In this study, we have compared the clinicopathologic characteristics of HER2-low breast cancer to HER2-zero and HER2-positive breast cancer, including response to neoadjuvant chemotherapy and prognosis.
Patients who underwent neoadjuvant chemotherapy between 2008 and 2018 at Asan Medical Center were included in this study. HER2-low was defined as immunohistochemistry (IHC) 1+ or IHC2+/in-situ hybridization negative and HER2-zero was defined as IHC 0.
A total of 1667 breast cancer patients who had neoadjuvant chemotherapy were included in this study. Among them 474 (28.4%) patients had a HER2-low tumor, 677 (40.6%) patients with a HER2-zero tumor and 516 (31.0%) patients with a HER2-positive tumor. The proportion of HER2-low tumors was higher in hormone receptor (HR)-positive patients compared to triple-negative breast cancer (TNBC) patients (49.5% vs 28.9%, respectively). HER2-low tumors had a significantly lower pCR rate compared to HER2-zero tumors (11% vs 15.4%, p=0.04). pCR rate was also significantly lower in HER2-low tumors compared to patients with HER2-positive tumors who were not treated with neoadjuvant HER2-targeted therapy (11% vs 17.4%, p=0.008). However, pCR rates did not differ according to HER2 status in HR-positive subgroups or TNBC subgroups. Patients with HER2-low tumors had significantly longer survival compared to patients with HER2-zero tumors (5-year RFS 78.8% vs 73.3%, log-rank test p=0.017; 5-year OS 90.8% vs 84.0%, log-rank test p=0.005). Survival differences were seen in patients with TNBC tumors (5-year RFS 73.5% vs 64.8%, log-rank test p=0.034), but not in patients with HR-positive tumors (5-year RFS 80.8% vs 81.5%, log-rank test p=0.87). Survival difference according to HER2-low status was only identified in TNBC patients with non-pCR, whereas no difference was noticed in TNBC patients with pCR (5-year RFS: low/pCR 92.7%, zero/pCR 90.0%, low/non-pCR 68.6%, zero/non-pCR 56.7%; log-rank test p<0.001).
HER2-low tumors have a distinct biology presenting with lower pCR but longer survival rate compared to patients with HER2-zero tumors. These results suggest a need for better understanding of the biology of HER2-low tumors and the refinement of future therapeutic strategies.
The authors.
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All authors have declared no conflicts of interest.