Women With Breast Cancer Can Safely Pause Hormonal Therapy for Pregnancy

One of the important questions for women who develop breast cancer during their childbearing years is whether they will be able to become pregnant. Although this may not be a priority at diagnosis or during treatment, it can become the leading question a year or two after treatment ends.

A Safe Pregnancy Is Possible

A new study indicates that women who have survived hormone receptor-positive (HR+) breast cancer can interrupt hormone-suppressing treatment for 2 years without affecting disease outcomes. The study included more than 500 premenopausal women from 20 countries worldwide. Pausing treatment did not affect recurrence rates.

The study, called POSITIVE, was shared in a presentation at the 2022 San Antonio Breast Cancer Symposium (SABCS) .

The study included more than 500 premenopausal women from 20 countries who had received at least 18 months of hormonal therapy for HR+ breast cancer. They were then given 2 years to have a baby and breastfeed before resuming treatment. Importantly, interrupting therapy did not affect cancer recurrence rates. In addition, more than a third of the women achieved at least one pregnancy, most within 2 years, and a very large majority had restarted hormonal therapy by the end of the study period.

Details of the POSITIVE Study

POSITIVE was a single-arm study involving premenopausal women up to age 42.

Participants had stage 1-3 hormone receptor-positive (HR+) breast cancer and had received at least 18 and no more than 30 months of adjuvant (postsurgical preventive) hormonal therapy, without cancer recurrence up to that point.

The women could also have previously received neoadjuvant (presurgical tumor-shrinking) chemotherapy, with or without egg preservation for fertility.

The women stopped hormonal therapy within 1 month of study enrollment, then underwent a 3-month treatment-free period before having up to 2 years to try to conceive, become pregnant, give birth and breastfeed.

They were then “strongly advised” to resume hormonal therapy to complete their planned 5-10 years of treatment, with follow-up planned for up to 10 years.

A total of 518 women were enrolled at 116 centers in 20 countries across four continents, and 516 were eligible for the primary efficacy analysis. The median time from breast cancer diagnosis to enrollment was 29 months.

At enrollment, the median age was 37, and 75% had not previously given birth. Patients with stage 1 or 2 breast cancer accounted for 93%.

The median duration of hormonal therapy before enrollment was 23.4 months.

Tamoxifen and other selective estrogen receptor modulators (SERMs) were given alone to 42% of patients, while 36% received a SERM plus ovarian function suppression. Another 16% received an aromatase inhibitor, such as arimidex, together with ovarian function suppression.

Most women (62%) had previously received neoadjuvant chemotherapy.

The study’s primary endpoint was the “3-year cancer-free interval.” This was assessed after a median follow-up of 41 months. The 3-year cancer-free interval failure rate was 8.9%, corresponding to 44 events. The “3-year distant cancer-free interval” failure rate was 4.5%, with 22 events. Both rates were similar to those in a historical control group of patients who had not taken such a treatment break.

For the secondary endpoint analysis, the team assessed 497 women in the POSITIVE study group. Of these, 368 (74%) had at least one pregnancy, with 507 pregnancies in total. At least one live birth was recorded in 64% of the women, or 86% of those who became pregnant.

Approximately 43% of women used some form of assisted reproductive technology at some point during the study.

Pregnancy complications occurred in 11% of pregnancies. The most common were hypertension/preeclampsia in 3% and diabetes in 2%.

A total of 317 women had 350 live births, comprising 335 single births and 15 twins. Only 8% of offspring had low birth weight, and 2% had birth defects. Breastfeeding was reported by 62% of women.

At 48 months of follow-up, 76% of women had resumed hormonal therapy. Another 8% experienced cancer recurrence or death before they could restart treatment, while 15% had not yet resumed it for other reasons.

Among disease-free women who had not resumed hormonal therapy, 79% reported at their latest follow-up that they were continuing to pursue pregnancy, were currently or recently pregnant, or were still breastfeeding.

This was a difficult study to design and conduct, and it was truly the first to examine the safety of interrupting ongoing hormonal therapy to become pregnant. Stopping treatment for pregnancy is an “exceptionally individual decision.”

It is important to remember that these results apply only to hormonal therapy and do not apply to women receiving newer-generation treatments such as abemaciclib .

Conclusion

In conclusion, it is important to discuss future fertility concerns and emphasize that pregnancy may be possible, particularly for women who developed early-stage, low-risk breast cancer before age 40 and especially those who have not previously had children. This study suggests that women in this situation receiving treatment for hormone receptor-positive breast cancer can interrupt hormonal therapy for pregnancy and breastfeeding.