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. 2016 Mar;27(3):467-73.
doi: 10.1093/annonc/mdv592. Epub 2015 Dec 17.

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

D M Eccles  1 , N Li  2 , R Handwerker  3 , T Maishman  3 , E R Copson  3 , L T Durcan  3 , S M Gerty  3 , L Jones  4 , D G Evans  5 , L Haywood  4 , I Campbell  6
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Free article

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

D M Eccles et al. Ann Oncol. 2016 Mar.
Free article

Abstract

Background: Young age at diagnosis for breast cancer raises the question of genetic susceptibility. We explored breast cancer susceptibility genes testing on ≤40-year-old patients with HER2-amplified invasive breast cancer.

Patients and methods: Patients were selected from a large UK cohort study. The inclusion criterion was age ≤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 used 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: Of the 591 eligible patients, clinical testing results were available for 133 cases and an additional 263 cases had panel testing results. BRCA testing across 396 cases found 8 BRCA2 (2%) and 6 BRCA1 (2%) pathogenic mutations. Of the 304 patients tested for TP53 mutations, overall 9 (3%) had deleterious TP53 mutations. Of the 396 patients, 101 (26%) met clinical criteria for BRCA testing (≥10% probability), among whom 11% had pathogenic BRCA mutations (6 BRCA2, 5 BRCA1). Where the probability was calculated to be <10%, only 4 of 295 (1%) patients had BRCA mutations. Among the 59 patients who had TP53 testing meeting the 10% threshold, 7 had mutations (12%). Likely functionally deleterious mutations in 14 lower penetrance CSGs were present in 12 of 263 (5%) panel-tested patients.

Conclusion: Patients aged <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.

Keywords: HER2 positive; breast cancer; gene panel; genetic testing; young onset.

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