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 < .001; protein: odds ratio, 7.32 [95% CI, 3.33-16.22];
P < .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 < .001). Conclusions
and Relevance: These findings suggest that SPAG5 transcript 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.
