A gonadotropin-releasing hormone (GnRH) analogue can temporarily suppress ovarian function, subsequently warding off the occurrence of early menopause induced by chemotherapy among women with early-stage breast cancer.
Systemic treatments put premenopausal breast cancer patients at high risk of premature ovarian failure, with no standard strategies available to combat this adverse effect, according to investigators involved in the phase III trial, Prevention of Menopause Induced by Chemotherapy: A Study in Early Breast Cancer Patients—Gruppo Italiano Mammella 6 (PROMISE-GIM6) study (JAMA. 2011;306:269-276). Earlier research had suggested that temporary ovarian suppression with a GnRH analogue during chemotherapy protects the ovaries in 67% to 96% of women with breast cancer receiving chemotherapy.
PROMISE-GIM6 enrolled 281 premenopausal, patients with stages I to III breast cancer from 16 sites in Italy between October 2003 and January 2008. The women, aged 24 to 45 years (median age 39 years), had had active menstrual cycles or normal menses in the 6 weeks prior to the start of chemotherapy. All were candidates for adjuvant or neoadjuvant chemotherapy.
Before beginning chemotherapy, 133 women were randomized to receive chemotherapy alone, and 148 to chemotherapy combined with the GnRH analogue triptorelin. Triptorelin 3.75 mg was administered intramuscularly at least 1 week before the start of chemotherapy and then every 4 weeks for the duration of chemotherapy.
One year after the last cycle of chemotherapy (last follow-up: August 18, 2009), 25.9% of the chemotherapy-only group experienced early menopause (defined as the absence of menstrual activity for at least 12 months with postmenopausal or unknown levels of FSH and E2), compared with just 8.9% of the triptorelin patients. This translated to an absolute reduction in early menopause occurrence of 17% for premenopausal patients with breast cancer undergoing adjuvant or neoadjuvant chemotherapy.
Approximately half of the chemotherapy-only women (49.6%; 60 women) had a resumption of menses, regardless of FSH and E2 levels, compared with 88 women (63.3%) in the triptorelin group—an absolute difference of 13.7%.
“In conclusion, our results suggest that temporarily suppressing ovarian function by administering triptorelin reduces the incidence of chemotherapy-induced early menopause,” wrote the PROMISE-GIM6 team. “This treatment can therefore be offered to premenopausal patients with breast cancer who wish to decrease the risk of permanent ovarian failure associated with chemotherapy.”