Molecular differences may be used to predict early or late recurrence in hormone receptor-positive breast cancer

Researchers may have discovered a set of genes that can help in predicting whether or not a woman with hormone receptor-positive (HR+) invasive breast cancer will experience early, late or no recurrence of her disease. Minetta C. Liu, MD, (Georgetown Lombardi Comprehensive Cancer Center, Washington D.C., USA), presented the findings during the 2011 CTRC-AACR San Antonio Breast Cancer Symposium. “There are clear biological differences within the supposedly unified group of HR+ 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. Although tamoxifen prevents or delays cancer recurrence in many women, some will recur 10 years or more after their initial diagnosis. Until now, the molecular basis for this recurrence pattern was unclear. In their study, Liu and colleagues, evaluated high-quality frozen tumor samples obtained at the time of breast cancer diagnosis. These tissue samples were then linked to data on treatment and clinical outcome, allowing researchers to analyse 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. “Already at the time of tumor development, there are biological drivers that define 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.”

These finding can potentially be used to help personalize treatment in day-to-day clinical practice. “Endocrine therapy and chemotherapy are not without toxicity,” Liu continued. “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.”

In a next step, this predictive model for the timing of recurrences on tamoxifen needs to be validated 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.