Tumour morphology predicts PALB2 germline mutation status

Z. L. Teo, E. Provenzano, G. S. Dite, D. J. Park, C. Apicella, S. D. Sawyer, P. A. James, G. Mitchell, A. H. Trainer, G. J. Lindeman, K. Shackleton, L. Cicciarelli, S. S. Buys, I. L. Andrulis, A. M. Mulligan, G. Glendon, E. M. John, M. B. Terry, M. Daly, F. A. OdefreyT. Nguyen-Dumont, G. G. Giles, J. G. Dowty, I. Winship, D. E. Goldgar, J. L. Hopper, M. C. Southey

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Background:Population-based studies of breast cancer have estimated that at least some PALB2 mutations are associated with high breast cancer risk. For women carrying PALB2 mutations, knowing their carrier status could be useful in directing them towards effective cancer risk management and therapeutic strategies. We sought to determine whether morphological features of breast tumours can predict PALB2 germline mutation status.Methods:Systematic pathology review was conducted on breast tumours from 28 female carriers of PALB2 mutations (non-carriers of other known high-risk mutations, recruited through various resources with varying ascertainment) and on breast tumours from a population-based sample of 828 Australian women diagnosed before the age of 60 years (which included 40 BRCA1 and 18 BRCA2 mutation carriers). Tumour morphological features of the 28 PALB2 mutation carriers were compared with those of 770 women without high-risk mutations.Results:Tumours arising in PALB2 mutation carriers were associated with minimal sclerosis (odds ratio (OR)=19.7; 95% confidence interval (CI)=6.0-64.6; P=5 × 10 -7). Minimal sclerosis was also a feature that distinguished PALB2 mutation carriers from BRCA1 (P=0.05) and BRCA2 (P=0.04) mutation carriers.Conclusion:This study identified minimal sclerosis to be a predictor of germline PALB2 mutation status. Morphological review can therefore facilitate the identification of women most likely to carry mutations in PALB2.

Original languageEnglish
Pages (from-to)154-163
Number of pages10
JournalBritish Journal of Cancer
Volume109
Issue number1
DOIs
StatePublished - Jul 9 2013

Keywords

  • Adult
  • BRCA2 Protein/genetics
  • Breast Neoplasms/genetics
  • Fanconi Anemia Complementation Group N Protein
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Humans
  • Middle Aged
  • Nuclear Proteins/genetics
  • Risk
  • Tumor Suppressor Proteins/genetics

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