Immunohistochemical HER2 score correlates with response to neoadjuvant chemotherapy in HER2-positive primary breast cancer.

The accuracy of biomarker assessment in breast cancer (BC) is paramount for therapy decisions and informs prognosis. We investigated neoadjuvant chemotherapy (NAC) response in HER2-positive BC with respect to immunohistochemistry (IHC) and in situ hybridization (ISH) results. We aimed to determine the role of HER2 protein expression in predicting NAC response and long-term outcome in two HER2-positive groups: IHC 3 + versus IHC 2 + ISH amplified groups. This retrospective study included 192 consecutive HER2 + primary BCs diagnosed from 2007 to 2019 treated with NAC and HER2-targeted agent (NACH). There were 158 HER2 3 + and 34 HER2 2 + ISH + cases. Clinicopathological parameters and long-term outcomes were analyzed. The Pathological Complete Response (pCR) rate was 85.7% (72/84) in ER-/HER2 + BCs and was lower in ER + /HER2 + BCs (42.6%, 46/108). The pCR was 55.1% (86/156) in the HER2 3 + group and was only 17.6% in HER2 2 + ISH + group (p < 0.001). Patients who achieved pCR in HER2 2 + ISH + group did not show a significantly higher HER2/CEP17 ratio or HER2 copy number. The overall survival (OS) and progression-free survival (PFS) were significantly higher in pCR compared to non-pCR cases (p = 0.011 and p = 0.015, respectively). There is significant heterogeneity in response to the NACH regimens in HER2 + cases. Our findings indicate that HER2 IHC score and ER expression determine NACH response in HER2 + BC. We recommend considering HER2 protein expression and ISH value to better select patients and assess the response for HER2-targeted therapy.

Citation

Yihong Wang, Kamaljeet Singh, Don Dizon, Teresa Graves, Ali Amin, Evgeny Yakirevich. Immunohistochemical HER2 score correlates with response to neoadjuvant chemotherapy in HER2-positive primary breast cancer. Breast cancer research and treatment. 2021 Apr;186(3):667-676

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PMID: 33598878

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