HER2-low status may predict poor neoadjuvant chemotherapy response in HR-negative breast cancer: a real-world multicenter study

Abstract

Objective We aimed to investigate the impact of human epidermal growth factor receptor 2 status (human epidermal growth factor receptor 2-low versus human epidermal growth factor receptor 2-zero) on pathological response to neoadjuvant chemotherapy and survival outcomes in early-stage breast cancer. Methods Patients with primary invasive breast cancer received neoadjuvant chemotherapy between July 2018 and July 2021 were identified from six hospitals. The primary efficacy end-point was total pathological complete response. The second short-term efficacy end-points include breast pathological complete response, axillary lymph nodes pathological complete response and the score of Miller-Payne grade. Long-term efficacy end-point was disease-free survival. Results 429 patients with human epidermal growth factor receptor 2 negative invasive tumors were included, 267 (62.24%) had human epidermal growth factor receptor 2-low tumors. Hormone receptor-positive patients had a higher percentage of human epidermal growth factor receptor 2-low tumors compared to hormone receptor-negative patients (71.97% versus 42.14%). The pathological response rate was significantly lower in human epidermal growth factor receptor 2-low tumors than in human epidermal growth factor receptor 2-zero tumors for total patients in univariate analysis, including the rates of total pathological complete response (5.2% versus 14.2%), breast pathological complete response (6.4% versus 17.3%), nodes pathological complete response (26.3% versus 37.7%) and MP4–5 (21.2% versus 33.8%). Subgroup analysis showed that the rates of total pathological complete response, breast pathological complete response and MP4–5 were also significantly lower in human epidermal growth factor receptor 2-low tumors versus human epidermal growth factor receptor 2-zero tumors in both univariate and multivariate analysis in hormone receptor-negative subgroup. With the median follow-up of 24 months, disease-free survival was comparable between these two subgroups (P = 0.816). Conclusions Our results demonstrate that human epidermal growth factor receptor 2-low tumors achieved a significantly lower pathological complete response rate with conventional chemotherapy than those with human epidermal growth factor receptor 2-zero tumors, especially for hormone receptor-negative group. Large, randomized, prospective studies are needed to confirm our data and further evaluate the prognostic value of human epidermal growth factor receptor 2-low expression.

Open questions, current challenges, and future perspectives in targeting human epidermal growth factor receptor 2-low breast cancer

“…While prognostic differences between HER2-low and HER2 IHC 0 breast cancers have been reported, 7 , 22 , 25 , 29 , 35 , 39 , 42 , 45 , 46 , 51 , 52 , 53 , 54 , 55 most studies found small or no differences in prognosis after adjusting for HR status 9 , 10 , 26 , 28 , 31 , 32 , 34 , 37 , 40 , 43 , 47 , 48 , 54 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ( Table 1 ). Taken together, the evidence does not support HER2-low as a biologically distinct breast cancer subtype.…”

“…2023 59 Nonmetastatic BC ( n = 2605) DFS X — OS — Longer OS in HER2-low for the HR− subgroup; no difference in the overall population or HR+ subgroup Xu et al. 2023 55 Primary invasive BC ( n = 429) pCR ✓ Lower pCR in HER2-low in the overall population and HR− subgroup DFS X — Zhang et al. 2022 34 Not specified ( n = 149) pCR — Lower pCR in HER2-low for the overall population; no difference when stratified by HR status DFS X — Zhou et al.…”

The Modified Neo-Bioscore System for Staging Breast Cancer Treated with Neoadjuvant Therapy Based on Prognostic Significance of HER2-Low Expression

“…Considerable attempts have been made to investigate the prognostic value of HER2-low status. Several studies revealed a better [2][3][4][5][6][7][8][9][10] or worse [11,12] prognosis for patients with HER2-low tumor when compared to those with HER2-zero (defined as IHC 0) tumor in various settings, while others hardly found any difference between HER2-low and HER2-zero tumors [13][14][15][16][17][18][19][20]. The biological behavior of a HER2-low tumor is yet to be elucidated, especially in those administered neoadjuvant chemotherapy.…”