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AUA 2016: BRCA Gene Mutations Associated With Increased Prostate Cancer Risk

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Key Points

  • African American men with prostate cancer may be more likely to have germline mutations in the BRCA1 and BRCA2 genes than Caucasian men with prostate cancer.
  • Men diagnosed with male breast cancer could benefit from screening for prostate cancer, according to new data from researchers who identified a possible association between the two conditions.
  • A meta-analysis of reported cases of prostate cancer in men with known BRCA2 mutations demonstrated that men with BRCA mutations are more likely to have a poorer risk at presentation including a higher rate of nonlocalized disease and worse outcomes than men who do not carry the mutation.

Though predominantly known for their increased associations with breast cancer risk, germline mutations in the BRCA1 and BRCA2 genes are also associated with an increased susceptibility to other diseases, including prostate cancer. New data being presented during the 111th Annual Scientific Meeting of the American Urological Association (AUA) highlighted new research on the role that genetic sequencing and testing could play in prostate cancer screening and treatment.

Higher Frequency of Germline BRCA1/2 Mutations in African Americans With Prostate Cancer

African American men with prostate cancer may be more likely to have germline mutations in the BRCA1 and BRCA2 genes than Caucasian men with prostate cancer, suggesting that genetic testing could provide important information for treatment stratification (Abstract MP39-18). Using archived blood DNA samples from 857 prostate cancer patients who underwent radical prostatectomy at the institution, researchers at Walter Reed National Military Medical Center analyzed previous gene sequencing data for known and novel mutations on the BRCA1 and BRCA2 genes and compared the mutations (classified as benign or likely benign, pathogenic, or “variant of unknown significance” [VUS]) with the known clinical/pathologic parameters for each patient.

Men with African ancestry were more likely to have pathogenic and VUS mutations (7.3%) than Caucasian men (2.2%). Patients with pathogenic or VUS mutations had an increased frequency of metastasis (9.4%) than those who did not have the mutations (2.4%) and were more likely to have a significantly shorter time to metastasis.

Screening Male Breast Cancer Survivors for Prostate Cancer

Men diagnosed with male breast cancer could benefit from screening for prostate cancer, according to new data from researchers who identified a possible association between the two conditions (Abstract PD09-07). In this retrospective study using data from the Surveillance, Epidemiology and End Results (SEER) program, researchers identified men 5,753 men with first primary breast cancers.

At a median follow up of 4.3 years, 250 men were subsequently diagnosed with second primary prostate cancer. A greater incidence was identified in men aged 65 to 74 and those with American Joint Committee on cancer (AJCC) stage I breast cancer, or hormone receptor positivity, suggesting that prostate cancer screening could be indicated for men in this age range with these disease characteristics.

High Rates of Metastatic Disease Among BRCA2 Mutation Carriers With Prostate Cancer

A meta-analysis of reported cases of prostate cancer in men with known BRCA2 mutations demonstrated that men with BRCA mutations are more likely to have a poorer risk at presentation including a higher rate of nonlocalized disease and worse outcomes than those men who do not carry the mutation (Abstract MP09-09). Using studies from the MEDLINE database, researchers identified and reviewed 261 cases of prostate cancer in men with BRCA2 mutations.

Of those men (mean age at diagnosis 61.7 years), 71% had a Gleason score of 7 or higher, 41% had stage T3/T4 disease, and 26% had M1 metastasis at presentation. Upon comparing these data with the general population (using SEER data), men with BRCA2 mutations had significantly higher rates of metastatic disease (17.4% vs 4.4%) and higher rates of stage T3/T4 cancer (40.3% vs 10.8%).

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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