Meredith M. Regan, ScD

Assessing the long-term effects and survival benefits of anti-estrogen therapies in premenopausal women.

Impact

Results from two international clinical trials—the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT)—led to new clinical guidelines for the treatment of estrogen receptor (ER)-positive breast cancer in premenopausal women. The initial results from the trials supported the use of ovarian suppression drugs in addition to anti-estrogen therapy to preserve fertility in women who intended to have children after treatment. However, further follow-up is needed to fully understand the implications of treatment decisions on overall survival and late side effects of therapy. With support from BCRF, Dr. Regan and her colleagues at the International Breast Cancer Study Group are able to extend the follow-up of all women participating in SOFT and TEXT to a minimum of 10 years. Their results will be important in clinical decision making for young women with ER-positive breast cancer.

Progress Thus Far

At ten years of follow-up, results from the SOFT and TEXT trials showed improved recurrence-free and overall survival outcomes for young breast cancer patients treated with ovarian suppression drugs plus tamoxifen, compared to tamoxifen alone. Those at highest risk of recurrence received greater benefits. After follow-up or over 15 yrs, a persistent benefit was evident with exemestane plus ovarian function suppression compared to tamoxifen plus ovarian suppression function or tamoxifen alone in reducing subsequent breast cancer events. Combining oral endocrine therapy with OFS did not result in a clinically meaningful overall survival benefit on average. But in higher-risk subgroups, including very young women (under 35 at enrollment), substantial improvements in survival were observed. Collaborative research using the SOFT and TEXT clinical database and biobank has shown depression at start of adjuvant endocrine therapy to be a risk factor for poorer outcomes, and patients with invasive lobular carcinoma have greater benefit with exemestane plus ovarian suppression function vs. tamoxifen alone than patients with invasive ductal carcinomas.

What’s next

Dr. Regan and her colleagues will continue to follow patients from the SOFT and TEXT trials with the goal of completing more than 20 years of follow-up. Her team credits BCRF as the core supporter for long term follow-up of SOFT and TEXT which is critical to ensure the efficacy of ovarian suppression in the reduction of late recurrence and identify any long-term side effects. Long term follow- up also enhances the reliability of biomarker research conducted using patient samples from these studies. In the next year, they plan to close the SOFT and TEXT trial participating sites and complete reporting of the final main results of the trials after >15 years median follow-up. They will also investigate post-treatment implications of therapy in the trials, specifically occurrence of clinically significant cardiovascular and cerebrovascular events, bone fractures, and the recovery of menstrual function and successful pregnancy. With long-term results of efficacy of the different adjuvant endocrine therapy regimens, these are the most significant potential long-term side effects important to consider when weighing the efficacy of different regimens. Finally, Dr. Regan and her team will leverage data from SOFT and TEXT trials to complement long-term follow-up of premenopausal patients with HR-positive tumors enrolled in the POSITIVE prospective trial testing endocrine therapy pause in patients with breast cancer to attempt pregnancy.