Abstract In breast cancer, one of the main objectives of neoadjuvant treatment, regardless of the specific breast cancer subtype, is to downstage the disease in both the breast and the lymph nodes, thereby allowing surgical de-escalation. In patients with inoperable disease, downstaging could lead to a feasible surgical resection; whereas, in patients presenting with operable disease, it could increase the eligibility for breast-conserving surgery (i.e., lumpectomy) instead of a mastectomy as well as spare some patients an axillary lymph node dissection. In patients with hormone receptor-positive (HR + ) human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer, neoadjuvant treatment modalities include chemotherapy (NCT) and endocrine therapy (NET). The 21-gene Oncotype DX Breast Recurrence Score® assay is a multigene assay that determines a Recurrence Score® (RS) result (range, 0–100) based on gene expression profile within the primary tumor. The RS is a validated prognosticator and predictor of benefit from adjuvant CT. Beyond its validation, it has shown clinical utility in 3 prospective randomized clinical trials in the adjuvant setting (TAILORx, RxPONDER, and WSG PlanB). In these studies, all assays were performed on surgical excision samples. This review focuses on the utility of the 21-gene assay in patients with HR + HER2-negative early-stage breast cancer in the neoadjuvant setting. It discusses the analytical validation of performing the assay on core biopsies, its clinical validation as a tool to guide neoadjuvant treatment decisions (primary surgery, NET, or NCT), the association of the RS result with clinical outcomes, the impact of the RS results on neoadjuvant treatment decisions in real-life clinical practice, the inclusion of the assay in the neoadjuvant setting in clinical-practice guidelines, access of patients worldwide to this approach, and potential directions for additional studies examining the role of the RS in other steps in the clinical pathway of HR + HER2-negative early-stage breast cancer.
Zotano et al. (Fri,) studied this question.