Pathological complete response and prognosis after neoadjuvant chemotherapy in patients with HER2-low breast cancer

An estimated 287,850 women living in the United States will be newly diagnosed with breast cancer in 2022 [1]. Breast cancer survival outcomes are influenced by the tumor stage and grade and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) statuses [1]. HER2-positive breast cancer, accounting for approximately 15–20 % of breast cancer phenotypes, has an aggressive biology and adverse prognosis [2]. The use of trastuzumab after chemotherapy regimens significantly improves survival outcomes for patients with early HER2-positive breast cancer [3]. Treatment with pertuzumab and docetaxel in addition to trastuzumab further improves survival outcomes for patients with HER2-positive breast cancer [4].

However, the presence of residual invasive HER2-positive breast cancer after neoadjuvant chemotherapy (NAC) and HER2-targeted therapy is associated with an unfavorable prognosis. Trastuzumab emtansine (T-DM1), an antibody drug conjugate (ADC) of trastuzumab, reduces the risk of recurrence or death after NAC by 50 % in patients with residual HER2-positive invasive breast cancer [5]. ADCs have three components – an antibody, a cytotoxic agent, and a linker – and a strong targeting ability with few adverse reactions due to the bystander effect [6], [7]. The ADC trastuzumab deruxtecan improves the outcome of HER2-negative breast cancer treatment [8], [9]. The emergence of novel ADCs alters the traditional diagnosis and treatment of HER2-low breast cancer. The study was performed to investigate the molecular biological characteristics of HER2-low breast cancer in terms of the pathological complete response (pCR) and prognosis after NAC.

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