13IN - Diagnostic and therapeutic implications of tumour-infiltrating lymphocytes in breast cancer

Date 29 September 2014
Event ESMO 2014
Session Cancer immunotherapy in breast cancer: Dream or reality?
Topics Breast Cancer, Metastatic
Cancer Immunology and Immunotherapy
Pathology/Molecular Biology
Presenter Carsten Denkert
Citation Annals of Oncology (2014) 25 (suppl_4): iv6-iv7. 10.1093/annonc/mdu292
Authors C. Denkert
  • Institute Of Pathology, Charité, Campus Virchow Klinikum, 10117 - Berlin/DE

Abstract

Body

Abstract:

In several types of tumors, approaches to modulate tumor-associated inflammation have resulted in comparably high response rates in first clinical evaluations. These targeted therapies included immune checkpoint inhibitors and have stimulated interest in the interaction between immune cells and tumor cells. Neoadjuvant therapy approaches in breast cancer have been used as a strategy to characterize subgroups of tumors with increased tumor-infiltrating lymphocytes (TILs). It has been shown that increased TILs are linked to an increased response rate to neoadjuvant therapy and improved prognosis after adjuvant therapy, in particular in triple-negative and HER2 positive breast cancer. We have recently described tumor-infiltrating lymphocytes (TILs) as predictors of pathological complete response to neoadjuvant chemotherapy in the GeparTrio, GeparQuinto and GeparSixto breast cancer trials. To further investigate the immunological status in tumor tissue we have evaluated a total of 12 immunologically relevant genes, including T-cell markers, B-cell markers, chemokines and immunoregulatory factors, in 481 pretherapeutic FFPE samples in the European FP7 project Responsify. All immune mRNAs had a strong positive correlation with each other and with stromal TILs. Hierarchical cluster analysis showed three different immune-subtypes of tumors with different expression of immunological genes and different amounts of tumor infiltrating lymphocytes. The results suggest that expression of immune marker mRNAs in breast cancer is predictive for response to neoadjuvant chemotherapy. In GeparSixto, these immunological parameters can be used in addition to TILs to identify patients with increased response rates to carboplatin. The results should be validated in other breast cancer trials evaluating carboplatin therapy. In addition, the studies investigating TILS and immune mRNA markers suggest that a subgroup of breast carcinomas is immunogenic. The presentation will provide an overview on recent results on immune markers for prediction of response to neoadjuvant chemotherapy and prognosis with a focus in standardized histomorphological evaluation of tumor-infiltrating lymphocytes. The project has been funded within the EU-FP7 project RESPONSIFY No 278659.

Disclosure:

C. Denkert: Sividon Diagnostics: research funding, co-founder and shareholder.