Genetic testing in a cohort of young patients with HER2 amplified breast cancer.

Eccles DM1, Li N2, Handwerker R1, Maishman T1, Copson ER1, Durcan LT1, Gerty SM1, Jones L3, Evans DG4, Haywood L3, Campbell I5.

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Abstract

BACKGROUND:

Young age at diagnosis for breast cancer raises the question of genetic susceptibility. We explored breast cancer susceptibility genes testing amongst patients with HER2 amplified invasive breast cancer aged 40 years or younger.

PATIENTS AND METHODS:

Patients were selected from a large UK cohort study and were aged ≤40 at diagnosis with confirmed HER2 amplified breast cancer. The probability of finding a BRCA gene mutation was calculated based on family history. Genetic testing was either clinical testing for BRCA1 and BRCA2 with a subset also tested for TP53 mutations, or research based testing using a typical panel comprising 17 breast cancer susceptibility genes (CSGs) including BRCA1, BRCA2 and TP53.

RESULTS:

There were 591 eligible patients. Clinical testing results were available for 133 cases; an additional 263 cases had panel testing. BRCA testing across 396 cases found 8 BRCA2 (2%) and 6 BRCA1 (2%) pathogenic mutations. Of 304 tested for TP53 mutations overall 9 (3%) had deleterious TP53 mutations.Of 396 patients, 101 (26%) met clinical criteria for BRCA testing (≥10% probability), amongst whom BRCA testing yielded 11% with pathogenic BRCA mutations (6 BRCA2, 5 BRCA1). Where the probability was calculated to be <10%, only 4/295 (1%) had BRCA mutations. Amongst the 59 patients meeting the 10% threshold who had TP53 testing, there were 7 mutations (12%). Likely functionally deleterious mutations in 14 lower penetrance CSGs were present in 12/263(5%) panel tested patients.

CONCLUSION:

Patients under 41 at diagnosis with HER2+ breast cancer and no family history of breast cancer can be reassured that they have a low chance of being a high risk gene carrier. If there is a strong family history, not only BRCA but also TP53 gene testing should be considered. The clinical utility of testing lower penetrance CSGs remains unclear.