Predictive value of DNA repair gene expression for response to neoadjuvant chemotherapy in breast cancer.

Content Provider	Europe PMC
Author	Kneubil, M.C. Goulart, K.O.B. Brollo, J. Coelho, G.P. Mandelli, J. Orlandin, B.C. Corso, L.L. Roesch-Ely, M. Henriques, J.A.P.
Abstract	Genome-wide analysis using microarrays has revolutionized breast cancer (BC)research. A substantial body of evidence supports the clinical utility of the21-gene assay (Oncotype DX) and 70-gene assay (MammaPrint) to predict BCrecurrence and the magnitude of benefit from chemotherapy. However, there iscurrently no genetic tool able to predict chemosensitivity and chemoresistanceto neoadjuvant chemotherapy (NACT) during BC treatment. In this study, weexplored the predictive value of DNA repair gene expression in the neoadjuvantsetting. We selected 98 patients with BC treated with NACT. We assessed DNArepair expression in 98 formalin-fixed, paraffin-embedded core biopsy fragmentsused at diagnosis and in 32 formalin-fixed, paraffin-embedded post-NACT residualtumors using quantitative reverse transcription-polymerase chain reaction. Thefollowing genes were selected: BRCA1, PALB2,RAD51C, BRCA2, ATM,FANCA, MSH2, XPA,ERCC1, PARP1, and SNM1.Of 98 patients, 33 (33.7%) achieved pathologic complete response (pCR). The DNAexpression of 2 genes assessed in pre-NACT biopsies (PALB2 andERCC1) was lower in pCR than in non-pCR patients (P=0.005and P=0.009, respectively). There was no correlation between molecular subtypeand expression of DNA repair genes. The genes BRCA2 (P=0.009),ATM (P=0.004), FANCA (P=0.001), andPARP1 (P=0.011) showed a lower expression in post-NACTresidual tumor samples (n=32) than in pre-NACT biopsy samples (n=98). Theexpression of 2 genes (PALB2 and ERCC1) waslower in pCR patients. These alterations in DNA repair could be consideredsuitable targets for cancer therapy.
ISSN	0100879X
Journal	Brazilian Journal of Medical and Biological Research
Volume Number	55
PubMed Central reference number	PMC8922549
PubMed reference number	35293552
e-ISSN	1414431X
DOI	10.1590/1414-431X2021e11857
Language	English
Publisher	Associação Brasileira de Divulgação Científica
Publisher Date	2022-03-11
Access Restriction	Open
Rights License	This is an Open Access article distributed under the terms of theCreative Commons Attribution License, which permits unrestricted use,distribution, and reproduction in any medium, provided the original work isproperly cited.
Subject Keyword	Breast cancer Neoadjuvant chemotherapy Expression of DNA repair genes
Content Type	Text
Resource Type	Article
Subject	Neuroscience Cell Biology Physiology Medicine Biochemistry Biophysics Immunology Pharmacology, Toxicology and Pharmaceutics