Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Breast Cancer. 2018 May;25(3):268-274. doi: 10.1007/s12282-017-0822-8. Epub 2017 Nov 28.
Immune responses play an important role in interrupting the progression of cancer cells. Tumor-infiltrating lymphocytes (TILs) are basic components of the immune system. In triple negative breast cancer, increased number of TILs is associated with excellent prognosis and response of chemotherapy. Here, we investigated whether TILs affect the efficacy of trastuzumab-based treatment in human epidermal growth factor receptor 2 (HER2)-positive breast cancer.
The study included 97 patients with stage I-III HER2-positive breast cancer. All patients were preoperatively treated with an anthracycline-based combination regimen, followed by taxane with trastuzumab from 2009 to 2013. Pathological complete response (pCR) was defined as the disappearance of invasive cancer cells regardless of the presence of in situ components. TILs were evaluated using pre-therapeutic needle biopsy specimens. We assessed the percentage of the breast stroma with TILs over the total intratumoral stroma and classified the specimens in three grades: TILs1+ < 30%, TILs2+ 30-50%, and TILs3+ > 50%.
Overall, 80.4% of the specimens were TILs1+, 15.5% were TILs2+ and 4.1% were TILs3+. The pCR rate was 44.9% (35/78) in the TILs1+ cases, 80.0% (12/15) in the TILs2+ cases and 75.0% (3/4) in the TILs3+ cases. TILs were significantly associated with pCR (P = 0.0228). Multivariate analysis using TILs, hormone receptor (HR), nuclear grade (NG) and age indicated that TILs (OR 4.32, 95% CI 1.04-23.33, P = 0.0436) and HR (OR 8.76, 95% CI 3.30-25.44, P < 0.0001) were independent predictors for pCR.
TILs are associated with the efficacy of trastuzumab-based treatment in HER2-positive breast cancer.
免疫反应在阻断癌细胞进展中起着重要作用。肿瘤浸润淋巴细胞（TILs）是免疫系统的基本组成部分。在三阴性乳腺癌中，TILs 数量的增加与良好的预后和化疗反应相关。在这里，我们研究了 TILs 是否会影响曲妥珠单抗为基础的治疗在人表皮生长因子受体 2（HER2）阳性乳腺癌中的疗效。
该研究纳入了 97 例 I-III 期 HER2 阳性乳腺癌患者。所有患者均于 2009 年至 2013 年接受了蒽环类药物为基础的联合方案治疗，随后进行紫杉烷联合曲妥珠单抗治疗。病理完全缓解（pCR）定义为无论原位成分是否存在，浸润性癌细胞均消失。TILs 使用术前活检标本进行评估。我们评估了肿瘤间质中 TILs 占总肿瘤间质的百分比，并将标本分为三个等级：TILs1+ < 30%、TILs2+ 30-50%和 TILs3+ > 50%。
总体而言，80.4%的标本为 TILs1+，15.5%为 TILs2+，4.1%为 TILs3+。TILs1+病例的 pCR 率为 44.9%（35/78），TILs2+病例为 80.0%（12/15），TILs3+病例为 75.0%（3/4）。TILs 与 pCR 显著相关（P=0.0228）。使用 TILs、激素受体（HR）、核分级（NG）和年龄进行多变量分析表明，TILs（OR 4.32，95%CI 1.04-23.33，P=0.0436）和 HR（OR 8.76，95%CI 3.30-25.44，P<0.0001）是 pCR 的独立预测因素。
TILs 与曲妥珠单抗为基础的治疗在 HER2 阳性乳腺癌中的疗效相关。
