Women with Breast Cancer Can Attempt Pregnancy

Women with hormone-responsive breast cancer can stop endocrine therapy to attempt pregnancy, according to findings from the POSITIVE trial (N Engl J Med 2023;388:1645–56). Investigators found that temporarily interrupting therapy did not raise the short-term risk of disease recurrence, and nearly 64% of women gave birth while therapy was paused.

Clinical guidelines recommend adjuvant endocrine therapy for 5 to 10 years to reduce the risk of recurrence following treatment for early-stage hormone receptor–positive breast cancer. Prior to this trial, there were little data on whether interrupting therapy to pursue pregnancy would increase the risk of relapse, which presented a clinical dilemma for women in their prime childbearing years.

“This is good news that is most relevant for women diagnosed with cancer before age 40 who may not have started a family or want to complete their families,” says the study's lead author, Ann Partridge, MD, MPH, of Dana-Farber Cancer Institute in Boston, MA. “We found that temporarily interrupting therapy for pregnancy did not worsen outcomes from any breast cancer events—including distant events, which are most concerning because they are not typically curable.”

The trial followed 497 women age 42 or younger who had received adjuvant endocrine therapy for 18 to 30 months. In total, 74% of study participants had at least one pregnancy and 63.8% had at least one live birth. After a median of 3 years, the incidence of breast cancer was 8.9% in the treatment interruption group versus 9.2% in an external control group. Researchers allowed for the possibility that the findings are biased by a “healthy mother” effect—meaning that women with a lower risk of recurrence were more likely than others to participate in the trial and become pregnant.

“The results of the POSITIVE trial provide a framework with concrete recommendations and critical safety data to guide conversations with our patients about the short-term safety of interrupting endocrine therapy to pursue pregnancy,” says Jennifer Specht, MD, of Fred Hutchinson Cancer Center in Seattle, WA. “With this data, we can provide advice to patients about the risks of breast cancer recurrence and important reassurance about pregnancy outcomes.”

In the trial, most pregnancies occurred within 2 years of enrollment and more than 40% of women used assisted reproductive technology, such as oocytes or embryos banked prior to surgery. Investigators are now parsing the data to determine whether women who used fertility preservation strategies were more likely to get pregnant compared with women who did not, says Partridge.

Most (73%) of the women resumed endocrine therapy within 2 years of treatment interruption, while the remaining participants had not yet resumed or planned to stop permanently, adds Partridge. Researchers will continue following patients for up to 10 years to determine whether longer interruptions lead to more cancers.

While the findings are compelling, Specht emphasizes that participants had very early-stage disease and were highly motivated to become pregnant.

“Caution is warranted for women with more advanced breast cancer or those patients who discontinue endocrine therapy indefinitely,” says Specht. “In addition, longer follow-up is essential due to the potential for late breast cancer recurrence, which can happen up to 20 years after diagnosis.” –Janet Colwell

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