Risk of Contralateral Breast Cancer in Women with and without Pathogenic Variants in BRCA1, BRCA2, and TP53 Genes in Women with Very Early-Onset (<36 Years) Breast Cancer

Zerin Hyder, Elaine Harkness, Emma Woodward, Naomi L Bowers, Marta Perreira, Andrew J. Wallace, Sacha Howell, Tony Howell, Fiona Lalloo, William Newman, Miriam J Smith, D Gareth Evans

Research output: Contribution to journalArticlepeer-review

Abstract

Early age at diagnosis of breast cancer is a known risk factor for hereditary predisposition and some studies show a high risk of contralateral breast cancer in BRCA1 carriers diagnosed at very young ages. However, little is published on the risk for TP53 carriers. 397 women with breast cancer diagnosed <36 years of age were obtained from three sources: (i) a population-based study of 283 women diagnosed sequentially from 1980-1997 in North West England, (ii) referrals to the Genomic Medicine Department at St Mary’s Hospital from 1990-2018 and iii) individuals from (i) and the Family History Clinic at Wythenshawe Hospital South Manchester who tested negative for pathogenic variants (PV) in all three genes. Sequencing of BRCA1, BRCA2 and TP53 genes was carried out alongside tests for copy number for pathogenic variants on all referred women. Rates of contralateral breast cancer were censored at death, last assessment or risk reducing mastectomy. In total, 47 TP53, 218 BRCA1 and 132 BRCA2 PV carriers were identified with breast cancer diagnosed aged 35 years and under, as well as a representative sample of 261 not known to carry a PV in BRCA1, BRCA2 and TP53. Annual rates of contralateral breast cancer (and percentage of synchronous breast cancers) were TP53: 7.03% (4.3%), BRCA1: 3.57% (1.8%) and BRCA2: 2.63% (1.5%). In non-PV carriers, contralateral rates in isolated presumed/tested non-carrier cases with no family history were 0.56%, and for those with a family history, 0.69%. Contralateral breast cancer rates are substantial in TP53, BRCA1 and BRCA2 PV carriers diagnosed with breast cancer aged 35 and under. Women need to be advised to help make informed decisions on contralateral mastectomy, guided by life expectancy from their index tumor.
Original languageEnglish
Article number378
JournalCancers
Volume12
Issue number2
DOIs
Publication statusPublished - 7 Feb 2020

Keywords

  • BRCA1
  • BRCA2
  • Breast cancer
  • Contralateral
  • Early-onset breast cancer
  • Pathogenic variants
  • TP53

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