Winer Leah, Ruth Karen J, Bleicher Richard J, Nagarathinam Rajeswari, McShane Melissa, Porpiglia Andrea S, Pronovost Mary T, Aggon Allison, Williams Austin D
Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Biostatistics Facility, Fox Chase Cancer Center, Philadelphia, PA, USA.
Ann Surg Oncol. 2025 Feb;32(2):931-943. doi: 10.1245/s10434-024-16470-8. Epub 2024 Nov 9.
Human epidermal growth factor receptor 2 (HER2) overexpression (HER2+) is defined by immunohistochemistry (IHC) and in situ hybridization (ISH) as IHC3+ or IHC2+/ISH+. Response differences to neoadjuvant anti-HER2 therapy (NT) in IHC3+ versus IHC2+/ISH+ breast cancer patients are poorly characterized. We explored whether pathologic complete response (pCR) varies by HER2 IHC status.
Patients with stage I-III HER2+ breast cancer undergoing NT and surgery between 2013 and 2020 were identified from the National Cancer Database and stratified by IHC status. Breast and nodal pCR were analyzed.
Of 40,711 HER2+ patients, 83% were IHC3+ and 17% were IHC2+/ISH+. IHC3+ patients were more likely to be hormone receptor (HR)-negative (33 vs. 21%), have cT3/4 tumors (24 vs. 21%), and be cN+ (52 vs. 47%; all p < 0.0001). Breast conservation rates were similar (each 43%, p = 0.32), although IHC3+ axillary lymph node dissection rates were lower (41 vs. 45%, p < 0.0001). Among all patients, breast pCR was 49%, while nodal pCR was 64%. Compared with IHC2+/ISH+, IHC3+ had higher unadjusted breast (54 vs. 22%, p < 0.0001) and nodal (69 vs. 37%, p < 0.0001) pCR rates. When stratified by HR status, pCR was lower for HR+ disease but remained higher among IHC3+ patients. Analysis of T1cN0 primaries mirrored these trends. In multivariable analysis, IHC3+ remained an independent predictor of breast (odds ratio [OR] 3.91, confidence interval [CI] 3.65-4.19, p < 0.0001) and nodal (OR 3.40, CI 3.12-3.71, p < 0.0001) pCR.
HER2 IHC status predicts pCR and may help select breast cancer patients who derive the greatest benefit from NT. These findings provide further evidence that revision of HER2 classification may improve clinical management.
人表皮生长因子受体2（HER2）过表达（HER2+）通过免疫组织化学（IHC）和原位杂交（ISH）定义为IHC3+或IHC2+/ISH+。IHC3+与IHC2+/ISH+乳腺癌患者对新辅助抗HER2治疗（NT）的反应差异尚未得到充分描述。我们探讨了病理完全缓解（pCR）是否因HER2 IHC状态而异。
从国家癌症数据库中识别出2013年至2020年间接受NT和手术的I-III期HER2+乳腺癌患者，并按IHC状态进行分层。分析乳腺和腋窝淋巴结的pCR情况。
在40711例HER2+患者中，83%为IHC3+，17%为IHC2+/ISH+。IHC3+患者更可能为激素受体（HR）阴性（33%对21%）、患有cT3/4期肿瘤（24%对21%）和cN+（52%对47%；所有p<0.0001）。保乳率相似（均为43%，p=0.32），尽管IHC3+患者腋窝淋巴结清扫率较低（41%对45%，p<0.0001）。在所有患者中，乳腺pCR为49%，腋窝淋巴结pCR为64%。与IHC2+/ISH+相比，IHC3+患者未经调整的乳腺（54%对22%，p<0.0001）和腋窝淋巴结（69%对37%，p<0.0001）pCR率更高。按HR状态分层时，HR+疾病的pCR较低，但在IHC3+患者中仍较高。对T1cN0原发肿瘤的分析反映了这些趋势。在多变量分析中，IHC3+仍然是乳腺（比值比[OR]3.91，置信区间[CI]3.65-4.19，p<0.0001）和腋窝淋巴结（OR 3.40，CI 3.12-3.71，p<0.0001）pCR的独立预测因素。
HER2 IHC状态可预测pCR，并可能有助于选择从NT中获益最大的乳腺癌患者。这些发现进一步证明修订HER2分类可能改善临床管理。
