Older women with breast cancer get a lower level of care than younger women, researchers at The University of Manchester have found.
Compared to younger women, older women with breast cancer are less likely to be diagnosed via needle biopsy and triple assessment, less likely to undergo surgery and less likely to receive radiotherapy, the researchers report in this week's British Journal of Cancer.
Such management of older women is likely to lead to higher rates of local recurrence of the disease and higher than necessary mortality.
Dr Katrina Lavelle, who led the study at the University's School of Nursing, Midwifery and Social Work, explains: "We have found that older women from aged 70 and over are less likely to receive the same breast cancer care as younger women and that this is related to their age rather than differences in the biology of their tumour."
The highest incidence of breast cancer in England occurs in women aged 70 years and older. Older women also experience the worst survival women aged 70-79 have a 76% five-year relative survival compared to 80% for all ages, and for women aged 80 plus this drops considerably to 61%, beyond what might be expected owing to an increase in age.
The team carried out a retrospective cohort study involving case note review based on the North Western Cancer Registry database of women aged 65 and over, resident in Greater Manchester with invasive breast cancer registered over a one year period. The results of the study, funded by an NHS R&D Training Fellowship, may be generalized nationally as variation in survival between regions is lower for breast cancer compared to other cancers.
The they found that, compared to women aged 65-69 years, women aged 80 plus with operable breast cancer have increased odds of not receiving triple assessment, not receiving primary surgery, not undergoing axillary node surgery and not undergoing steroid receptor tests (which indicate suitability for hormone therapy). Compared with her 65-69-year-old counterpart, the odds of a woman aged 80 or older not receiving triple assessment for operable breast cancer are five-and-a-half times higher, and the odds of her not receiving surgery are more than 40 times higher. Even women as young as 70-74 have over 7 times the odds of not receiving radiotherapy following breast conservation surgery compared to women aged 65-69 years.
In addition, the team discovered that the overall percentage of women in all the age groups not receiving steroid receptor tests was high at 41%, which resulted in treatment decisions being taken without this fundamental information. Three quarters of the patients who did not receive steroid receptor tests were given the hormone therapy, tamoxifen: that is, prescribed a treatment without evidence that it would work.
In a survey of UK breast cancer surgeons in 2004, 75% reported that they would treat older breast cancer patients in a similar way to younger patients and 98% responded that the cut off point for breast cancer surgery was not age related.
Dr Lavelle says: "Clearly there is a difference in clinicians' perceptions of how older breast cancer patients should be treated and their actual practice.
"Standard management of breast cancer was infrequent in older women in Greater Manchester. The lack of diagnostic and steroid receptor testing resulted in older cancer patients having no effective treatment with 41% not undergoing a steroid receptor test, 32% of whom received tamoxifen as their sole form of treatment.
"Mortality of elderly breast cancer patients is unlikely to improve where this pattern of management persists."
Research lead for the School of Nursing, Midwifery and Social Work, Professor Chris Todd, commented: "It would be wrong to conclude that ageism is to be found in the NHS on the basis of these results alone, as this study has not been able to take the preferences of older women themselves into account. This is something we intend to investigate in the next phase of our research."
MANCHESTER UNIVERSITY
Oxford Road
Manchester
M13 9PL
manchester.ac.uk
вторник, 30 августа 2011 г.
суббота, 27 августа 2011 г.
Device Promising For Detecting Metastatic Breast Cancer Cells
Research by engineers and cancer biologists at Virginia Tech indicate that using specific silicon microdevices might provide a new way to screen breast cancer cells' ability to metastasize.
An image of their work provided to Biomaterials was selected as one of the 12 best biomaterials-related images published in the journal's 2010 catalogue.
The Virginia Tech researchers are: Masoud Agah, director of Virginia Tech's Microelectromechanical Systems Laboratory (MEMS) Laboratory in the Bradley Department of Electrical and Computer Engineering; Jeannine Strobl, a research professor in the Bradley Department of Electrical and Computer Engineering; Mehdi Nikkhah of mechanical engineering; and Raffaella DeVita of engineering science and mechanics and the director of the soft biological systems laboratory. Nikkhah was Virginia Tech's Outstanding Doctoral Student in the College of Engineering for 2009.
Their work appeared in two journal articles they authored in 2010 issues of Biomaterials, titled "Actions of the anti-cancer drug suberoylanilide hydroaxamic acid (SAHA) on human breast cancer cytoarchitecture in silicon microstructures," and "The cytoskeletal organization of breast carcinoma and fibroblast cells inside three dimensional isotropic microstructures."
Cell cytoskeleton refers to the cell's shape and its mechanical properties, Agah explained. "Any change in the cytoskeletal structure can affect the interaction of cells with their surrounding microenvironments. Biological events in normal cells such as embryonic development, tissue growth and repair, and immune responses, as well as cancer cell motility and invasiveness are dependent upon cytoskeletal reorganization," the electrical engineer added.
Understanding how the cell interacts with the contents of its surrounding environment inside the human body, including the introduction of a drug, is a fundamental biological question. The answers have implications in cancer diagnosis and therapy, as well as tissue engineering, Agah said.
In previous experimentation by others in the field, researchers have exposed cells to mechanical, chemical and three-dimensional topographical stimuli. They recorded the cells' various responses in terms of migration, growth, and ability to adhere. Also, in the past, researchers have created substrates of precise micro- and nano-topographical and chemical patterns to mimic in vivo microenvironments for biological and medical applications.
What distinguishes the work of Agah, a National Science Foundation (NSF) CAREER Award recipient, and his colleagues, is they developed a specific three-dimensional silicon microstructure for their work. Due to its curved isotropic surfaces, they were able to characterize and compare the growth and adhesion behavior of normal fibroblast and metastatic human beast cancer cells, they reported in Biomaterials.
"In invasive breast carcinoma, tumor cells will fill a milk duct, and the basement membrane," they wrote. This action allows the carcinoma cells and the fibroblast cells of the breast tissue to be in close proximity, constituting "a critical pathobiological transition that leads to the progression of the disease," Strobl said.
Using their uniquely designed three-dimensional silicon microstructure, they were able to incorporate three key cellular components found in any breast tumor microenvironment. Additionally, they were able to determine the detailed interaction of the cells within this environment, including the normal breast cells, the metastatic breast cancer cells, and the fibroblast cells.
Their understanding of the behavior of the cells within the microstructures is what leads them to believe their research could "provide important diagnostic and prognostic markers unique to the tumor, which could ultimately be used to develop new tools for the detection and treatment of cancer."
Following their initial findings, Strobl, Nikkhah and Agah identified a unique application of the experimental anti-cancer drug SAHA in their studies with the silicon microstructure. SAHA, also known as Vorinostat, is the first drug of its type to receive Food and Drug Administration approval for clinical use in cancer treatment.
Unlike many of the conventional cytotoxic chemotherapy agents that target DNA to kill cancer cells, SAHA's unique properties include its ability to inhibit a family of enzymes referred to medically as "histone deacetylases." These enzymes are known to "increase levels of acetylation of many proteins, including beta-actin, alpha-, and beta-tubulin, and additional actin binding proteins comprising the cytoskeleton.
"The role of drugs such as SAHA in the control of cancer cell metastasis is only beginning to be understood," explained Strobl, "however our work shows that SAHA elicits a very characteristic cytoskeletal alteration specifically in metastatic breast cells that provides a handle for predicting which breast cells in a cell mixture might have the ability to metastasize."
Cell motility is "one hallmark of metastatic cancer cells involving the coordinated actions of actin and other cytoskeleton proteins," Agah explained. When metastatic disease develops, it is usually fatal.
They found SAHA caused cancer cells to stretch and attach to the microstructures through actin-rich cell extensions. By contrast, control cells conformed to the microstructures. This result allowed them to "conclude that isotropically etched silicon microstructures comprise microenvironments that discriminate metastatic mammary cancer cells in which cytoskeletal elements reorganized in response to the anti-cancer agent SAHA."
The Virginia Tech work in this area "is the first to address the use of microdevices to study this emerging class of anti-cancer agents," Agah said.
Source:
Virginia Tech (Virginia Polytechnic Institute and State University)
An image of their work provided to Biomaterials was selected as one of the 12 best biomaterials-related images published in the journal's 2010 catalogue.
The Virginia Tech researchers are: Masoud Agah, director of Virginia Tech's Microelectromechanical Systems Laboratory (MEMS) Laboratory in the Bradley Department of Electrical and Computer Engineering; Jeannine Strobl, a research professor in the Bradley Department of Electrical and Computer Engineering; Mehdi Nikkhah of mechanical engineering; and Raffaella DeVita of engineering science and mechanics and the director of the soft biological systems laboratory. Nikkhah was Virginia Tech's Outstanding Doctoral Student in the College of Engineering for 2009.
Their work appeared in two journal articles they authored in 2010 issues of Biomaterials, titled "Actions of the anti-cancer drug suberoylanilide hydroaxamic acid (SAHA) on human breast cancer cytoarchitecture in silicon microstructures," and "The cytoskeletal organization of breast carcinoma and fibroblast cells inside three dimensional isotropic microstructures."
Cell cytoskeleton refers to the cell's shape and its mechanical properties, Agah explained. "Any change in the cytoskeletal structure can affect the interaction of cells with their surrounding microenvironments. Biological events in normal cells such as embryonic development, tissue growth and repair, and immune responses, as well as cancer cell motility and invasiveness are dependent upon cytoskeletal reorganization," the electrical engineer added.
Understanding how the cell interacts with the contents of its surrounding environment inside the human body, including the introduction of a drug, is a fundamental biological question. The answers have implications in cancer diagnosis and therapy, as well as tissue engineering, Agah said.
In previous experimentation by others in the field, researchers have exposed cells to mechanical, chemical and three-dimensional topographical stimuli. They recorded the cells' various responses in terms of migration, growth, and ability to adhere. Also, in the past, researchers have created substrates of precise micro- and nano-topographical and chemical patterns to mimic in vivo microenvironments for biological and medical applications.
What distinguishes the work of Agah, a National Science Foundation (NSF) CAREER Award recipient, and his colleagues, is they developed a specific three-dimensional silicon microstructure for their work. Due to its curved isotropic surfaces, they were able to characterize and compare the growth and adhesion behavior of normal fibroblast and metastatic human beast cancer cells, they reported in Biomaterials.
"In invasive breast carcinoma, tumor cells will fill a milk duct, and the basement membrane," they wrote. This action allows the carcinoma cells and the fibroblast cells of the breast tissue to be in close proximity, constituting "a critical pathobiological transition that leads to the progression of the disease," Strobl said.
Using their uniquely designed three-dimensional silicon microstructure, they were able to incorporate three key cellular components found in any breast tumor microenvironment. Additionally, they were able to determine the detailed interaction of the cells within this environment, including the normal breast cells, the metastatic breast cancer cells, and the fibroblast cells.
Their understanding of the behavior of the cells within the microstructures is what leads them to believe their research could "provide important diagnostic and prognostic markers unique to the tumor, which could ultimately be used to develop new tools for the detection and treatment of cancer."
Following their initial findings, Strobl, Nikkhah and Agah identified a unique application of the experimental anti-cancer drug SAHA in their studies with the silicon microstructure. SAHA, also known as Vorinostat, is the first drug of its type to receive Food and Drug Administration approval for clinical use in cancer treatment.
Unlike many of the conventional cytotoxic chemotherapy agents that target DNA to kill cancer cells, SAHA's unique properties include its ability to inhibit a family of enzymes referred to medically as "histone deacetylases." These enzymes are known to "increase levels of acetylation of many proteins, including beta-actin, alpha-, and beta-tubulin, and additional actin binding proteins comprising the cytoskeleton.
"The role of drugs such as SAHA in the control of cancer cell metastasis is only beginning to be understood," explained Strobl, "however our work shows that SAHA elicits a very characteristic cytoskeletal alteration specifically in metastatic breast cells that provides a handle for predicting which breast cells in a cell mixture might have the ability to metastasize."
Cell motility is "one hallmark of metastatic cancer cells involving the coordinated actions of actin and other cytoskeleton proteins," Agah explained. When metastatic disease develops, it is usually fatal.
They found SAHA caused cancer cells to stretch and attach to the microstructures through actin-rich cell extensions. By contrast, control cells conformed to the microstructures. This result allowed them to "conclude that isotropically etched silicon microstructures comprise microenvironments that discriminate metastatic mammary cancer cells in which cytoskeletal elements reorganized in response to the anti-cancer agent SAHA."
The Virginia Tech work in this area "is the first to address the use of microdevices to study this emerging class of anti-cancer agents," Agah said.
Source:
Virginia Tech (Virginia Polytechnic Institute and State University)
среда, 24 августа 2011 г.
Scientists Discover Cause Of Breast Cancer Spread
Scientists in London have identified a molecule that could be helping breast cancer to spread, according to research published recently.
Dr Amanda Harvey, based at London's Brunel University, has previously established that a molecule called Brk, found in 60 per cent of breast tumours, plays an important role in making breast cancer cells grow quicker. According to her latest research findings, published in the American Journal of Pathology, Brk has also been shown to be involved in helping breast cancer cells to spread (metastasis).
Metastasis occurs when cancer spreads from its original site to a new location and is responsible for almost all breast cancer deaths.
Dr Harvey studied aggressive breast cancer tumours from patients who normally have an extremely poor outcome. The molecule Brk was found in high levels in these tumours, but crucially it was not found in normal breast cells.
In further laboratory tests, Dr Harvey found that tumour cells died if she stopped Brk from working, but when Brk was re-introduced they survived. This demonstrates that Brk has a significant involvement in helping breast cancer cells to both survive and spread.
Dr Harvey said, "We are now investigating exactly how Brk helps breast cancer to grow and spread so that we can develop ways to prevent this from happening. Our ultimate aim is to develop new ways to kill the breast cancer cells."
Arlene Wilkie, Director of Research and Policy, Breast Cancer Campaign which funded the study said, "Dr Harvey's findings are encouraging and we hope they will take us a step closer to being able to halt the spread of breast cancer, the main cause of death in women with this disease."
Source
Breast Cancer Campaign
Dr Amanda Harvey, based at London's Brunel University, has previously established that a molecule called Brk, found in 60 per cent of breast tumours, plays an important role in making breast cancer cells grow quicker. According to her latest research findings, published in the American Journal of Pathology, Brk has also been shown to be involved in helping breast cancer cells to spread (metastasis).
Metastasis occurs when cancer spreads from its original site to a new location and is responsible for almost all breast cancer deaths.
Dr Harvey studied aggressive breast cancer tumours from patients who normally have an extremely poor outcome. The molecule Brk was found in high levels in these tumours, but crucially it was not found in normal breast cells.
In further laboratory tests, Dr Harvey found that tumour cells died if she stopped Brk from working, but when Brk was re-introduced they survived. This demonstrates that Brk has a significant involvement in helping breast cancer cells to both survive and spread.
Dr Harvey said, "We are now investigating exactly how Brk helps breast cancer to grow and spread so that we can develop ways to prevent this from happening. Our ultimate aim is to develop new ways to kill the breast cancer cells."
Arlene Wilkie, Director of Research and Policy, Breast Cancer Campaign which funded the study said, "Dr Harvey's findings are encouraging and we hope they will take us a step closer to being able to halt the spread of breast cancer, the main cause of death in women with this disease."
Source
Breast Cancer Campaign
воскресенье, 21 августа 2011 г.
Wall Street Journal Examines Breast Cancer Screening Device
The Wall Street Journal on Tuesday examined a breast cancer screening device called the "Halo system," which extracts a fluid from the nipple to test for "atypical" cells that are believed to be a precursor to cancer and has been nicknamed "the breast pap." The device -- developed and sold by NeoMatrix of Irvine, Calif. -- extracts the fluid called nipple aspirate using a warming technique and small suction cups. The test is noninvasive and lasts about five minutes, according to the Journal. The company estimates that atypical cells will be found in about 1% of women who undergo the procedure. Atypical breast cells are benign, but many scientists believe that they are a precursor to cancer, the Journal reports. The presence of atypical breast cells in nipple aspirate increases by as much as five times the risk of developing breast cancer, according to NeoMatrix. Women with atypical cells and a family history of breast cancer have 20 times the risk of developing breast cancer as an average woman, the company says. Although scientists have long known about the potential of nipple aspirate to assess breast cancer risk, the test is not widely used in part because it can be difficult to extract the fluid, according to the Journal. According to physicians, aspirate can only be extracted from 40% to 50% of women, and it is difficult to obtain a sufficient amount of fluid from women over age 55. Victor Vogel, a professor at the University of Pittsburgh School of Medicine, said that the procedure is beneficial for women whose mothers or sisters had breast cancer and women who had their first child after the age of 30 or who have never had children. According to the Journal, the company estimates that the procedure, which is not covered by insurance, will cost $50 to $75. NeoMatrix suggests that women testing positive for abnormal cells be seen by a breast cancer specialist, receive more frequent mammograms and possibly undergo a breast ultrasound to detect tumors missed by conventional mammograms. Mayo Clinic scientist Lynn Hartmann says the company's estimates of increased risk of developing breast cancer are too high. According to a study of 9,087 women Hartmann published in the July 21, 2005, edition of the New England Journal of Medicine, a family history of breast cancer is not associated with an increased risk of cancer in women who have atypical cells (Johannes, Wall Street Journal, 8/8).
"Reprinted with 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 . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
"Reprinted with 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 . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
четверг, 18 августа 2011 г.
Appetite-inducing Hormone Receptor Found Active In Breast Cancer
A hormone receptor with regulatory roles as diverse as food intake, fear response, and cardiovascular function may also be involved in breast cancer, according to University of Cincinnati (UC) researchers.
The UC research team, led by Hassane Amlal, PhD, and Sulaiman Sheriff, PhD, report their laboratory findings on the hormone, neuropeptide Y, and its receptor in the April edition of the journal Cancer Research.
Earlier studies have shown that neuropeptide Y's receptor, known as Y1, is overproduced in human ovarian, prostate and breast cancers. This study, however, is the first to demonstrate that the Y1 receptor is actually working in breast cancer cells and can be "turned on" by excessive estrogen--a known cause of about 60 to 70 percent of breast cancers, they say.
"The high incidence and activity of the Y1 receptor in human breast tumor cells suggests that it may play an important role in breast cancer," explains Dr. Sheriff, a UC research assistant professor in the department of surgery.
Pilot data suggests that about 40 percent of all breast cancer patients have increased levels of the Y1 receptor, he says.
"We knew this receptor was overproduced in breast cancer tissue," adds Dr. Amlal, a research assistant professor in the department of internal medicine, "but now the real question is what does it do in breast cancer cells, and how can we use it as a target to fight cancer."
The UC researchers were able to slow the growth of breast cancer cells with abnormally high levels of the Y1 receptor by treating them with neuropeptide Y hormone produced by chemical synthesis.
"This finding gives us a promising new investigational target in the fight against breast cancer," the authors report. "If we can find a way to selectively activate the Y1 receptor, we can limit breast cancer growth in the body."
Further studies of the Y1 receptor's role, they explain, may ultimately lead to more targeted drug therapy for many breast cancer patients.
According to the American Cancer Society, more than 214,000 women and men will be diagnosed with breast cancer in 2006. About 19 percent will die from the disease.
This study was sponsored by UC and the National Institutes of Health. The research team also included Somia Faroqui, and Ambikaipakan Balasubramaniam, PhD.
Contact: Amanda Harper
amanda.harperuc
University of Cincinnati
The UC research team, led by Hassane Amlal, PhD, and Sulaiman Sheriff, PhD, report their laboratory findings on the hormone, neuropeptide Y, and its receptor in the April edition of the journal Cancer Research.
Earlier studies have shown that neuropeptide Y's receptor, known as Y1, is overproduced in human ovarian, prostate and breast cancers. This study, however, is the first to demonstrate that the Y1 receptor is actually working in breast cancer cells and can be "turned on" by excessive estrogen--a known cause of about 60 to 70 percent of breast cancers, they say.
"The high incidence and activity of the Y1 receptor in human breast tumor cells suggests that it may play an important role in breast cancer," explains Dr. Sheriff, a UC research assistant professor in the department of surgery.
Pilot data suggests that about 40 percent of all breast cancer patients have increased levels of the Y1 receptor, he says.
"We knew this receptor was overproduced in breast cancer tissue," adds Dr. Amlal, a research assistant professor in the department of internal medicine, "but now the real question is what does it do in breast cancer cells, and how can we use it as a target to fight cancer."
The UC researchers were able to slow the growth of breast cancer cells with abnormally high levels of the Y1 receptor by treating them with neuropeptide Y hormone produced by chemical synthesis.
"This finding gives us a promising new investigational target in the fight against breast cancer," the authors report. "If we can find a way to selectively activate the Y1 receptor, we can limit breast cancer growth in the body."
Further studies of the Y1 receptor's role, they explain, may ultimately lead to more targeted drug therapy for many breast cancer patients.
According to the American Cancer Society, more than 214,000 women and men will be diagnosed with breast cancer in 2006. About 19 percent will die from the disease.
This study was sponsored by UC and the National Institutes of Health. The research team also included Somia Faroqui, and Ambikaipakan Balasubramaniam, PhD.
Contact: Amanda Harper
amanda.harperuc
University of Cincinnati
понедельник, 15 августа 2011 г.
Mammograms Not Main Reason For Drop In Breast Cancer Death Rate
Screening mammographies do not reduce the death rate from breast cancer as much as people had thought, especially among women aged 50 years or more, scientists in a large Norwegian study report in the New England Journal of Medicine (NEJM). In fact, better treatment and greater awareness about breast cancer are the main reasons for lower mortality, while mammography screening is estimated to account for about a third, the authors say.
The investigators explain that measuring the effect of breast cancer screening on mortality is not easy - the main problem being having access to valid comparison groups. Using historical control subjects does not factor in awareness and treatment changes that occur over time.
This study reveals that even though mammograms do reduce mortality (risk of dying), the benefit is surprisingly unexceptional. Women who underwent screening were found to have a 10% lower risk of dying from breast cancer; however, only one third of that 10% was because of the screening. To save one life, 2,500 women would have to undergo mammography screening regularly for over a decade, an accompanying editorial in the NEJM points out.
A breast-cancer screening program started in Norway in 1996 and spread throughout the country during the subsequent nine years. Females aged from 50 to 69 years were offered mammogram screening every two years.
The researchers compared mortality rates in four groups of women:
Women living in counties with screening - the screening group (1996 to the end of 2005)
Women living in counties without screening - the non-screening group (1996 to the end of 2005)
Two groups of women from the same areas as the two groups above, ten years before the screening program started
By splitting the women into the four groups, the investigators were able to separate the screening effects from other factors which might have altered mortality rates, such as better awareness and improved therapies.
Team leader, Dr. Mette Kalager of Oslo University Hospital and team, with collaboration from Harvard University and the Dana-Farber Cancer Institute examined the medical documents of 40,075 women with breast cancer.
Breast cancer mortality dropped by 7.2 per 100,000 for the women in the screening group, compared to the women in the same area ten years before the screening program was launched.
Mortality in the non-screening group dropped by 4.8 per 100,000 when compared to women in the same area ten years before the launching of the screening program.
The real impact of screening was consequently:
7.2 minus 4.8 = 2.4 fewer deaths per 100,000 women.
In other words, the screening program's impact on total mortality (risk of death) was just one third of the total.
Norway's screening program did not include women over 70 years of age. When studying breast cancer mortality among this age group, the researchers found that mortality had dropped 8% compared to the previous decade - as this improvement had not been due to screening, it was most likely the result of better therapy, the authors believe.
The authors wrote in the NEJM, as a conclusion:
The availability of screening mammography was associated with a reduction in the rate of death from breast cancer, but the screening itself accounted for only about a third of the total reduction.
Breast cancer is the most common cancer for women. About one in every nine women will develop breast cancer in her lifetime. 99% of all breast cancers are diagnosed in women, 1% affect men. However, men with breast cancer tend to have poorer outcomes than women.
Globally, breast cancer represents 10.4% of all female cancer incidence, making it the most common type of non-skin cancer in females, as well as the fifth most common cause of cancer death.
"Effect of Screening Mammography on Breast-Cancer Mortality in Norway"
Mette Kalager, M.D., Marvin Zelen, Ph.D., FrГёydis Langmark, M.D., and Hans-Olov Adami, M.D., Ph.D.
N Engl J Med 2010; 363:1203-1210September 23, 2010
Written by
The investigators explain that measuring the effect of breast cancer screening on mortality is not easy - the main problem being having access to valid comparison groups. Using historical control subjects does not factor in awareness and treatment changes that occur over time.
This study reveals that even though mammograms do reduce mortality (risk of dying), the benefit is surprisingly unexceptional. Women who underwent screening were found to have a 10% lower risk of dying from breast cancer; however, only one third of that 10% was because of the screening. To save one life, 2,500 women would have to undergo mammography screening regularly for over a decade, an accompanying editorial in the NEJM points out.
A breast-cancer screening program started in Norway in 1996 and spread throughout the country during the subsequent nine years. Females aged from 50 to 69 years were offered mammogram screening every two years.
The researchers compared mortality rates in four groups of women:
Women living in counties with screening - the screening group (1996 to the end of 2005)
Women living in counties without screening - the non-screening group (1996 to the end of 2005)
Two groups of women from the same areas as the two groups above, ten years before the screening program started
By splitting the women into the four groups, the investigators were able to separate the screening effects from other factors which might have altered mortality rates, such as better awareness and improved therapies.
Team leader, Dr. Mette Kalager of Oslo University Hospital and team, with collaboration from Harvard University and the Dana-Farber Cancer Institute examined the medical documents of 40,075 women with breast cancer.
Breast cancer mortality dropped by 7.2 per 100,000 for the women in the screening group, compared to the women in the same area ten years before the screening program was launched.
Mortality in the non-screening group dropped by 4.8 per 100,000 when compared to women in the same area ten years before the launching of the screening program.
The real impact of screening was consequently:
7.2 minus 4.8 = 2.4 fewer deaths per 100,000 women.
In other words, the screening program's impact on total mortality (risk of death) was just one third of the total.
Norway's screening program did not include women over 70 years of age. When studying breast cancer mortality among this age group, the researchers found that mortality had dropped 8% compared to the previous decade - as this improvement had not been due to screening, it was most likely the result of better therapy, the authors believe.
The authors wrote in the NEJM, as a conclusion:
The availability of screening mammography was associated with a reduction in the rate of death from breast cancer, but the screening itself accounted for only about a third of the total reduction.
Breast cancer is the most common cancer for women. About one in every nine women will develop breast cancer in her lifetime. 99% of all breast cancers are diagnosed in women, 1% affect men. However, men with breast cancer tend to have poorer outcomes than women.
Globally, breast cancer represents 10.4% of all female cancer incidence, making it the most common type of non-skin cancer in females, as well as the fifth most common cause of cancer death.
"Effect of Screening Mammography on Breast-Cancer Mortality in Norway"
Mette Kalager, M.D., Marvin Zelen, Ph.D., FrГёydis Langmark, M.D., and Hans-Olov Adami, M.D., Ph.D.
N Engl J Med 2010; 363:1203-1210September 23, 2010
Written by
пятница, 12 августа 2011 г.
New NICE Guidance To Improve Care For Early Breast Cancer, UK
The National Institute for Health and Clinical Excellence (NICE) has today issued guidance to the NHS on the use of docetaxel and paclitaxel for the treatment of early breast cancer following surgery.
NICE has recommended that:
Docetaxel, when given concurrently with doxorubicin and cyclophosphamide (the TAC regimen) in accordance with its licensed indication, is recommended as an option for the treatment of women with early node-positive breast cancer following surgery.
Paclitaxel, within its licensed indication, is not recommended for the treatment of women with early node-positive breast cancer following surgery.
Andrea Sutcliffe, Deputy Chief Executive at NICE and Executive Lead for this appraisal, said: "NICE has issued clear advice to the NHS on the use of docetaxel and paclitaxel for early breast cancer following surgery which will give the best care to patients and use NHS resources most effectively. This is the latest guidance to be developed using the new NICE rapid appraisal process, and we hope to continue to assess individual drugs quickly to provide robust guidance to the NHS close to when they are licensed"
About this appraisal
1. Docetaxel and paclitaxel are anticancer drugs that belong to a class of drugs known as taxanes.
2. NICE has assessed the use of these drugs as adjuvant chemotherapy, drug treatments that are given following cancer surgery.
3. Docetaxel has a UK marketing authorisation for the adjuvant treatment of patients with operable node-positive breast cancer in combination with doxorubicin and cyclophosphamide.
4. Paclitaxel has a UK marketing authorisation for the adjuvant treatment of node-positive breast carcinoma following anthracycline and cyclophosphamide therapy.
5. Full recommendations can be found on the NICE website at nice.uk.
6. NICE issued guidance on the use of docetaxel and paclitaxel for advanced breast cancer in September 2001 and recommended that they should be made available as an option for the treatment of advanced breast cancer where the initial chemotherapy (including an anthracycline) has failed or is inappropriate. Full recommendations can be found at nice.uk/page.aspx?o=TA030.
About the Single Technology Appraisal (STA) process
7. The new STA process enables NICE to issue faster guidance by:
* Asking for a single submission of evidence from the technology's manufacturer.
* Carrying out an independent review of this evidence more quickly.
* Moving more quickly to the final (appeal) stage of the process where the draft recommendations are in line with the licensed use of the technology.
* Normally, formal consultation, which involves the production of an ACD (draft recommendations) rather than a FAD (final guidance) only takes place if the recommendations emerging from the Committee are substantively restrictive. A substantively restrictive recommendation is one that is more limited than the terms of the licensed indication to an extent judged to be significant in clinical practice.
About NICE
8. The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health.
9. NICE produces guidance in three areas of health
public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector
health technologies - guidance on the use of new and existing medicines, treatments and procedures within the NHS
clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.
NICE is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health.
For further information please visit:
nice.uk
NICE has recommended that:
Docetaxel, when given concurrently with doxorubicin and cyclophosphamide (the TAC regimen) in accordance with its licensed indication, is recommended as an option for the treatment of women with early node-positive breast cancer following surgery.
Paclitaxel, within its licensed indication, is not recommended for the treatment of women with early node-positive breast cancer following surgery.
Andrea Sutcliffe, Deputy Chief Executive at NICE and Executive Lead for this appraisal, said: "NICE has issued clear advice to the NHS on the use of docetaxel and paclitaxel for early breast cancer following surgery which will give the best care to patients and use NHS resources most effectively. This is the latest guidance to be developed using the new NICE rapid appraisal process, and we hope to continue to assess individual drugs quickly to provide robust guidance to the NHS close to when they are licensed"
About this appraisal
1. Docetaxel and paclitaxel are anticancer drugs that belong to a class of drugs known as taxanes.
2. NICE has assessed the use of these drugs as adjuvant chemotherapy, drug treatments that are given following cancer surgery.
3. Docetaxel has a UK marketing authorisation for the adjuvant treatment of patients with operable node-positive breast cancer in combination with doxorubicin and cyclophosphamide.
4. Paclitaxel has a UK marketing authorisation for the adjuvant treatment of node-positive breast carcinoma following anthracycline and cyclophosphamide therapy.
5. Full recommendations can be found on the NICE website at nice.uk.
6. NICE issued guidance on the use of docetaxel and paclitaxel for advanced breast cancer in September 2001 and recommended that they should be made available as an option for the treatment of advanced breast cancer where the initial chemotherapy (including an anthracycline) has failed or is inappropriate. Full recommendations can be found at nice.uk/page.aspx?o=TA030.
About the Single Technology Appraisal (STA) process
7. The new STA process enables NICE to issue faster guidance by:
* Asking for a single submission of evidence from the technology's manufacturer.
* Carrying out an independent review of this evidence more quickly.
* Moving more quickly to the final (appeal) stage of the process where the draft recommendations are in line with the licensed use of the technology.
* Normally, formal consultation, which involves the production of an ACD (draft recommendations) rather than a FAD (final guidance) only takes place if the recommendations emerging from the Committee are substantively restrictive. A substantively restrictive recommendation is one that is more limited than the terms of the licensed indication to an extent judged to be significant in clinical practice.
About NICE
8. The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health.
9. NICE produces guidance in three areas of health
public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector
health technologies - guidance on the use of new and existing medicines, treatments and procedures within the NHS
clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.
NICE is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health.
For further information please visit:
nice.uk
вторник, 9 августа 2011 г.
Loyola Study Finds The Hormone Estrogen Inhibits A Protein That Causes Normal Cell Death In Breast Tumors
A new study is providing insight into how estrogen fuels many breast cancers, and researchers say the findings could lead to new cancer-fighting drugs.
Researchers found that estrogen inhibits a protein called MLK3 that causes normal cell death. Blocking MLK3 leads to uncontrolled growth of cancer cells and resistance to chemotherapy.
Researchers from Loyola University Health System and three other centers reported the findings in the journal Cancer Research.
"This could give us a new angle to treating breast cancer," said senior author Ajay Rana, PhD, a professor in the Department of Pharmacology at Loyola University Chicago Stritch School of Medicine.
About 60 percent of all breast cancers are estrogen-positive or progesterone-positive. This means the cancer cells have receptors for the female hormones estrogen and progesterone. Consequently, the hormones fuel the tumor's growth.
In laboratory experiments, researchers found that in estrogen-positive and progesterone-positive cancer cells, there is a reduction in the activity of MLK3. Consequently, cells can continue growing, changing and developing resistance to chemotherapy. "Cancer cells are very smart," Dr. Rana said.
By contrast, Dr. Rana's team found that MLK3 activity was much higher in estrogen-negative and progesterone-negative cancer cells.
The next step, Dr. Rana said, is to look for a drug that would overcome the inhibitory effect of estrogen on MLK3. Such a drug would be taken in combination with chemotherapy drugs.
Loyola co-authors are Velusamy Rangasamy, PhD (first author); Rajakishore Mishra, PhD; Suneet Mehrotra, PhD; Gautam Sondarva, PhD, Rajarshi S.Ray, PhD and Basabi Rana, PhD. Other co-authors are Arundhati Rao, MD, of Scott and White Hospital in Temple, Tx and Malay Chatterjee, PhD of Jadavpur University in Kolkata, India. Basabi Rana and Ajay Rana also are affiliated with Edward Hines Jr. VA Hospital.
Source:
Jim Ritter
Loyola University Health System
Researchers found that estrogen inhibits a protein called MLK3 that causes normal cell death. Blocking MLK3 leads to uncontrolled growth of cancer cells and resistance to chemotherapy.
Researchers from Loyola University Health System and three other centers reported the findings in the journal Cancer Research.
"This could give us a new angle to treating breast cancer," said senior author Ajay Rana, PhD, a professor in the Department of Pharmacology at Loyola University Chicago Stritch School of Medicine.
About 60 percent of all breast cancers are estrogen-positive or progesterone-positive. This means the cancer cells have receptors for the female hormones estrogen and progesterone. Consequently, the hormones fuel the tumor's growth.
In laboratory experiments, researchers found that in estrogen-positive and progesterone-positive cancer cells, there is a reduction in the activity of MLK3. Consequently, cells can continue growing, changing and developing resistance to chemotherapy. "Cancer cells are very smart," Dr. Rana said.
By contrast, Dr. Rana's team found that MLK3 activity was much higher in estrogen-negative and progesterone-negative cancer cells.
The next step, Dr. Rana said, is to look for a drug that would overcome the inhibitory effect of estrogen on MLK3. Such a drug would be taken in combination with chemotherapy drugs.
Loyola co-authors are Velusamy Rangasamy, PhD (first author); Rajakishore Mishra, PhD; Suneet Mehrotra, PhD; Gautam Sondarva, PhD, Rajarshi S.Ray, PhD and Basabi Rana, PhD. Other co-authors are Arundhati Rao, MD, of Scott and White Hospital in Temple, Tx and Malay Chatterjee, PhD of Jadavpur University in Kolkata, India. Basabi Rana and Ajay Rana also are affiliated with Edward Hines Jr. VA Hospital.
Source:
Jim Ritter
Loyola University Health System
суббота, 6 августа 2011 г.
What Is Herceptin (trastuzumab)? What Is Herceptin For?
Trastuzumab, known by the brand name Herceptin is a medication given to patients with breast cancer. It halts the growth of breast cancer and can sometimes shrink tumors.
Herceptin, which is administered intravenously, is sometimes given along with chemotherapy or on its own. Typically, the patient has already undergone two courses of chemotherapy.
According to Medilexicon's medical dictionary:
Herceptin (trastuzumab) is "a monoclonal antibody used in treating her 2 neu-positive carcinoma of breast."
Trastuzumab, made by biotech company Genentech, was approved by the FDA in 1998.
Preliminary studies showed that Herceptin improved survival rates in late-stage breast cancer - metastatic cancer. There is still controversy regarding this medication for patients with earlier stage breast cancer.
Some experts believe Herceptin's effectiveness has been overstated. Various media outlets have been accused of giving trastuzumab an undeserved miracle-drug status. These controversies and media statements have confused patients who wonder whether they should take the drug or not.
Herceptin (trastuzumab) is expensive. Some US private health insurance companies and governments where universal health care cover exists refuse to pay for Herceptin treatment. Some companies have since accepted Herceptin treatment as a covered preventative treatment. In 2010 NICE (National Institute for Health and Clinical Evidence) approved Herceptin use for some patients with advanced and early stage breast cancers. NICE decides whether a drug gets covered by the UK National Health Service (NHS).
How does Herceptin work?
Herceptin is a monoclonal antibody, it interferes with the HER2/neu receptor. Only patients with high HER2 protein levels should be given this drug. HER2 exists on the surface of some breast cancer cells. The HER receptors are proteins that are routed in the cell membrane.
HER receptors communicate molecular signals to within the cells from the surface, and switch genes on and off. HER proteins are important factors in cell growth, adhesion, migration, differentiation and survival. In breast cancers the HER2 receptor is faulty - its "on" switch never goes to "off", resulting in the uncontrollable reproduction of breast cells, causing breast cancer.
Herceptin sticks to the HER2 protein, preventing the epidermal growth factor (a protein) from getting into the cancer cells. Herceptin effectively stops the breast cancer cells from reproducing uncontrollably.
Patients without high levels of HER2 protein do not benefit from Herceptin therapy. Only approximately 20% of females with breast cancer have Herceptin-sensitive tumors. In other words, if the breast cancer does not have overactive HER2 receptors, Herceptin will have no beneficial effect. There are tests doctors can order which determine whether a patient's HER2 is over-expressed.
The best duration of adjuvant Herceptin (trastuzumab) is currently unknown. Experts say that one year of Herceptin treatment is ideal. According to clinical trial findings, extending the treatment period for longer provides the patient with no additional benefits.
Debate about treatment duration has become a relevant issue for many public health policy makers due to the high financial costs involved in the administration of this treatment for one year. Current clinical trials are in progress hoping to answer this question by directly comparing short versus long duration of therapy.
If you have a pre-existing heart condition you should not take Herceptin. Health authorities recommend that patients be assessed for heart function before considering using this drug.
Possible side effects of Herceptin include:
Stomach pain
Pneumonia
Nausea and vomiting
Heart problems
Headaches
Fevrer
Flu-like symptoms
Diarrhea
Cough and shortness of breath
Chest pain
Aches and pains
Some patients may develop allergic reactions and experience breathlessness, itching and a rash. This is rare.
Most of Herceptin's side effects are treatable, often with medication.
Written by
View drug information on Herceptin.
Herceptin, which is administered intravenously, is sometimes given along with chemotherapy or on its own. Typically, the patient has already undergone two courses of chemotherapy.
According to Medilexicon's medical dictionary:
Herceptin (trastuzumab) is "a monoclonal antibody used in treating her 2 neu-positive carcinoma of breast."
Trastuzumab, made by biotech company Genentech, was approved by the FDA in 1998.
Preliminary studies showed that Herceptin improved survival rates in late-stage breast cancer - metastatic cancer. There is still controversy regarding this medication for patients with earlier stage breast cancer.
Some experts believe Herceptin's effectiveness has been overstated. Various media outlets have been accused of giving trastuzumab an undeserved miracle-drug status. These controversies and media statements have confused patients who wonder whether they should take the drug or not.
Herceptin (trastuzumab) is expensive. Some US private health insurance companies and governments where universal health care cover exists refuse to pay for Herceptin treatment. Some companies have since accepted Herceptin treatment as a covered preventative treatment. In 2010 NICE (National Institute for Health and Clinical Evidence) approved Herceptin use for some patients with advanced and early stage breast cancers. NICE decides whether a drug gets covered by the UK National Health Service (NHS).
How does Herceptin work?
Herceptin is a monoclonal antibody, it interferes with the HER2/neu receptor. Only patients with high HER2 protein levels should be given this drug. HER2 exists on the surface of some breast cancer cells. The HER receptors are proteins that are routed in the cell membrane.
HER receptors communicate molecular signals to within the cells from the surface, and switch genes on and off. HER proteins are important factors in cell growth, adhesion, migration, differentiation and survival. In breast cancers the HER2 receptor is faulty - its "on" switch never goes to "off", resulting in the uncontrollable reproduction of breast cells, causing breast cancer.
Herceptin sticks to the HER2 protein, preventing the epidermal growth factor (a protein) from getting into the cancer cells. Herceptin effectively stops the breast cancer cells from reproducing uncontrollably.
Patients without high levels of HER2 protein do not benefit from Herceptin therapy. Only approximately 20% of females with breast cancer have Herceptin-sensitive tumors. In other words, if the breast cancer does not have overactive HER2 receptors, Herceptin will have no beneficial effect. There are tests doctors can order which determine whether a patient's HER2 is over-expressed.
The best duration of adjuvant Herceptin (trastuzumab) is currently unknown. Experts say that one year of Herceptin treatment is ideal. According to clinical trial findings, extending the treatment period for longer provides the patient with no additional benefits.
Debate about treatment duration has become a relevant issue for many public health policy makers due to the high financial costs involved in the administration of this treatment for one year. Current clinical trials are in progress hoping to answer this question by directly comparing short versus long duration of therapy.
If you have a pre-existing heart condition you should not take Herceptin. Health authorities recommend that patients be assessed for heart function before considering using this drug.
Possible side effects of Herceptin include:
Stomach pain
Pneumonia
Nausea and vomiting
Heart problems
Headaches
Fevrer
Flu-like symptoms
Diarrhea
Cough and shortness of breath
Chest pain
Aches and pains
Some patients may develop allergic reactions and experience breathlessness, itching and a rash. This is rare.
Most of Herceptin's side effects are treatable, often with medication.
Written by
View drug information on Herceptin.
среда, 3 августа 2011 г.
Future Hope For Patients With Breast Cancers Resistant To Tamoxifen
Researchers have found a new family of therapeutic agents that interferes with the ability of estrogen to stimulate the growth of breast cancer cells. The results of the new study were presented by Nicole Patterson at The Endocrine Society's 90th Annual Meeting in San Francisco.
The cell-based study suggests that a small-molecule therapeutic called TPBM and related compounds are likely to be effective against breast cancers that depend on estrogen to grow (called estrogen receptor-positive) but that are resistant to current therapies, team leader David Shapiro, PhD, said.
Shapiro, a biochemist at the University of Illinois at Urbana-Champaign, said at detection, about two-thirds of breast cancers are estrogen receptor-positive, and virtually all of these cancers become resistant over time to the breast cancer drug tamoxifen. In some tamoxifen-resistant tumors, tamoxifen begins to act like estrogen and can actually stimulate tumor growth, he explained.
Therefore, researchers are trying to find new ways to block resistance to drugs such as tamoxifen. Shapiro's team developed a technique to screen for chemical compounds that would inhibit the ability of estrogen and the estrogen receptor protein to bind to DNA and turn on gene expression in breast cancer cells.
"We targeted a different step in the pathway of estrogen action, one that is not targeted by current therapeutics," Shapiro said.
They then tested various agents in estrogen receptor-positive breast cancer cells in the laboratory. The team identified a family of compounds related to TPBM that Shapiro said inhibited the estrogen-dependent growth of breast cancer cells.
"TPBM is highly targeted and has little or no toxic effect on other cells - those that don't depend on the estrogen receptor," Shapiro said. "Also important, these compounds are effective in breast cancer cells in which tamoxifen acts like estrogen."
Thus, these compounds might prevent tamoxifen-resistant breast cancer from becoming more aggressive. However, Shapiro cautioned that their research is in the early stage. A future step will be testing the new estrogen receptor inhibitors in animal models of breast cancer.
Researchers from the University of North Carolina, Chapel Hill, and the University of Colorado Health Sciences Center, Denver, collaborated with the University of Illinois, Urbana-Champaign on this study. It was funded by NIDDK of the National Institutes of Health.
Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones, and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society, and the field of endocrinology, visit our web site at endo-society/.
Source: Aaron Lohr
The Endocrine Society
The cell-based study suggests that a small-molecule therapeutic called TPBM and related compounds are likely to be effective against breast cancers that depend on estrogen to grow (called estrogen receptor-positive) but that are resistant to current therapies, team leader David Shapiro, PhD, said.
Shapiro, a biochemist at the University of Illinois at Urbana-Champaign, said at detection, about two-thirds of breast cancers are estrogen receptor-positive, and virtually all of these cancers become resistant over time to the breast cancer drug tamoxifen. In some tamoxifen-resistant tumors, tamoxifen begins to act like estrogen and can actually stimulate tumor growth, he explained.
Therefore, researchers are trying to find new ways to block resistance to drugs such as tamoxifen. Shapiro's team developed a technique to screen for chemical compounds that would inhibit the ability of estrogen and the estrogen receptor protein to bind to DNA and turn on gene expression in breast cancer cells.
"We targeted a different step in the pathway of estrogen action, one that is not targeted by current therapeutics," Shapiro said.
They then tested various agents in estrogen receptor-positive breast cancer cells in the laboratory. The team identified a family of compounds related to TPBM that Shapiro said inhibited the estrogen-dependent growth of breast cancer cells.
"TPBM is highly targeted and has little or no toxic effect on other cells - those that don't depend on the estrogen receptor," Shapiro said. "Also important, these compounds are effective in breast cancer cells in which tamoxifen acts like estrogen."
Thus, these compounds might prevent tamoxifen-resistant breast cancer from becoming more aggressive. However, Shapiro cautioned that their research is in the early stage. A future step will be testing the new estrogen receptor inhibitors in animal models of breast cancer.
Researchers from the University of North Carolina, Chapel Hill, and the University of Colorado Health Sciences Center, Denver, collaborated with the University of Illinois, Urbana-Champaign on this study. It was funded by NIDDK of the National Institutes of Health.
Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones, and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society, and the field of endocrinology, visit our web site at endo-society/.
Source: Aaron Lohr
The Endocrine Society
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