Department of Oncology, Rigshospitalet, Copenhagen University Hospital, section 5703 Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
The Danish Breast Cancer Group, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Breast Cancer Res. 2020 May 14;22(1):46. doi: 10.1186/s13058-020-01285-8.
The presence of tumour-infiltrating lymphocytes (TILs) is associated with response to neoadjuvant chemotherapy among patients with triple-negative and HER2-positive breast cancer. However, the significance of TILs is less clear in luminal breast cancer. Here, we in postmenopausal patients with primary oestrogen receptor-positive (ER+), HER2 normal, operable breast cancer assessed the importance of inducing TILs during 4 months of letrozole on response in a neoadjuvant phase II study.
Participants were postmenopausal women with ER+, HER2 normal operable breast cancer assigned to 4 months of neoadjuvant letrozole. Pretreatment core biopsies and surgical specimens were assessed centrally for the percentage of TILs on haematoxylin and eosin-stained slides according to the International Immuno-Oncology Biomarker Working Group on Breast Cancer guidelines. Pathological response was assessed by the Residual Cancer Burden (RCB) index and a modified Miller-Payne grading system and was analysed according to change in TILs.
Tumour specimens were available from 106 of the 112 patients treated per protocol. TIL concentration increased with mean 6.8 percentage point (p < 0.0001) during treatment (range - 39 to 60). An increase in TILs was significantly associated with pathological response with OR = 0.71 (95% CI 0.53-0.96; p = 0.02) per 10% absolute increase for pathological response and correspondingly OR = 0.56 (95% CI 0.40-0.78; p = 0.0007) for lower RCB index per 10% increase.
Increasing TILs during letrozole was significantly associated with a poor treatment response. An increase in TILs during endocrine therapy might imply immunogenicity, and these patients could be targetable by immunotherapy.
ClinicalTrials.govNCT00908531, registered 27 May 2009.
肿瘤浸润淋巴细胞（TILs）的存在与三阴性和 HER2 阳性乳腺癌患者接受新辅助化疗的反应相关。然而，在 luminal 乳腺癌中，TILs 的意义尚不清楚。在这里，我们评估了在新辅助 II 期研究中，接受 4 个月来曲唑治疗的绝经后原发性雌激素受体阳性（ER+）、HER2 正常、可手术的乳腺癌患者中，诱导 TILs 的重要性。
参与者为绝经后 ER+、HER2 正常、可手术的乳腺癌患者，接受 4 个月的新辅助来曲唑治疗。根据国际免疫肿瘤生物标志物工作组的乳腺癌指南，对预处理核心活检和手术标本进行中央评估，以评估苏木精和伊红染色切片上 TILs 的百分比。根据残留癌症负担（RCB）指数和改良 Miller-Payne 分级系统评估病理反应，并根据 TILs 的变化进行分析。
按方案治疗的 112 例患者中有 106 例可获得肿瘤标本。TIL 浓度在治疗期间平均增加 6.8 个百分点（p<0.0001）（范围为-39 至 60）。TIL 增加与病理反应显著相关，OR=0.71（95%CI 0.53-0.96；p=0.02），每增加 10%的绝对病理反应，OR=0.56（95%CI 0.40-0.78；p=0.0007），RCB 指数每增加 10%。
来曲唑期间 TIL 的增加与治疗反应不良显著相关。内分泌治疗期间 TIL 的增加可能暗示免疫原性，这些患者可能可通过免疫治疗靶向治疗。
ClinicalTrials.govNCT00908531，于 2009 年 5 月 27 日注册。
