BRCA1 or BRCA2 – risk management (male)

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

• Known or obligate male BRCA1 pathogenic variant carrier with no personal history of cancer
• Known or obligate male BRCA2 pathogenic variant carrier with no personal history of cancer
• Male at 50% risk of being a BRCA1 or BRCA2 pathogenic variant carrier with no personal history of cancer

Exclusion criteria

• Known female BRCA1 or BRCA2 pathogenic variant carrier with no personal history of cancer - see BRCA1 or BRCA2 – risk management (female)
• BRCA1 or BRCA2 pathogenic variant carrier with a personal history of cancer
• Individuals with a BRCA1 or BRCA2 variant of uncertain significance
• Individuals with Fanconi anaemia due to biallelic BRCA1 or BRCA2 pathogenic variants are NOT covered by this protocol

Cancer/tumour type	Average risk for BRCA1 pathogenic variant carrier*	Average risk for BRCA2 pathogenic variant carrier	General male population risk**
Breast	0.4% to age 80 years (95% CI, 0.1% to 1.5%)r	3.8% to age 80 years (95% CI, 1.9% to 7.7%)r	0.15% to age 80 years
Prostate	Possible increase in risk 21% to age 75 years (95% CI, 13% to 34%)rr	26.9% to age 80 years (95% CI, 20.5% to 34.7%)r	12.6% to age 75 years 16.3% to age 80 years
Pancreatic	<3%rr	<4%rr	1.4% to age 80 years

^* These are average risks. An individual’s risk can be substantially more or less than average depending on other factors (e.g. family history and non-genetic (lifestyle) factors) 
^** Source: Australian Institute of Health and Welfare (AIHW) 2022 Cancer Data in Australia; Canberra: AIHW. <https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/contents/cancer-risk-data-visualisation>. (2018 data, unadjusted for competing mortality)

Breast cancer

Surveillance

Routine mammographic screening is not recommended in males with a BRCA1 or BRCA2 pathogenic variant. Although recent studies have demonstrated that mammography can detect clinically occult breast cancers in high-risk men, further research is needed to assess the value of this screening strategy.^r There have been no trials to evaluate the effectiveness of manual palpation. 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 male breast cancer occurring in individuals without a BRCA pathogenic variant.^r

Prostate cancer

Surveillance

Pathogenic variants in the BRCA1 and BRCA2 genes have been widely linked with increased prostate cancer risk. The evidence for increased risk is stronger for males with pathogenic variants in BRCA2.^rrr A recent study did not find an elevated prostate cancer risk in BRCA1 pathogenic variant carriers.^r

In the general population surveillance can be associated with overdiagnosis and overtreatment with no evidence for improved short-term survival (10-year period). There is evidence for value in surveillance of men with BRCA pathogenic variants,^r as data suggests that BRCA-related prostate cancer is aggressive and occurs at a younger age than sporadic prostate cancer.^rr

Pancreatic cancer

Surveillance

Some studies suggest offering surveillance from age 50 years in BRCA1 or BRCA2 germline pathogenic variant carriers with a first- or second-degree relative with pancreatic cancer. Studies suggest surveillance can achieve ‘downstaging’ at diagnosis, although advanced interval cancers are common, and there is no evidence for improved survival. However, in one recently published screening study of patients at high risk of developing pancreatic cancer, most screen-detected pancreatic cancers were stage I with favourable long-term outcomes.^r

If surveillance is offered it should be undertaken in an experienced high-volume centre after detailed discussion regarding limitations of screening including cost, high incidence of benign or indeterminate pancreatic abnormalities and uncertainties about the benefit. Most small cystic lesions found on screening will not warrant biopsy, surgical resection, or any other intervention.

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

Read abstract

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.

Version 10

Date	Summary of changes
01/08/2023	Protocol reviewed at March 2023 cancer genetics reference committee meeting. Discussions continued via email and MS Teams. Approved for publication with the following changes made:  Flag added to top of protocol Target population: minor wording changes Lifetime risk of cancer/tumour: Cancer risk figures updated for BRCA1 and BRCA2 General population cancer risk figures updated with AIHW 2018 data Cancer risk management guidelines: Wording updated in template sentences above table Multiple changes to recommendations in the table - refer to PDF of previous table to compare changes  Evidence for risk management guidelines: Prostate cancer: evidence updated Pancreatic cancer: evidence updated Version increased to V.10. Review in 2 years.
08/08/2024	Added to Exclusion criteria "Individuals with Fanconi anaemia due to biallelic BRCA1 or BRCA2 pathogenic variants are NOT covered by this protocol"

Version 9

Date

Summary of changes

13/02/2023

The following sections of the document were updated to align with the new eviQ cancer genetics risk management template: Summary: Template sentence updated.  Target population: Added to exclusion criteria "Individual with a variant of uncertain significance". Cancer/tumour risk management guidelines: Template sentence updated.  Lifestyle factors sentence moved above table. Version number increased to V.9.

Version 8

Date	Summary of changes
02/08/2021	Protocol reviewed electronically by cancer genetics reference committee. Approved for publication with the following changes made:  Related pages: link to 'Cancer predisposition genes: population carrier frequency' added Summary: 'prostate cancer' added into first sentence Lifetime risk of cancer table: Prostate cancer risk for BRCA1 and BRCA2 changed to include 'risk to age 65 years', 'risk to age 75 years' and 'risk to age 85 years'  Prostate cancer general population risk changed to include 'risk to age 65 years', 'risk to age 75 years' and 'risk to age 85 years' and figures updated to AIHW 2016 data. Footnote to table added 'Prostate cancer risk is higher if there is a family history of prostate cancer' Cancer risk management guidelines: Template sentence added above table 'The choice of risk management strategy should take into account current age, other health issues and residual cancer risk.'  Breast - Surveillance: removed 'pectoral area palpation on a regular basis' Prostate - Surveillance: minor wording changes Pancreatic - Surveillance (BRCA2): 'No evidence of benefit from surveillance' changed to 'Lack of evidence of benefit from screening. Should be undertaken only as part of clinical trial'  Footnote added: 'Refer to Australian Pancreatic Cancer Genome Initiative for up-to-date screening trials.' and link to website added Evidence for risk management guidelines Breast cancer: added paragraph 'Routine mammographic screening is not recommended...' Prostate cancer: new reference added for 'evidence for value of surveillance in men with BRCA pathogenic variants...' Support and information: template wording updated Website resources: link to 'Australian Pancreatic Cancer Genome' added Protocol version number increased to V.8. Review in 2 years.
11/11/2021	Following feedback from RC members the following change was made to the document and approved by the Chairs:  Lifetime risk of cancer: Prostate cancer- Risk for BRCA2 pathogenic variant carrier: '60% to age 85 years' changed to 'Up to 60% to age 85 years'.
03/06/2022	Protocol updated with the following change: Lifetime risk of cancer/tumour  Pancreatic Cancer - BRCA1: added 'Unknown but unlikely to be increased'

Version 7

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.
3/10/2019	"Mutation" changed to "pathogenic variant" throughout document for consistency among eviQ cancer genetics protocols per agreement among the cancer genetics reference committees' chairs. Definition of "pathogenic variant" added as a pop-up. Version number increased to V.7.