Residual Disease Burden After Neoadjuvant Therapy Among US Patients With High-Risk HER2-positive Early-Stage Breast Cancer: A Population Effectiveness Model.

Background: Approximately half of patients with high-risk HER2-positive early-stage breast cancer (ESBC) do not have pathologic complete response (pCR) after neoadjuvant therapy. The residual burden of disease among this population has not been previously quantified.

Materials And Methods: We used decision-modeling techniques to simulate recurrence, progression from locoregional to distant cancer, breast cancer-related mortality, and mortality from other causes over a 10-year period in a hypothetical cohort. We derived progression probabilities primarily from the KATHERINE trial of T-DM1 (ado-trastuzumab emtansine) and mortality outcomes from the published literature. Modeled outcomes included recurrences, breast cancer deaths, deaths from other causes, direct medical costs, and costs due to lost productivity. To estimate the residual disease burden, we compared outcomes from a cohort of patients treated with T-DM1 versus a hypothetical cohort with no disease recurrence.

Results: We estimated that 9,300 people would experience incident high-risk HER2-positive ESBC in the United States in 2021 based on cancer surveillance databases, clinical trial data, and expert opinion. We estimated that, in this group, 2,118 would experience disease recurrence, including 1,576 distant recurrences, and 1,358 would experience breast cancer deaths. This residual disease burden resulted in 6,435 life-years lost versus the recurrence-free cohort, and healthcare-related costs totaling $644 million, primarily associated with treating distant cancers.

Conclusion: Patients with HER2-positive ESBC who do not achieve pCR after neoadjuvant therapy are at ongoing risk of recurrence despite the effectiveness of neoadjuvant treatment. There is substantial clinical and economic value in further reducing the residual disease burden in this population.