Pausing Adjuvant Endocrine Therapy to Attempt Pregnancy Shows No Additional Short-Term Risk For Select Women With Early-Stage Breast Cancer

A temporary interruption of endocrine therapy to attempt pregnancy did not lead to a greater short-term risk of breast cancer events among a select group of patients with hormone receptor–positive (HR+) early breast cancer when compared with an external control cohort, according to results from the Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine Responsive Breast Cancer (POSITIVE) trial.

Although continued use of adjuvant endocrine therapy greatly reduces the risk of recurrence in this patient population, pregnancy is contraindicated during treatment. Despite advances in breast cancer treatment, there is a lack of prospective data on the risk of recurrence among women with HR+ early breast cancer who temporarily discontinue endocrine therapy for the purpose of attempting pregnancy.

The international, single-group, multicenter POSITIVE trial included 516 women aged 42 years or younger from 20 countries who had previously been diagnosed with stage I, II, or III HR+ early breast cancer. These patients had received adjuvant endocrine therapy for 18 to 30 months and expressed a desire for pregnancy. Patients were required to have a 3-month washout period after pausing endocrine therapy before attempting pregnancy. Partridge and colleagues enrolled participants between December 2014 and December 2019. The primary endpoint was the number of breast cancer events (local, regional, or distant recurrence) during follow-up, with a prespecified safety threshold of 46 events after 1600 patient-years. Patient outcomes were compared with those in an external control cohort of 1499 women with HR+ disease from the SOFT and TEXT trials.

At 1638 patient-years of follow-up (median follow-up = 41 months), 44 patients experienced a breast cancer event, which did not exceed the safety threshold. Among the 497 participants followed for pregnancy status, 74.0% achieved at least one pregnancy and 63.8% had at least one live birth. A total of 365 babies were born during the study period. The 3-year incidence of breast cancer events was 8.9% in the treatment-interruption group (95% CI, 6.3% – 11.6%) and 9.2% in the control cohort (95% CI, 7.6% – 10.8%), demonstrating comparable risks between the two groups (absolute difference = −0.2 percentage points; 95% CI, −3.1 to 2.8 percentage points; HR = 0.81, 95% CI, 0.57–1.15).

There were limitations to this study. For example, a follow-up of 3.4 years may not be enough time to substantially inform patients about the risk of pausing treatment considering breast cancer’s long-term risk of recurrence. Additionally, the researchers noted the potential for “the healthy mother effect”, where those with breast cancer who had a lower risk of recurrence may have been more likely to participate in the trial compared with those with a higher risk of recurrence. Still, the overall results of the trial are promising, even as the authors point out that more research is needed.

“In well-matched comparisons to an external control cohort, the POSITIVE trial showed no clear worsening of breast cancer outcomes in the short-term after temporary interruption of endocrine therapy to allow for pregnancy in select women with a history of hormone receptor–positive breast cancer,” the authors concluded. “Longer-term follow-up is needed to further inform the safety of this strategy. Nevertheless, these results provide an improved understanding of the effect of subsequent pregnancy on breast cancer outcomes in women.”

Reference:
Partridge AH, Niman SM, Ruggeri M, et al. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388(18):1645-1656. doi:10.1056/NEJMoa2212856.