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Global Disparities in Breast Cancer Genetics Testing, Counselling and Management

  • C. H. YipEmail author
  • D. G. Evans
  • G. Agarwal
  • I. Buccimazza
  • A. Kwong
  • R. Morant
  • I. Prakash
  • C. Y. Song
  • N. A. Taib
  • C. Tausch
  • O. Ung
  • S. Meterissian
Surgical Symposium Contribution

Abstract

Hereditary breast cancers, mainly due to BRCA1 and BRCA2 mutations, account for only 5–10% of this disease. The threshold for genetic testing is a 10% likelihood of detecting a mutation, as determined by validated models such as BOADICEA and Manchester Scoring System. A 90–95% reduction in breast cancer risk can be achieved with bilateral risk-reducing mastectomy in unaffected BRCA mutation carriers. In patients with BRCA-associated breast cancer, there is a 40% risk of contralateral breast cancer and hence risk-reducing contralateral mastectomy is recommended, which can be performed simultaneously with surgery for unilateral breast cancer. Other options for risk management include surveillance by mammogram and breast magnetic resonance imaging, and chemoprevention with hormonal agents. With the advent of next-generation sequencing and development of multigene panel testing, the cost and time taken for genetic testing have reduced, making it possible for treatment-focused genetic testing. There are also drugs such as the PARP inhibitors that specifically target the BRCA mutation. Risk management multidisciplinary clinics are designed to quantify risk, and offer advice on preventative strategies. However, such services are only possible in high-income settings. In low-resource settings, the prohibitive cost of testing and the lack of genetic counsellors are major barriers to setting up a breast cancer genetics service. Family history is often not well documented because of the stigma associated with cancer. Breast cancer genetics services remain an unmet need in low- and middle-income countries, where the priority is to optimise access to quality treatment.

Notes

References

  1. 1.
    Bray F, McCarron P, Parkin DM (2004) The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res 6:229–239CrossRefGoogle Scholar
  2. 2.
    Kurian AW (2010) BRCA1 and BRCA2 mutations across race and ethnicity: distribution and clinical implications. Curr Opin Obstet Gynecol 22:72–78CrossRefGoogle Scholar
  3. 3.
    Antoniou A, Pharoah PD, Narod S et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72:1117–1130CrossRefGoogle Scholar
  4. 4.
    Daly MB, Pilarski R, Berry M et al (2017) NCCN guidelines insights: genetic/familial high-risk assessment: breast and ovarian, version 2.2017. J Natl Compr Canc Netw 15:9–20CrossRefGoogle Scholar
  5. 5.
    Trujillano D, Weiss ME, Schneider J et al (2015) Next-generation sequencing of the BRCA1 and BRCA2 genes for the genetic diagnostics of hereditary breast and/or ovarian cancer. J Mol Diagn 17:162–170CrossRefGoogle Scholar
  6. 6.
    Easton DF, Pharoah PD, Antoniou AC et al (2015) Gene-panel sequencing and the prediction of breast-cancer risk. N Engl J Med 372:2243–2257CrossRefGoogle Scholar
  7. 7.
    Kean S (2014) Breast cancer. The ‘other’ breast cancer genes. Science 343:1457–1459CrossRefGoogle Scholar
  8. 8.
    McIntosh A, Shaw C, Evans G, Turnbull N, Bahar N, Barclay M, Easton D, Emery J, Gray J, Halpin J, Hopwood P, McKay J, Sheppard C, Sibbering M, Watson W, Wailoo A, Hutchinson A (2004 updated 2006, 2013 and 2017) Clinical guidelines and evidence review for the classification and care of women at risk of familial breast cancer, London: National Collaborating Centre for Primary Care/University of Sheffield. NICE guideline CG164. https://www.nice.org.uk/Guidance/CG164. Accessed 27 Aug 2018
  9. 9.
    Antoniou AC, Cunningham AP, Peto J et al (2008) The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br J Cancer 98:1457–1466CrossRefGoogle Scholar
  10. 10.
    Evans DG, Harkness EF, Plaskocinska I et al (2017) Pathology update to the Manchester Scoring System based on testing in over 4000 families. J Med Genet 54:674–681CrossRefGoogle Scholar
  11. 11.
    Buys SS, Sandbach JF, Gammon A et al (2017) A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes. Cancer 123:1721–1730CrossRefGoogle Scholar
  12. 12.
    Thompson ER, Rowley SM, Li N et al (2016) Panel testing for familial breast cancer: calibrating the tension between research and clinical care. J Clin Oncol 34:1455–1459CrossRefGoogle Scholar
  13. 13.
    Couch FJ, Shimelis H, Hu C et al (2017) Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol 3:1190–1196CrossRefGoogle Scholar
  14. 14.
    Manchanda R, Patel S, Gordeev VS et al (2018) Cost-effectiveness of population-based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 mutation testing in unselected general population women. J Natl Cancer Inst 110:714–725CrossRefGoogle Scholar
  15. 15.
    Carbine NE, Lostumbo L, Wallace J et al (2018) Risk-reducing mastectomy for the prevention of primary breast cancer. Cochrane Database Syst Rev 4:CD002748Google Scholar
  16. 16.
    Kuchenbaecker KB, Hopper JL, Barnes DR et al (2017) Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 317:2402–2416CrossRefGoogle Scholar
  17. 17.
    Folli S, Curcio A, Buggi F et al (2012) Improved sub-areolar breast tissue removal in nipple-sparing mastectomy using hydrodissection. Breast 21:190–193CrossRefGoogle Scholar
  18. 18.
    Colwell AS, Tessler O, Lin AM et al (2014) Breast reconstruction following nipple-sparing mastectomy: predictors of complications, reconstruction outcomes, and 5-year trends. Plast Reconstr Surg 133:496–506CrossRefGoogle Scholar
  19. 19.
    Kotsopoulos J, Huzarski T, Gronwald J et al (2017) Bilateral oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst.  https://doi.org/10.1093/jnci/djw177 Google Scholar
  20. 20.
    FH01 collaborative teams (2010) Mammographic surveillance in women younger than 50 years who have a family history of breast cancer: tumour characteristics and projected effect on mortality in the prospective, single-arm, FH01 study. Lancet Oncol 11:1127–1134CrossRefGoogle Scholar
  21. 21.
    Evans DG, Thomas S, Caunt J et al (2014) Mammographic surveillance in women aged 35–39 at enhanced familial risk of breast cancer (FH02). Fam Cancer 13:13–21CrossRefGoogle Scholar
  22. 22.
    Leach MO, Boggis CR, Dixon AK et al (2005) Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet 365:1769–1778CrossRefGoogle Scholar
  23. 23.
    Evans DG, Kesavan N, Lim Y et al (2014) MRI breast screening in high-risk women: cancer detection and survival analysis. Breast Cancer Res Treat 145:663–672CrossRefGoogle Scholar
  24. 24.
    Maurice A, Evans DG, Affen J et al (2012) Surveillance of women at increased risk of breast cancer using mammography and clinical breast examination: further evidence of benefit. Int J Cancer 131:417–425CrossRefGoogle Scholar
  25. 25.
    Vogel VG, Costantino JP, Wickerham DL et al (2010) Update of the national surgical adjuvant breast and bowel project Study of Tamoxifen and Raloxifene (STAR) P-2 trial: preventing breast cancer. Cancer Prev Res (Phila) 3:696–706CrossRefGoogle Scholar
  26. 26.
    Cuzick J, Sestak I, Cawthorn S et al (2015) Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol 16:67–75CrossRefGoogle Scholar
  27. 27.
    Cuzick J, Sestak I, Forbes JF et al (2014) Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet 383:1041–1048CrossRefGoogle Scholar
  28. 28.
    Smith SG, Sestak I, Forster A et al (2016) Factors affecting uptake and adherence to breast cancer chemoprevention: a systematic review and meta-analysis. Ann Oncol 27:575–590CrossRefGoogle Scholar
  29. 29.
    Trainer AH, Lewis CR, Tucker K et al (2010) The role of BRCA mutation testing in determining breast cancer therapy. Nat Rev Clin Oncol 7:708–717CrossRefGoogle Scholar
  30. 30.
    Metcalfe K, Gershman S, Ghadirian P et al (2014) Contralateral mastectomy and survival after breast cancer in carriers of BRCA1 and BRCA2 mutations: retrospective analysis. BMJ 348:g226CrossRefGoogle Scholar
  31. 31.
    Byrski T, Huzarski T, Dent R et al (2014) Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat 147:401–405CrossRefGoogle Scholar
  32. 32.
    Kaufman B, Shapira-Frommer R, Schmutzler RK et al (2015) Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 33:244–250CrossRefGoogle Scholar
  33. 33.
    Domchek SM, Aghajanian C, Shapira-Frommer R et al (2016) Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. Gynecol Oncol 140:199–203CrossRefGoogle Scholar
  34. 34.
    Meiser B, Quinn VF, Gleeson M et al (2016) When knowledge of a heritable gene mutation comes out of the blue: treatment-focused genetic testing in women newly diagnosed with breast cancer. Eur J Hum Genet 24:1517–1523CrossRefGoogle Scholar
  35. 35.
    Lobb EA, Barlow-Stewart K, Suthers G et al (2010) Treatment-focused DNA testing for newly diagnosed breast cancer patients: some implications for clinical practice. Clin Genet 77:350–354CrossRefGoogle Scholar
  36. 36.
    Kromberg JG, Sizer EB, Christianson AL (2013) Genetic services and testing in South Africa. J Community Genet 4:413–423CrossRefGoogle Scholar
  37. 37.
    Nakamura S, Kwong A, Kim SW et al (2016) Current status of the management of hereditary breast and ovarian cancer in Asia: first report by the Asian BRCA consortium. Public Health Genom 19:53–60CrossRefGoogle Scholar
  38. 38.
    Li ST, Yuen J, Zhou K et al (2017) Impact of subsidies on cancer genetic testing uptake in Singapore. J Med Genet 54:254–259CrossRefGoogle Scholar
  39. 39.
    Yoon SY, Thong MK, Taib NA et al (2011) Genetic counseling for patients and families with hereditary breast and ovarian cancer in a developing Asian country: an observational descriptive study. Fam Cancer 10:199–205CrossRefGoogle Scholar
  40. 40.
    Mohanty D, Das K (2011) Genetic counselling in tribals in India. Indian J Med Res 134:561–571Google Scholar
  41. 41.
    Murff HJ, Byrne D, Syngal S (2004) Cancer risk assessment: quality and impact of the family history interview. Am J Prev Med 27:239–245Google Scholar
  42. 42.
    Wood ME, Kadlubek P, Pham TH et al (2014) Quality of cancer family history and referral for genetic counseling and testing among oncology practices: a pilot test of quality measures as part of the American Society of Clinical Oncology Quality Oncology Practice Initiative. J Clin Oncol 32:824–829CrossRefGoogle Scholar
  43. 43.

Copyright information

© Société Internationale de Chirurgie 2019

Authors and Affiliations

  • C. H. Yip
    • 1
    Email author
  • D. G. Evans
    • 2
  • G. Agarwal
    • 3
  • I. Buccimazza
    • 4
  • A. Kwong
    • 5
  • R. Morant
    • 6
  • I. Prakash
    • 7
  • C. Y. Song
    • 8
  • N. A. Taib
    • 9
  • C. Tausch
    • 10
  • O. Ung
    • 11
  • S. Meterissian
    • 7
  1. 1.Department of SurgeryRamsay Sime Darby Health CareSubang JayaMalaysia
  2. 2.NIHR Manchester Biomedical Research Centre, Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and HealthUniversity of Manchester, Manchester Academic Health Science CentreManchesterUK
  3. 3.Department of Endocrine and Breast SurgerySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
  4. 4.Department of Surgery, Nelson R Mandela School of MedicineUniversity of KwaZulu-NatalDurbanSouth Africa
  5. 5.Department of SurgeryUniversity of Hong KongHong KongHong Kong
  6. 6.Tumour and Breast CentreSt GallenSwitzerland
  7. 7.Department of SurgeryMcGill University Health CenterMontrealCanada
  8. 8.University of GalwayGalwayIreland
  9. 9.Department of SurgeryUniversity of MalayaKuala LumpurMalaysia
  10. 10.Department of SurgeryBreast-Center ZurichZurichSwitzerland
  11. 11.Department of SurgeryUniversity of QueenslandBrisbaneAustralia

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