A series of genes that will help predict whether or not a woman with hormone receptor-positive invasive breast cancer will experience early, late or no recurrence have been identified by researchers.
Minetta C. Liu, M.D., associate professor of medicine and oncology and director of translational breast cancer research at Georgetown Lombardi Comprehensive Cancer Center, presented the findings at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.
"There are clear biological differences within the supposedly unified group of hormone receptor (HR)-positive breast cancers, and these differences distinguish subtypes relative to the time at which they recur," Liu said. "Understanding what drives these distinctions will allow us to tailor treatment and improve patient outcomes."
Women with HR-positive breast cancer are frequently treated with tamoxifen, which is credited with saving the lives of hundreds of thousands of women. Although tamoxifen prevents or delays cancer recurrence in many women, some will recur 10 years or more from their original diagnosis. Until now, the molecular basis for this recurrence pattern was unknown.
Liu and colleagues, in collaboration with investigators from the University of Edinburgh, evaluated high-quality frozen tumor samples obtained at the time of breast cancer diagnosis. These tissue samples were linked to data on treatment and clinical outcomes, allowing researchers to analyze gene expression patterns present before the initiation of any systemic therapy.
Together with engineers at Virginia Polytechnic Institute, Liu and colleagues identified significant gene expression patterns among the tumor samples. These patterns correlated strongly with the development of distant metastatic disease.
"We confirmed what many have already suspected," said Liu. "There are biological drivers that define — at the time of tumor development — whether or not breast cancer will recur early, late or not at all. Now we need to validate these findings and take our knowledge to the next step."
Liu hopes that this research can be used to help personalize treatment in day-to-day clinical practice. "Endocrine therapy and chemotherapy are not without toxicity," she said. "The ability to predict which patients will recur early in their treatment course can lead to more appropriate recommendations for adjuvant chemotherapy. It might also identify those women who would benefit most from studies using investigational agents to enhance the effects of tamoxifen or aromatase inhibitors."
She added: "At the other extreme are those patients with HR-positive tumors who recur long after completing five years of endocrine therapy. These are the patients for whom extended endocrine therapy and its related side effects are really worth it."
The team's next step is to validate their predictive model for the timing of recurrences on tamoxifen so that physicians and patients can make more informed decisions about the potential added benefits of adjuvant chemotherapy, extended endocrine therapy and involvement in clinical trials. They will also investigate combinations of molecular targets with the ultimate goal of delaying or preventing the development of metastatic breast cancer, Liu said.