Follicle stimulating hormone (FSH) as a surrogate parameter for the effectiveness of endocrine therapy with or without zoledronic acid in premenopausal patients with breast cancer: An analysis of the prospective ABCSG-12 trial.

577 Background: Endocrine therapy is an effective, targeted therapy in patients with hormone receptor positive breast cancer (BC). However, in the adjuvant setting no indicator exists visualizing its effectiveness during therapy. In this analysis we test whether FSH serum levels during therapy might be a surrogate parameter for the effectiveness of adjuvant endocrine therapy. Methods: ABCSG-12 examined the efficacy of ovarian suppression using goserelin (3.6mgq4wSC) in combination with anastrozole or tamoxifen ± zoledronic acid (ZOL, (4mgIVq6mo) in premenopausal women with endocrine-responsive BC. Prospective collected data on FSH serum levels were used for the analyses. Disease-free survival (DFS), distant metastasis free survival (DMFS) and overall survival (OS) were calculated by Kaplan-Meier method, results were compared by using the log-rank test and Cox proportional hazard modelling. Results: Analyses are based on 503 patients with FSH levels at baseline, 562 patients with FSH levels during therapy and 641 patients with FSH levels during follow up. Mean FSH levels were significantly lower during therapy, when compared to baseline and follow up, respectively (4.87mIU/ml vs. 14.16mIU/ml vs. 22.28mIU/ml, p<0.001). Patients treated with anastrozole had significantly higher FSH levels during therapy compared to patients treated with tamoxifen (7.05mIU/ml vs. 2.45mIU/ml, p<0.001). Patients with FSH levels above the mean during therapy (4.87mIU/ml) had a worse outcome compared to patients with FSH levels below 4.87mIU/ml (DFS HR 1.347, p=0.18; DMFS HR 1.939, p=0.035; OS HR 2.208, p=0.096). This could be confirmed with borderline significance in the subgroup of patients treated with ZOL (DFS HR 1.886, p=0.075; DMFS HR 2.537, p=0.077; OS HR 1.306, p=0.726). BMI had no impact on FSH serum levels in any group during therapy. Conclusions: This study suggests that FSH serum levels during therapy might be a good surrogate parameter for the effectiveness of adjuvant endocrine therapy.