Analyzing Neoadjuvant Chemotherapy Effects in HER2-Low Breast Cancer: Real World Data.

Purpose: Neoadjuvant chemotherapy (NAC) can be used as upfront therapy in aggressive breast cancer (BC). human epidermal growth factor receptor 2 (HER2)-low BC, defined as tumors scoring +1 or +2 on immunohistochemistry without HER2 gene amplification by in situ hybridization, lacks information on real-world data (RWD) outcomes, especially in the NAC setting. This subgroup, which does not reach the HER2 positive criteria due to its lower receptor expression, represents a distinct clinical category potentially requiring tailored therapeutic approaches.

Study Objective:  The objective of this study is to characterize patients with BC with HER2-low status who received NAC in a Brazilian public reference center for female tumors and key outcomes such as pathological complete response (pCR), overall survival (OS), and metastasis-free survival (MFS).

Methods: A retrospective cohort study based on a large BC database from a reference cancer center in Brazil. Patients with BC that received NAC, diagnosed between 2011 and 2020, were included if they presented HER2-low status (defined as tumors scoring +1 or +2 on immunohistochemistry without HER2 gene amplification by in situ hybridization) and had complete data on outcomes. Clinical and demographic data were collected, such as age, menopausal status, Ki-67, hormone receptor expression and others. Key outcomes from the study comprised pCR (defined as ypT0/TIs/ypN0), overall survival, and metastasis-free survival (MFS). Survival analyses were conducted through the semiparametric Kaplan-Meier method to assess OS and MFS by pCR status, considering BC diagnosis as the index date.

Results: Overall, 297 patients were eligible and 141 were included in the study after matching the HER2-low definition. The pCR was seen in 18 out of 141 patients (12.7%). The median overall survival was 8.2 years, and the median MFS was 2.7 years. The OS of pCR was 83.4% and non-pCR was 58.1%; the DFS of pCR was 55.5% and non-pCR 40.6%.

Conclusion: This study gives updated insights on pCR, OS, and MFS in women with HER2-low BC exposed to NAC.