Prostate cancer and prostate cancer-specific survival of men from breast cancer-prone families

An Australian research team has used data from 148 men from 1,423 families identified through the Kathleen Cunningham Consortium for Research into Familial Breast Cancer (kConFab) to assess the risks associated with prostate cancer in males from breast cancer-prone families, and most particularly from those families in which the BRCA2 gene mutation is prevalent.

Although it is well understood that there is a strong association between the presence of the BRCA2 gene mutation and the risk for development of prostate cancer, the consequent clinical presentation of prostate caner in such men, and their treatment-related outcomes, have not previously been thoroughly characterized.

kConFab is a multi-center research consortium that identifies and studies families at high risk for breast cancer from across Australia and New Zealand. Thorne et al. were able to search the kConFab database to identify 148 male patients who met the following three criteria:

  • They had all been diagnosed with prostate cancer.
  • They were all confirmed as either a carrier or a non-carrier of a family-specific BRCA pathogenic mutation.
  • Comprehensive clinical and treatment data were available on all 148 men.

Detailed analysis of the clinical and familial data from these 148 male prostate cancer patients established the following:

  • The men all had high risk of disease progression, irrespective of mutation status.
  • Carriers of the BRCA2 mutation had an increased risk of overall and prostate cancer-specific mortality (hazard ratio [HR] = 4.5;  P = 8.9 × 10<sup>-5</sup>) by comparison with non-carriers.
  • For both carriers and non-carriers of the BRCA2 mutation given first-line treatment with curative intent, long-term survival outcomes were relatively poor (when compared to the survival outcomes of men from non-breast cancer-prone families
  • Serum PSA readings taken prior to diagnosis in 90 percent of these men, after age adjustment, were above clinical significance.
  • Based on the D’Amico risk stratification criteria
    • 77.5 percent of the carriers of the BRCA2 mutation had high-risk disease
    • 58.7 percent of non-carriers also had high-risk disease.
  • BRCA2 mutation status was an independent prognostic indicator of overall survival.

Thorne et al. conclude that:

  • If diagnosed with prostate cancer, all men in breast cancer-prone families are at significant risk of developing an aggressive form of the disease.
  • This information should be made clear by genetic counselors and medical professionals in discussions about cancer risk with men in such families, whether the individual is a carrier or a non-carrier of a BRCA gene mutation.

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