Department of Surgical Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, Japan.
Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.
Breast Cancer Res Treat. 2018 Feb;168(1):135-145. doi: 10.1007/s10549-017-4575-z. Epub 2017 Nov 22.
The therapeutic effect of systemic treatment for breast cancer (BC) generally depends on its intrinsic subtypes. In addition, tumor infiltrating lymphocytes (TILs) are considered to be an independent factor for tumor shrinkage and disease prognosis. High TILs at baseline or after primary systemic chemotherapy are reported to be associated with better survival in triple-negative or human epithelial growth factor receptor 2 (HER2)-positive BCs. However, the prognostic value of TILs in estrogen receptor (ER)-positive and HER2-negative (ER+/HER2-) BC is still controversial.
We assessed TIL score (low, intermediate, and high) before and after primary systemic chemotherapy in every subtype of BC, and compared the clinical outcomes. Biopsy specimens of 47 triple-negative, 58 HER2+ and 91 ER+/HER2- BCs were used to assess TILs before treatment. To assess TILs after treatment, we examined residual invasive carcinoma in surgically resected samples of 28 triple-negative, 30 HER2+ and 80 ER+/HER2- BCs.
A high TIL score in triple-negative BC before treatment resulted in a significantly higher proportion of pathological complete response (pCR). In contrast, ER+/HER2- BC exhibited fewer instances of pCR than other subtypes. Although not statistically significant, ER+/HER2- cases with a high TIL score also tended to achieve pCR (p = 0.088). Moreover, we revealed that low TIL BCs after chemotherapy, but not at baseline, had significantly better relapse-free survival in ER+/HER2- BC (p = 0.034).
Pathological examination of TILs after treatment may be a surrogate marker for prognosis in ER+/HER2- BC.
乳腺癌（BC）的全身治疗疗效通常取决于其固有亚型。此外，肿瘤浸润淋巴细胞（TILs）被认为是肿瘤缩小和疾病预后的独立因素。有报道称，基线或初次全身化疗后 TILs 较高与三阴性或人表皮生长因子受体 2（HER2）阳性 BC 的生存改善相关。然而，TILs 在雌激素受体（ER）阳性和 HER2 阴性（ER+/HER2-）BC 中的预后价值仍存在争议。
我们评估了每种 BC 亚型初次全身化疗前后的 TIL 评分（低、中、高），并比较了临床结局。47 例三阴性、58 例 HER2+和 91 例 ER+/HER2-BC 的活检标本用于治疗前 TILs 的评估。为了评估治疗后 TILs，我们检查了 28 例三阴性、30 例 HER2+和 80 例 ER+/HER2-BC 手术切除样本中残留的浸润性癌。
治疗前三阴性 BC 中 TIL 评分高与更高比例的病理完全缓解（pCR）相关。相比之下，ER+/HER2-BC 的 pCR 发生率较低。尽管没有统计学意义，但 ER+/HER2-BC 中 TIL 评分高的病例也倾向于获得 pCR（p=0.088）。此外，我们发现化疗后 TIL 低的 BC，但不是基线时 TIL 低的 ER+/HER2-BC 无复发生存率显著更好（p=0.034）。
治疗后 TIL 的病理检查可能是 ER+/HER2-BC 预后的替代标志物。
