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01-06-2017 | Clinical trial

Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2− breast cancer: results from two prospective trials

Authors: M. V. Dieci, A. Frassoldati, D. Generali, G. Bisagni, F. Piacentini, L. Cavanna, K. Cagossi, F. Puglisi, A. Michelotti, R. Berardi, G. Banna, A. Goubar, G. Ficarra, G. Griguolo, Pierfranco Conte, V. Guarneri

Published in: Breast Cancer Research and Treatment | Issue 2/2017

Abstract

Purpose

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.

Methods

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.

Results

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 high vs low 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.

Conclusions

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.

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Title: Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2− breast cancer: results from two prospective trials
Authors: M. V. Dieci
A. Frassoldati
D. Generali
G. Bisagni
F. Piacentini
L. Cavanna
K. Cagossi
F. Puglisi
A. Michelotti
R. Berardi
G. Banna
A. Goubar
G. Ficarra
G. Griguolo
Pierfranco Conte
V. Guarneri
Publication date: 01-06-2017
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-017-4191-y

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