A Medical Device Daily

The latest in breast cancer research - from a test capable of identifying patients who are most likely to respond to the drug Herceptin, to a study revealing that not all node-positive patients benefit from chemotherapy - were presented throughout the weekend in San Antonio.

The 30th annual San Antonio Breast Cancer Symposium (SABCS) wrapped up yesterday at the Henry B. Gonzalez Convention Center.

Among the companies presenting new data was Monogram Biosciences (South San Francisco), detailing its HERmark assay's ability to identify metastatic breast cancer patients who are most likely to respond to Herceptin.

HERmark is a diagnostic designed to accurately quantify HER2 expression and dimerization in patients with breast cancer. According to the company, preliminary data suggest that the test can identify patients who are likely to respond to Herceptin with greater precision than currently available tests.

In the study, Monogram analyzed tissue samples from patients with metastatic breast cancer who were treated with Herceptin, having been selected for such treatment by centralized IHC testing. While current testing methods identified all these patients as being appropriate for Herceptin treatment, Monogram's HERmark assay was able to distinguish separate sub-populations of patients with different clinical outcomes, the company noted.

Those patients with higher HER2 expression levels experienced a 59% objective response rate while those with lower levels of HER2 expression had a response rate of only 18%.

Additional analyses revealed that patients with higher HER2 expression values had a median time-to-progression of 12.8 months, while those in the lower half of the distribution had a median time-to-progression of only four months. Finally, multivariate Cox proportional hazards models identified HER2 expression (HR = 0.16, p < 0.001) and HER2:HER2 dimer levels (HR = 0.32, p < 0.001) as measured by HERmark as being statistically significant predictors of time-to-progression, Monogram said.

The company also reported confirmation from the College of Pathologists (CAP) that the HERmark assays are approved for routine patient testing in the company's CLIA-certified clinical reference laboratory.

"The results presented today are an important step along the way to clinical validation of HERmark, the first product based on the VeraTag technology platform," said William Young, CEO of Monogram.

According to Young, current testing technologies do not provide an accurate or precise view of HER2 biology in breast caner, classifying patients as either HER2 positive or HER2 negative.

"At best, conventional technologies provide a semi-quantitative analysis. However, only about half of metastatic patients selected by current technologies for Herceptin treatment respond to the drug. Data are now emerging to suggest that patients who could benefit from Herceptin may be missed by currently used assays," Young said.

"Our HERmark studies have provided data, which consistently indicate that HERmark can precisely measure HER2 expression and HER2:HER2 dimer levels in clinical FFPE samples, and that those patients with higher levels of expression have significantly better clinical outcomes than those with lower levels. These data strongly suggest that HERmark can identify patients who are likely to respond to Herceptin better than the assays currently in use."

VeraTag is a proximity-based assay technology platform designed to accurately quantify proteins and functional protein complexes. The platform is intended to provide a researcher or clinician a more thorough understanding of protein-protein interactions or signaling pathway activity allowing for disease characterization at the molecular level. VeraTag is designed to run on standard formalin-fixed paraffin embedded (FFPE) patient samples.

In other news from the symposium: Kathy Albain, MD, of Loyola University Chicago, presented new data showing the predictive value of the 21-gene Recurrence Score (RS) assay in patients with node-positive breast cancer.

The Breast Cancer Intergroup of North America trial conducted by the Southwest Oncology Group (San Antonio) originally showed that patients treated with six cycles of chemotherapy with cyclophosphamide, doxorubicin, and 5-fluorouracil followed by five years of tamoxifen (CAF-T) had superior disease-free survival (DFS) and overall survival (OS) compared with patients treated with tamoxifen alone.

This RS assay was performed on the breast cancer tumor specimens collected on this trial, and measured the same groups of genes already in use to predict outcomes and chemotherapy benefit in lymph node-negative disease.

Previous to this study, standard practice was to give chemotherapy to women with positive nodes, the group said. This study sought to determine if the RS assay would be useful to predict who might avoid chemotherapy.

Albain's group first showed that the RS is prognostic for 10-year DFS and OS in patients treated with tamoxifen alone. They then compared DFS in patients treated with tamoxifen versus patients treated with CAF-T across RSs.

They found that there was a significant benefit in DFS over 10 years from adding CAF in patients with a high RS.

In contrast, there was no benefit in patients with a low RS. Interaction between CAF benefit and the linear RS was significant overall and in the first five years.

There was a strong carryover benefit of CAF in high RSs out to 10 years, but no effect whatsoever in low RSs long term, the group said. This interaction of RS with treatment effect was true in greater than or equal to four positive nodes and one to three positive nodes.

"These data collectively challenge chemotherapy mandates for patients with node-positive, ER-positive disease: not all benefit from chemotherapy, whereas others derive greater benefit than previously predicted," Albain said.

She said the research adds to other studies that provide a consistent message regarding the value of the RS for individualized adjuvant therapy, and "for the first time shows its value in a population of women with node-positive breast cancer who were treated with a tamoxifen-alone control."

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