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21-05-2022 | Breast Cancer | Preclinical study

Identification of tumor biomarkers for pathological complete response to neoadjuvant treatment in locally advanced breast cancer

Authors: Prarthana Gopinath, Sridevi Veluswami, Gopal Gopisetty, Shirley Sundersingh, Swaminathan Rajaraman, Rajkumar Thangarajan

Published in: Breast Cancer Research and Treatment | Issue 2/2022

Abstract

Background

Therapeutic response predictors like age, nodal status, and tumor grade and markers, like ER/PR, HER2, and Ki67, are not reliable in predicting the response to a specific form of chemotherapy. The current study aims to identify and validate reliable markers that can predict pathological complete response (pCR) in fluorouracil, epirubicin, and cyclophosphamide (FEC)-based neoadjuvant therapy with (NACT/RT) and without concurrent radiation (NACT).

Materials and methods

Tandem mass tag (TMT) quantitative liquid chromatography-tandem mass spectrometry (LC–MS/MS) was used to identify differentially expressed proteins from core needle breast biopsy between pCR (n = 4) and no-pCR (n = 4). Immunoblotting of shortlisted proteins with the tissue lysates confirmed the differential expression of the markers. Further, immunohistochemistry (IHC) was performed on formalin-fixed paraffin-embedded sections of treatment-naive core needle biopsies. In the NACT, 29 pCR and 130 no-pCR and in NACT/RT, 32 pCR and 71 no-pCR were used.

Results

733 and 807 proteins were identified in NACT and NACT/RT groups, respectively. Ten proteins were shortlisted for validation as potential pCR-predictive markers. THBS1, TNC, and DCN were significantly overexpressed in no-pCR in both the groups. In NACT, CPA3 was significantly upregulated in the no-pCR. In NACT/RT, HnRNPAB was significantly upregulated and HMGB1 significantly downregulated in the no-pCR. HMGB1 was the only marker to show prognostic significance.

Conclusion

Quantitative proteomics followed by IHC identified and validated potential biomarkers for predicting patient response to therapy. These markers can be used, following larger-scale validation, in combination with routine histological analysis providing vital indications of treatment response.

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Title: Identification of tumor biomarkers for pathological complete response to neoadjuvant treatment in locally advanced breast cancer
Authors: Prarthana Gopinath
Sridevi Veluswami
Gopal Gopisetty
Shirley Sundersingh
Swaminathan Rajaraman
Rajkumar Thangarajan
Publication date: 21-05-2022
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Biomarkers
Published in: Breast Cancer Research and Treatment / Issue 2/2022
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-022-06617-0

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Abstract

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