Agendia Highlights Study Showing MammaPrint/BluePrint Tests Predict Response to Current Breast Cancer Chemotherapy and Targeted Therapy Regimens

Agendia's MammaPrint® and BluePrint® tests provide new insights that may provide many more women with beneficial treatment for breast cancer before surgery, according to findings presented at the 2015 Breast Cancer Symposium.

Researchers analyzed a cohort of 889 early-stage breast cancer patients in the NBRST ("N-breast") study who had functional molecular subtyping with the BluePrint test. The data underscored the ability of MammaPrint and BluePrint to predict the result of contemporary, commonly used chemotherapy and targeted therapy regimens. A competing assay, by comparison, has been validated to be predictive with older chemotherapy regimens that are less widely used today.

The analysis presented at the Breast Cancer Symposium identified a substantial group of patients who were said to be, by standard IHC-FISH clinical lab testing, HER2-positive and ER-positive -- but who did not respond well to the type of neoadjuvant (presurgical) treatment that is usually prescribed for patients believed to be HER2+ and ER+ by IHC-FISH.

Researchers discovered that the MammaPrint-BluePrint tests in fact reclassified a group of these patients as having the Luminal-type molecular subtype of breast cancer. For this group, when another drug called pertuzumab (Perjeta®) was added to their presurgical treatment, these women had a far greater benefit from therapy (10-fold increase), as measured by whether they had a pathologic complete response (pCR) when treated with chemotherapy before their surgery.

"These Luminal-type patients are far less likely to benefit from the standard use of neoadjuvant chemotherapy and trastuzumab (Herceptin®)," as measured by whether or not they had a pCR," said Peter Beitsch, M.D., who presented the findings in a podium talk at the Breast Cancer Symposium. "By contrast, we found that the pCR rate among these Luminal-type molecular subtypes was nearly 10 times better if their neoadjuvant treatment also included pertuzumab along with chemotherapy and trastuzumab.

"This research may upend the conventional thinking and resolve a well-known conundrum in breast cancer research," he said. "Many HER2-positive and ER-positive patients, as identified by IHC-FISH, respond well to presurgical chemo and trastuzumab, though as a group not nearly as well as HER2-positive and ER-negative patients. There is a subgroup of HER2-positive, ER-positive patients whose cancers do not respond favorably to that standard treatment. These new findings indicate the tumors in this subgroup are in fact Luminal-type (not HER type) molecular subtype as assessed by BluePrint. For better survival, this group of patients may require dual drug treatment that combines pertuzumab with chemotherapy and trastuzumab."

Agendia CEO Mark Straley underscored the significance of the research: "These findings are further evidence that Agendia's research and development place us in a unique position to work with pharmaceutical companies, to better understand breast cancer biology and to refine treatment by predicting response," Straley said. "Predicting which patients will benefit the most from costly and potentially toxic therapies - and which patients can safely forego them - is a critically important part of improving breast cancer care. Agendia's assays continue to demonstrate that they can help physicians make the most personalized and most current predictive treatment decisions for each breast cancer patient."

Among the findings presented in Dr. Beitsch's talk were these:

• MammaPrint/BluePrint reclassified 23% of patients and yielded significantly better correlation with both neoadjuvant chemotherapy responsiveness and resistance compared to IHC-FISH
• MammaPrint/BluePrint subtyping divided triple positive (HER2+/ER+/HR+) cancers into Luminal-type and HER2-type molecular subtypes of approximately equal proportion
• Triple positive/BluePrint Luminal-type cancers are relatively resistant to NCT/trastuzumab
• Perjeta added to NCT/trastuzumab overcomes this resistance.

"We believe this data is the first prospectively gathered evidence of its kind," said Dr. Beitsch. "It provides further evidence for the substantial value of functional molecular subtyping and its utility in predicting which patients will require dual neoadjuvant drug therapy, combining trastuzumab and pertuzumab."

Agendia's MammaPrint 70-gene assay and BluePrint 80-gene molecular subtyping assay are the most widely available tests that provide the functional molecular subtype of a woman's breast cancer. Molecular subtyping is a form of precision medicine increasingly used to personalize treatment. It allows physicians to more accurately understand the biology of a woman's breast cancer and better allocate treatment that fits her particular cancer. The MammaPrint 70-gene assay has received FDA 510(k) clearance for use in FFPE tissue samples. MammaPrint was the first breast cancer risk of recurrence multi-gene assay to receive FDA 510(k) clearance. With the most recent clearance, Agendia now has six FDA clearances in its breast cancer portfolio.

Among the study co-authors were Pat Whitworth, M.D. a surgical oncologist at Nashville Breast Center, and clinicians from 11 other institutions around the U.S. Dr. Beitsch is Director of the Dallas Breast Center and practices at North Central Surgical Central Hospital. A widely published researcher, he is a Fellow of the Society of Surgical Oncology and past President of the American Society of Breast Surgeons

The 2015 Breast Cancer Symposium was held Sept. 25-27 in San Francisco. It was cosponsored by the American Society of Clinical Oncology, the Society of Surgical Oncology and the American Society for Radiation Oncology.