Dieci M V, Frassoldati A, Generali D, Bisagni G, Piacentini F, Cavanna L, Cagossi K, Puglisi F, Michelotti A, Berardi R, Banna G, Goubar A, Ficarra G, Griguolo G, Conte Pierfranco, Guarneri V
Department of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, 35128, Padua, Italy.
Division of Medical Oncology 2, Istituto Oncologico Veneto IRCCS, via Gattamelata 64, 35128, Padua, Italy.
Breast Cancer Res Treat. 2017 Jun;163(2):295-302. doi: 10.1007/s10549-017-4191-y. Epub 2017 Mar 13.
The aim was to evaluate the role of tumor-infiltrating lymphocytes (TIL) in predicting molecular response after preoperative endocrine or cytotoxic treatment for HR+/HER2- patients who do not achieve a pathological complete response.
Stromal (Str) TIL were centrally evaluated on samples from diagnostic core-biopsies of HR+/HER2- patients included in two prospective randomized trials: the LETLOB trial (neoadjuvant endocrine-based treatment) and the GIOB trial (neoadjuvant chemotherapy-based treatment). Pre- and post-treatment Ki67 was centrally assessed.
StrTIL were evaluable in 111 cases (n = 73 from the LETLOB trial and n = 38 from the GIOB trial). Median StrTIL was 2%. Patients with high StrTIL (StrTIL ≥10%, n = 28) had more frequently breast cancer of ductal histology (p = 0.02), high grade (p = 0.049), and high Ki67 (p = 0.02). After neoadjuvant endocrine treatment (LETLOB cohort), a significant Ki67 suppression (p < 0.01) from pre- to post-treatment was observed in both the low and high StrTIL groups. High StrTIL patients achieve more frequently a relative Ki67 suppression ≥50% from baseline as compared to low StrTIL patients (55 vs. 35%, p non significant). After neoadjuvant chemotherapy (GIOB cohort), a significant Ki67 suppression was observed only for low StrTIL patients (Wilcoxon p = 0.001) and not in the high StrTIL group (p = 0.612). In this cohort, the rate of patients achieving a relative Ki67 suppression ≥50% from baseline was significantly higher in the low vs high StrTIL group (64% vs 10%, p = 0.003). Geometric mean Ki67 suppression was evaluated in each cohort according to StrTIL: the lowest value (-41%) was observed for high StrTIL cases treated with chemotherapy.
This hypothesis-generating study suggests that in HR+/HER2- breast cancer StrTIL at baseline may influence the achievement of a molecular response after neoadjuvant treatment. Further evaluation in large studies is needed, and interaction with the type of treatment warrants to be explored.
本研究旨在评估肿瘤浸润淋巴细胞（TIL）在预测HR+/HER2-患者术前接受内分泌或细胞毒性治疗后未达到病理完全缓解时分子反应中的作用。
对两项前瞻性随机试验中纳入的HR+/HER2-患者诊断性核心活检样本中的基质（Str）TIL进行集中评估：LETLOB试验（新辅助内分泌治疗）和GIOB试验（新辅助化疗）。对治疗前后的Ki67进行集中评估。
111例患者的StrTIL可评估（LETLOB试验73例，GIOB试验38例）。StrTIL中位数为2%。高StrTIL患者（StrTIL≥10%，n = 28）更常出现导管组织学乳腺癌（p = 0.02）、高级别（p = 0.049）和高Ki67（p = 0.02）。在新辅助内分泌治疗（LETLOB队列）后，低StrTIL组和高StrTIL组从治疗前到治疗后均观察到显著的Ki67抑制（p < 0.01）。与低StrTIL患者相比，高StrTIL患者从基线起更常实现相对Ki67抑制≥50%（55%对35%，p无统计学意义）。在新辅助化疗（GIOB队列）后，仅在低StrTIL患者中观察到显著的Ki67抑制（Wilcoxon p = 0.001），而在高StrTIL组中未观察到（p = 0.612）。在该队列中，低StrTIL组从基线起实现相对Ki67抑制≥50%的患者比例显著高于高StrTIL组（64%对10%，p = 0.003）。根据StrTIL对每个队列的几何平均Ki67抑制进行评估：接受化疗的高StrTIL病例观察到最低值（-41%）。
这项产生假设的研究表明，在HR+/HER2-乳腺癌中，基线时的StrTIL可能会影响新辅助治疗后分子反应的实现。需要在大型研究中进行进一步评估，并探索其与治疗类型的相互作用。
