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BRCA1 or BRCA2 – risk management (male)

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Familial breast cancer predisposition due to a germline mutation in either BRCA1 or BRCA2 genes is an autosomal dominant condition.

This risk management guideline has been developed for individuals who have NOT been diagnosed with a relevant cancer/tumour. The care of affected individuals should be individualised based on their clinical situation, and the monitoring they need as part of their treatment and post-treatment follow up.

  • Unaffected known or obligate male BRCA1 or BRCA2 mutation carrier.
  • Male at 50% risk of being a BRCA1 or BRCA2 mutation carrier.

Exclusion criteria

  • Unaffected female BRCA1 or BRCA2 mutation carrier.
  • Affected BRCA1 or BRCA2 mutation carrier, male or female.
Cancer BRCA1 mutation carrier
by age 70 yrs		 BRCA2 mutation carrier
by age 70 yrs		 General male population by age 70 yrs*
Breast

1.2%

(0.22-2.8)r

 ~7% (3.2-12)rr <<1%
Prostate 8.6%r 15%r 5.3%
Pancreatic May be increased** <5%** <1%

*Annual NSW cancer incidence and mortality data set, 2014 (sourced from the NSW Cancer Registry).

**Substantially associated with smoking.

Cancer type Recommendations***
Breast Surgical

Not applicable.
Surveillance

Chest area awareness and pectoral area palpation on a regular basis.
Risk-reducing medication

No evidence.
Prostate Surveillance

If persistent elevation of PSA above normal refer to a urologist. Consider annual PSA +/- digital rectal exam (DRE) from early 40s.
Pancreas Surveillance
  • No evidence of benefit from surveillance.
  • Avoid smoking.

***the impact of lifestyle on cancer risk should be discussed e.g. recommend regular exercise, maintain healthy weight, have a healthy diet, limit alcohol intake, do not smoke.

Breast cancer

No trials have evaluated whether manual palpation is effective but mammography not useful. Other factors such as obesity, chest wall radiation and gynaecomastia can increase the risk of male breast cancer.r BRCA related (especially BRCA2) male breast cancer is known to be more aggressive and have a more unfavourable prognosis than those occurring in individuals without a BRCA gene mutation.r

Prostate cancer

In the general population surveillance can be associated with over-diagnosis and over treatment with no evidence for improved short term survival (ten year period). There is preliminary evidence for value in surveillance of men with BRCA mutations,rr as data suggests that BRCA-related prostate cancer is aggressive and occurs at a younger age than sporadic prostate cancer.rr

Pancreatic cancer

There is currently no effective surveillance that detects early pancreatic cancer.

First degree (blood) relatives (parents/brothers/sisters/children) are at 50% risk of having inherited the BRCA1 or BRCA2 mutation.  First degree relatives should be referred to a local family cancer clinic.

Link to information sheet on Informing family members about hereditary cancer.

Centre for Genetics Education NSW Health
Genetic Alliance Australia
Breast Cancer Network Australia (BCNA)
Gene Support Connect Programme
Cancer Australia

Research studies

Research is taking place in all aspects of hereditary breast and ovarian cancer. Families may be invited to participate in research trials. Speak to your doctor for more information.

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Bibliography

Moran, A., C. O'Hara, S. Khan, et al. 2012. "Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations." Fam Cancer 11(2):235-242

The risks of cancers other than breast and ovarian amongst BRCA1 and BRCA2 mutation carriers are based on relatively few family based studies with the risk of specific cancers tested in population based samples of cancers from founder populations. We assessed risks of other cancers in 268 BRCA1 families and 222 BRCA2 families using a person years at risk analysis from 1975 to 2005. Cancer confirmations were overall higher than in previous family based studies at 64%. There was no overall increase in risk for BRCA1 carriers although oesophagus had a significant increased RR of 2.9 (95% CI 1.1-6.0) and stomach at 2.4 (95% CI 1.2-4.3), these were based mainly on unconfirmed cases. For BRCA2 increased risks for cancers of the pancreas (RR 4.1, 95% CI 1.9-7.8) and prostate (RR 6.3, 95% CI 4.3-9.0) and uveal melanoma (RR 99.4, 95% CI 11.1-359.8) were confirmed. Possible new associations with oesophagus (RR 4.1, 95% CI 1.9-7.8) and stomach (RR 2.7, 95% CI 1.3-4.8) were detected but these findings should be treated with caution due to lower confirmation rates. In contrast to previous research a higher risk of prostate cancer was found in males with mutations in the BRCA2 OCCR region. The present study strengthens the known links between BRCA2 and pancreatic and prostate cancer, but throws further doubt onto any association with BRCA1. New associations with upper gastro-intestinal malignancy need to be treated with caution and confirmed by large prospective studies.

Tracey E, Kerr T, Dobrovic A, Currow D. 2010 “Cancer in New South Wales: Incidence and Mortality Report 2008”. Sydney: Cancer Institute NSW, August 2010

Version 6

Date Summary of changes
16/06/2011 Taken to reference committee meeting.
01/07/2011 Approved
15/04/2013 Discussed at March 6, 2013 reference committee meeting and the following changes made:
  • Lifetime risk of cancer table - updated.
  • Cancer risk management guidelines table - prostate surveillance updated from consider annual PSA + digital rectal exam (DRE) from early 40s as part of trial or shared decision making process to consider annual PSA + digital rectal exam (DRE) from early 40s.
  • Evidence for risk management guidelines - prostate cancer - deleted - surveillance should be offered as part of a trial or shared decision making process.
  • Research studies - section updated. 
  • Reference list - updated. 
31/07/2015 Link to AGSA changed to Genetic Alliance Australia.
23/09/2015

Discussed at May 2015 reference committee meeting and the following changes made:

  • Target group - point 1 updated.
  • Lifetime risk of cancer - age increased to 70 yrs, figures and references updated.
  • Cancer risk management table - updated.
  • References - updated.
07/01/2016 Sentence added to risk management template: "The impact of lifestyle on cancer risk should be discussed".
14/04/2016 Sentence added to risk management template: " This risk management guideline has been developed for individuals who have NOT been diagnosed with a relevant cancer/tumour.  The care of affected individuals should be individualised based on their clinical situation, and the monitoring they need as part of their treatment and post-treatment follow up". 
28/09/2016 'Unaffected' removed from title.
31/05/2017 Transferred to new eviQ website. Version number changed to V.4.
17/04/2018

Protocol reviewed and presented at the November 2017 eviQ Cancer Genetics Reference Committee meeting. Discussion continued over email and document approved for publication with the following changes: 

  • Lifetime risk of cancer statistics updated as per more recent papers.
  • Melanoma removed from cancer risk management guidelines to align with the female BRCA risk management protocols.  
  • References updated 
  • Version number changed to V.5. 
28/08/2019 Protocol title changed from 'Risk management for male BRCA1 or BRCA2 mutation carrier' to 'BRCA1 or BRCA2 – risk management (male)' in accordance with Cancer Genetics Reference Committees' consensus. Version number increased to V.6.

The information contained in this document is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to care or treatment. Any clinician seeking to apply or consult this document is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/656

17 Nov 2019