Prognostic effect of amenorrhoea and elevated serum gonadotropin levels induced by adjuvant chemotherapy in premenopausal node-positive breast cancerpatients

The purpose of the study was to determine the correlation between prognosis and chemotherapy induced amenorrhoea or elevated gonadotropin levels in no de-positive breast cancer patients. Since we have previously found a better prognosis in patients with more profound leucopenia induced by adjuvant ch emotherapy, we examined whether this effect war mediated through more effic ient induction of amenorrhoea. The study population consisted of 126 premen opausal, primarily operable, node-positive breast cancer patients treated w ith cyclophosphamide, methotrexate and 5-fluorouracil (CMF) adjuvant chemot herapy at the Department of Oncology, Helsinki University Central Hospital between 1990 and 1993. 12 months after the beginning of adjuvant chemothera py, the patients were divided into groups with respect to their menstrual f unction (regular menstruation, irregular menstruation or amenorrhoea). Info rmation about menstruation status and serum concentration of follicle stimu lating hormone (FSH) and oestradiol were recorded at 12 and 24 months from the beginning of adjuvant chemotherapy. Median follow-up time was 72 months . Women who experienced amenorrhoea or had irregular menstruation after che motherapy had a significantly better 5-year disease-free survival (DFS) in univariate analysis than women who continued to menstruate (P=0.02). Amenor rhoea and irregular menstruation were associated with a better DFS among pa tients with oestrogen receptor (ER) positive primary tumours (P=0.007), whe reas no such association was found in ER negative cases (P=0.86). 5-year ov erall survival (OS) in univariate analysis was also better in patients who experienced amenorrhoea (81%) or who had irregular menstruation (90%) after chemotherapy as compared with patients with regular menstruation (68%; 81 versus 68%, P=0.05). The serum FSH level did not correlate significantly wi th outcome irrespective of the cut-off point chosen. Nodal status, tumour s ize and menstruation status after chemotherapy were also significantly asso ciated with DFS in a multivariate analysis. The menstruation status after c hemotherapy lost its significance for OS in a multivariate analysis whilst the number of affected lymph nodes, tumour size and oestrogen/progesterone receptor status retained their impact. There was no association between the degree of leucopenia and induction of amenorrhoea by CMF. Chemotherapy-ind uced ovarian function suppression (amenorrhoea/irregular menstruation) afte r chemotherapy had a favourable effect on DFS in premenopausal breast cance r patients. The post-chemotherapy menstruation status is a clinically usabl e marker for sufficient endocrine effect of chemotherapy in ER/PR-positive patients in all premenopausal age groups. FSH level seemed to be a less rel iable indicator of the castration effect of adjuvant chemotherapy in this s tudy. (C) 2000 Elsevier Science Ltd. All rights reserved.