Association of Sperm-Associated Antigen 5 and Treatment Response in Patients With Estrogen Receptor-Positive Breast Cancer.

Importance There is no proven test that can guide the optimal treatment, either endocrine therapy or chemotherapy, for estrogen receptor–positive breast cancer. Objective To investigate the associations of sperm-associated antigen 5 (SPAG5) transcript and SPAG5 protein expressions with treatment response in systemic therapy for estrogen receptor–positive breast cancer. Design, Settings, and Participants This retrospective cohort study included patients with estrogen receptor–positive breast cancer who received 5 years of adjuvant endocrine therapy with or without neoadjuvant anthracycline-based combination chemotherapy (NACT) derived from 11 cohorts from December 1, 1986, to November 28, 2019. The associations ofSPAG5transcript and SPAG5 protein expression with pathological complete response to NACT were evaluated, as was the association ofSPAG5mRNA expression with response to neoadjuvant endocrine therapy. The associations of distal relapse–free survival withSPAG5transcript or SPAG5 protein expressions were analyzed. Data were analyzed from September 9, 2015, to November 28, 2019. Main Outcomes and Measures The primary outcomes were breast cancer–specific survival, distal relapse–free survival, pathological complete response, and clinical response. Outcomes were examined using Kaplan-Meier, multivariable logistic, and Cox regression models. Results This study included 12 720 women aged 24 to 78 years (mean [SD] age, 58.46 [12.45] years) with estrogen receptor–positive breast cancer, including 1073 women withSPAG5transcript expression and 361 women with SPAG5 protein expression of locally advanced disease stage IIA through IIIC. Women withSPAG5transcript and SPAG5 protein expressions achieved higher pathological complete response compared with those withoutSPAG5transcript or SPAG5 protein expressions (transcript: odds ratio, 2.45 [95% CI, 1.71-3.51];P  Conclusions and Relevance These findings suggest thatSPAG5transcript and SPAG5 protein expressions could be used to guide the optimal therapies for estrogen receptor–positive breast cancer. Retrospective and prospective clinical trials are warranted.