PALB2 Interest Group

Men – affected by breast cancer and PALB2 mutations

Recent publication: Whole-exome sequencing and targeted gene sequencing provide insights into the role of PALB2 as a male breast cancer susceptibility gene

Most associate breast cancer and women but breast cancer affects men too.  In fact, 20% of men with breast cancer have an affected first-degree family member.1 This suggests inheritance and a genetic link for men and their risk of developing breast cancer. We think that mutations in genes such as BRCA2 are responsible for a significant number of hereditary breast cancer cases in men.2,3 But there are also mutations in other genes that affect the development of breast cancer. One of these genes is PALB2.3

In a recent study, the researchers around Valentina Silvestri applied a technique called whole-exome sequencing (WES) to identify rare mutations in genes that can cause complex diseases like male breast cancer.4 For their analysis, they applied whole-exome or target sequencing and identified (1) a c.419delA truncating mutation carried by three members of the same family, the female proband, her father and paternal uncle who were all affected by breast cancer at 45, 66 and 65 years respectively and (2) a c.1984A>T nonsense mutation in 1 out of 48 BRCA1/2 mutation-negative male-breast cancer cases.4

The researchers concluded: “These results add strength to the evidence showing that PALB2 is involved in breast cancer risk for both sexes and indicate that consideration should be given to clinical testing of PALB2 for BRCA1/2 mutation-negative families with multiple male and female breast cancer cases.”4

 

  1. Korde LA, Zujewski JA, Kamin L, et al. Multidisciplinary meeting on male breast cancer: summary and research recommendations. J Clin Oncol. 2010;28:2114-2122.
  2. Frank TS, Deffenbaugh AM, Reid JE, et al. Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2:analysis of 10,000 individuals. J Clin Oncol. 2002;20:1480-1490.4.
  3. Rizzolo P, Silvestri V, Tommasi S, et al. Male breast cancer: genetics, epigenetics, and ethical aspects. Ann Oncol. 2013;24(suppl 8):viii75-viii8.
  4. Silvestri V, Zelli V, Valentini V, et al. Whole-exome sequencing and targeted gene sequencing provide insights into the role of PALB2 as a male breast cancer susceptibility gene. Cancer. 2017 Jan 1;123(2):210-218.
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