“Similarly to radiosensitivity, we are yet to stratify the patients based on the benefits that they may receive from chemotherapy,” adds Kenneth J. Bloom, CMO at Clarient, a GE Healthcare company.
“Traditionally, tumor recurrence was estimated by looking at tumor burden and proliferation status,” he explains. “Approximately 85% of lymph-node negative breast cancer patients who express hormone receptors could be cured by surgery alone, but since our current methods of evaluating tumor specimens cannot accurately predict who benefits from the addition of chemotherapy, thousands of women worldwide may be treated with chemotherapy unnecessarily.”
Clarient has developed a new tool for pathologists to aid them in assessing the biologic aggressiveness of a breast cancer specimen. Its InSight® Dx Mammostrat® assay assigns a patient’s tumor to one of three risk categories—low risk, intermediate risk, or high risk—indicating the relative risk of recurrence. The pathology sample is evaluated with a five-antibody reagent assay that corresponds to gene-expression clusters found to be predictive of recurrence.
“The Mammostrat test fits perfectly into the currently established prognostic workup of biopsy specimens. The pathologist, who already visually evaluates tumor size and grade, will now also have a chance to look at the staining localized to the specific cancer cells,” says Dr. Bloom. “Conversely, with genomic analysis, DNA or mRNA is extracted from tissue sections containing not only tumor but variable amounts of stroma cells, inflammatory cells, and other cell types that are all blended together, diluting the signal from actual cancer cells.”
The antibodies used in the Mammostrat assay were chosen after several rounds of validation. An initial set of 700 antibodies was evaluated, but most of these antibodies were eliminated from further exploration because of poor staining characteristics or limited discriminatory ability on a training set with known outcomes.
A final set of five antibodies was modeled into an algorithm that was tested on three independent cohorts and then on two national randomized sets of samples from patients receiving tamoxifen or placebo in one trial and tamoxifen or tamoxifen plus chemotherapy in the other trial. Based on the data from these trials, 58% of the patients were assigned to the low-risk category while 21% of patients were assigned to each of the moderate- and high-risk categories.
The ten-year recurrence rates for the three categories are 7.6%, 16.3%, and 20.9% based on a 1,500 patient cohort from Scotland. “Adding this independent data element to the typical pathology evaluation has the potential to decrease the number of women treated with chemotherapy by one-third,” remarks Dr. Bloom. “It is now possible to combine clinical assessment, tumor burden, tumor proliferation, and tumor biology to give women the best possible treatment recommendations.”
The Mammostrat test is available through Clarient’s CLIA-certified laboratory. Clarient plans to continue to improve the test and incorporate next-generation quantitative microscopy being developed at GE for readouts.