Summary

Mutations in two genes, BRCA1 and BRCA2, significantly increase a person’s risk of developing breast and ovarian cancer.1 2 Specialists identify these mutations using a blood test in a process known as genetic testing.3 The identification of a BRCA mutation can bolster preventive measures to reduce the risk of a person developing breast or ovarian cancer.2 4 For people with a diagnosed cancer, genetic testing can guide treatment choices and prompt the testing of family members.2 4 Several countries have introduced guidelines and care pathways for genetic testing to identify BRCA mutations.4 5

Challenge

Mutations in two genes, BRCA1 and BRCA2, are linked to an increased risk of several types of cancer.1 2 In women with a BRCA mutation, the risk of developing breast and ovarian cancer is 72% and 40%, respectively, compared with 13% and 1% in women without a mutation.1  Women with BRCA mutations are more likely to develop cancer in both breasts (bilateral breast cancer) and be diagnosed at a young age.6 These diagnoses may be missed by national breast cancer screening programmes that typically target women above the age of 50.7 8

People with a BRCA mutation have a 50% chance of passing it on to their biological children.9 These mutations are more common in people of Ashkenazi Jewish heritage and in families with:

  • women diagnosed with breast cancer before the age of 50
  • women diagnosed with bilateral breast cancer
  • a history of both breast and ovarian cancer
  • men diagnosed with breast cancer
  • multiple cases of breast cancer.10

Solution

Genetic testing for BRCA mutations can inform preventive measures and targeted treatment options for breast and ovarian cancer.4 3 Opting for genetic testing can be a complex and emotional decision, and should be supported by a trained expert.11 Genetic counsellors can discuss a person’s family history and, if needed, the process and implications of genetic testing for the person and their family.10

Healthcare professionals may recommend genetic counselling and testing when indicated by a person’s family history.10 For people without cancer, screening can support preventive measures to reduce their risk.2 4 These may include access to cancer screening at a younger age and risk-reducing medication and surgery, such as preventive mastectomy (removal of breast tissue) or oophorectomies (removal of one or both ovaries).2 10 12

For people with a diagnosis of breast or ovarian cancer, the identification of BRCA mutations can inform decisions about treatment and surgery.2 6 For example, women with cancer in one breast may choose to have a double mastectomy to reduce the risk of tumours spreading.13 14 Some targeted therapies are particularly effective for breast and ovarian cancers linked to BRCA mutations.15 16 Family members may also choose to be tested to determine their risk of developing cancer.17

What has been achieved

Guidance for BRCA mutation genetic testing has been developed by clinical societies, cancer centres and advocacy groups in Australia, Canada, Italy, Japan, Spain, Sweden, the UK and the US.5 18-23 The European Society of Medical Oncology has also introduced European guidelines.24

Several countries have approved genetic testing pathways for BRCA mutations, including Israel, Italy and Sweden (see Table 1).4 18 25

Table 1. Examples of genetic testing pathways for BRCA mutations

Country Pathway
Israel Comprehensive genetic testing is available in 15 public hospitals, with at least one medical genetic specialist and genetic counsellor working at each centre.26 Eligible individuals are first- and second-degree relatives of people with a BRCA mutation and people with ovarian, breast or pancreatic cancer.4 Specialist multidisciplinary clinics provide ongoing care for people with BRCA mutations.26 27
Italy The Emilia-Romagna region introduced 13 referral centres and four specialist hubs to conduct genetic testing for BRCA mutations.28 Women with a high-risk family history or breast cancer at a young age are eligible for referral. Genetic specialists or oncologists trained in genetic counselling provide ongoing support.28
Sweden Large university hospitals offer genetic testing for BRCA mutations for women diagnosed with ovarian cancer or breast cancer before the age of 40.4 18 29 They can self-refer or be referred by their general practitioner. Genetic counsellors and psychologists provide support before and after testing.14 30

Next steps

Researchers are building international databases to study BRCA mutations, which should make it easier to detect who is at highest risk of developing cancer.17

Further information

References:

  1. National Cancer Institute. 2020. BRCA Gene Mutations: Cancer Risk and Genetic Testing. [Updated 19/11/20]. Available here: https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet#how-much-does-an-inherited-harmful-variant-in-brca1-or-brca2-increase-a-womans-risk-of-breast-and-ovarian-cancer
  2. McCarthy AM, Armstrong K. 2014. The role of testing for BRCA1 and BRCA2 mutations in cancer prevention. JAMA internal medicine 174(7): 1023-24
  3. Breast Cancer Now. 2017. Genetic testing for breast cancer risk. [Updated 01/03/17]. Available here: https://breastcancernow.org/information-support/have-i-got-breast-cancer/am-i-risk/breast-cancer-in-families/genetic-testing
  4. The Health Policy Partnership. 2019. Genetic testing for BRCA mutations: A policy paper. London, UK: The Health Policy Partnership
  5. Forbes C, Fayter D, de Kock S, et al. 2019. A systematic review of international guidelines and recommendations for the genetic screening, diagnosis, genetic counseling, and treatment of BRCA-mutated breast cancer. Cancer Manag Res 11: 2321-37
  6. Breast Cancer Now. 2017. Breast cancer family history risk assessment. [Updated 01/03/17]. Available here: https://breastcancernow.org/information-support/have-i-got-breast-cancer/am-i-risk/breast-cancer-in-families/family-history
  7. NHS. 2018. Overview: Breast Cancer Screening. [Updated 27/03/18]. Available here: https://www.nhs.uk/conditions/breast-cancer-screening/
  8. Centers for Disease Control and Prevention. 2020. What is breast cancer screening? [Updated 14/09/20]. Available here: https://www.cdc.gov/cancer/breast/basic_info/screening.htm
  9. Macmillan Cancer Support. 2018. BRCA Gene. [Updated 28/09/18]. Available here: https://www.macmillan.org.uk/cancer-information-and-support/worried-about-cancer/causes-and-risk-factors/brca-gene
  10. Moyer VA. 2014. Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine 160(4): 271-81
  11. Mella S, Muzzatti B, Dolcetti R, et al. 2017. Emotional impact on the results of BRCA1 and BRCA2 genetic test: an observational retrospective study. Hereditary Cancer in Clinical Practice 15(1): 16
  12. Franceschini G, Di Leone A, Terribile D, et al. 2019. Bilateral prophylactic mastectomy in BRCA mutation carriers: what surgeons need to know. Ann Ital Chir 90: 1-2
  13. Nilsson MP, Winter C, Kristoffersson U, et al. 2017. Efficacy versus effectiveness of clinical genetic testing criteria for BRCA1 and BRCA2 hereditary mutations in incident breast cancer. Fam Cancer 16(2): 187-93
  14. Nilsson M. 2017. Treatment of BRCA1/2-associated breast cancer and identification of mutation carriers among breast cancer patients. Lund, Sweden: Medicine LUFo
  15. Ledermann JA. 2016. PARP inhibitors in ovarian cancer. Ann Oncol 27 Suppl 1: i40-i44
  16. American Association for Cancer Research. 2018. FDA approves first targeted therapeutic for BRCA-mutant breast cancer. [Updated 18/01/18]. Available here: https://www.aacr.org/blog/2018/01/12/fda-approves-first-targeted-therapeutic-for-brca-mutant-breast-cancer/
  17. Lau C, Suther G. 2011. BRCA testing for familial breast cancer. Australian Prescriber 34: 49-51
  18. Regionala Cancercentrum I Samverken. 2015. Äggstockscancer. Nationellt vårdprogram. Stockholm: Regionala Cancercentrum I Samverken
  19. eviQ. 2021. Breast cancer - referring to genetics. [Updated 03/03/21]. Available here: https://www.eviq.org.au/cancer-genetics/referral-guidelines/1620-breast-cancer-referring-to-genetics
  20. Taira N, Arai M, Ikeda M, et al. 2016. The Japanese Breast Cancer Society clinical practice guidelines for epidemiology and prevention of breast cancer, 2015 edition. Breast Cancer 23(3): 343-56
  21. Heisey R, Carroll JC. 2016. Identification and management of women with a family history of breast cancer. Practical guide for clinicians 62(10): 799-803
  22. National Institute for Health and Care Excellence. 2013. Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer. [Updated 20/11/19]. Available here: https://www.nice.org.uk/guidance/cg164/chapter/recommendations
  23. Gori S, Barberis M, Bella MA, et al. 2019. Recommendations for the implementation of BRCA testing in ovarian cancer patients and their relatives. Crit Rev Oncol Hematol 140: 67-72
  24. Balmaña J, Díez O, Rubio IT, et al. 2011. BRCA in breast cancer: ESMO Clinical Practice Guidelines. Annals of Oncology 22: vi31-vi34
  25. The Royal Marsden NHS Foundation Trust. 2013. A beginner's guide to BRCA1 and BRCA2. London, UK: The Royal Marsden NHS Foundation Trust
  26. Zlotogora J. 2014. Genetics and genomic medicine in Israel. Mol Genet Genomic Med 2(2): 85-94
  27. Yerushalmi R, Rizel S, Zoref D, et al. 2016. A Dedicated Follow-Up Clinic for BRCA Mutation Carriers. Isr Med Assoc J 18(9): 549-52
  28. Cortesi L, Baldassarri B, Ferretti S, et al. 2020. A regional population-based hereditary breast cancer screening tool in Italy: First 5-year results. Cancer Med 9(7): 2579-89
  29. orpha.net. 2021. Hereditary breast and ovarian cancer syndrome. Expert centres in Sweden. Available here: https://www.orpha.net/consor/cgi-bin/Clinics_Search_Simple.php?lng=EN
  30. Pestoff R, Ingvoldstad C, Skirton H. 2016. Genetic counsellors in Sweden: their role and added value in the clinical setting. Eur J Hum Genet 24(3): 350-5