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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalBreast Cancer Research and Treatment
DOIs
Publication statusAccepted/In press - Mar 13 2017

Keywords

  • Chemotherapy
  • Endocrine therapy
  • Ki67
  • Neoadjuvant
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Dieci, M. V., Frassoldati, A., Generali, D., Bisagni, G., Piacentini, F., Cavanna, L., Cagossi, K., Puglisi, F., Michelotti, A., Berardi, R., Banna, G. L., Goubar, A., Ficarra, G., Griguolo, G., Conte, P., & Guarneri, V. (Accepted/In press). Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2− breast cancer: results from two prospective trials. Breast Cancer Research and Treatment, 1-8. https://doi.org/10.1007/s10549-017-4191-y