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

• Main Authors: Zerin Hyder, Elaine F. Harkness, Emma R. Woodward, Naomi L. Bowers, Marta Pereira, Andrew J. Wallace, Sacha J. Howell, Anthony Howell, Fiona Lalloo, William G. Newman, Miriam J. Smith, D Gareth Evans
• Format: Article
• Language: English
• Published: MDPI AG 2020-02-01
• Series: Cancers
• Subjects: breast cancer; contralateral; pathogenic variants; early-onset breast cancer; <i>brca1</i>; <i>brca2</i>; tp53
• Online Access: https://www.mdpi.com/2072-6694/12/2/378

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 <i>BRCA1</i> carriers diagnosed at very young ages. However, little is published on the risk of <i>TP53</i> carriers. 397 women with breast cancer diagnosed &lt;36 years of age were obtained from three sources: (i) a population-based study of 283 women diagnosed sequentially from 1980&#8722;1997 in North-West England, (ii) referrals to the Genomic Medicine Department at St Mary&#8217;s Hospital from 1990&#8722;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 <i>BRCA1, BRCA2</i>, and <i>TP53</i> 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 <i>TP53</i>, 218 <i>BRCA1</i>, and 132 <i>BRCA2</i> 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 <i>BRCA1</i>, <i>BRCA2</i>, and <i>TP53</i>. Annual rates of contralateral breast cancer (and percentage of synchronous breast cancers) were <i>TP53</i>: 7.03% (4.3%), <i>BRCA1</i>: 3.57% (1.8%), and <i>BRCA2</i>: 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 <i>TP53, BRCA1</i>, and <i>BRCA2</i> 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.