Data are limited regarding the optimal management of breast cancer in pregnancy, particularly for human epidermal receptor-2 (HER2+) tumors and the potential fetotoxicity of subtype-specific chemotherapy. We sought to compare strategies for the management of HER2+ tumors and to determine the optimal gestational age for induction in regards to chemotherapy status and maternal-fetal outcomes.METHODS:
A decision-analytic model was designed for women with HER2+ breast cancer at 20 weeks electing to continue their pregnancies, comparing 32 different strategies for scheduled delivery between 24-39 weeks gestation, with chemotherapy induction either at 24 weeks or delayed until after delivery. Baseline estimates of stage-specific mortality and the impact of delayed cancer treatment on 5-year survival rates were obtained from the literature. Outcomes factored into the model included the risk of intrauterine fetal demise, spontaneous delivery, respiratory distress syndrome, cerebral palsy, and neonatal demise at each gestational age. Univariate and multivariate sensitivity analyses were performed to test the robustness of our model.RESULTS:
For women assigned to antepartum chemotherapy, delivery at 39 weeks yielded the highest maternal and overall QALYs at all cancer stages. For women with HER2+ breast cancer deferring chemotherapy until after delivery, maternal quality-adjusted life years (QALYs) were maximized with induction at 37 weeks for stage I cancer, 32 weeks for stage II cancer, and 28 weeks for stage III cancer. Our model was heavily driven by the baseline probability of maternal death within 5 years, in addition to the expected progression of disease and decrease in survival rates with each week of non-treatment, and remained robust across reasonable ranges for all variables of interest.CONCLUSION:
For women with HER2+ breast cancer diagnosed in early pregnancy, initiation of chemotherapy and delivery at term is recommended.