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International Journal of Clinical Oncology

, Volume 23, Issue 1, pp 45–51 | Cite as

Management of hereditary breast and ovarian cancer

Invited Review Article

Abstract

Hereditary breast and ovarian cancer (HBOC) syndrome represents 5−10% of all breast cancers. In Japan, the HBOC syndrome is frequently diagnosed in patients with breast cancer. Therefore, a treatment strategy combining a plan for existing breast cancer and for reduction of future breast and ovarian cancer risk is necessary. Breast cancer risk-reducing management involves three options—surveillance, chemoprevention, and risk-reducing mastectomy (RRM). RRM can prevent >90% of new breast cancers. Ovarian cancer risk management options are more limited, and risk-reduction salpingo-oophorectomy is the only option since there is no proven effective early detection method available. The local recurrence rate following breast-conserving surgery in BRCA1/2 mutation-associated breast cancer is not significantly higher than that in sporadic breast cancer. Furthermore, there is no difference in prognosis between surgical methods. Clinicians should inform patients that there are no data on long-term monitoring and fully discuss risks of re-developing breast cancer with patients when choosing the surgical method. In HBOC, BRCA1/2 mutations lead to failure of double-strand DNA break repair, with poly ADP-ribose polymerase (PARP) playing an important role in single-strand DNA nick repair. Use of PARP inhibitors in HBOC prevents DNA repair (synthetic lethality) leading to cell death. This review summarizes management of the HBOC syndrome based on recent evidence.

Keywords

Hereditary breast and ovarian cancer (HBOC) syndrome BRCA1 BRCA2 Risk-reduction mastectomy (RRM) Risk-reduction salpingo-oophorectomy (RRSO) PARP inhibitor 

Notes

Compliance with ethical standards

Conflict of interest

Hideko Yamauchi received lecture fees from Taiho Pharma.

References

  1. 1.
    Ford D et al (1994) Risks of cancer in BRCA1-mutation carriers. Lancet 343:692–695.  https://doi.org/10.1016/S0140-6736(94)91578-4 CrossRefPubMedGoogle Scholar
  2. 2.
    Ford D, Easton DF, Stratton M et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. Am J Hum Genet 62:676–689. https://doi.org/10.1086/301749
  3. 3.
    Easton DF, Ford D, Bishop DT (1995) Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet 56:265–271.  https://doi.org/10.1002/ajmg.1320560305 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Kasner E, Hunter CA, Ph D et al (2013) NIH public access 70:646–656.  https://doi.org/10.1002/ana.22528.Toll-like Google Scholar
  5. 5.
    Valachis A, Nearchou AD, Lind P (2014) Surgical management of breast cancer in BRCA-mutation carriers: a systematic review and meta-analysis. Breast Cancer Res Treat.  https://doi.org/10.1007/s10549-014-2890-1 PubMedGoogle Scholar
  6. 6.
    Graeser MK, Engel C, Rhiem K et al (2009) Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol.  https://doi.org/10.1200/JCO.2008.19.9430 PubMedGoogle Scholar
  7. 7.
    Metcalfe K, Gershman S, Lynch HT et al (2011) Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer.  https://doi.org/10.1038/bjc.2011.120 Google Scholar
  8. 8.
    NCCN. NCCN clinical practice guidelines in oncology (NCCN Guidelines®) genetic/familial high-risk assecessment: breast and ovarian version 2. 2017, pp 1–77Google Scholar
  9. 9.
    Pijpe A, Andrieu N, Easton DF et al (2012) Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK). BMJ 345:e5660.  https://doi.org/10.1136/bmj.e5660 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Breast E, Trialists C, Group C (1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet 351:1451–1467CrossRefGoogle Scholar
  11. 11.
    King MC, Wieand S, Hale K et al (2001) Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA.  https://doi.org/10.1001/jama.286.18.2251 Google Scholar
  12. 12.
    Cauley JA, Norton L, Lippman ME et al (2001) Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Breast Cancer Res Treat.  https://doi.org/10.1023/A:1006478317173 PubMedGoogle Scholar
  13. 13.
    Martino S, Cauley JA, Barrett-Connor E et al (2004) Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst.  https://doi.org/10.1093/jnci/djh319 PubMedGoogle Scholar
  14. 14.
    Vogel VG, Costantino JP, Wickerham DL et al (2006) Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA.  https://doi.org/10.1001/jama.295.23.joc60074 Google Scholar
  15. 15.
    Heemskerk-Gerritsen BAM, Rookus MA, Aalfs CM et al (2015) Improved overall survival after contralateral risk-reducing mastectomy in brca1/2 mutation carriers with a history of unilateral breast cancer: a prospective analysis. Int J Cancer.  https://doi.org/10.1002/ijc.29032 PubMedGoogle Scholar
  16. 16.
    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.  https://doi.org/10.1093/jnci/djn442 PubMedPubMedCentralGoogle Scholar
  17. 17.
    Domchek SM, Friebel TM, Singer CF et al (2010) Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 304:967–975CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Finch APM, Lubinski J, Møller P et al (2014) Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. J Clin Oncol 32:1547–1553.  https://doi.org/10.1200/JCO.2013.53.2820 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Zakhour M, Danovitch Y, Lester J et al (2016) Occult and subsequent cancer incidence following risk-reducing surgery in BRCA mutation carriers. Gynecol Oncol.  https://doi.org/10.1016/j.ygyno.2016.08.336 Google Scholar
  20. 20.
    Yamauchi H (2016) Merits and demerits of practice for hereditary breast and ovarian cancer syndrome (advices and issues). In: Toi M, Winer E, Benson J, Klimberg S (eds) Personalized treatment of breast cancer. Springer Japan, Tokyo, pp 33–45.  https://doi.org/10.1007/978-4-431-55552-0_3 Google Scholar
  21. 21.
    Rebbeck TR, Levin AM, Eisen A et al (1999) Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. J Natl Cancer Inst.  https://doi.org/10.1093/jnci/91.17.1475 Google Scholar
  22. 22.
    Rebbeck TR, Lynch HT, Neuhausen SL et al (2002) Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 346:1616–1622.  https://doi.org/10.1056/NEJMoa012158 CrossRefPubMedGoogle Scholar
  23. 23.
    Kauff ND, Satagopan JM, Robson ME et al (2002) Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med.  https://doi.org/10.1056/NEJMoa020119 PubMedGoogle Scholar
  24. 24.
    Finch A, Beiner M, Lubinski J et al (2006) Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation. JAMA.  https://doi.org/10.1001/jama.296.2.185 PubMedGoogle Scholar
  25. 25.
    Kramer JL, Velazquez IA, Chen BE et al (2005) Prophylactic oophorectomy reduces breast cancer penetrance during prospective, long-term follow-up of BRCA1 mutation carriers. J Clin Oncol 23:8629–8635.  https://doi.org/10.1200/JCO.2005.02.9199 CrossRefPubMedGoogle Scholar
  26. 26.
    Domchek S, Friebel T, Neuhausen S (2006) Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study. Lancet Oncol.  https://doi.org/10.1016/S1470-2045(06)70585-X Google Scholar
  27. 27.
    Chang-Claude J, Andrieu N, Rookus M et al (2007) Age at menarche and menopause and breast cancer risk in the International BRCA1/2 Carrier Cohort Study. Cancer Epidemiol Biomark Prev.  https://doi.org/10.1158/1055-9965.EPI-06-0829 Google Scholar
  28. 28.
    Eisen A, Lubinski J, Klijn J et al (2005) Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol.  https://doi.org/10.1200/JCO.2004.00.7138 Google Scholar
  29. 29.
    Kauff ND, Domchek SM, Friebel TM et al (2008) Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol.  https://doi.org/10.1200/JCO.2007.13.9626 PubMedCentralGoogle Scholar
  30. 30.
    Giusti RM, Rutter JL, Duray PH et al (2003) A twofold increase in BRCA mutation related prostate cancer among Ashkenazi Israelis is not associated with distinctive histopathology. J Med Genet.  https://doi.org/10.1136/jmg.40.10.787 PubMedPubMedCentralGoogle Scholar
  31. 31.
    Heemskerk-Gerritsen BAM, Seynaeve C, Van Asperen CJ et al (2015) Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. J Natl Cancer Inst.  https://doi.org/10.1093/jnci/djv033 PubMedCentralGoogle Scholar
  32. 32.
    Robson ME, Chappuis PO, Satagopan J et al (2004) A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment. Breast Cancer Res.  https://doi.org/10.1186/bcr.658 PubMedGoogle Scholar
  33. 33.
    Kirova YM, Stoppa-Lyonnet D, Savignoni A et al (2005) Risk of breast cancer recurrence and contralateral breast cancer in relation to BRCA1 and BRCA2 mutation status following breast-conserving surgery and radiotherapy. Eur J Cancer 41:2304–2311.  https://doi.org/10.1016/j.ejca.2005.02.037 CrossRefPubMedGoogle Scholar
  34. 34.
    Brekelmans CT, Tilanus-Linthorst MM, Seynaeve C et al (2007) Tumour characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, BRCA1- and non-BRCA1/2 families as compared to sporadic breast cancer cases. Eur J Cancer 43:867–876.  https://doi.org/10.1016/J.EJCA.2006.12.009 CrossRefPubMedGoogle Scholar
  35. 35.
    Pierce LJ, Levin AM, Rebbeck TR et al (2006) Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol.  https://doi.org/10.1200/JCO.2005.02.7888 Google Scholar
  36. 36.
    Haffty BG, Harrold E, Khan AJ et al (2002) Outcome of conservatively managed early onset breast cancer by BRCA1/2 status. Lancet.  https://doi.org/10.1016/S0140-6736(02)08434-9 PubMedGoogle Scholar
  37. 37.
    Pierce LJ, Phillips KA, Griffith KA et al (2010) Local therapy in BRCA1 and BRCA2 mutation carriers with operable breast cancer: comparison of breast conservation and mastectomy. Breast Cancer Res Treat.  https://doi.org/10.1007/s10549-010-0894-z Google Scholar
  38. 38.
    Bernier J, Poortmans P (2015) Clinical relevance of normal and tumour cell radiosensitivity in BRCA1/BRCA2 mutation carriers: a review. Breast 24:100–106.  https://doi.org/10.1016/j.breast.2014.12.003 CrossRefPubMedGoogle Scholar
  39. 39.
    Templeton AJ, Gonzalez LD, Vera-Badillo FE et al (2016) Interaction between hormonal receptor status, age and survival in patients with BRCA1/2 germline mutations: a systematic review and meta-regression. PLoS One.  https://doi.org/10.1371/journal.pone.0154789 Google Scholar
  40. 40.
    Arun B, Bayraktar S, Liu DD et al (2011) Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers: a single-institution experience. J Clin Oncol.  https://doi.org/10.1200/JCO.2011.35.2682 PubMedPubMedCentralGoogle Scholar
  41. 41.
    Narod SA, Metcalfe K, Lynch HT et al (2013) Should all BRCA1 mutation carriers with stage I breast cancer receive chemotherapy? Breast Cancer Res Treat.  https://doi.org/10.1007/s10549-013-2429-x PubMedCentralGoogle Scholar
  42. 42.
    Chabalier C, Lamare C, Racca C et al (2006) BRCA1 downregulation leads to premature inactivation of spindle checkpoint and confers paclitaxel resistance. Cell Cycle.  https://doi.org/10.4161/cc.5.9.2726 PubMedGoogle Scholar
  43. 43.
    Zhou C, Smith JL, Liu J (2003) Role of BRCA1 in cellular resistance to paclitaxel and ionizing radiation in an ovarian cancer cell line carrying a defective BRCA1. Oncogene.  https://doi.org/10.1038/sj.onc.1206319 Google Scholar
  44. 44.
    Byrski T, Gronwald J, Huzarski T et al (2010) Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol.  https://doi.org/10.1200/JCO.2008.20.7019 PubMedGoogle Scholar
  45. 45.
    Schreiber V, Dantzer F, Ame J-C et al (2006) Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol.  https://doi.org/10.1038/nrm1963 PubMedGoogle Scholar
  46. 46.
    Gelmon KA, Tischkowitz M, Mackay H et al (2011) Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol.  https://doi.org/10.1016/s1470-2045(11)70214-5 PubMedGoogle Scholar
  47. 47.
    Robson ME, Im S-A, Senkus E et al (2017) OlympiAD: phase III trial of olaparib monotherapy versus chemotherapy for patients (pts) with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm). J Clin Oncol 35:LBA4.  https://doi.org/10.1200/JCO.2017.35.18_suppl.LBA4 CrossRefGoogle Scholar
  48. 48.
    Tutt ANJ, Kaufman B, Gelber RD et al OlympiA: a randomized phase III trial of olaparib as adjuvant therapy in patients with high-risk HER2-negative breast cancer (BC) and a germline BRCA1/2 mutation (gBRCAm). ASCO Meet Abstr 2015Google Scholar
  49. 49.
    Pujade-Lauraine E, Ledermann JA, Selle F et al (2017) Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol.  https://doi.org/10.1016/S1470-2045(17)30469-2 PubMedGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2017

Authors and Affiliations

  1. 1.Department of Breast Surgical OncologySt. Luke’s Internation HospitalTokyoJapan

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