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) breast cancer

D Gareth Evans

Manchester, Manchester, United Kingdom


Objectives:Early age of breast cancer is a known risk factor for hereditary predisposition and some studies have shown higher risks of contralateral breast cancer in BRCA1 carriers in those diagnosed at very young age, though little is published onTP53 carriers. Contralateral breast cancer rates were assessed in BRCA1, BRCA2 and TP53  carriers aged <36years.

Methods:Women with breast cancer diagnosed aged <36 years  where obtained from two sources:1.A population based study (n=283) diagnosed sequentially from 1980-1997 in North-West England 2.Referrals to the Genomic Medicine Department, St Mary’s Hospital 1990-2018. Sequencing of the BRCA1, BRCA2 and TP53 genes was carried out alongside tests for copy number variants on all referred women. Rates of contralateral breast cancer were censored at death, last assessment and risk reducing mastectomy.

Results:In total 48 TP53, 218 BRCA1 and  132 BRCA2 pathogenic variant carriers were identified with breast cancer aged <36 years as well as a representative sample of 283 not known to carry a variant. Annual rates of contralateral breast cancer (and synchronous) were TP53:7.6% (4.2%), BRCA1:3.6% (1.8%), and BRCA2:2.6% (1.5%). Rates were lower at 2.8% and 1.1% for BRCA1 and BRCA2 when left censored at date of mutation report, but not for TP53. Contralateral rates in non-carriers were 0.5% with those with a family history having a rate of 0.8%.

Conclusions: Contralateral breast cancer rates are very high for TP53 and BRCA1 carriers who develop breast cancer aged <36 and women need to be told in order to make  informed decisions on contralateral mastectomy guided by life expectancy from their index tumour.