HER2 Testing Characteristics Can Predict Residual Cancer Burden following Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer

Abstract

Objectives. The response to HER2-targeted neoadjuvant chemotherapy (NAC) in HER2-positive (+) breast cancer can be quantified using residual cancer burden (RCB) pathologic evaluation to predict relapse free/overall survival. However, more information is needed to characterize the relationship between patterns of HER2 testing results and response to NAC. We evaluated clinicopathologic characteristics associated with RCB categories in HER2+ patients who underwent HER2-directed NAC. Methods. A retrospective chart review was conducted with Stage I–III HER2+ breast cancer cases following NAC and surgical resection. HER2 immunohistochemistry (IHC) staining and fluorescence in situ hybridization (FISH), histologic/clinical characteristics, hormone receptor status, and RCB scores (RCB-0, RCB-I, RCB-II, and RCB-III) were evaluated. Results. 64/151 (42.4%) patients with HER2+ disease had pathologic complete response (pCR). Tumors with suboptimal response (RCB-II and RCB-III) were more likely to demonstrate less than 100% HER2 IHC 3+ staining ( p < 0.0001 ), lower HER2 FISH copies ( p < 0.0001 ), and lower HER2/CEP17 ratios ( p = 0.0015 ) compared to RCB-I and RCB-II responses. Estrogen receptor classification using ≥10% versus ≥1% staining showed greater association with higher RCB categories. Conclusions. HER2+ characteristics show differing response to therapy despite all being categorized as positive; tumors with less than 100% IHC 3+ staining, lower HER2 FISH copies, and lower HER2/CEP17 ratios resulted in higher RCB scores.

Atezolizumab With Neoadjuvant Anti–Human Epidermal Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: Primary Results of the Randomized Phase III IMpassion050 Trial

“…30 Similar to the results observed with the ITT and PD-L1positive populations in IMpassion050, no other biomarker showing an increased treatment benefit from atezolizumab versus placebo was identified. As observed previously, [34][35][36][37][38][39][40][41][42] patients with tumors either hormone receptor-positive, HER2 IHC 21, or PIK3CA-mutated tended to have lower pCR rates in IMpassion050, compared with those with hormone receptor-negative, HER2 IHC 31, or PIK3CA-wildtype tumors, respectively, potentially reflecting lower addiction to the HER2 pathway and/or intrinsic resistance to anti-HER2 therapies. However, it is important to note the small sample size of some of these subgroups, limiting interpretation of the results.…”