Prognostic impact of amenorrhoea after adjuvant chemotherapy in premenopausal breast cancer patients with axillary node involvement: Results of the International Breast Cancer Study Group (IBCSG) Trial VI

Adjuvant chemotherapy-induced amenorrhoea has been shown to be associated with reduced relapses and improved survival for premenopausal breast cancer patients. Amenorrhoea was, therefore, studied to define features of chemotherapy (i.e. duration and timing) and disease-related factors which are associated with its treatment effects. We reviewed data from IBCSG Trial VI, in which accrual was between July 1986 and April 1993. 1196 of the 1475 eligible patients (81%) were evaluable for this analysis. The median follow-up was 60 months. Women who experienced amenorrhoea had a significantly better disease-free survival (DFS) than those who did not (P=0.0004), although the magnitude of the effect was reduced when adjusted for other prognostic factors (P=0.09). The largest treatment effect associated with amenorrhoea was seen in patients assigned to receive only three initial CMF courses (5-yr DFS: 67% versus 49%, no amenorrhoea; hazard ratio, 0.55; 95% confidence interval, 0.38 to 0.81; P=0.002). DFS differences between amenorrhoea categories were larger for patients with ER/PR positive tumours (hazard ratio, 0.65; 95% confidence interval, 0.53 to 0.80; P= 0.0001). Furthermore, patients whose menses returned after brief amenorrhoea had a DFS similar to those whose menses ceased and did not recover (hazard ratio, 1.10; 95% confidence interval, 0.75 to 1.62; P=0.63). The effects associated with a permanent or temporary chemotherapy-induced amenorrhoea are especially significant for node-positive breast cancer patients who receive a suboptimal duration of CMF chemotherapy. Cessation of menses, even for a limited time period after diagnosis of breast cancer, might be beneficial and should be prospectively investigated, especially in patients with oestrogen receptor-positive primaries.