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
Howell, Sacha J
Evans, D Gareth R
AffiliationManchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester M13 9WL
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AbstractEarly 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 of 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 PV 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.
CitationHyder Z, Harkness EF, Woodward ER, Bowers NL, Pereira M, Wallace AJ, et al. 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. Cancers (Basel). 2020;12.
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- Authors: Petridis C, Arora I, Shah V, Megalios A, Moss C, Mera A, Clifford A, Gillett C, Pinder SE, Tomlinson I, Roylance R, Simpson MA, Sawyer EJ
- Issue date: 2019 May 6
- Haplotype analysis of TP53 polymorphisms, Arg72Pro and Ins16, in BRCA1 and BRCA2 mutation carriers of French Canadian descent.
- Authors: Cavallone L, Arcand SL, Maugard C, Ghadirian P, Mes-Masson AM, Provencher D, Tonin PN
- Issue date: 2008 Apr 10
- Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers.
- Authors: Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, Jervis S, van Leeuwen FE, Milne RL, Andrieu N, Goldgar DE, Terry MB, Rookus MA, Easton DF, Antoniou AC, BRCA1 and BRCA2 Cohort Consortium., McGuffog L, Evans DG, Barrowdale D, Frost D, Adlard J, Ong KR, Izatt L, Tischkowitz M, Eeles R, Davidson R, Hodgson S, Ellis S, Nogues C, Lasset C, Stoppa-Lyonnet D, Fricker JP, Faivre L, Berthet P, Hooning MJ, van der Kolk LE, Kets CM, Adank MA, John EM, Chung WK, Andrulis IL, Southey M, Daly MB, Buys SS, Osorio A, Engel C, Kast K, Schmutzler RK, Caldes T, Jakubowska A, Simard J, Friedlander ML, McLachlan SA, Machackova E, Foretova L, Tan YY, Singer CF, Olah E, Gerdes AM, Arver B, Olsson H
- Issue date: 2017 Jun 20
- Long-term outcomes of breast cancer in women aged 30 years or younger, based on family history, pathology and BRCA1/BRCA2/TP53 status.
- Authors: Evans DG, Moran A, Hartley R, Dawson J, Bulman B, Knox F, Howell A, Lalloo F
- Issue date: 2010 Mar 30
- Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi-ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early-onset breast cancer patients.
- Authors: Lee DS, Yoon SY, Looi LM, Kang P, Kang IN, Sivanandan K, Ariffin H, Thong MK, Chin KF, Mohd Taib NA, Yip CH, Teo SH
- Issue date: 2012 Apr 16