The Oncotype DX® 21-gene recurrence score and clinical outcomes in hormone receptor-positive, HER2-negative male breast cancer: a scoping review

Purpose: Male breast cancer (MBC) is a rare malignancy that remains significantly underrepresented in clinical trials. As a result, the clinical utility of Oncotype DX (ODx) 21-gene recurrence score (RS) in men has not been well established. This scoping review aims to systematically examine the current literature regarding the prognostic and predictive role of the ODx in MBC, identify relevant factors that may influence its interpretation, and highlight key research gaps that may hinder its appropriate clinical application in male patients. Methods: A comprehensive literature search was conducted in PubMed and Scopus databases for studies published from 2010 onward. Studies reporting RS results, based on the ODx 21-gene RT-PCR, along with associated clinical outcome, were included. Results: Three studies evaluating RS in relation to clinical outcomes in MBC met the inclusion criteria. A higher proportion of MBC patients exhibited RS ≥ 31 compared to female breast cancer cohorts. RS showed significant associations with clinical outcomes, including higher mortality rates in high-risk MBC patients. However, in node-negative cases, RS did not retain independent prognostic value. Although RS was prognostically significant in both sexes, outcomes tended to be worse in MBC, particularly in the intermediate- and high-risk groups, where hazard ratios associated with chemotherapy benefit changed minimally after treatment adjustment. Conclusion: The prognostic value of RS in MBC appears evident; however, sex-specific thresholds may be necessary to optimize treatment stratification. Given current data limitations, male-inclusive clinical trials are needed to elucidate the predictive value of RS in men and improve personalized treatment strategies.