SAN ANTONIO – Gene expression profile testing to guide decisions regarding the use of adjuvant chemotherapy for early-stage breast cancer should not be used to override the results of standard pathologic measures, Dr. Antonio C. Wolff asserted at the annual San Antonio Breast Cancer Symposium.
Two gene expression profile tests commonly used in breast cancer are the Oncotype DX and MammaPrint assays. The excitement surrounding this whole field is such that Dr. Wolff suspects many clinicians see the molecular assays as being superior to standard clinicopathologic data in their predictive information. This actually hasn’t been shown to be the case to date, he stressed.
Dr. Antonio C. Wolff
"One of the big messages I bring today is that one method is not necessarily better than the other. The standard pathologic tests and the molecular assays may be complementary in the information they provide," said Dr. Wolff, professor of oncology at Johns Hopkins University, Baltimore.
He added that while guideline-based use of these first-generation molecular assays as recommended by the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the European St. Gallen’s Expert Consensus group is appropriate, it’s important to recognize that these tests have their shortcomings. For one, they leave a lot of patients in the gray intermediate-risk zone. Also, the tests aren’t applicable to the 25%-35% of breast cancer patients with estrogen receptor–negative tumors. But a host of new technologies are in the pipeline, he observed.
A recent study of 7,375 breast cancer patients with hormone receptor–positive breast cancer diagnosed in 2006-2008 was enlightening with regard to how clinicians are using gene expression profile testing. The study, an analysis of NCCN prospective registry data conducted by investigators at Boston’s Dana-Farber Cancer Institute, showed a progressive increase in the use of the Oncotype DX test. The test was employed in 14.7% of the patients diagnosed in 2006, nearly doubling to 27.5% of those diagnosed in 2008. Meanwhile, use of chemotherapy decreased from 53.9% to 47%.
Gene expression profile testing was associated with an overall 30% reduction in the likelihood of receiving chemotherapy. What Dr. Wolff found particularly interesting was that testing of small, node-negative cancers was associated with an 11.1-fold increased likelihood of chemotherapy, while testing of lymph node–positive or large node-negative cancers was associated with an 89% reduction in chemotherapy (J. Clin. Oncol. 2012;30:2218-26).
African American women were 30% less likely to undergo testing. Women with no more than a high school education were 37% less likely to be tested than were those with more schooling. Dr. Wolff suspects these disparities are a reflection of better-educated women asking more questions of their physician about their planned treatment course, and the physician in response seeking more laboratory data to help in making treatment decisions.
Dr. Wolff said that while clinicians await studies to determine whether molecular and standard clinicopathologic information can be combined to improve prediction, one of the most important things they can do is to pay close attention to preanalytic issues.
"It’s critical to get tissue from patient to pathologist within 1 hour to avoid cold ischemia and necrosis and deterioration of the specimen that will not only adversely affect the quality of standard measures, but also of the new measures. This is a big deal!" he emphasized.
Dr. Wolff reported that he serves as an investigator for Genentech.