Young women with early-stage, hormone receptor (HR)-positive breast cancer attempting to become pregnant can safely pause endocrine therapy and resume it later, according to initial results from the international POSITIVE trial. These results were presented by the study’s lead investigator, Ann Partridge, MD, MPH, Eric P. Winer, MD, Chair in Breast Cancer Research; Founder and Director, Program for Young Adults with Breast Cancer; Director, Adult Survivorship Program; and Vice Chair, Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; and Professor, Medicine, Harvard Medical School, Boston, at the 2022 San Antonio Breast Cancer Symposium.
In this study of premenopausal women, the majority who opted to interrupt endocrine therapy for up to 2 years became pregnant and the majority of pregnancies led to the birth of a healthy baby, with a low risk for recurrence of breast cancer.
“Over the short term, these data stress the need to incorporate patient-centered reproductive healthcare in the care of young women with breast cancer. These fairly reassuring data will probably encourage more women to try to get pregnant. People with breast cancer have to make many decisions. These data will help families, patients, and doctors to pursue pregnancy and interrupt—not stop—endocrine therapy,” Dr Partridge told attendees.
Young women with early-stage, HR-positive breast cancer are frequently treated with endocrine therapy, such as ovarian function suppression, aromatase inhibitors, or selective estrogen receptor modulators. Unfortunately, endocrine therapy may reduce ovarian reserve and decrease the likelihood of subsequent successful pregnancy. In addition, conception is contraindicated during endocrine therapy. POSITIVE is the first international, single-arm trial designed to answer the question: “Is it safe, from a breast cancer relapse perspective, to temporarily pause endocrine therapy to attempt pregnancy?”
From December 2014 through December 2019, the study’s investigators enrolled 518 premenopausal women (median age, 37 years; 75% nulliparous; 93.4% stage I-II disease; 66.3% node-negative disease) who expressed a desire to become pregnant. These women were recruited from 116 centers across 20 countries, including 61% in Europe, 23% in North America, and 16% in Asia/Pacific and Middle East nations. The median time from breast cancer diagnosis to enrollment was 29 months.
All participants were required to have undergone 18 to 30 months of adjuvant endocrine therapy, with a 3-month washout period to ensure the endocrine therapy was out of their system. Women were then encouraged to attempt to become pregnant and resume endocrine therapy within 24 months and then were followed over time.
If more than 46 breast cancer recurrences had occurred within approximately 3 years of average follow-up, the trial would have been suspended, but that threshold was not reached.
At a median follow-up of 41 months, the 3-year breast cancer recurrence rate for women who interrupted endocrine therapy to pursue pregnancy was 8.9%. According to Dr Partridge, this recurrence rate was comparable to the 9.2% rate in the external control cohort from the SOFT/TEXT trials, which examined adjuvant endocrine therapy in premenopausal women. The distant relapse rate of 4.5% in the current study was also comparable to that in the SOFT/TEXT cohort.
“We formally compared our recurrence data from POSITIVE to a selected control group of women from the SOFT/TEXT study of women who would have been eligible for POSITIVE but did not take a break from endocrine therapy for pregnancy. Our results revealed the 2 groups’ outcomes were not different [apparently or statistically],” she explained.
Of the 497 women who were followed for pregnancy status, 368 (74%) had at least 1 pregnancy and 317 (63.8%) had at least 1 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 population.
The investigators reported that among the 365 babies born, 8% had low birth weight and 2% had birth defects.
At 4 years of follow-up, 9 deaths were reported in women before resuming endocrine therapy, 76% had resumed endocrine therapy, and 15% had not, mostly because they were still trying to become pregnant.
“These data will change the way I counsel patients, because prospective data are very reassuring and will make us more comfortable supporting patients to pursue this approach, especially for lower risk patients. The fetal outcomes seem similar to that of the general population,” Dr Partridge noted.
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