Liefaard M C, van der Voort A, van Seijen M, Thijssen B, Sanders J, Vonk S, Mittempergher L, Bhaskaran R, de Munck L, van Leeuwen-Stok A E, Salgado R, Horlings H M, Lips E H, Sonke G S
Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
NPJ Breast Cancer. 2024 Apr 18;10(1):29. doi: 10.1038/s41523-024-00636-4.
Tumor-infiltrating lymphocytes (TILs) have been associated with outcomes in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy and trastuzumab. However, it remains unclear if TILs could be a prognostic and/or predictive biomarker in the context of dual HER2-targeting treatment. In this study, we evaluated the association between TILs and pathological response (pCR) and invasive-disease free survival (IDFS) in 389 patients with stage II-III HER2 positive breast cancer who received neoadjuvant anthracycline-containing or anthracycline-free chemotherapy combined with trastuzumab and pertuzumab in the TRAIN-2 trial. Although no significant association was seen between TILs and pCR, patients with TIL scores ≥60% demonstrated an excellent 3-year IDFS of 100% (95% CI 100-100), regardless of hormone receptor status, nodal stage and attainment of pCR. Additionally, in patients with hormone receptor positive disease, TILs as a continuous variable showed a trend to a positive association with pCR (adjusted Odds Ratio per 10% increase in TILs 1.15, 95% CI 0.99-1.34, p = 0.070) and IDFS (adjusted Hazard Ratio per 10% increase in TILs 0.71, 95% CI 0.50-1.01, p = 0.058). We found no interactions between TILs and anthracycline treatment. Our results suggest that high TIL scores might be able to identify stage II-III HER2-positive breast cancer patients with a favorable prognosis.
肿瘤浸润淋巴细胞（TILs）已被证明与接受新辅助化疗和曲妥珠单抗治疗的HER2阳性乳腺癌患者的预后相关。然而，在双重HER2靶向治疗的背景下，TILs是否可作为一种预后和/或预测性生物标志物仍不清楚。在本研究中，我们评估了389例II-III期HER2阳性乳腺癌患者中TILs与病理缓解（pCR）及无侵袭性疾病生存期（IDFS）之间的关联，这些患者在TRAIN-2试验中接受了含蒽环类或不含蒽环类的新辅助化疗联合曲妥珠单抗和帕妥珠单抗治疗。虽然未观察到TILs与pCR之间存在显著关联，但TIL评分≥60%的患者3年IDFS率高达100%（95%CI 100-100），无论激素受体状态、淋巴结分期及是否达到pCR。此外，在激素受体阳性疾病患者中，TILs作为连续变量与pCR（TILs每增加10%，调整后的优势比为1.15，95%CI 0.99-1.34，p = 0.070）及IDFS（TILs每增加10%，调整后的风险比为0.71，95%CI 0.50-1.01，p = 0.058）呈正相关趋势。我们未发现TILs与蒽环类治疗之间存在相互作用。我们的结果表明，高TIL评分可能能够识别出预后良好的II-III期HER2阳性乳腺癌患者。
