Effect of Estrogen Receptor on the Relationship Between HER2 Immunohistochemistry Score and Pathological Complete Response to Neoadjuvant Treatment in HER2-Positive Breast Cancer

Abstract

Purpose: We aimed to investigate whether estrogen receptor (ER) status affects the predictive role of the human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) score on the efficacy of neoadjuvant treatment for HER2-positive breast cancer. Methods: This retrospective study comprised 167 individuals diagnosed with HER2-positive invasive breast cancer who had undergone neoadjuvant treatment and surgery. Uni- and multivariable logistic regression analyses were performed on the relationship between the HER2 IHC score and total pathological complete response (tpCR), breast pathological complete response (bpCR), or axillary partial response (apCR). Subgroup analyses were used to investigate whether the relationship between the HER2 IHC score and tpCR, bpCR, or apCR differed by ER or PR status. Results: The overall tpCR rate for HER2-positive breast cancers treated with neoadjuvant treatment was 41.32% (69 of 167). The tpCR, bpCR, and apCR rates were greater in the HER2 IHC 3+ group (tpCR: IHC 3 + 47.69% vs. IHC 2 + 18.92%, p=0.009). Significant interactions between HER2 IHC score and tpCR or bpCR were found in subgroup analyses based on ER status (tpCR: p for interaction = 0.001; bpCR: p for interaction = 0.001). Among ER-positive patients, the HER2 IHC 2+ group had substantially decreased tpCR, bpCR, and apCR rates than the HER2 IHC 3+ group (tpCR rate: p=0.003; bpCR rate: p=0.002; apCR rate: p=0.002). For ER-negative individuals, the tpCR, bpCR, and apCR rates did not differ significantly among the HER2 IHC 3+ versus HER2 IHC 2+ groups. Similarly, interactions between HER2 IHC score and tpCR, bpCR, or apCR were found in subgroup analyses based on PR status. Conclusion: HER2 IHC 2+ may indicate a decreased tpCR rate, bpCR rate, and apCR rate to neoadjuvant treatment in HR-positive patients having HER2-positive breast cancer, but not in HR-negative patients.

Keywords: breast cancer; estrogen receptor; human epidermal growth factor receptor 2; pathological complete response.