Young patients with HER2+ breast cancer rarely have a germline mutation in a known cancer predisposition gene

Diana Eccles1,Li Na2,Tom Maishman1,Ellen Copson1,Ian Campbell2

1University of Southampton, Southampton, UK,2Peter Macallum Cancer Centre, Melbourne, Australia

Presenting date: Tuesday 3 November
Presenting time: 16.10 - 16.25



Young age at diagnosis for breast cancer often raises the question of genetic susceptibility. We explored the outcome of germline genetic testing in a cohort of patients diagnosed with HER2 amplified breast cancer aged 40 years or younger to determine parameters that could help oncologists and geneticists inform patients about the likelihood of an underlying familial risk.




Patients were recruited to the POSH study (1). HER2 status was established from a combination of clinical records and immunohistochemistry in tumour microarrays (TMA). Family histories (FH) from questionnaires were submitted at recruitment and available for over 90% of cases. DNA extracted from white blood cells was tested for known breast cancer susceptibility genes.




Amongst 376 cases tested for BRCA1/2 only 12 (3%) had mutations in BRCA1 (4) or BRCA2 (8). Of the 376 cases, 113 had clinical BRCA testing, 52 met current FH based criteria for BRCA testing amongst whom 7 germline mutation carriers were identified 3 in BRCA2 (7.6%), 2 in BRCA1 (4%). Clinical testing data for TP53 was available for 40 patients, 2 mutations were detected (5%). Panel testing was performed in 263 additional cases with revealed only 3 (1%) BRCA2 mutations, no BRCA1 mutations and 1 (0.3%) TP53 mutation. Out of the cases tested on the panel who met current testing criteria (n=21), only 1 BRCA2 mutation was detected (5%). There were surprisingly few mutations (6/263 = 2%) in other lower penetrance susceptibility genes (truncating mutations in BRIP1=2, CHEK2=2, ATM=2).




Conclusions: Even at very young ages of diagnosis of breast cancer, patients with HER2+ breast cancer and no family history can be reassured that testing for germline mutations is very unlikely to reveal a causative mutation.