Stopping Hormone Therapy for Pregnancy in Patients with Hormone-Receptor Positive Breast Cancer

Women with hormone-receptor-positive (HR+) breast cancer take endocrine therapy for five to ten years following initial treatment to prevent recurrence. For premenopausal women who desire pregnancy, this presents a major dilemma: Endocrine therapy is contraindicated during conception and pregnancy, so should they risk stopping cancer treatment to have a child?

“We don’t want patients to miss out on the benefits of endocrine therapy for their breast cancer, but we recognize how important pregnancy can be to some breast cancer survivors,” says Halle Moore, MD, Director of Breast Medical Oncology in the Department of Hematology and Oncology at Cleveland Clinic Taussig Cancer Institute and Co-Director of the Cleveland Clinic Comprehensive Breast Cancer Program. “Patients and providers have been concerned about whether stopping hormone therapy could increase risk of recurrence. We have been more comfortable having patients wait about five years before attempting pregnancy, but this affects fertility since it declines as a woman gets older.”

With limited evidence about endocrine therapy and pregnancy in this population, oncologists had difficulty providing informed guidance to patients. Cleveland Clinic joined an international consortium conducting the first prospective trial looking at this issue — Pregnancy Outcome and Safety of Interrupting Therapy for women with endocrine responsIVE breast cancer (POSITIVE). The initial results were presented at the annual meeting of the San Antonio Breast Cancer Symposium (SABCS).

Cohort characteristics and study precautions

Recruited from 116 centers worldwide from December 2014 to December 2019, 518 participants were enrolled in the study. Their median age was 37 years (range: 27-43 years); 75.0% were nulliparous, 93.4% had stage I/II disease and 66.3% were node negative. The median time from breast cancer diagnosis to enrollment was 29 months. Tamoxifen alone was the most prescribed endocrine therapy (41.7%), followed by tamoxifen and ovarian function suppression (35.7%). Most participants — 62.0% — received adjuvant or neoadjuvant chemotherapy. To be eligible, participants had to have hormone receptor-positive breast cancer treated with endocrine therapy for 18-36 months and have a desire for pregnancy.

The primary endpoint was breast cancer-free interval (BCFI), defined as the time from enrollment to the first breast cancer event (local, regional or distant recurrence or a new invasive contralateral breast cancer). Three interim analyses of BCFI were reviewed by the Data Safety Monitoring Committee (DSMC) to assure a 95% chance of stopping the trial early if the annual BCFI event rate exceeded 4%; and no more than 46 BCFI events were defined as the safety threshold. The DSMC recommended continuing the study following each interim analysis.

Encouraging results

At a median follow-up of 41 months, 44 participants had experienced a BCFI event, which didn’t exceed the pre-specified safety threshold of 46 events. The three-year BCFI event percent was 8.9% (95% CI: 6.3 to 11.6%), which was similar to the 9.2% BCFI event percent (95% CI: 7.6 to 10.8%) from the comparative external control cohort in the SOFT/TEXT trials, which studied the efficacy of different types of endocrine therapy in premenopausal women. Of 497 women followed for pregnancy status, 368 (74.0%) have had at least one pregnancy, 317 (63.8%) had at least one live birth, with a total of 365 babies born. Of 415 women who were followed disease-free beyond two years from the interruption of endocrine therapy, 304 (73.3%) have already resumed treatment.

“The findings are incredibly reassuring for young women with hormone receptor-positive breast cancer who want to become pregnant,” says Dr. Moore. “There is no suggestion of increased risk of recurrence at three years, in spite of temporary interruption of endocrine therapy. We hope that these data will help oncologists to guide patients to make the best decision for themselves.”

The investigators will continue to follow the study cohort to confirm long-term safety. “It’s important to learn as much as we can from this cohort,” says Dr. Moore.

Hear our podcast with Dr. Moore about the POSITIVE trial.