Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer

Abstract

Background: 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.

Methods: We conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point 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 planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial.

Results: Among 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for 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. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort.

Conclusions: 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. (Funded by ETOP IBCSG Partners Foundation and others; POSITIVE ClinicalTrials.gov number, NCT02308085.).

Figure 1.

Trial Enrollment and Analysis Populations.

Figure 2.. Cumulative Incidence of Breast Cancer Events and Distant Recurrences.

Estimates of the cumulative incidence of breast cancer events (Panel A) and distant recurrences of breast cancer (Panel B) were compared with the use of the bootstrap-matching method. Plots showing the results of both the bootstrap-matching method and the direct-comparison method are provided in Figures S2 and S3. Of the 22 total distant recurrences (Panel B), 21 were the first site of recurrence, and 1 occurred after a local recurrence. The percentage-point differences between the 3-year percentages in the treatment-interruption group in this trial and the external control cohort may not match the absolute differences shown because of rounding. The 0 time point on the x axis for the treatment-interruption group is the date of enrollment after 18 to 30 months of previous endocrine therapy (median duration of previous endocrine therapy, 23 months). The 0 time point on the x axis for the control cohort refers to the date by which the patients had received endocrine therapy for 2 years (see Sun et al.). The insets show the same data on an expanded y axis.

Figure 3.. Cumulative Incidence of Breast Cancer Events at 3 Years, According to Demographic and Disease Characteristics and Previous Treatment.

Six patients were excluded from the analysis according to body-mass index owing to missing data. The subgroup labeled “no documented mutation” includes one patient whose BRCA mutation status was unknown. Three patients were excluded from the analyses according to tumor size and tumor grade owing to missing data. Tumor grade was assessed locally as histologic grade 1 (well differentiated), 2 (moderately differentiated), or 3 (poorly differentiated). The size of the boxes is proportional to the number of patients in the subgroup, and arrows on the confidence interval bars indicate that the upper boundary of the confidence interval is off the scale. The confidence intervals have not been adjusted for multiplicity, and analyses are considered to be descriptive. AI denotes aromatase inhibitors, HER2 human epidermal growth factor receptor 2, OFS ovarian function suppression, and SERM selective estrogen-receptor modulator.