AviaraDx Confirms That Combination Of Two Molecular Biomarkers Improves Prediction Of Disease Recurrence In Early Stage Breast Cancer Patients

AviaraDx, Inc. announced the
publication of an article describing the discovery, development and
validation of a new molecular biomarker, Aviara MGI(SM) (Molecular Grade
Index), that improves the accuracy of breast cancer tumor grading for the
prediction of distant disease recurrence. The authors also report that
combining Aviara MGI with Aviara H/I(SM) (HOXB13:IL17BR), a biomarker
previously shown to predict endocrine benefit, provides superior
stratification of recurrence risk. The article, "A Five-Gene Molecular
Grade Index and HOXB13:IL17BR Are Complementary Prognostic Factors in Early
Stage Breast Cancer," appeared in the May 1, 2008 edition of Clinical
Cancer Research.


The Aviara MGI and Aviara H/I ("H over I") biomarkers measure specific,
independent and clinically relevant aspects of tumor biology. According to
the paper published this month, the combination of these markers provides
superior risk stratification as it relates to endocrine benefit and
treatment outcome. After development and testing, the combination was
clinically validated through retrospective analyses of 239 ER-positive,
lymph-node negative patients treated at Massachusetts General Hospital,
Boston, MA, and an independent cohort of 84 patients from John Radcliffe
Hospital, Oxford (UK).



Aviara MGI is a new molecular assay comprising only five genes that are
activated at different cell cycle stages and are involved in invasive tumor
growth. This assay assists pathologists and oncologists by improving the
accuracy of tumor grading.



To predict tumor aggressiveness and a potential response to
chemotherapy, pathologists traditionally evaluate a breast cancer biopsy by
light microscopy and assign a tumor grade. Patients with more aggressive,
high grade (Grade 3) tumors have been shown to derive varying degrees of
benefit from chemotherapy, while patients with less aggressive, low grade
(Grade 1) tumors usually derive no benefit. However, approximately 50
percent of all early stage breast cancer patients are diagnosed with an
intermediate tumor grade (Grade 2). For these patients the appropriate
choice of therapy is unclear. The clinical data published this month
demonstrate that Aviara MGI accurately identifies Grade 1 and 3 tumors, and
successfully re-classifies intermediate tumor grade (Grade 2) into cases
with Grade 1-like or Grade 3-like outcomes.



"The importance of accurate tumor grading cannot be understated," said
Dennis C. Sgroi, director of breast pathology at Massachusetts General
Hospital and associate professor of pathology at Harvard Medical School, a
senior author of the article. "A molecular tool such as MGI that can help
separate intermediate-grade tumors into two distinct prognostic groups will
go a long way in stratifying risk and improving treatment selection for
breast cancer patients."
















Researchers combined Aviara MGI and Aviara H/I in order to assess the
overall impact of both molecular tumor grade and endocrine therapy benefit
on patient outcome. H/I is a well-established biomarker that has been shown
to predict both recurrence risk and endocrine benefit in more than 2,000
patients in numerous clinical studies. It assesses the likelihood of a
patient to benefit from endocrine therapy by measuring the functionality of
the estrogen signaling pathway inside the tumor cell itself. As such, H/I
goes beyond conventional estrogen and progesterone receptor (ER/PR)
testing. While patients who are ER/PR positive are assumed to benefit from
endocrine therapy, the therapy fails in approximately 25 percent of those
patients.



"Other gene-signature assays developed for breast cancer provide an
improvement over tumor grade as a measure of breast cancer aggressiveness
and likely benefit from chemotherapy. These different proliferation gene
signatures are essentially redundant, and they do not go beyond ER/PR in
determining the likelihood of responding to endocrine therapy," said
Antonius Schuh, PhD, chief executive officer of AviaraDx, Inc. "H/I and MGI
together provide a more complete diagnostic picture that should help
clinicians make more appropriate treatment decisions for their breast
cancer patients."



"This is the first analysis linking H/I to our new, five-gene tumor
grading index, MGI," said Mark Erlander, PhD, chief scientific officer for
AviaraDx, Inc. "For patients whose tumors have high MGI values, it is
important to measure H/I in order to determine likely benefit from
endocrine therapy within the setting of a highly proliferating tumor."



The authors conclude that these two markers together should enable
oncologists to identify a large subgroup of women with low risk of
recurrence who may be spared from toxic chemotherapy regimens. In addition,
they may also identify a significant population of patients for whom
intensive chemotherapy regimens or new therapeutic agents should be
considered.



"As molecular diagnostics enable the personalization of patient care,
we will help patients and clinicians determine appropriate therapies and
avoid both over- and under-treatment," added Schuh.



Approximately 100,000 women present with ER-positive, node-negative
breast cancer in the United States every year. The data included in this
month's Clinical Cancer Research publication show that the combination of
Aviara MGI and Aviara H/I provides objective information to better assess
both recurrence risk and potential for response to systemic therapies in
these early stage breast cancer patients. The combination of these two
biomarkers is now commercially available as the Aviara Breast Cancer
Index(SM).



About AviaraDx, Inc.



AviaraDx discovers, develops, and commercializes new molecular
diagnostic tests in oncology, enabling physicians to personalize cancer
treatment through better understanding of the molecular biology underlying
a patient's tumor. The company's current offerings include a molecular
cancer classification assay, Aviara CancerTYPE ID(SM) capable of
classifying up to 39 tumor types; Aviara H/I(SM), which predicts endocrine
benefit in breast cancer; and Aviara MGI(SM), a molecular grade index to
objectively measure tumor grade. Aviara H/I and Aviara MGI are available
separately, or can be combined in the Aviara Breast Cancer Index(SM).
Additional tests are in development. AviaraDx offers these diagnostic tests
to qualified physicians or laboratories through its CLIA-certified, CAP
accredited laboratory service operations. For more information, visit
aviaradx.


AviaraDx, Inc.

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