Comparison of clinicopathological characteristics and response to neoadjuvant systemic therapy in patients with HER2-low-positive and HER2-zero breast cancer

Abstract

Previous studies have observed that human epidermal growth factor receptor 2 (HER2)-low-positive patients and HER2-zero patients have different prognoses. This study was conducted to investigate whether there are differences in clinicopathological characteristics and the response to neoadjuvant systemic therapy (NST) defined as systemic treatment prior to surgery between HER2-low-positive patients and HER2-zero patients. We retrospectively analyzed the data of patients with HER2-negative breast cancer who received NST at the First Affiliated Hospital of Nanjing Medical University from 2014 to 2021. There were 238 patients with HER2-low-positive status and 198 patients with HER2-zero status. The proportion of hormone receptor (HR)-positive patients in the HER2-low-positive group was significantly higher than that in the HER2-zero group (82.8% vs 52.0%, p < 0.001). The HER2-low-positive group had more patients with low Ki67 expression (23.9% vs 16.2%, p = 0.045), higher mastectomy rate (94.5% vs 88.9%, p = 0.031), and larger pathological tumor size (21.6 vs 17.8 mm, p = 0.028) than the HER2-zero group. However, no significant differences were found in pathologic complete response (pCR) rates between the two groups. We draw a conclusion that patients with HER2-low status and HER2-zero status were not found to have different pCR rates after NST, irrespective of HR status. However, differences were observed in some clinicopathological characteristics between the two groups.

Insights Into the Emerging Entity of HER2‐Low Breast Cancer

“…Several other studies have also revealed the higher prevalence of positive HR in HER2-low tumors when compared with HER2-zero and HER2-positive tumors [ 25 – 27 ]. Zhang et al further reported a significantly lower Ki67 expression level in HER2-low tumors when compared with HER2-zero [ 9 ], with other studies reporting similar conclusions [ 27 , 28 ]. Moreover, HER2-low tumors are more likely to exhibit histological Grade 2 than HER2-zero (59.3% vs. 34.4%, p < 0.001) and HER2-positive (59.3% vs. 39.6%, p < 0.001) tumors.…”

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

“… 7 , 9 , 10 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 A higher proportion of HER2-low (55%-91%) versus HER2 IHC 0 (34%-82%) tumors are HR+. 9 , 22 , 23 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 Additionally, a continuous association exists between higher estrogen receptor expression and higher prevalence of HER2-low expression. 32 …”

“…Robust differences in other clinicopathologic features have not been identified between HER2-low and HER2 IHC 0 breast cancer. Differences in tumor size, tumor grading, Ki-67 proliferation rate, or nodal status between HER2-low and HER2 IHC 0 breast cancer exist 9 , 22 , 26 , 28 , 29 , 30 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ; however, they are not consistent across studies 9 , 23 , 26 , 27 , 37 , 41 , 45 , 46 , 47 and may depend on HR status. 9 , 22 , 40 , 48 Genomic alteration and prediction analysis of microarray 50 (PAM50) intrinsic subtype differences between HER2-low and HER2 IHC 0 tumors have been observed, 9 , 22 , 48 , 49 but these were largely dependent on HR status.…”

“…2022 62 Not specified ( n = 314) pCR — Lower pCR in HER2-low for the overall population and HR+ subgroup d ; no difference for the HR− subgroup DFS X — OS X — Shi et al. 2023 36 Primary unilateral BC ( n = 436) Total pCR X — Breast pCR X — Axillary pCR — Higher pCR in HER2-low for the HR− subgroup among patients with high Ki67 expression only; no differences for overall population or HR+ subgroup among those with high Ki67 expression; no differences among patients without high Ki67 expression Shi et al. 2023 138 Recurrent BC ( n = 180) b BCSS — Marginally longer BCSS in HER2-low for the overall population; longer BCSS in HER2-low for the HR− subgroup; no difference for the HR+ subgroup Tan et al.…”