Survival outcomes are associated with genomic instability in luminal breast cancers

Abstract

Breast cancer is the leading cause of cancer related death among women. Breast cancers are generally diagnosed and treated based on clinical and histopathological features, along with subtype classification determined by the Prosigna Breast Cancer Prognostic Gene Signature Assay (also known as PAM50). Currently the copy number alteration (CNA) landscape of the tumour is not considered. We set out to examine the role of genomic instability (GI) in breast cancer survival since CNAs reflect GI and correlate with survival in other cancers. We focused on the 70% of breast cancers classified as luminal and carried out a comprehensive survival and association analysis using Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data to determine whether CNA Score Quartiles derived from absolute CNA counts are associated with survival. Analysis revealed that patients diagnosed with luminal A breast cancer have a CNA landscape associated with disease specific survival, suggesting that CNA Score can provide a statistically robust prognostic factor. Furthermore, stratification of patients into subtypes based on gene expression has shown that luminal A and B cases overlap, and it is in this region we largely observe luminal A cases with reduced survival outlook. Therefore, luminal A breast cancer patients with quantitatively elevated CNA counts may benefit from more aggressive therapy. This demonstrates how individual genomic landscapes can facilitate personalisation of therapeutic interventions to optimise survival outcomes.

Apurinic/apyrimidinic nuclease 1 drives genomic evolution contributing to chemoresistance and tumorigenesis in solid tumor

“…Luminal B tumors of breast, that are positive for estrogen receptor but negative for progesterone receptor, have increased genomic instability and demonstrate increased growth rate and tendency to develop resistance to tamoxifen 32 . Similarly, it has been demonstrated that a genomic instability-related score calculated based on copy number alterations can predict prognosis in luminal A breast cancer 33 . It is now becoming quite evident that genomic instability is a promising target in cancer 34,35 .…”

QNBC Is Associated with High Genomic Instability Characterized by Copy Number Alterations and miRNA Deregulation

“…Similarly, gains at 2p25-p11.1/12p13.33-p11.1 and 9p24.3-p13.1 were five and four times, respectively, more common in QNBC than in TNBC. Gains or amplifications in these regions were previously reported in TNBC tumors uncharacterized for AR status and have been associated with tumor progression [29,34,36,52,[56][57][58]. For example, the region 6p21-p23 encompasses approximately half of the genes on chromosome 6 and one-third of all CpG islands on this chromosome [59].…”

Bioinformatic identification of genomic instability-associated lncRNAs signatures for improving the clinical outcome of cervical cancer by a prognostic model

“…Recently, more and more scholars have been drawn to genomic instability. Genomic instability can not only initiate cancer, augment progression, and influence the overall prognosis of the affected patient, but also the survival of CC patients 3 , 5 , 22 , 23 . Recent studies have shown that epigenetic modifications and DNA damage from endogenous and exogenous sources could affect genomic instability 24 – 27 .…”