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.
Highlights
Neoadjuvant chemotherapy (NAC) has historically been administered to breast cancer patients presenting with more advanced disease stages to reduce tumor size prior to surgery, rendering previously inoperable tumors operable, and potentially making breast conserving surgery a more viable option
The HER2 IHC or fluorescence in situ hybridization (FISH) results are often viewed as binary, in reality, there is a spectrum of HER2 results inherent in both testing methods
Our study shows that in the HER2-positive group of tumors, the degree of HER2 positivity by IHC staining and FISH copy number/ratio are both correlated with response to neoadjuvant
Summary
Neoadjuvant chemotherapy (NAC) has historically been administered to breast cancer patients presenting with more advanced disease stages to reduce tumor size prior to surgery, rendering previously inoperable tumors operable, and potentially making breast conserving surgery a more viable option. Many studies have shown that pathological complete response (pCR) after HER2-directed NAC is predictive of recurrence-free survival in HER2+ breast cancers; [1,2,3,4,5] a significant number of patients have residual tumor following NAC. The residual cancer burden (RCB) index was developed by MD Anderson Cancer Center to quantify residual disease upon pathological review and predict survival after NAC for breast cancer [6,7,8]. The RCB index incorporates the remaining post-NAC primary tumor dimensions, cellularity of the tumor bed, in situ cancer remaining within the tumor bed, number of involved lymph nodes, and size of largest axillary metastasis.
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