Chemotherapy induced amenorrhoea in a randomised trial of adjuvant chemotherapy duration in breast cancer

We have previously reported the results of a clinical trial in patients with stage II breast cancer which compared a 12 week chemohormonal regimen with a 36 week chemotherapy regimen. Both pre and post menopausal women were entered. The 12 week regimen was inferior both in terms of disease-free survival and overall survival. The effect of chemotherapy on menstrual function was prospectively documented in 95 of 114 premenopausal women at 3 of the 4 participating centres. 67 of the 95 women (70.5%) developed permanent amenorrhoea. There was a statistically significant difference in the rate of induced amenorrhea between the 12 week and the 36 week groups; 23/42 vs. 44/53, respectively (P = 0.003). Recurrence and mortality rates were lower in the patients who became amenorrheic; 38% vs. 57% (P = 0.03) and 18% vs. 32% (P = 0.17), respectively. Similar trends were observed within treatment groups. The effect of induced amenorrhoea on outcome was seen predominantly in patients under 40 years old. These results suggest that the induction of ovarian failure is a potential mechanism for the observed effect of adjuvant chemotherapy in these patients. The difference in the ovarian failure rates between groups may be a possible explanation for the inferiority of the 12 week regimen.