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

Authors

  • Anna-Mária Tőkés 2nd Department of Pathology, Semmelweis University, Budapest, Hungary
  • Orsolya Rusz Department of Oncotherapy, University of Szeged, Szeged, Hungary
  • Gábor Cserni Department of Pathology, University of Szeged, Szeged, Hungary;  Department of Pathology, Bács-Kiskun County Teaching Hospital, Kecskemét, Hungary
  • Erika Tóth National Institute of Oncology, Budapest, Hungary
  • Gábor Rubovszky National Institute of Oncology, Budapest, Hungary
  • Tímea Tőkés Oncology Center, Semmelweis University, Budapest, Hungary
  • Laura Vízkeleti 2nd Department of Pathology, Semmelweis University, Budapest, Hungary;  ;2nd Department of Pathology, SE-NAP Brain Metastasis Research Group, Semmelweis University, Budapest, Hungary
  • Lilla Reiniger 2nd Department of Pathology, SE-NAP Brain Metastasis Research Group, Semmelweis University, Budapest, Hungary;  1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
  • Renáta Kószó Department of Oncotherapy, University of Szeged, Szeged, Hungary
  • Zsuzsanna Kahán Department of Oncotherapy, University of Szeged, Szeged, Hungary
  • Janina Kulka 2nd Department of Pathology, Semmelweis University, Budapest, Hungary
  • Marco Donia Department of Hematology, Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark;  Department of Oncology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
  • András Vörös Department of Pathology, University of Szeged, Szeged, Hungary
  • Zoltan Szallasi 2nd Department of Pathology, SE-NAP Brain Metastasis Research Group, Semmelweis University, Budapest, Hungary;  Danish Cancer Society Research Center, Copenhagen, Denmark;  Computational Health Informatics Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

DOI:

https://doi.org/10.1080/0284186X.2019.1633015

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.

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Published

2019-11-02

How to Cite

Tőkés, A.-M., Rusz, O., Cserni, G., Tóth, E., Rubovszky, G., Tőkés, T., … 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

Issue

Vol. 58 No. 11 (2019): Acta Oncologica

Section

Articles