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Individualized preventive and therapeutic management of hereditary breast ovarian cancer syndrome

Abstract

Life-saving, risk-reducing medical interventions are required for women with a BRCA1/2 mutation. Interventions comprise a four-stage approach that involves risk assessment, genetic counseling, gene-mutation analysis and medical intervention strategies. Genetic counseling should be offered at specialized familial breast-cancer clinics and gene-mutation analysis should be recommended on the basis of personal and family-history-based risk criteria. Prophylactic bilateral salpingo-oophorectomy appears to offer the optimal benefit–risk ratio compared with prophylactic bilateral mastectomy, chemoprevention, or intensified surveillance. Tamoxifen is an alternative approach only for BRCA2 mutation carriers. The comprehensive, clinical decision-making Ioannina algorithm provided here can facilitate the complex preventive strategic approach. Newly diagnosed BRCA1/2 carriers might benefit from extensive surgery and a specific pharmacological treatment, but data to support this strategy are limited. Microarray gene-expression studies show that breast tumors from BRCA1 carriers are predominantly of basal subtype (i.e. triple negative) and BRCA2 carriers are of luminal subtype (i.e. estrogen-receptor-positive). Although optimum management of women with familial susceptibility to breast and ovarian cancer has not yet been prospectively validated, data indicate substantial benefits when an individualized evidence-based prevention strategy is provided by an experienced team.

Key Points

  • Genetic testing can identify the BRCA1 and/or BRCA2 mutation carriers who are at the highest risk of developing breast cancer and ovarian cancer in the general population

  • For high-risk women, prophylactic surgery (i.e. bilateral salpingo-oophorectomy or bilateral mastectomy) is more effective and beneficial than close surveillance and chemoprevention but with a higher side-effects profile

  • Women with a family history who test negative for a BRCA1 and/or BRCA2 mutation may benefit from CHEK2 genetic testing and intensive surveillance

  • At the Ioannina University we have developed an integrated algorithm to help in the complex decision process for genetic testing and selection of the best preventive intervention in individual high-risk women

  • For BRCA1 and/or BRCA2 mutation carriers with a breast cancer diagnosis, extensive surgery (i.e. bilateral mastectomy) should be considered, but more data about ipsilateral and contralateral breast recurrence are needed

  • Research on identification of genetic and nongenetic modifiers and BRCA gene-expression profiling hold great promise for guiding optimum prevention and treatment strategies for high-risk women, and should dramatically improve survival and quality of life

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Figure 1: Proposed individualized management algorithm for women at high risk for the hereditary breast ovarian cancer (HBOC) syndrome.

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Acknowledgements

The authors would like to thank Dr Angelos Kappas, Professor of Surgery at Ioannina University for his contribution to concept and content discussions and clinical support, and Dr Dimitrios Trichopoulos, Professor of Cancer Prevention at the Harvard School of Public Health, Boston, Massachusetts and Dr Nikos Pandis, Associate Professor of Medical Genetics, University of Lund Sweden, Head of the Department of Genetics, “Saint Savas” Anticancer Hospital, Athens, Greece, for critical reading of the manuscript and insightful comments. Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Roukos, D., Briasoulis, E. Individualized preventive and therapeutic management of hereditary breast ovarian cancer syndrome. Nat Rev Clin Oncol 4, 578–590 (2007). https://doi.org/10.1038/ncponc0930

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