Premenopausal women who received ovarian suppression treatment along with tamoxifen had a lower risk of breast cancer recurrence

A clinical trial sponsored and supported by NCI showed that suppressing ovarian function reduced breast cancer recurrence in premenopausal women receiving the drug tamoxifen after surgery for early-stage breast cancer. The trial, SOFT (Suppression of Ovarian Function Trial), used either monthly injections of the drug triptorelin, surgical removal of both ovaries, or radiation of the ovaries as methods of ovarian suppression in women with hormone receptor-positive breast cancer. Women in the trial were randomly assigned to treatment with tamoxifen alone (the standard post-surgery hormone therapy for premenopausal women with hormone-sensitive breast cancer) for 5 years, treatment with tamoxifen plus ovarian suppression for 5 years, or treatment with exemestane plus ovarian suppression for 5 years. Exemestane is a newer hormone therapy drug that inhibits aromatase, an enzyme necessary for the production of estrogen. The International Breast Cancer Study Group (IBSCG), which received support and funding from NCI, presented results of the randomized, phase III SOFT clinical trial at the 2014 San Antonio Breast Cancer Symposium on Dec. 11, 2014. The results were also published online in the New England Journal of Medicine.

Researchers involved in SOFT studied the three treatments in two different groups of premenopausal women with early-stage, hormone receptor-positive breast cancer: those who had received chemotherapy post-surgery and those who had not. Chemotherapy can cause premature menopause, but only women who remained premenopausal after chemotherapy were included in the trial. Treatment with tamoxifen plus ovarian suppression reduced the relative risk of breast cancer recurrence by 22 percent in women who had received chemotherapy compared to treatment with tamoxifen alone. Treatment with exemestane plus ovarian suppression reduced the relative risk of breast cancer recurrence in chemotherapy-treated patients by 35 percent compared to treatment with tamoxifen alone. The benefit of adding ovarian suppression to tamoxifen was especially evident in women younger than age 35. Women in this age group also benefited the most from exemestane plus ovarian suppression. Among women who did not receive chemotherapy after surgery (because they had a more favorable prognosis than the women who received chemotherapy), the recurrence rate with tamoxifen alone was so low (95 percent of women remained free from breast cancer after 5 years of tamoxifen treatment) that no benefit of ovarian suppression has been seen. SOFT enrolled more than 3,000 premenopausal women with hormone receptor-positive early-stage breast cancer between December 2003 and April 2011. The women in this trial will be followed for life to assess long-term prognosis and side-effects. The trial is led by IBCSG in partnership with the Breast International Group and the North American Breast Cancer Group and is supported by NCI as well as IBSCG and the pharmaceutical firms Pfizer and Ipsen.