Analysis of Factors Associated With Pathological Complete Response in Patients With HER2-Positive Breast Cancer Receiving Neoadjuvant Chemotherapy

We investigated the impact of HER2-overexpression level on efficacy of neoadjuvant therapy (NAT) with trastuzumab in early breast cancer (BC). In our retrospective study of 161 patients, those with HER2-high versus HER2-intermediate disease were more likely to achieve pathological complete response after NAT. Importantly, patients with residual disease had lower disease-free survival, highlighting a need to develop personalized neoadjuvant strategies. Purpose: This study aimed to examine the impact of the level of HER2 overexpression on pathologic and clinical outcomes in HER2-positive breast cancer (BC) patients treated with neoadjuvant therapy (NAT). Methods: Women with Stage II or III HER2-positive BC who received anthracycline-taxane-trastuzumab NAT regimens followed by curativeintent surgery were included. Patients were classified according to tumor HER2 expression into HER2-high (immunohistochemistry (IHC) 3 + or fluorescence in situ hybridization (FISH) HER2/CEP17 ratio >5 or HER2 copy number >10) and HER2-intermediate (IHC 2 + with HER2/CEP17 ratio >2 to < 5 or copy number >4 to < 10). Univariate and multivariate logistic regression analyses were performed using HER2 expression as a categorical variable. The primary outcome was pathological complete response (pCR). Estimated 3-year disease-free survival (DFS) and Overall Survival (OS) were secondary outcomes. Results: Among 161 patients with HER2-positive BC, 139 (86%) and 22 (14%) were classified as HER2-high and HER2-intermediate, respectively; 105 (65.2%) had hormone receptor (HR)-positive tumors; 72 (45%) achieved a pCR. In the overall population, pCR rates of 18% and 49% were achieved in HER2-intermediate and HER2-high cases, respectively (odds ratio [OR] = 0.23 95% CI 0.07-0.72; P = .007). No pCRs were observed among HR-positive, HER2-intermediate cases. Estimated 3-year DFS was 97.1% versus 89.3% for patients achieving a pCR versus those with residual disease, respectively ( P = .0011). Conclusion: We found that patients with HER2-high disease were more likely to achieve pCR after NAT compared to patients with HER2-intermediate BC, a subgroup of patients that may benefit from more personalized NAT strategies.