In patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, achievement of pathologic complete response (pCR) is a known prognostic indicator after neoadjuvant systemic therapy (NAST). We investigated the clinicopathological factors associated with pCR in patients with HER2-positive breast cancer treated with dual HER2-blockade. In this retrospective study, 348 patients with HER2-positive breast cancer who received NAST with docetaxel and carboplatin, combined with trastuzumab and pertuzumab (TCHP), were included. Of the 348 patients with HER2 protein expression data, 278 (79.9%) had HER2 immunochemistry (IHC) 3+. Data on tumor-infiltrating lymphocyte (TIL) levels were available for 305 patients, showing a median TIL level of 20% (IQR 5–50), among which 121 (39.7%) had high TIL levels (≥30%). Estrogen receptor (ER) status (77.9% in ER-negative vs. 47.5% in ER-positive;p< 0.001), HER2 protein expression (71.6% in IHC 3+ vs. 34.3% in IHC 2+;p< 0.001), and TIL levels (71.9% in high vs. 57.6% in low;p= 0.011) were significantly associated with the pCR rate. In addition, we observed a significant link between numerical TIL levels (per 10% increment) and the pCR rate. After adjusting other clinicopathologic factors, ER status (low expression [defined as 1–9% expression] or negative), HER2 IHC 3+ and numerical TIL levels (per 10% increment), and high TIL levels (≥30%) were found to be independent predictors of pCR. Notably, in ER-negative breast cancer, the treatment response was excellent, irrespective of HER2 expression and TIL levels. Conversely, in ER-positive cases, low ER expression, HER2 IHC 3+, and numerical TIL levels or high TIL levels emerged as independent predictors of pCR. Our results suggest that ER expression, HER2 protein expression, and TIL levels serve as valuable predictors of the treatment response to neoadjuvant TCHP.
在人表皮生长因子受体2（HER2）阳性乳腺癌患者中，获得病理完全缓解（pCR）是新辅助系统治疗（NAST）后已知的预后指标。本研究探讨了接受双重HER2阻断治疗的HER2阳性乳腺癌患者中与pCR相关的临床病理因素。这项回顾性研究纳入了348例接受多西他赛和卡铂联合曲妥珠单抗和帕妥珠单抗（TCHP）方案NAST的HER2阳性乳腺癌患者。在348例具有HER2蛋白表达数据的患者中，278例（79.9%）为HER2免疫组化（IHC）3+。305例患者可获得肿瘤浸润淋巴细胞（TIL）水平数据，中位TIL水平为20%（四分位距5-50），其中121例（39.7%）具有高TIL水平（≥30%）。雌激素受体（ER）状态（ER阴性组77.9% vs. ER阳性组47.5%；p<0.001）、HER2蛋白表达（IHC 3+组71.6% vs. IHC 2+组34.3%；p<0.001）和TIL水平（高TIL组71.9% vs. 低TIL组57.6%；p=0.011）与pCR率显著相关。此外，我们观察到数值化TIL水平（每增加10%）与pCR率之间存在显著关联。在调整其他临床病理因素后，ER状态（低表达[定义为1-9%表达]或阴性）、HER2 IHC 3+和数值化TIL水平（每增加10%）以及高TIL水平（≥30%）被确定为pCR的独立预测因子。值得注意的是，在ER阴性乳腺癌中，无论HER2表达和TIL水平如何，治疗反应均表现优异。相反，在ER阳性病例中，低ER表达、HER2 IHC 3+以及数值化TIL水平或高TIL水平成为pCR的独立预测因子。我们的研究结果表明，ER表达、HER2蛋白表达和TIL水平可作为预测新辅助TCHP治疗反应的重要指标。
Predictive Markers of Treatment Response to Neoadjuvant Systemic Therapy with Dual HER2-Blockade
肿瘤(癌症)患者之家