From the University of Arizona Cancer Center, Tucson, AZ (Dr. Ehsani), and University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, WI (Dr. Wisinski).
- Objectives: To describe common genomic tests being used clinically to assess prognosis and guide adjuvant chemotherapy and endocrine therapy decisions for early-stage breast cancer.
- Methods: Case presentation and review of the literature.
- Results: Hormone receptor–positive (HR-positive) breast cancers, which express the estrogen and/or progesterone receptor, account for the majority of breast cancers. Endocrine therapy can be highly effective for patients with these HR-positive tumors, and identification of HR-positive breast cancers that do not require the addition of chemotherapy is critical. Clinicopathological features of the breast cancer, including tumor size, nodal involvement, grading, and HR status, are insufficient in predicting the risk for recurrence or the need for chemotherapy. Furthermore, a portion of HR-positive breast cancers have an ongoing risk for late recurrence, and longer durations of endocrine therapy are being used to reduce this risk.
- Conclusion: There is sufficient evidence for use of genomic testing in early-stage HR-positive breast cancer to aid in chemotherapy recommendations. Further confirmation of genomic assays for prediction of benefit from prolonged endocrine therapy is needed.
Key words: molecular testing; decision aids; HR-positive cancer; recurrence risk; adjuvant chemotherapy; endocrine therapy.
Despite the increase in incidence of breast cancer, breast cancer mortality has decreased over the past several decades. This is likely due to both early detection and advances in systemic therapy. However, with more widespread use of screening mammography, there are increasing concerns regarding potential overdiagnosis of cancer . One key challenge is that breast cancer is a heterogeneous disease. Thus, improved tools for determining breast cancer biology can help physicians individualize treatments, with low-risk cancers approached with less aggressive treatments, thus preventing unnecessary toxicities, and higher-risk cancers treated appropriately.
Traditionally, adjuvant chemotherapy was recommended based on tumor features such as stage (tumor size, regional nodal involvement), grade, expression of hormone receptors (estrogen receptor [ER] and progesterone receptor [PR]) and human epidermal growth factor receptor-2 (HER2), and patient features (age, menopausal status). However, this approach is not accurate enough to guide individualized treatment recommendations, which are based on the risk for recurrence and the reduction in this risk that can be achieved with various systemic treatments. In particular, there are individuals with low-risk HR-positive, HER2-negative breast cancers who could be spared the toxicities of cytotoxic chemotherapies without compromising the prognosis.
Beyond chemotherapy, endocrine therapies also have risks, especially when given for extended durations. Recently, extended endocrine therapy has been shown to prevent late recurrences of HR-positive breast cancers. In the MA.17R study, extended endocrine therapy with letrozole for a total of 10 years (beyond 5 years of an aromatase inhibitor [AI]) decreased the risk for breast cancer recurrence or the occurrence of contralateral breast cancer by 34% . However, the overall survival was similar between the 2 groups and the results were not confirmed in other studies [3–5]. Identifying the subgroup of patients who benefit from this extended AI therapy is important in the era of personalized medicine. Several tumor genomic assays have been developed to provide additional prognostic and predictive information with the goal of individualizing adjuvant therapies for breast cancer. Although assays are also being evaluated in HER2-positive and triple negative breast cancer, this review will focus on HR-positive, HER2-negative breast cancer.