breast cancer that has progressed following anthracycline and taxane chemotherapy administered for metastatic disease. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Avastin in breast cancer.
The effectiveness of Avastin in glioblastoma is based on an improvement in objective response rate as assessed by magnetic resonance imaging (MRI) and measured using World Health Organization radiographic criteria along with decreased or stable corticosteroid use. MRI does not necessarily distinguish between the tumor, swelling (edema) or tissue death (necrosis) caused by prior radiation therapy. Currently, no data are available from randomized controlled trials demonstrating an improvement in disease-related symptoms or increased survival with Avastin in glioblastoma.
BOXED WARNINGS and Additional Important Safety Information
Patients treated with Avastin may experience side effects. In clinical trials, some patients treated with Avastin experienced serious side effects, including:
Gastrointestinal (GI) perforation:
Treatment with Avastin can result in the development of a serious side effect called GI perforation, which is the development of a hole in the stomach, small intestine, or large intestine. In clinical trials, this side effect occurred in 0.3 to 2.4 percent of patients and in some cases resulted in fatality. Avastin therapy should be permanently stopped in people with GI perforation.
Surgery and wound healing problems:
Treatment with Avastin can lead to slow or incomplete wound healing (for example, when a surgical incision has trouble healing or staying closed). In some cases this event resulted in fatality. In a clinical trial, 15 percent of patients with metastatic colorectal cancer who had surgery while receiving Avastin treatment had serious and fatal complications compared to 4 percent of patients who did not receive Avastin. Avastin should not be initiated for at least 28 days following surgery and until the surgical wound is fully healed. Avastin therapy should be permanently stopped in patients with wound healing problems that require medical treatment. The appropriate waiting time between stopping treatment with Avastin and having surgery has not been determined.
Severe bleeding:
Severe or fatal bleeding, including hemoptysis (coughing up of blood), GI bleeding, hematemesis (bloody vomit), central nervous system (CNS) hemorrhage (bleeding in the brain), epistaxis (nose bleeds), and vaginal bleeding occurred up to five-fold more frequently in patients receiving Avastin compared to patients receiving only chemotherapy. Across indications, Grade 3 or higher (severe or fatal) bleeding events have occurred in 1.2 to 4.6 percent of patients receiving Avastin. In patients with previously treated glioblastoma, intracranial hemorrhage (bleeding within the brain) occurred in 8 of 163 patients and two people had Grade 3 to 4 (severe) bleeding. In patients treated with Avastin and chemotherapy for lung cancer, serious and sometimes fatal pulmonary hemorrhage (bleeding in the lungs) occurred in four of 13 (31 percent) patients with squamous cell histology and two of 53 (4 percent) patients with non-squamous NSCLC, compared to none of 32 (0 percent) patients treated with chemotherapy. People with serious bleeding or recent hemoptysis (>/= to ВЅ tsp of red blood) should not receive Avastin. Discontinue Avastin if serious bleeding (ie, requiring medical care).
In clinical trials, additional serious side effects seen across different cancer types, in some cases resulting in fatality, included the following: formation of an abnormal passage from parts of the body to another part (non-GI fistula formation - less than 0.3 percent); stroke or heart problems (arterial thromboembolic events - 2.4 percent); high blood pressure (5 to 18 percent); nervous system and vision disturbances known as RPLS (reversible posterior leukoencephalopathy syndrome - less than 0.1 percent); severe infusion reactions (0.2 percent of people), too much protein in the urine and kidney damage (nephrotic syndrome - less than 1 percent). Infusion reactions with the first dose of Avastin were uncommon (less than 3 percent), and severe reactions occurred on 0.2% of patients.
The most common adverse reactions observed in Avastin patients at a rate of more than 10 percent and at least twice the control arm rate were nose bleeds, headache, high blood pressure, irritation of the nose (rhinitis), protein in the urine, taste alteration, dry skin, rectal bleeding, tear production disorder (lacrimation), back pain and inflammation of the skin (exfoliative dermatitis). Across all studies, Avastin was stopped in 8.4 to 20.3% of patients because of adverse reactions.
Grade 3-5 (nonhematologic) and 4-5 (hematologic) events in Study E2100 increased by 20.5% in the Avastin plus paclitaxel vs paclitaxel groups. The most common grade 3-5 (nonhematologic) and 4-5 (hematologic) events in Study E2100, which occurred at a higher absolute incidence (≥5%) in the Avastin plus paclitaxel vs. paclitaxel groups, were sensory neuropathy (24.2% vs. 17.5%), hypertension (16.0% vs. 1.4%), and fatigue (10.7% vs. 5.2%). The rate of CHF (defined as NCI-CTC grade 3-4) in the Avastin plus paclitaxel arm was 2.2% vs. 0.3% in the control arm. Among patients receiving anthracyclines, the rate of CHF was 3.8% for Avastin-treated patients and 0.6% for patients receiving paclitaxel alone. Only NCI-CTC grade 3-5 (nonhematologic) and grade 4-5 (hematologic) adverse events were reported. Therefore, grade 1-2 adverse events were not collected in Study E2100, and common adverse events of Avastin in combination with paclitaxel for metastatic breast cancer are not known. Fatal adverse reactions occurred in 1.7% (6/363) of patients who received Avastin plus paclitaxel in Study E2100. Causes of death were GI perforation (2), myocardial infarction (2), and diarrhea/abdominal pain/weakness/hypotension (2).
Avastin may cause problems getting pregnant. People who are pregnant or thinking of becoming pregnant should talk with their doctor about the potential risks of loss of pregnancy or the potential risk of Avastin to the fetus. Nursing mothers should not breast-feed while receiving Avastin or for a short period of time after treatment is finished. Avastin may impair fertility.
For full Prescribing Information and Boxed WARNINGS on Avastin visit avastin.
Source
Genentech
View drug information on Avastin.
"Advanced breast cancer is aggressive and nearly all women will need additional treatment when initial chemotherapy stops working," said Hal Barron, M.D., executive vice president, Global Development and chief medical officer. "We have learned for the first time that Avastin given in the second-line with standard chemotherapies helped women live longer without the disease worsening and look forward to discussing these new data with the FDA."
Avastin, in combination with paclitaxel, was approved for first-line treatment of advanced HER2-negative breast cancer in February 2008 under the U.S. Food and Drug Administration's (FDA) accelerated approval program, which allows provisional approval of medicines for cancer or other life-threatening diseases. Avastin, in combination with paclitaxel, is indicated for the treatment of patients who have not received chemotherapy for advanced HER2-negative breast cancer. The effectiveness of Avastin in metastatic breast cancer is based on an improvement in PFS. Avastin is not indicated for patients with breast cancer that has progressed following anthracycline and taxane chemotherapy administered for metastatic disease. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Avastin in breast cancer.
A full review of data from the previously announced RIBBON 1 and AVADO studies is required for the accelerated approval of Avastin for the treatment of patients who have not received chemotherapy for advanced HER2-negative breast cancer (first-line treatment) to be converted into a full approval. Results from these trials will be submitted to the FDA later this year. Genentech is committed to understanding the potential role of Avastin in breast cancer and will submit data from the new study (RIBBON 2) of Avastin in the second-line to the FDA. Additionally, the data from two other ongoing randomized Phase III trials in the first-line setting will also be submitted to the FDA when available.
About RIBBON 2 (AVF3693g)
RIBBON 2 is an international, multicenter, randomized, double-blind, placebo-controlled clinical study that enrolled 684 patients with metastatic HER2-negative breast cancer who had previously received chemotherapy for their metastatic disease. The trial evaluated the addition of either Avastin or placebo to an investigator's choice of chemotherapy. The following chemotherapy regimens were used in the study:
- Taxanes: paclitaxel, protein-bound paclitaxel or docetaxel
- Gemcitabine
- Capecitabine
- Vinorelbine
In the study, PFS was defined as the time from randomization to disease progression or death as assessed by the treating physicians in the study. Secondary endpoints included objective response rate, duration of response, one-year survival rate, overall survival, PFS assessment by chemotherapy type and safety.
About Avastin
Avastin is a biologic antibody designed to specifically bind to a protein called vascular endothelial growth factor (VEGF) that plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. Avastin interferes with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. Avastin does not bind to receptors on normal or cancer cells. The tumor blood supply is thought to be critical to a tumor's ability to grow and spread in the body (metastasize). For more information about angiogenesis, visit gene.
Avastin was the first anti-angiogenesis therapy approved by the FDA and is approved for the treatment of five tumor types. Avastin is indicated for the first- and second-line treatment of metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy; for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel; for the treatment of metastatic renal cell carcinoma in combination with interferon alfa; for previously untreated, metastatic HER2-negative breast cancer in combination with paclitaxel; and for glioblastoma that has progressed following prior therapy.
The effectiveness of Avastin in metastatic breast cancer is based on an improvement in PFS. Avastin is not indicated for patients with breast cancer that has progressed following anthracycline and taxane chemotherapy administered for metastatic disease. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Avastin in breast cancer.
The effectiveness of Avastin in glioblastoma is based on an improvement in objective response rate as assessed by magnetic resonance imaging (MRI) and measured using World Health Organization radiographic criteria along with decreased or stable corticosteroid use. MRI does not necessarily distinguish between the tumor, swelling (edema) or tissue death (necrosis) caused by prior radiation therapy. Currently, no data are available from randomized controlled trials demonstrating an improvement in disease-related symptoms or increased survival with Avastin in glioblastoma.
BOXED WARNINGS and Additional Important Safety Information
Patients treated with Avastin may experience side effects. In clinical trials, some patients treated with Avastin experienced serious side effects, including:
Gastrointestinal (GI) perforation:
Treatment with Avastin can result in the development of a serious side effect called GI perforation, which is the development of a hole in the stomach, small intestine, or large intestine. In clinical trials, this side effect occurred in 0.3 to 2.4 percent of patients and in some cases resulted in fatality. Avastin therapy should be permanently stopped in people with GI perforation.
Surgery and wound healing problems:
Treatment with Avastin can lead to slow or incomplete wound healing (for example, when a surgical incision has trouble healing or staying closed). In some cases this event resulted in fatality. In a clinical trial, 15 percent of patients with metastatic colorectal cancer who had surgery while receiving Avastin treatment had serious and fatal complications compared to 4 percent of patients who did not receive Avastin. Avastin should not be initiated for at least 28 days following surgery and until the surgical wound is fully healed. Avastin therapy should be permanently stopped in patients with wound healing problems that require medical treatment. The appropriate waiting time between stopping treatment with Avastin and having surgery has not been determined.
Severe bleeding:
Severe or fatal bleeding, including hemoptysis (coughing up of blood), GI bleeding, hematemesis (bloody vomit), central nervous system (CNS) hemorrhage (bleeding in the brain), epistaxis (nose bleeds), and vaginal bleeding occurred up to five-fold more frequently in patients receiving Avastin compared to patients receiving only chemotherapy. Across indications, Grade 3 or higher (severe or fatal) bleeding events have occurred in 1.2 to 4.6 percent of patients receiving Avastin. In patients with previously treated glioblastoma, intracranial hemorrhage (bleeding within the brain) occurred in 8 of 163 patients and two people had Grade 3 to 4 (severe) bleeding. In patients treated with Avastin and chemotherapy for lung cancer, serious and sometimes fatal pulmonary hemorrhage (bleeding in the lungs) occurred in four of 13 (31 percent) patients with squamous cell histology and two of 53 (4 percent) patients with non-squamous NSCLC, compared to none of 32 (0 percent) patients treated with chemotherapy. People with serious bleeding or recent hemoptysis (>/= to ВЅ tsp of red blood) should not receive Avastin. Discontinue Avastin if serious bleeding (ie, requiring medical care).
In clinical trials, additional serious side effects seen across different cancer types, in some cases resulting in fatality, included the following: formation of an abnormal passage from parts of the body to another part (non-GI fistula formation - less than 0.3 percent); stroke or heart problems (arterial thromboembolic events - 2.4 percent); high blood pressure (5 to 18 percent); nervous system and vision disturbances known as RPLS (reversible posterior leukoencephalopathy syndrome - less than 0.1 percent); severe infusion reactions (0.2 percent of people), too much protein in the urine and kidney damage (nephrotic syndrome - less than 1 percent). Infusion reactions with the first dose of Avastin were uncommon (less than 3 percent), and severe reactions occurred on 0.2% of patients.
The most common adverse reactions observed in Avastin patients at a rate of more than 10 percent and at least twice the control arm rate were nose bleeds, headache, high blood pressure, irritation of the nose (rhinitis), protein in the urine, taste alteration, dry skin, rectal bleeding, tear production disorder (lacrimation), back pain and inflammation of the skin (exfoliative dermatitis). Across all studies, Avastin was stopped in 8.4 to 20.3% of patients because of adverse reactions.
Grade 3-5 (nonhematologic) and 4-5 (hematologic) events in Study E2100 increased by 20.5% in the Avastin plus paclitaxel vs paclitaxel groups. The most common grade 3-5 (nonhematologic) and 4-5 (hematologic) events in Study E2100, which occurred at a higher absolute incidence (≥5%) in the Avastin plus paclitaxel vs. paclitaxel groups, were sensory neuropathy (24.2% vs. 17.5%), hypertension (16.0% vs. 1.4%), and fatigue (10.7% vs. 5.2%). The rate of CHF (defined as NCI-CTC grade 3-4) in the Avastin plus paclitaxel arm was 2.2% vs. 0.3% in the control arm. Among patients receiving anthracyclines, the rate of CHF was 3.8% for Avastin-treated patients and 0.6% for patients receiving paclitaxel alone. Only NCI-CTC grade 3-5 (nonhematologic) and grade 4-5 (hematologic) adverse events were reported. Therefore, grade 1-2 adverse events were not collected in Study E2100, and common adverse events of Avastin in combination with paclitaxel for metastatic breast cancer are not known. Fatal adverse reactions occurred in 1.7% (6/363) of patients who received Avastin plus paclitaxel in Study E2100. Causes of death were GI perforation (2), myocardial infarction (2), and diarrhea/abdominal pain/weakness/hypotension (2).
Avastin may cause problems getting pregnant. People who are pregnant or thinking of becoming pregnant should talk with their doctor about the potential risks of loss of pregnancy or the potential risk of Avastin to the fetus. Nursing mothers should not breast-feed while receiving Avastin or for a short period of time after treatment is finished. Avastin may impair fertility.
For full Prescribing Information and Boxed WARNINGS on Avastin visit avastin.
Source
Genentech
View drug information on Avastin.
High Blood Pressure In Part Explains Black, White Breast Cancer Mortality Disparity, Study Finds
High blood pressure appears to be a contributing factor in the breast cancer mortality disparity between black and white women, according to a study published March 1 in the International Journal of Cancer, Reuters Health reports. For the study, Dejana Braithwaite of the University of California-San Francisco and colleagues analyzed data of 416 black women and 838 white women with invasive breast cancer who were undergoing treatment in Northern California at Kaiser Permanente between 1973 and 1986 and were followed through 1999.
Black women's mortality rate was 39.7%, compared with 33.3% for white women. More than 28% of black women died of breast cancer, compared with 21.6% of white women. Researchers also found that 43.3% of the black women had high blood pressure, compared with 28.3% of the white women. After controlling for age, race, tumor characteristics and breast cancer treatment, researchers found that high blood pressure was significantly linked to mortality, explaining 30.3% of the racial disparity in mortality, according to the study.
The findings suggest that "hypertension is an important [co-existing condition] to consider in the context of research on racial disparity in breast cancer and our findings warrant its inclusion" in breast cancer predictor measures, according to the study. The study adds that "better management of hypertension has potential to improve patient outcomes, particularly among" black women who have breast cancer (Reuters Health, 3/12).
An abstract of the study is available online.
Please note: The Kaiser Family Foundation is not associated with the Kaiser Foundation Health Plan, Kaiser Permanente or Kaiser Industries.
Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation.
© 2009 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
Black women's mortality rate was 39.7%, compared with 33.3% for white women. More than 28% of black women died of breast cancer, compared with 21.6% of white women. Researchers also found that 43.3% of the black women had high blood pressure, compared with 28.3% of the white women. After controlling for age, race, tumor characteristics and breast cancer treatment, researchers found that high blood pressure was significantly linked to mortality, explaining 30.3% of the racial disparity in mortality, according to the study.
The findings suggest that "hypertension is an important [co-existing condition] to consider in the context of research on racial disparity in breast cancer and our findings warrant its inclusion" in breast cancer predictor measures, according to the study. The study adds that "better management of hypertension has potential to improve patient outcomes, particularly among" black women who have breast cancer (Reuters Health, 3/12).
An abstract of the study is available online.
Please note: The Kaiser Family Foundation is not associated with the Kaiser Foundation Health Plan, Kaiser Permanente or Kaiser Industries.
Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation.
© 2009 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
пятница, 3 июня 2011 г.
New Test Discovered To Better Predict Breast Cancer Outcomes
Researchers from McGill University's Rosalind and Morris Goodman Cancer Research Centre (GCRC), the Research Institute of the McGill University Health Centre (RI MUHC), the Dana-Farber Cancer Institute and Harvard Medical School have discovered a gene signature that can accurately predict which breast cancer patients are at risk of relapse, thereby sparing those who are not from the burdens associated with unnecessary treatment.
For years, clinicians have been faced with the problem that breast cancer cannot be treated with a one-size-fits-all approach. Some cancers respond to specific treatments while others do not. Close to 50 per cent of breast cancer patients belong to a group - defined as "estrogen receptor positive/lymph node negative (ER+/LR-)"- that is at low risk of relapse. The majority of patients in this group may not require any treatment beyond the surgical removal of their tumour, while a small minority should receive additional treatment.
"The added information provided by our test would enable oncologists to identify those at very low risk of relapse, for whom the risk-benefit ratio might be in favour of withholding chemotherapy, and to identify patients in this low-risk group who would benefit from more aggressive treatments," explains Dr. Alain Nepveu, GCRC and RI MUHC researcher and co-author of the study. "Since many treatments are associated with short- and long-term complications including premature menopause, cardiotoxicity and the development of secondary cancers, risks must be balanced against the potential benefit for each patient to avoid unnecessary suffering, needless expense and added burdens on the health-care system."
While more research is required before the test would be ready for market and incorporated into existing diagnostic procedures, Nepveu suggests it has the potential to be commercialized within five years.
Aside from Nepveu, authors include Laurent Sansregret (GCRC and McGill's Dept. of Biochemistry; currently at Cancer Research UK London Research Institute); Charles Vadnais (GCRC and McGill's Dept. of Biochemistry); Julie Livingstone (GCRC and McGill Centre for Bioinformatics); Nicholas Kwiatkowski (Department of Cancer Biology, Dana-Farber Cancer Institute and Dept. of Biological Chemistry and Molecular Pharmacology, Harvard Medical School); Arif Awan (GCRC and McGill's Dept. of Biochemistry); Chantal Cadieux (GCRC and McGill's Dept. of Biochemistry); Lam Leduy (GCRC) and Michael T. Hallett (GCRC and McGill Centre for Bioinformatics).
These findings were published in a recent issue the Proceedings of the National Academy of Sciences of the United States of America (PNAS).
Source:
McGill University
For years, clinicians have been faced with the problem that breast cancer cannot be treated with a one-size-fits-all approach. Some cancers respond to specific treatments while others do not. Close to 50 per cent of breast cancer patients belong to a group - defined as "estrogen receptor positive/lymph node negative (ER+/LR-)"- that is at low risk of relapse. The majority of patients in this group may not require any treatment beyond the surgical removal of their tumour, while a small minority should receive additional treatment.
"The added information provided by our test would enable oncologists to identify those at very low risk of relapse, for whom the risk-benefit ratio might be in favour of withholding chemotherapy, and to identify patients in this low-risk group who would benefit from more aggressive treatments," explains Dr. Alain Nepveu, GCRC and RI MUHC researcher and co-author of the study. "Since many treatments are associated with short- and long-term complications including premature menopause, cardiotoxicity and the development of secondary cancers, risks must be balanced against the potential benefit for each patient to avoid unnecessary suffering, needless expense and added burdens on the health-care system."
While more research is required before the test would be ready for market and incorporated into existing diagnostic procedures, Nepveu suggests it has the potential to be commercialized within five years.
Aside from Nepveu, authors include Laurent Sansregret (GCRC and McGill's Dept. of Biochemistry; currently at Cancer Research UK London Research Institute); Charles Vadnais (GCRC and McGill's Dept. of Biochemistry); Julie Livingstone (GCRC and McGill Centre for Bioinformatics); Nicholas Kwiatkowski (Department of Cancer Biology, Dana-Farber Cancer Institute and Dept. of Biological Chemistry and Molecular Pharmacology, Harvard Medical School); Arif Awan (GCRC and McGill's Dept. of Biochemistry); Chantal Cadieux (GCRC and McGill's Dept. of Biochemistry); Lam Leduy (GCRC) and Michael T. Hallett (GCRC and McGill Centre for Bioinformatics).
These findings were published in a recent issue the Proceedings of the National Academy of Sciences of the United States of America (PNAS).
Source:
McGill University
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