In a study reported in The New England Journal of Medicine, Ann H. Partridge, MD, MPH, and colleagues found that temporary interruption of adjuvant endocrine therapy to attempt pregnancy was not associated with an increased short-term risk of breast cancer events among women with hormone receptor–positive early breast cancer.

As stated by the investigators, “Prospective data on the risk of recurrence among women with hormone receptor–positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking.”

Ann H. Partridge, MD, MPH

Study Details

In the multicenter International Breast Cancer Study Group study, 516 women aged ≤ 42 years with stage I to III disease who had received adjuvant endocrine therapy for 18 to 30 months and desired pregnancy were enrolled between December 2014 and December 2019. The study protocol specified that patients have a 3-month washout period after discontinuing endocrine therapy before attempting pregnancy. The duration of interruption of endocrine therapy could be up to 2 years. Fertility assessment was strongly encouraged if pregnancy did not occur after 1 year.

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. The primary analysis was to be performed after 1,600 patient-years of follow-up; the prespecified safety threshold was occurrence of 46 breast cancer events during this period. Breast cancer outcomes in the study population were compared with those in an external control cohort of 1,499 women with hormone receptor–positive disease (from the SOFT and TEXT trials) who met age, disease stage, and duration of endocrine therapy entry criteria for the current study.  

Key Findings

Among the 516 women, median age was 37 years; median time from breast cancer diagnosis to enrollment was 29 months; and 93.4% had stage I or II disease. Among 497 women who provided information on pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth; in total, 365 babies were born.

With 1,638 patient-years of follow-up (median = 41 months), 44 patients experienced a breast cancer event—a number not exceeding the safety threshold of 46 events. The hazard ratio (HR) for a breast cancer event to be associated with pregnancy was 0.53 (95% confidence interval [CI] = 0.27–1.04).

Analysis using a bootstrap-matching method for the study population vs the control cohort showed that the 3-year incidence of breast cancer events was 8.9% (95% CI = 6.3%–11.6%) in the study cohort vs 9.2% (95% CI = 7.6%–10.8%) in the control cohort (absolute difference = −0.2 percentage points; 95% CI, −3.1 to 2.8 percentage points; HR = 0.81, 95% CI = 0.57–1.15). The 3-year incidence of distant recurrence was 4.5% (95% CI = 2.7%–6.4%) vs 5.8% (95% CI = 4.5%–7.2%; absolute difference = −1.4 percentage points, 95% CI = −3.5 to 1.0 percentage points; HR = 0.70, 95% CI = 0.44–1.12). Results were similar when a direct comparison method was used for the unadjusted study and control cohorts.

Among the 497 patients with information on pregnancy status, 43.3% reported using assisted reproductive technology. The cumulative incidence of first pregnancy was 28.8% at 6 months from enrollment, 53.6% at 12 months, and 70.5% at 24 months.

Among 415 patients who were disease-free for ≥ 2 years, 304 (73.3%) resumed endocrine therapy during the study period; approximately half resumed therapy within 26 months after treatment interruption. Among 111 women who had not resumed endocrine therapy at the time of the database lock, 88 (79.3%) reported that they were currently attempting to become pregnant, actively or recently pregnant, or actively or recently breastfeeding. A total of 15.4% women had not resumed endocrine therapy by 48 months after interruption.

The investigators concluded, “Among select women with previous hormone receptor–positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort. Further follow-up is critical to inform longer-term safety.”

Dr. Partridge, of the Department of Medical Oncology, Dana-Farber Cancer Institute, is the corresponding author for The New England Journal of Medicine article.

Disclosure: The Study was funded by the ETOP (European Thoracic Oncology Platform) and IBCSG (International Breast Cancer Study Group) Partners Foundation and others. For full disclosures of the study authors, visit nejm.org.