Titles and Affiliations
Professor of Medicine, Division of Biostatistics
Dana-Farber Cancer Institute and Harvard Medical School
Research area
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
In the next year Dr. Regan and her team 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. The POSITIVE trial, which investigates the safety of interrupting adjuvant endocrine therapy to attempt pregnancy, continues the 10-year long-term follow-up of participants, to be completed in December 2029. To provide additional insights to support premenopausal patients and their clinicians in discussions about adjuvant endocrine therapy, the main goals for the upcoming year are two-fold: 1) to support the long-term follow-up of the POSITIVE trial and the design and reporting of the psycho-oncological companion study, which asked participants about distress, fertility concerns and decisional conflict; and 2) to support ongoing collaborative clinical and translational research of the SOFT/TEXT trials, with focus on evaluating menstrual recovery and pregnancy attempts after ~5 years of ovarian function suppression-containing endocrine therapy or tamoxifen alone.
Biography
Meredith Regan, ScD is Associate Professor of Medicine, Division of Biostatistics, Dana-Farber Cancer Institute and Harvard Medical School. She is the Director, Statistical and Data Management Center for the International Breast Cancer Study Group (IBCSG), a Swiss non-profit research organization dedicated for over 40 years to innovative clinical research to improve treatment options and the quality of life of breast cancer patients. Since 2003 she has been the lead statistician for the IBCSG’s SOFT and TEXT phase III clinical trials. Together with the trials’ co-chairs, she has led the analysis and reporting of the trials’ primary efficacy results—supporting the use of aromatase inhibitor (AI) with ovarian function suppression (OFS) as adjuvant endocrine therapy option for premenopausal women, and clarifying the role of OFS in addition to tamoxifen. She continues in this role as the trials continue to collect longer-term patient follow-up to understand the impact of these therapies on late recurrence and survival and any associated late side effects of the therapies. Dr. Regan’s research interests extend to clinical-translational investigations to individualize endocrine therapy treatment selection, and clinical trial design and endpoints.
