Pre-treatment circulating reproductive hormones levels predict pathological and survival outcomes in breast cancer submitted to neoadjuvant chemotherapy

Purpose: This study aimed to evaluate the correlation of pre-treatment circulating reproductive hormones levels with pathological and survival outcomes in breast cancer patients received neoadjuvant chemotherapy (NAC).

Methods: Information from 196 premenopausal and 137 postmenopausal breast cancer patients who received NAC were retrospectively analyzed. Treatment response to NAC, with odds ratios (OR) and 95% confidence intervals (95% CI) was estimated using logistic regression adjusted for key confounders. Survival outcomes with hazard ratios (HR) and 95% CI were estimated using Cox regression adjusted for key confounders. The Kaplan-Meier method was applied in the survival analysis.

Results: Premenopausal patients with lower testosterone levels (OR = 0.996, 95% CI 0.992-0.999, P = 0.026), and postmenopausal patients with higher follicle-stimulating hormone (FSH) levels (OR = 1.045, 95% CI 1.014-1.077, P = 0.005) were likely to achieve pathological complete response (pCR). In multivariate survival analysis, the lowest tertile (T) progesterone was associated with worse overall survival (OS) in premenopausal patients (T2 vs T1, HR = 0.113, 95% CI 0.013-0.953, P = 0.045; T3 vs T1, HR = 0.109, 95% CI 0.013-0.916, P = 0.041). Premenopausal patients with the lowest tertile progesterone exhibited worse 3-year OS compared with those with higher tertiles (72.9% vs 97.4%, log-rank, P = 0.007).

Conclusion: Pre-treatment testosterone and FSH are significant independent predictors for pCR to NAC in premenopausal and postmenopausal patients, respectively. Low progesterone levels are correlated with worse OS in premenopausal patients. These findings may provide a theoretical basis for pre-operative endocrine therapy combined with NAC in breast cancer.