Dana-Farber Researchers Lead Study Providing Hope for Younger Breast Cancer Patients Looking To Pursue Pregnancy

There is good news for young women with breast cancer who would like to have a baby. A landmark international study, POSITIVE, led by a team that included Dana-Farber researchers, and presented at the recent San Antonio Breast Cancer Symposium, found that young women with early-stage hormone receptor-positive breast cancer could safely interrupt their endocrine therapy to pursue a pregnancy.

Young women with hormone receptor-positive breast cancer are often treated with endocrine therapy which seeks to impede tumor growth by blocking the production of certain hormones or preventing them from reaching tumor cells. Examples include ovarian function suppression, aromatase inhibitors, and selective estrogen receptor modulators. Endocrine therapy can last for 5-10 years, during which time young women are counselled by their physicians to forgo having a child until the completion of therapy, a reality that may prohibit many young women from starting a family or expanded their existing one.

“Fortunately, the vast majority of women with early-stage breast cancer are going to be cured of their disease,” says Ann Partridge, MD, MPH, vice chair of medical oncology and founder and director of the Institute’s Program for Young Adults with Breast Cancer who co-chaired the POSITIVE study. “Among the many unique survivorship challenges faced by young women with breast cancer though, is future fertility. We wanted to evaluate the safety of women pausing their endocrine therapy to pursue pregnancy.”

Dana-Farber researchers Richard Gelber, PhDSam Niman, MS, and Meredith Regan, ScD, of Data Science designed and led the statistical collaboration for the POSITIVE study (Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine Responsive Breast Cancer), a clinical trial to evaluate if a pause in endocrine therapy leads to an increased risk of breast cancer recurrence.

The trial, which enrolled participants from December 2014 through December 2019, involved 518 women between the ages of 18 and 42 who had previously been treated for breast cancer and desired to become pregnant. In enrolling in the study, participants opted to pause endocrine therapy for approximately two years to try to get pregnant. Before pausing their treatment, women had completed between 18 and 30 months of post-surgical endocrine therapy.

After a median follow-up of 41 months, 44 participants had experienced a recurrence of breast cancer. The three-year rate of recurrence was 8.9%, similar to the 9.2% rate in an external control cohort.

Of 497 women followed for pregnancy status, 368 (74%) had at least one pregnancy, and 317 (63.8%) had at least one live birth, with a total of 365 babies born. These rates of conception and childbirth were on par with or higher than rates in the general public.

These results from the POSTIVE study provide encouraging guidance to younger women diagnosed with breast cancer who hope to have children, the study authors said. Previous research had suggested that pregnancy after breast cancer would not increase a woman’s risk of developing a recurrence of the cancer. However, these data were collected retrospectively, from trials conducted for other purposes. A controlled prospective study like POSITIVE was needed to conclusively answer these questions. This academic trial was made possible through an international collaboration involving 116 centers and 20 countries on 4 continents, sponsored and conducted globally by International Breast Cancer Study Group (IBCSG), Alliance for Clinical Trials in Oncology and Breast International Group (BIG) with support from research foundations and donors.

Since 1977, Dana-Farber has been home of the International Breast Cancer Study Group (IBCSG) Statistical Center, led by Regan. As members of the Institute’s Department of Data Science, the IBCSG statisticians have collaborated with clinical colleagues world-wide to design, analyze, and report practice-changing clinical trial results, which have improved outcomes for patients with early breast cancer.

“One of the challenges with a trial like POSITIVE is that, ethically, it cannot randomly assign participants to either attempt or not attempt pregnancy,” explains Regan. “IBCSG statisticians worked with colleagues to design the POSITIVE trial – balancing the challenge to both provide anti-cancer care and improve patients’ survivorship experience by permitting family plans to proceed.”

The statistical design included stringent stopping criteria and frequent reviews by the IBCSG’s Independent Data Monitoring Committee to monitor safety, and its analysis used an external control group from other IBCSG clinical trials that enrolled similar patients who didn’t interrupt their endocrine therapy. The researchers are continuing to follow the POSITIVE study participants to assess recurrence risk over time.

“It is extremely gratifying to see to the POSITIVE trial results, and we are forever indebted to the bravery of the women who chose to participate,” says Niman. “Due to the unique trial design and research questions, the analyses at times were challenging, but it gave us the opportunity to stretch our imaginations and put together a thoughtful and robust final product that will hopefully impact the lives young breast survivors across the globe.”

Trial participants were strongly recommended to resume endocrine therapy after a pregnancy attempt or success.

“These data stress the need to incorporate patient-centered reproductive healthcare, treatments, and choices in working with and following up on our young women with breast cancer so that they can not only survive, but thrive in their survivorship,” says Partridge.

– Dana-Farber Cancer Institute, 2023

Back to List »