Age of menopause among women who remain premenopausal following treatment for early breast cancer: Long-term results from International Breast Cancer Study Group Trials V and VI

Abstract

Background The likelihood of premature menopause has not been thoroughly explored in women who remain premenopausal after adjuvant chemotherapy for breast cancer. Methods We used data from the International Breast Cancer Study Group (IBCSG) Trials V and VI. Trial V enrolled 1407 eligible premenopausal women randomised to no systemic therapy (No CT) or 1 cycle of perioperative CMF-based chemotherapy (PeCT) if node negative, and 6 cycles of CMF-based chemotherapy postoperatively (CMF × 6) or 1 cycle perioperative CMF-based chemotherapy plus CMF × 6 postoperatively (CMF × 7) if node positive. From Trial VI (a 2 × 2 factorial designed study of 3 versus 6 initial cycles of CMF and a reintroduction of three additional courses of CMF), we included 375 women randomised to receive only six initial cycles of CMF (CMF × 6). Findings We excluded women who reported no menses during 12–24 months after randomisation ( N = 934), hysterectomy ( N = 16) or bilateral oophorectomy ( N = 8), or missing menses data ( N = 57), creating a cohort of 767 women; 540 women had been randomised to PeCT or no CT, 227 randomised to CMF × 6 or 7. A Cox proportional hazards model revealed that CMF × 6 or 7 (HR = 2.03, p < 0.0001) and temporary amenorrhea (HR = 1.96, p < 0.0001) were associated with premature menopause. Interpretation Women who remain premenopausal after 6 or 7 cycles of CMF-based chemotherapy have a higher likelihood of going through menopause at an earlier age than women who received little or no chemotherapy. Temporary cessation of menses appears to be a marker for earlier onset of menopause. These findings may assist women and clinicians when making treatment and reproductive decisions after a diagnosis of breast cancer.