For premenopausal women who have undergone definitive surgery for node-negative invasive breast cancer, adjuvant therapy with tamoxifen plus ovarian function suppression significantly impairs quality of life, compared with tamoxifen alone, according to a report published online October 27 in Journal of Clinical Oncology.
The role of ovarian function suppression in this setting remains uncertain because most studies examining the issue have been relatively short (2 years or less) and have included patients undergoing cytotoxic chemotherapy, which makes it difficult to tease out which drugs produce which outcomes of interest. In contrast, this open-label, phase III, randomized trial by the Eastern Cooperative Oncology Group had a mean follow-up of 10 years, and it included only women with hormone receptor–positive tumors measuring 3 cm or less who received no adjuvant chemotherapy, said Dr. Amye J. Tevaawerk of the University of Wisconsin, Madison, and her associates.
The 345 study participants were randomly assigned to receive either tamoxifen plus ovarian function suppression via goserelin, leuprolide, surgical ablation, or radiation ablation (174 women) or tamoxifen alone (171 women). The median age at baseline was 45 years (range, 26-55 years). The trial was designed to compare multiple outcomes, including disease-free survival, overall survival, and quality of life, but it was terminated early because of slow accrual and ultimately was only powered to detect differences in quality of life (QOL).
Throughout follow-up, women who received tamoxifen plus ovarian suppression reported inferior health-related QOL as measured by the Functional Assessment of Cancer Therapy – General (FACT-G) and the Functional Assessment of Cancer Therapy – Breast (FACT-B). They had more menopausal symptoms and lower levels of sexual function than women who received tamoxifen alone, regardless of patient age or race, tumor hormone-receptor status, tumor size, or type of surgical procedure. The differences between the two study groups were both statistically significant and clinically meaningful, Dr. Tevaawerk and her associates said (J. Clin. Oncol. 2014 October 27 [doi:10.1200/JCO.2014.55.6993]).
The negative impact of ovarian suppression gradually diminished after 3 years, most likely because increasing numbers of women receiving tamoxifen alone reached menopause. “Our results suggest that [studies with] durations of less than 3 years fail to capture the adverse effect peak and the health-related QOL nadir from ovarian function suppression,” the investigators said. “Given these data and in the absence of definitive data for improvement in disease-free survival or overall survival with ovarian function suppression, the American Society of Clinical Oncology guidelines are appropriately cautious about adding ovarian function suppression to tamoxifen,” they noted.