Profiling molecular regulators of recurrence in chemorefractory triple-negative breast cancers

Breast Cancer Research : BCR
Bradley A HancockMilan Radovich

Abstract

Approximately two thirds of patients with localized triple-negative breast cancer (TNBC) harbor residual disease (RD) after neoadjuvant chemotherapy (NAC) and have a high risk-of-recurrence. Targeted therapeutic development for TNBC is of primary significance as no targeted therapies are clinically indicated for this aggressive subset. In view of this, we conducted a comprehensive molecular analysis and correlated molecular features of chemorefractory RD tumors with recurrence for the purpose of guiding downstream therapeutic development. We assembled DNA and RNA sequencing data from RD tumors as well as pre-operative biopsies, lymphocytic infiltrate, and survival data as part of a molecular correlative to a phase II post-neoadjuvant clinical trial. Matched somatic mutation, gene expression, and lymphocytic infiltrate were assessed before and after chemotherapy to understand how tumors evolve during chemotherapy. Kaplan-Meier survival analyses were conducted categorizing cancers with TP53 mutations by the degree of loss as well as by the copy number of a locus of 18q corresponding to the SMAD2, SMAD4, and SMAD7 genes. Analysis of matched somatic genomes pre-/post-NAC revealed chaotic acquisition of copy gains and losses includi...Continue Reading

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Citations

Mar 27, 2020·Medical Sciences : Open Access Journal·Ugo TestaElvira Pelosi
Feb 6, 2020·International Journal of Molecular Sciences·Saioa MendazaDavid Guerrero-Setas
Feb 6, 2021·Cancer Chemotherapy and Pharmacology·Xianglan YiSheng Zhou

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Methods Mentioned

BETA
biopsies
RNA Assay
RNA-Seq
PCR
chip

Clinical Trials Mentioned

NCT01074970

Software Mentioned

Integrated Genomics Viewer ( IGV )
Upstream Regulator
Ingenuity Pathway
fastq
CIBERSORT
Ingenuity Pathway Analysis ( IPA )
Ingenuity Pathway Analysis
Torrent Suite
bam2fastq

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