Temporary ET break for pregnancy safe in the short term for breast cancer survivors

Temporary interruption of adjuvant endocrine therapy (ET) to allow for pregnancy has demonstrated short-term safety, with no increase in risk of breast cancer events, including distant recurrence, in hormone receptor–positive breast cancer survivors who have completed 18–30 months of adjuvant ET.

These results, after a median follow-up of 3.4 years in the multicentre single-group POSITIVE trial, provide “the strongest evidence to date on the short-term safety” of the choice to pursue pregnancy among some young breast cancer survivors. [N Engl J Med 2023;388:1709-1710]

The trial included 516 women aged ≤42 years (median age, 37 years) with previous stage I, II or III hormone receptor–positive breast cancer (stage I or II disease, 93.4 percent; median time from diagnosis to enrolment, 29 months) who had received adjuvant ET for 18–30 months and wished to temporarily discontinue ET to attempt pregnancy. Following a protocol-specified 3-month washout period, ET was interrupted for ≤2 years to allow for attempting pregnancy, childbirth, and breastfeeding (if desired). Study participants were strongly recommended to resume ET after completion of pregnancy and breastfeeding or after unsuccessful conception, to complete the planned 5–10 years of treatment. [N Engl J Med 2023:388:1645-1656]

The primary endpoint was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. Breast cancer outcomes in the treatment-interruption group were compared with those in an external control cohort comprising 1,499 patients from the SOFT and TEXT trials who would have been eligible for the POSITIVE trial. [N Engl J Med 2018;379:122-137; Breast 2020;53:1-7]

At 1,638 patient-years of follow-up (median follow-up, 41 months), 44 study participants had a breast cancer event – a result that was within the prespecified safety threshold of 46 events. The 3-year incidence of breast cancer events was 8.9 percent in the treatment-interruption group and 9.2 percent in the external control cohort (adjusted hazard ratio [HR], 0.81; 95 percent confidence interval [CI], 0.57–1.15).

Among 497 participants who were followed for pregnancy status, 368 (74.0 percent) had ≥1 pregnancy and 317 (63.8 percent) had ≥1 live birth during the study. “In a multivariate-adjusted Cox model, the HR for a breast cancer event associated with pregnancy was 0.53 [95 percent CI, 0.27–1.04],” reported the researchers from the International Breast Cancer Study Group. “Similarly, a landmark analysis showed no increased risk of breast cancer events associated with pregnancy.”

Pregnancy complication was reported in 41 participants (11.1 percent). The most common complications were hypertension or pre-eclampsia (3.8 percent), diabetes mellitus (2.4 percent), and placental abnormalities (1.6 percent). “The incidence of birth defects was low [2.2 percent of 365 offspring] and consistent with general population estimates,” the researchers noted. [J Community Genet 2018;9:387-396]

ET was resumed in 304 of 415 participants (73.3 percent) who were disease-free for ≥2 years, with half of the participants having resumed therapy within 26 months after ET interruption. Only 15.4 percent of the participants who had been expected to resume ET had not done so by 48 months after ET interruption.

“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 ET to allow for pregnancy in select women with a history of hormone receptor–positive breast cancer. Longer-term follow-up is needed to further inform the safety of this strategy,” the researchers concluded.