LAUSR

Key Points Question Are sperm-associated antigen 5 (SPAG5) transcript or protein expressions associated with treatment response in patients with estrogen receptor–positive breast cancer? Findings In this cohort study including 12 720 patients with estrogen receptor–positive breast cancer, SPAG5 transcript and SPAG5 protein overexpressions were associated with worse outcomes in patients who received endocrine therapy alone. Overexpressions of SPAG5 transcript or SPAG5 protein were associated with resistance to endocrine therapy but sensitivity to anthracycline-based combination chemotherapy, and downregulation of SPAG5 during the course of preoperative systemic therapies was associated with clinical benefit. Meaning These findings suggest that SPAG5 transcript or SPAG5 protein expression could be used as a clinical tool for selecting and monitoring response to neoadjuvant therapies and guide adjuvant therapy in estrogen receptor–positive breast cancer.