Shorter telomeres in luminal B, HER-2 and triple-negative breast cancer subtypes

Christopher M Heaphy, Andrea Proctor Subhawong, Amy L. Gross, Yuko Konishi, Nina Kouprina, Pedram Argani, Kala Visvanathan, Alan Keith Meeker

Research output: Contribution to journalArticle

Abstract

Telomeres are nucleoprotein structures that protect chromosome ends from degradation and recombination. Cancers often have critically shortened telomeres, contributing to genomic instability. Many of these tumors activate telomerase to stabilize telomeric ends and achieve a capacity for unlimited replication. Telomere shortening has been reported in in situ and invasive carcinomas, including breast, and has been associated with disease recurrence after surgical resection. However, previous studies have not evaluated breast cancer subtypes. The objective of this study was to evaluate telomere lengths in different subtypes of breast cancer. Breast carcinomas (n=103) identified between 2001 and 2010 from patients seen at the Johns Hopkins Hospital were categorized into luminal A (n=18), luminal B (n=28), HER-2-positive (n=20) and triple-negative carcinomas (n=37) based on tumor characteristics. Telomere lengths were assessed directly at the single cell level by fluorescence in situ hybridization, and patient groups were compared using Fisher's exact tests. ER-negative status (P=0.022), PR-negative status (P=0.008), HER-2-positive status (P=0.023) and p53-positive status (P=0.022) were associated with shorter telomere length. A larger proportion of luminal A cancers had normal or long telomere lengths as compared with luminal B cases (P=0.002), HER-2-positive cases (P=0.011) or triple-negative cases (P=0.0003). Luminal B, HER-2-positive and triple-negative cases did not differ significantly. Telomere length was shorter in more aggressive subtypes, such as luminal B, HER-2-positive and triple-negative tumors, suggesting that tumor telomere length may have utility as a prognostic and/or risk marker for breast cancer.

Original languageEnglish (US)
Pages (from-to)194-200
Number of pages7
JournalModern Pathology
Volume24
Issue number2
DOIs
StatePublished - Feb 2011

Fingerprint

Triple Negative Breast Neoplasms
Telomere
Breast Neoplasms
Telomere Shortening
Neoplasms
Chromosome Structures
Nucleoproteins
Genomic Instability
Telomerase
Carcinoma in Situ
Fluorescence In Situ Hybridization
Genetic Recombination
Breast
Carcinoma
Recurrence

Keywords

  • breast cancer
  • HER-2
  • luminal A
  • luminal B
  • subtype
  • telomere
  • triple-negative

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Shorter telomeres in luminal B, HER-2 and triple-negative breast cancer subtypes. / Heaphy, Christopher M; Subhawong, Andrea Proctor; Gross, Amy L.; Konishi, Yuko; Kouprina, Nina; Argani, Pedram; Visvanathan, Kala; Meeker, Alan Keith.

In: Modern Pathology, Vol. 24, No. 2, 02.2011, p. 194-200.

Research output: Contribution to journalArticle

Heaphy, Christopher M ; Subhawong, Andrea Proctor ; Gross, Amy L. ; Konishi, Yuko ; Kouprina, Nina ; Argani, Pedram ; Visvanathan, Kala ; Meeker, Alan Keith. / Shorter telomeres in luminal B, HER-2 and triple-negative breast cancer subtypes. In: Modern Pathology. 2011 ; Vol. 24, No. 2. pp. 194-200.
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