Familial Cancer

, Volume 11, Issue 3, pp 473–482

Breast and ovarian cancer risk management in a French cohort of 158 women carrying a BRCA1 or BRCA2 germline mutation: patient choices and outcome

  • Pascale This
  • Anne de la Rochefordière
  • Alexia Savignoni
  • Marie Christine Falcou
  • Anne Tardivon
  • Fabienne Thibault
  • Séverine Alran
  • Virgine Fourchotte
  • Alfred Fitoussi
  • Benoit Couturaud
  • Sylvie Dolbeault
  • Remy J. Salmon
  • Brigitte Sigal-Zafrani
  • Bernard Asselain
  • Dominique Stoppa-Lyonnet
Original Article

Abstract

Description of the various modalities of breast and ovarian cancer risk management, patient choices and their outcome in a single-center cohort of 158 unaffected women carrying a BRCA1 or BRCA2 germline mutation. Between 1998 and 2009, 158 unaffected women carrying a BRCA1 or BRCA2 gene mutation were prospectively followed. The following variables were studied: general and gynecological characteristics, data concerning any prophylactic procedures, and data concerning the outcome of these patients. Median age at inclusion was 37 years and median follow-up was 54 months. Among the 156 women who received systematic information about prophylactic mastectomy, 5.3 % decided to undergo surgery within 36 months after disclosure of genetic results. Prophylactic salpingo-oophorectomy was performed in 68 women. Among women in whom follow-up started between the ages of 40 and 50 years, prophylactic salpingo-oophorectomy was performed, within 24 months after start of follow-up, in 83.7 and 52 % of women with BRCA1 and BRCA2 mutations, respectively. Twenty four women developed breast cancer. Ovarian cancer was detected during prophylactic salpingo-oophorectomy in two women (2.9 %). In this cohort of French women carrying BRCA1/2 mutations, prophylactic mastectomy was a rarely used option. However, good compliance with prophylactic salpingo-oophorectomy was observed. This study confirms the high breast cancer risk in these women.

Keywords

Breast cancer Ovarian cancer Prophylactic mastectomy Prophylactic salpingo-oophorectomy BRCA1/2 

Abbreviations

PM

Prophylactic mastectomy

PSO

Prophylactic salpingo-oophorectomy

MRI

Magnetic resonance imaging

References

  1. 1.
    Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL 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 72:1117–1130PubMedCrossRefGoogle Scholar
  2. 2.
    Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25:1329–1333PubMedCrossRefGoogle Scholar
  3. 3.
    Belot A, Velten M, Grosclaude P, Bossard N, Launoy G, Remontet L et al. 2008 Estimation nationale de l’incidence et de la mortalité par cancer en France entre 1980 et 2005. St Maurice (Fra): Institut de Veille sanitaire, décembre 2008. Disponible sur www.invs.sante.fr
  4. 4.
    Eisinger F, Alby N, Bremond A, Dauplat J, Espie M, Janiaud P et al (1998) Recommendations for medical management of hereditary breast and ovarian cancer: the French National Ad Hoc Committee. Ann Oncol 9:939–950PubMedCrossRefGoogle Scholar
  5. 5.
    Eisinger F, Bressac B, Castaigne D, Cottu P, Lansac J, Lefranc J et al (2004) Identification et prise en charge des prédispositions héréditaires aux cancers du sein et de l’ovaire (mise à jour 2004). Bull Cancer 91:219–237PubMedGoogle Scholar
  6. 6.
    Schwartz GF, Hughes KS, Lynch HT, Fabian CJ, Is Fentiman, Me Robson et al (2008) Proceedings of the international consensus conference on breast cancer risk, genetics, and risk management, April, 2007. Cancer 113:2627–2637PubMedCrossRefGoogle Scholar
  7. 7.
    Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD et al (2007) American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 57:75–89PubMedCrossRefGoogle Scholar
  8. 8.
    Warner E, Hill K, Causer P, Plewes D, Jong R, Yaffe M et al (2011) Prospective Study of Breast Cancer Incidence in Women With a BRCA1 or BRCA2 Mutation Under Surveillance With and Without Magnetic Resonance Imaging. J Clin Oncol 29:1664–1669PubMedCrossRefGoogle Scholar
  9. 9.
    Bermejo-Perez MJ, Marquez-Calderon S, Llanos-Mendez A (2007) Effectiveness of preventive interventions in BRCA1/2 gene mutation carriers: a systematic review. Int J Cancer 121:225–231PubMedCrossRefGoogle Scholar
  10. 10.
    Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C et al (2010) Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 304:967–975PubMedCrossRefGoogle Scholar
  11. 11.
    Frost MH, Schaid DJ, Sellers TA, Slezak JM, Arnold PG, Woods JE et al (2000) Long-term satisfaction and psychological and social function following bilateral prophylactic mastectomy. JAMA 284:319–324PubMedCrossRefGoogle Scholar
  12. 12.
    Brandberg Y, Sandelin K, Erikson S, Jurell G, Liljegren A, Lindblom A et al (2008) Psychological reactions, quality of life, and body image after bilateral prophylactic mastectomy in women at high risk for breast cancer: a prospective 1-year follow-up study. J Clin Oncol 26:3943–3949PubMedCrossRefGoogle Scholar
  13. 13.
    Gahm J, Wickman M, Brandberg Y (2010) Bilateral prophylactic mastectomy in women with inherited risk of breast cancer–prevalence of pain and discomfort, impact on sexuality, quality of life and feelings of regret two years after surgery. Breast 19:462–469PubMedCrossRefGoogle Scholar
  14. 14.
    Cuzick J (2005) Aromatase inhibitors for breast cancer prevention. J Clin Oncol 23:1636–1643PubMedCrossRefGoogle Scholar
  15. 15.
    Goss PE, Ingle JN, Ales-Martinez JE, Cheung AM, Chlebowski RT, Wactawski-Wende J et al (2011) Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med 364:2381–2391PubMedCrossRefGoogle Scholar
  16. 16.
    Pujol P, Lasset C, Berthet P, Dugast C, Delaloge S, Fricker JP et al (2012) Uptake of a randomized breast cancer prevention trial comparing letrozole to placebo in BRCA1/2 mutations carriers: the LIBER trial. Fam Cancer 11:77–84PubMedCrossRefGoogle Scholar
  17. 17.
    Woodward ER, Sleightholme HV, Considine AM, Williamson S, Mchugo JM, Cruger DG (2007) Annual surveillance by CA125 and transvaginal ultrasound for ovarian cancer in both high-risk and population risk women is ineffective. BJOG 114:1500–1509PubMedCrossRefGoogle Scholar
  18. 18.
    Inca (2009) Principales recommandations de prise en charge des personnes porteuses d’une mutation de BRCA 1 ou BRCA2 In: http://wwwe-cancerfr/soins/prise-en-charge-specifiques/oncogénétique
  19. 19.
    Rebbeck TR, Kauff ND, Domchek SM (2009) Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 101:80–87PubMedCrossRefGoogle Scholar
  20. 20.
    Stoppa-Lyonnet D, Laurent-Puig P, Essioux L, Pages S, Ithier G, Ligot L et al (1997) BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Institut Curie Breast Cancer Group. Am J Hum Genet 60:1021–1030PubMedGoogle Scholar
  21. 21.
    Gad S, Caux-Moncoutier V, Pages-Berhouet S, Gauthier-Villars M, Coupier I, Pujol P et al (2002) Significant contribution of large BRCA1 gene rearrangements in 120 French breast and ovarian cancer families. Oncogene 21:6841–6847PubMedCrossRefGoogle Scholar
  22. 22.
    Tournier I, Bb Paillerets, Sobol H, Stoppa-Lyonnet D, Lidereau R, Barrois M et al (2004) Significant contribution of germline BRCA2 rearrangements in male breast cancer families. Cancer Res 64:8143–8147PubMedCrossRefGoogle Scholar
  23. 23.
    Weber J, Miserere S, Champ J, Looten R, Stoppa-Lyonnet D, Viovy JL et al (2007) High-throughput simultaneous detection of point mutations and large-scale rearrangements by CE. Electrophoresis 28:4282–4288PubMedCrossRefGoogle Scholar
  24. 24.
    Caux-Moncoutier V, Castera L, Tirapo C, Michaux D, Remon MA, Lauge A et al (2010) EMMA, a cost- and time-effective diagnostic method for simultaneous detection of point mutations and large-scale genomic rearrangements: application to BRCA1 and BRCA2 in 1,525 patients. Hum Mutat 32:325–334CrossRefGoogle Scholar
  25. 25.
    R Development Core Team (2010) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. http://www.R-project.org/
  26. 26.
    Singletary SE, Allred C, Ashley P, Bassett LW, Berry D, Bland KI et al (2002) Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol 20:3628–3636PubMedCrossRefGoogle Scholar
  27. 27.
    Wainberg S, Husted J (2004) Utilization of screening and preventive surgery among unaffected carriers of a BRCA1 or BRCA2 gene mutation. Cancer Epidemiol Biomarkers Prev 13:1989–1995PubMedGoogle Scholar
  28. 28.
    Evans DG, Lalloo F, Ashcroft L, Shenton A, Clancy T, Baildam AD et al (2009) Uptake of risk-reducing surgery in unaffected women at high risk of breast and ovarian cancer is risk, age, and time dependent. Cancer Epidemiol Biomarkers Prev 18:2318–2324PubMedCrossRefGoogle Scholar
  29. 29.
    Scheuer L, Kauff N, Robson M, Kelly B, Barakat R, Satagopan J et al (2002) Outcome of preventive surgery and screening for breast and ovarian cancer in BRCA mutation carriers. J Clin Oncol 20:1260–1268PubMedCrossRefGoogle Scholar
  30. 30.
    Lodder LN, Frets PG, Trijsburg RW, Meijers-Heijboer EJ, Klijn JG, Seynaeve C et al (2002) One year follow-up of women opting for presymptomatic testing for BRCA1 and BRCA2: emotional impact of the test outcome and decisions on risk management (surveillance or prophylactic surgery). Breast Cancer Res Treat 73:97–112PubMedCrossRefGoogle Scholar
  31. 31.
    Julian-Reynier CM, Bouchard LJ, Evans DG, Eisinger FA, Foulkes WD, Kerr B et al (2001) Women’s attitudes toward preventive strategies for hereditary breast or ovarian carcinoma differ from one country to another: differences among English, French, and Canadian women. Cancer 92:959–968PubMedCrossRefGoogle Scholar
  32. 32.
    Julian-Reynier C, Eisinger F, Evans G, Foulkes W, Sobol H (2000) Variation in prophylactic surgery decisions. Lancet 356:1687PubMedCrossRefGoogle Scholar
  33. 33.
    Bradbury AR, Ibe CN, Dignam JJ, Cummings SA, Verp M, White MA et al (2008) Uptake and timing of bilateral prophylactic salpingo-oophorectomy among BRCA1 and BRCA2 mutation carriers. Genet Med 10:161–166PubMedCrossRefGoogle Scholar
  34. 34.
    Rebbeck TR, Friebel T, Wagner T, Lynch HT, Garber JE, Daly MB et al (2005) Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 23:7804–7810PubMedCrossRefGoogle Scholar
  35. 35.
    This P, Salmon RJ, Dolbeault S, De La Rochefordiere A, Sigal-Zafrani B, Stoppa-Lyonnet D (2005) Hormone replacement therapy after prophylactic adnexectomy. Hered Cancer Clin Pract 3:181–182PubMedCrossRefGoogle Scholar
  36. 36.
    Meijers-Heijboer H, Van Geel B, Van Putten WL, Henzen-Logmans SC, Seynaeve C, Menke-Pluymers MB et al (2001) Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 345:159–164PubMedCrossRefGoogle Scholar
  37. 37.
    Milne RL, Antoniou AC (2011) Genetic modifiers of cancer risk for BRCA1 and BRCA2 mutation carriers. Ann Oncol 22(Suppl 1):i11–i17PubMedCrossRefGoogle Scholar
  38. 38.
    Finch A, Beiner M, Lubinski J, Lynch HT, Moller P, Rosen B et al (2006) Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation. JAMA 296:185–192PubMedCrossRefGoogle Scholar
  39. 39.
    Laki F, Kirova YM, This P, Plancher C, Asselain B, Sastre X et al (2007) Prophylactic salpingo-oophorectomy in a series of 89 women carrying a BRCA1 or a BRCA2 mutation. Cancer 109:1784–1790PubMedCrossRefGoogle Scholar
  40. 40.
    Robson M, Offit K (2007) Clinical practice. Management of an inherited predisposition to breast cancer. N Engl J Med 357:154–162PubMedCrossRefGoogle Scholar
  41. 41.
    Kurian AW, Sigal BM, Plevritis SK (2010) Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers. J Clin Oncol 28:222–231PubMedCrossRefGoogle Scholar
  42. 42.
    Grann VR, Patel PR, Jacobson JS, Warner E, Df Heitjan, Ashby-Thompson M et al (2011) Comparative effectiveness of screening and prevention strategies among BRCA1/2-affected mutation carriers. Breast Cancer Res Treat 125:837–847PubMedCrossRefGoogle Scholar
  43. 43.
    Trainer AH, Lewis CR, Tucker K, Meiser B, Friedlander M, Ward RL (2010) The role of BRCA mutation testing in determining breast cancer therapy. Nat Rev Clin Oncol 7:708–717PubMedCrossRefGoogle Scholar
  44. 44.
    Metcalfe KA, Poll A, O’connor A, Gershman S, Armel S, Finch A et al (2007) Development and testing of a decision aid for breast cancer prevention for women with a BRCA1 or BRCA2 mutation. Clin Genet 72:208–217PubMedCrossRefGoogle Scholar
  45. 45.
    Landsbergen KM, Prins JB, Kamm YJ, Brunner HG, Hoogerbrugge N (2010) Female BRCA mutation carriers with a preference for prophylactic mastectomy are more likely to participate an educational-support group and to proceed with the preferred intervention within 2 years. Fam Cancer 9:213–220PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Pascale This
    • 1
  • Anne de la Rochefordière
    • 2
  • Alexia Savignoni
    • 3
  • Marie Christine Falcou
    • 3
  • Anne Tardivon
    • 4
  • Fabienne Thibault
    • 4
  • Séverine Alran
    • 5
  • Virgine Fourchotte
    • 5
  • Alfred Fitoussi
    • 5
  • Benoit Couturaud
    • 5
  • Sylvie Dolbeault
    • 6
  • Remy J. Salmon
    • 5
  • Brigitte Sigal-Zafrani
    • 1
    • 7
  • Bernard Asselain
    • 3
  • Dominique Stoppa-Lyonnet
    • 1
    • 8
  1. 1.Department of Tumor BiologyInstitut CurieParis cedex 05France
  2. 2.Department of Radiation OncologyInstitut CurieParisFrance
  3. 3.Department of BiostatisticsInstitut CurieParisFrance
  4. 4.Department of RadiologyInstitut CurieParisFrance
  5. 5.Department of Breast SurgeryInstitut CurieParisFrance
  6. 6.Department of Psycho-OncologyInstitut CurieParisFrance
  7. 7.Head of the Institut Curie Breast GroupParisFrance
  8. 8.Université Paris Descartes, Sorbonne Paris CitéParisFrance

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