Influence of mutagenic versus non-mutagenic pre-operative chemotherapy on the immune infiltration of residual breast cancer

Anna Mária Tőkés, Orsolya Rusz, Gábor Cserni, Erika Tóth, Gábor Rubovszky, Tímea Tőkés, Laura Vízkeleti, Lilla Reiniger, Renáta Kószó, Zsuzsanna Kahán, Janina Kulka, Marco Donia, András Vörös, Zoltan Szallasi

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Abstract

Background: Chemotherapeutic agents are often mutagenic. Induction of mutation associated neo-epitopes is one of the mechanisms by which chemotherapy is thought to increase the number of tumor-infiltrating lymphocytes. It is not known, however, whether treatment with various chemotherapeutic agents with different mutagenic capacity induce a significantly different number of stromal tumor-infiltrating lymphocytes (StrTIL) in residual cancer. Methods: One hundred and twenty breast carcinoma cases with residual disease that were treated with one of three types of pre-operative chemotherapy regimens were selected for the study. The percentage of StrTIL was evaluated in pretreatment core biopsies (pre-StrTIL) and post-treatment surgical tumor samples (post-StrTIL). TIL changes (ΔStrTIL) were calculated from the difference between post-StrTIL and pre-StrTIL. Results: When analyzing the pre-StrTIL and post-StrTIL among the three treatment groups, we detected significant StrTIL increase independently of the treatment applied. Based on distant metastases-free survival analysis, both post-StrTIL and ΔStrTIL was found to be independent prognostic factor in HR negative cases. Conclusions: Significant increase of StrTIL in the residual disease was observed in patients treated with the highly (platinum), moderately (cyclophosphamide) and marginally mutagenic chemotherapeutic agents (taxane, anthracycline). Increase in StrTIL in residual cancer compared to pretreatment tumor tissue is associated with improved distant metastasis-free survival in cases with HR negative breast carcinoma.

Original languageEnglish
Pages (from-to)1603-1611
Number of pages9
JournalActa Oncologica
Volume58
Issue number11
DOIs
Publication statusPublished - Nov 2 2019

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ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Tőkés, A. M., Rusz, O., Cserni, G., Tóth, E., Rubovszky, G., Tőkés, T., Vízkeleti, L., Reiniger, L., Kószó, R., Kahán, Z., Kulka, J., Donia, M., Vörös, A., & Szallasi, Z. (2019). Influence of mutagenic versus non-mutagenic pre-operative chemotherapy on the immune infiltration of residual breast cancer. Acta Oncologica, 58(11), 1603-1611. https://doi.org/10.1080/0284186X.2019.1633015