Among premenopausal women with early stage, hormone receptor-positive breast cancer, adding ovarian suppression to tamoxifen reduced breast cancer recurrence in those who had previously received chemotherapy and remained premenopausal, according to data from the randomized, phase III suppression of ovarian function trial (SOFT) presented at the 2014 San Antonio Breast Cancer Symposium.
“We found that adding ovarian suppression to tamoxifen was somewhat beneficial for those women with early stage, hormone receptor-positive breast cancer who remained premenopausal after chemotherapy,” said Prudence Francis, MD, head of breast medical oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia. “However, we found a greater reduction in recurrence in this same patient group with the use of ovarian suppression plus the aromatase inhibitor exemestane.
“I believe that these results will result in changes in clinical practice,” continued Francis. “For women who have not reached menopause and have hormone receptor-positive breast cancer that carries sufficient risk of recurrence that they receive chemotherapy, physicians are likely to discuss the option of treatment with ovarian suppression plus an aromatase inhibitor.”
Analysis of data from all patients assigned tamoxifen or tamoxifen with ovarian suppression showed that there was not a statistically significant improvement in disease-free survival with the addition of ovarian suppression overall. Just over half of the patients had received chemotherapy prior to enrollment in SOFT, and there was a 22% decrease in risk of breast cancer recurrence for those patients assigned tamoxifen with ovarian suppression who had received prior chemotherapy compared with their counterparts assigned tamoxifen; the decrease was a trend and not statistically significant.
A 35% decrease in risk of breast cancer recurrence was observed for premenopausal women who received chemotherapy for early stage, hormone receptor-positive breast cancer and were assigned exemestane with ovarian suppression compared with those assigned tamoxifen.
This comparison was a secondary question of the trial, but the results of the statistical analysis were conclusive.
“We found that with the addition of ovarian suppression to tamoxifen, four or five fewer patients out of 100 experienced a breast cancer recurrence within 5 years in the group of patients who remained premenopausal after chemotherapy,” said Francis. “However, we found an even greater reduction in recurrence in this same patient group with the use of ovarian suppression plus the aromatase inhibitor exemestane, which resulted in seven or eight fewer patients out of 100 experiencing a breast cancer recurrence within 5 years.”
Francis and colleagues enrolled 3,066 women with early stage, hormone receptor-positive breast cancer in SOFT, led by the International Breast Cancer Study Group (IBCSG). Patients were randomized to 5 years of tamoxifen (1,021 patients), tamoxifen and ovarian suppression (1,024 patients), or exemestane and ovarian suppression (1,021 patients). In most patients, ovarian suppression was achieved by monthly triptorelin injections. The data reported were obtained after a median follow-up of 67 months.
SOFT receives financial support for trial conduct from Pfizer, the IBCSG, and the National Cancer Institute (NCI). Pfizer and Ipsen provide drug supply. Support for the coordinating group, IBCSG: Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research (SAKK), NCI (CA75362), Swiss Cancer Research/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). The pharmaceutical companies have no role in the reporting or interpretation of the trials, other than a minority representation on the Steering Committee. The cooperative groups received grant support from various national funding sources.