Genetic Susceptibility to Triple‐Negative Breast Cancers


Triple‐negative breast cancer (TNBC) is a histological classification of breast cancer, where there is no expression of either the oestrogen or the progesterone receptor and no amplification of the HER2 receptor. TNBC is an important breast cancer subtype as it is aggressive in nature and has a poorer disease prognosis, mainly due to a paucity of targeted therapies. Studies in recent years have tried to elucidate the genetic aetiology of TNBC to better understand the disease and to predict response to treatments based on their genetic profile. TNBC has been shown to be very similar to BRCA1 mutation‐associated breast tumours, where it is estimated that approximately 20% of TNBC patients harbour germline BRCA (especially BRCA1) mutations. The contribution of germline mutations in other breast cancer susceptibility genes to TNBC still remains to be determined. Several common and novel breast cancer susceptibility loci have also been specifically linked to TNBC. These findings support the argument that genetic testing should be offered to patients based on the triple‐negative phenotype of their breast tumours.

Key Concepts:

  • TNBC is an important area of study due to the aggressive nature of this tumour subtype and the difficulties in disease treatment.

  • Women with TNBC have a poorer prognosis due to lack of endocrine therapies.

  • TNBC has histopathological characteristics similar to BRCA1‐ and BRCA2‐associated tumours, and could have similar molecular aetiology.

  • Germline mutations in BRCA1 and BRCA2 have been associated with up to 20% of TNBC cohorts unselected for family history of the disease.

  • The contribution of germline mutations in other breast cancer susceptibility genes to TNBC remains to be determined.

  • Several known breast cancer susceptibility loci have been shown to be specifically associated with TNBC.

  • Patients with TNBC could benefit from genetic screening of both BRCA genes based solely on the phenotype of their breast tumour.

Keywords: triple‐negative breast cancer; genetic; BRCA1 and BRCA2; germline mutations; mutation prevalence; genetic testing; targeted therapies

Figure 1.

Pathway diagram showing a small part on the DNA repair pathway involving BRCA1, BRCA2, CHEK2, ATM, BACH1 and PALB2 (encoded by BRCA1, BRCA2, CHEK2, ATM, BRIP1 and PALB2, respectively). These genes have been investigated in determining their mutation prevalence in TNBC.



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Wong‐Brown, Michelle W, and Scott, Rodney J(May 2014) Genetic Susceptibility to Triple‐Negative Breast Cancers. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0025352]