Chemotherapy-induced amenorrhea in premenopausal breast cancer patients treated with adjuvant anthracycline and taxane based chemotherapy within the SUCCESS study.

Abstract

554 Background: Chemotherapy induced amenorrhea (CIA) is often used as a surrogate marker for cytotoxic gonadal damage. The aim of this analysis was to identify predicitve factors for CIA in premenopausal breast cancer patients treated with adjuvant chemotherapy. Methods: The German multicenter, phase III SUCCESS trial compared 3 cycles of FEC q3w followed by 3x docetaxel q3w vs. FEC followed by Doc+gemcitabine as adjuvant treatment in patients with node positive or high risk node negative primary breast cancer. Premenopausal patients with hormone receptor positive tumors underwent endocrine treatment with tamoxifen (Tam) for 5 years. Additional goserelin (GnRH) for 2 years was given in the following cases: Age <40 years at study entry, premenopausal hormone status or regular menses within 6 months after chemotherapy. We retrospectively investigated CIA rates of 1.189 initially premenopausal patients during disease-free follow-up. Results: Median age at diagnosis was 44 years (range 21-50). The median follow up time was 44 months (range 1-62). 791 patients (66.5%) received endocrine treatment. Tam intake was reported in 370 patients, GnRH in 29 patients, Tam+GnRH in 392 patients. In 963 patients (81.0%) CIA occurred for ≥3 months after chemotherapy. In 22.7% of initially amenorrheic patients CIA was temporary. 192 patients (16.2%) had continuous menstrual bleeding. In multivariate analysis the risk of CIA was significantly higher in older patients, increasing by factor 1.32 per life year (p<0.0001). Tam intake was also associated with increased CIA rates (p=0.0032). Patients with combined Tam+GnRH were more likely to resume menses compared to patients without endocrine therapy (p=0.0056). Factors like the cytotoxic regimen, tumor stage, grading, the patient`s BMI or the use of GnRH analogues as ovarian protectants during chemotherapy did not correlate with CIA rates. Conclusions: Age was the strongest predictor for CIA. Tam administered alone increased CIA rates. Opposite effects were observed for patients who received Tam+GnRH. The addition of gemcitabine to sequential anthracyline-taxane based chemotherapy did not influence CIA.