Early onset HER2-positive breast cancer is associated with germline TP53 mutations

Cancer. 2012 Feb 15;118(4):908-13. doi: 10.1002/cncr.26377. Epub 2011 Jul 14.


Background: Germline TP53 mutations predispose to early onset breast cancer in women and are associated with Li-Fraumeni syndrome. Published data on the pathological characteristics of breast cancer among women with TP53 mutations is limited.

Methods: We retrospectively reviewed the clinical records of women who underwent genetic testing for suspected germline TP53 mutations and who were diagnosed with breast cancer between 2000 and 2011. The pathological characteristics of the breast tumors from patients testing positive for a mutation (cases) were compared with those testing negative (controls).

Results: Patients who tested positive for germlineTP53 mutations (n = 30) were compared with controls (n = 79). Human epidermal growth factor receptor 2 (HER2) amplification and/or overexpression was found in 67% of the tumors from the cases, compared with 25% for the controls (P = .0001). Among patients with a mutation, 70% had estrogen receptor- and/or progesterone receptor-positive tumors, compared with 68% in the control group (P = .87). After adjusting for age at breast cancer diagnosis, having a HER2-positive tumor increased the odds of testing positive for a germline TP53 mutation (odds ratio, 6.9; 95% confidence interval, 2.6-18.2). For each yearly increment in age at breast cancer diagnosis, there was decreased likelihood of having a TP53 mutation of 5% (odds ratio, 0.95; 95% confidence interval0.91-0.99).

Conclusions: This study suggests an association between germline TP53 mutations and early onset HER2-positive breast cancer. If confirmed in a larger cohort, these results could guide genetic testing strategies, lead to chemoprevention trials incorporating HER2-targeted therapies, and elucidate some of the molecular pathways involved in breast cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aging / genetics
  • Aging / metabolism
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Germ-Line Mutation / genetics*
  • Humans
  • Middle Aged
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Retrospective Studies
  • Signal Transduction
  • Time Factors
  • Tumor Suppressor Protein p53 / genetics*


  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • ERBB2 protein, human
  • Receptor, ErbB-2