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

Abdel-Fatah, Tarek M.A.; Ball, Graham R.; Thangavelu, Pulari U.; Reid, Lynne E.; Reed, Amy E. Mccart; Saunus, Jodi M.; Duijf, Pascal H.G.; Simpson, Peter T.; Lakhani, Sunil R.; Pongor, Lorinc; Gyorffy, Balazs; Moseley, Paul M.; Green, Andrew R.; Pockley, Alan G.; Caldas, Carlos; Ellis, Ian O.; Chan, Stephen Y.T.

Abstract

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 of SPAG5 transcript and SPAG5 protein expression with pathological complete response to NACT were evaluated, as was the association of SPAG5 mRNA expression with response to neoadjuvant endocrine therapy. The associations of distal relapse–free survival with SPAG5 transcript 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 with SPAG5 transcript expression and 361 women with SPAG5 protein expression of locally advanced disease stage IIA through IIIC. Women with SPAG5 transcript and SPAG5 protein expressions achieved higher pathological complete response compared with those without SPAG5 transcript or SPAG5 protein expressions (transcript: odds ratio, 2.45 [95% CI, 1.71-3.51]; P [less than] .001; protein: odds ratio, 7.32 [95% CI, 3.33-16.22]; P [less than] .001). Adding adjuvant anthracycline chemotherapy to adjuvant endocrine therapy for SPAG5 mRNA expression in estrogen receptor–positive breast cancer was associated with prolonged 5-year distal relapse–free survival in patients without lymph node involvement (hazard ratio, 0.34 [95% CI, 0.14-0.87]; P = .03) and patients with lymph node involvement (hazard ratio, 0.35 [95% CI, 0.18-0.68]; P = .002) compared with receiving 5-year endocrine therapy alone. Mean (SD) SPAG5 transcript was found to be downregulated after 2 weeks of neoadjuvant endocrine therapy compared with pretreatment levels in 68 of 92 patients (74%) (0.23 [0.18] vs 0.34 [0.24]; P [less than].001).

Citation

Abdel-Fatah, T. M., Ball, G. R., Thangavelu, P. U., Reid, L. E., Reed, A. E. M., Saunus, J. M., Duijf, P. H., Simpson, P. T., Lakhani, S. R., Pongor, L., Gyorffy, B., Moseley, P. M., Green, A. R., Pockley, A. G., Caldas, C., Ellis, I. O., & Chan, S. Y. (2020). Association of Sperm-Associated Antigen 5 and Treatment Response in Patients With Estrogen Receptor–Positive Breast Cancer. JAMA Network Open, 3(7), Article e209486. https://doi.org/10.1001/jamanetworkopen.2020.9486

• Journal Article Type: Article
• Acceptance Date: Apr 17, 2020
• Online Publication Date: Jul 7, 2020
• Publication Date: Jul 7, 2020
• Deposit Date: Jun 16, 2020
• Publicly Available Date: Jul 31, 2020
• Journal: JAMA Network Open
• Electronic ISSN: 2574-3805
• Publisher: American Medical Association
• Peer Reviewed: Peer Reviewed
• Volume: 3
• Issue: 7
• Article Number: e209486
• DOI: https://doi.org/10.1001/jamanetworkopen.2020.9486
• Keywords: General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/4660249
• Publisher URL: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2767944