More extensive mutation study of familial #MaleBreastCancer by Deb et al shows subtypes, similarity to women

Mutational profiling of familial male breast cancers reveals similarities with luminal A female breast cancer with rare TP53 mutations

S Deb, S Q Wong1, J Li, H Do, J Weiss, D Byrne, A Chakrabarti, T Bosma, kConFab Investigators, A Fellowes, A Dobrovic and S B Fox

British Journal of Cancer (2014) 111, 2351–2360 | doi: 10.1038/bjc.2014.511


This paper follows on from several others by this group from the Peter MacCallum Cancer Center in Melbourne, exploring the molecular characteristics of male breast cancer. Here the focus is on familial breast cancers – the investigators have collected 48 male breast cancers where there is evidence of a strong inherited component. Of these 3 are identified as BRCA1 mutations, 17 as BRCA2 and the remainder unknown, or BRCAX. Often studies of families with inherited cancers have proven helpful in identifying key molecular switches, and this is one of the reasons these authors have looked at their large collection of inherited male breast cancers.

In the introduction the authors provide a brief description of the state of the field, and highlight why the present study makes such an important contribution:

Little is known about the risk factors and biology of [male breast cancer] […]. Only seven studies have specifically investigated [male breast cancers] comprising a total of 208 males […] with all but one study not reporting on BRCA-status or family history of the patients. Furthermore, only a limited panel of genes have been examined.

This paper looks at a more extensive panel of 48 genes, and does so in a large number of familial cases.


The detailed findings of the paper can be distilled to a relatively simple conclusion:

  • tumors with mutations in BRCA2 tend to have mutations in the tumor suppressor gene TP53
  • BRCAX tumors tend to have mutations in an oncogene known as PIK3CA
  • additional as yet not fully understood changes in gene expression or structure were associated with these two groups
  • overall the pattern of mutations was not very different from female breast cancers of the luminal A subtype, which is what most male breast cancers are
  • BRCA2 and BRCAX male breast cancers may have different tumor pathways, meaning that they arise by a different set of mutational steps and/or from a different cell of origin


In line with many other studies, the overall big picture of male breast cancer suggests that the similarities to female breast cancer of the same type outnumber the differences. This is reassuring, and helpful, as clinical approaches to the female disease are therefore likely to also work for men. Furthermore, the molecular specifics of BRCA2 and BRCAX subtypes in men is similar to that in women.

The knowledge that these two subtypes are associated with TP53 and PIK3CA mutations, respectively, may provide important information for picking therapies that are being developed to target cancers who have lost these pathways. The biology of the TP53 and PIK3CA pathways are quite well understood, and many attempts to target them are being developed.

Lastly, the paper paves the way for analyses of sporadic, non-familial cancers. In general pathways and associations in sporadic cancers are similar to familial cancers, if perhaps less pronounced. A testable hypothesis from this work would be to examine whether in sporadic male breast cancers there is also a separation of alterations in the TP53 and PIK3CA pathways, with the attending implications for personalized therapy, eventually.

2 thoughts on “More extensive mutation study of familial #MaleBreastCancer by Deb et al shows subtypes, similarity to women

  1. Thank you for offering this very useful summary, Oliver.
    Certainly encouraging to see more similarities among female & male breast cancer – this can bring good news for both genders down the road.
    Hopefully not too long.

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