Prognosis of BRCA-associated breast cancer: a summary of evidence

  • L. BordeleauEmail author
  • S. Panchal
  • P. Goodwin


The purpose of the study is to review the clinical studies relevant to the prognosis and prognostic associations of BRCA1- and BRCA2-associated breast cancers. Reports of relevant studies obtained from a MEDLINE search and references from these articles were critically reviewed. A number of methodologic limitations have been identified in the early studies. More recent studies have failed to demonstrate, for the most part, a significant overall survival difference between BRCA-associated breast cancers and sporadic breast cancers. The risk of in-breast tumor recurrence also appears to be similar in the first 5 years following a breast cancer diagnosis with apparent increase in the risk after 5 years in one study. Many in-breast tumor recurrences are now considered to be secondcond primary breast cancers. There is a significant increase in the risk of contralateral breast cancers in BRCA mutation carriers with an estimated 10-year risk ranging from 20–40%. The prognosis of BRCA-associated breast cancers appears to be similar to that of sporadic breast cancers based on the current literature. Future data from large prospective cohort studies will be of interest.


BRCA1 BRCA2 Breast Cancer Prognosis 


  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 72:1117–1130CrossRefPubMedGoogle Scholar
  2. 2.
    Narod SA, Foulkes WD (2004) BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer 4:665–676CrossRefPubMedGoogle Scholar
  3. 3.
    Eisinger F, Nogues C, Birnbaum D, Jacquemier J, Sobol H (1998) Low frequency of lymph-node metastasis in BRCA1-associated breast cancer. Lancet 351:1633–1634CrossRefPubMedGoogle Scholar
  4. 4.
    Atchley DP, Albarracin CT, Lopez A, Valero V, Amos CI, Gonzalez-Angulo AM et al (2008) Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer. J Clin Oncol 26:4282–4288CrossRefPubMedGoogle Scholar
  5. 5.
    Hedenfalk I, Duggan D, Chen Y, Radmacher M, Bittner M, Simon R et al (2001) Gene-expression profiles in hereditary breast cancer. N Engl J Med 344:539–548CrossRefPubMedGoogle Scholar
  6. 6.
    Palacios J, Honrado E, Osorio A, Cazorla A, Sarrio D, Barroso A et al (2003) Immunohistochemical characteristics defined by tissue microarray of hereditary breast cancer not attributable to BRCA1 or BRCA2 mutations: differences from breast carcinomas arising in BRCA1 and BRCA2 mutation carriers. Clin Cancer Res 9:3606–3614PubMedGoogle Scholar
  7. 7.
    Lakhani SR, Jacquemier J, Sloane JP, Gusterson BA, Anderson TJ, van de Vijver MJ et al (1998) Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst 90:1138–1145CrossRefPubMedGoogle Scholar
  8. 8.
    Albano WA, Recabaren JA, Lynch HT, Campbell AS, Mailliard JA, Organ CH et al (1982) Natural history of hereditary cancer of the breast and colon. Cancer 50:360–363CrossRefPubMedGoogle Scholar
  9. 9.
    Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B et al (1990) Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250:1684–1689CrossRefPubMedGoogle Scholar
  10. 10.
    Narod SA, Feunteun J, Lynch HT, Watson P, Conway T, Lynch J et al (1991) Familial breast-ovarian cancer locus on chromosome 17q12–q23. Lancet 338:82–83CrossRefPubMedGoogle Scholar
  11. 11.
    Hall JM, Friedman L, Guenther C, Lee MK, Weber JL, Black DM et al (1992) Closing in on a breast cancer gene on chromosome 17q. Am J Hum Genet 50:1235–1242PubMedGoogle Scholar
  12. 12.
    Porter DE, Dixon M, Smyth E, Steel CM (1993) Breast cancer survival in BRCA1 carriers. Lancet 341:184–185CrossRefPubMedGoogle Scholar
  13. 13.
    Porter DE, Cohen BB, Wallace MR, Smyth E, Chetty U, Dixon JM et al (1994) Breast cancer incidence, penetrance and survival in probable carriers of BRCA1 gene mutation in families linked to BRCA1 on chromosome 17q12–21. Br J Surg 81:1512–1515CrossRefPubMedGoogle Scholar
  14. 14.
    Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N et al (1994) Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12–13. Science 265:2088–2090CrossRefPubMedGoogle Scholar
  15. 15.
    Marcus JN, Watson P, Page DL, Narod SA, Lenoir GM, Tonin P et al (1996) Hereditary breast cancer: pathobiology, prognosis, and BRCA1 and BRCA2 gene linkage. Cancer 77:697–709CrossRefPubMedGoogle Scholar
  16. 16.
    Johannsson OT, Ranstam J, Borg A, Olsson H (1998) Survival of BRCA1 breast and ovarian cancer patients: a population-based study from southern Sweden. J Clin Oncol 16:397–404PubMedGoogle Scholar
  17. 17.
    Lynch HT, Watson P (1998) BRCA1, pathology, and survival. J Clin Oncol 16:395–396PubMedGoogle Scholar
  18. 18.
    Ansquer Y, Gautier C, Fourquet A, Asselain B, Stoppa-Lyonnet D (1998) Survival in early-onset BRCA1 breast-cancer patients. Institut Curie Breast Cancer Group. Lancet 352:541CrossRefPubMedGoogle Scholar
  19. 19.
    Gaffney DK, Brohet RM, Lewis CM, Holden JA, Buys SS, Neuhausen SL et al (1998) Response to radiation therapy and prognosis in breast cancer patients with BRCA1 and BRCA2 mutations. Radiother Oncol 47:129–136CrossRefPubMedGoogle Scholar
  20. 20.
    Pierce LJ, Strawderman M, Narod SA, Oliviotto I, Eisen A, Dawson L et al (2000) Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations. J Clin Oncol 18:3360–3369PubMedGoogle Scholar
  21. 21.
    Verhoog LC, Brekelmans CT, Seynaeve C, van den Bosch LM, Dahmen G, van Geel AN et al (1998) Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet 351:316–321CrossRefPubMedGoogle Scholar
  22. 22.
    Verhoog LC, Brekelmans CT, Seynaeve C, Dahmen G, van Geel AN, Bartels CC et al (1999) Survival in hereditary breast cancer associated with germline mutations of BRCA2. J Clin Oncol 17:3396–3402PubMedGoogle Scholar
  23. 23.
    Loman N, Johannsson O, Bendahl P, Dahl N, Einbeigi Z, Gerdes A et al (2000) Prognosis and clinical presentation of BRCA2-associated breast cancer. Eur J Cancer 36:1365–1373CrossRefPubMedGoogle Scholar
  24. 24.
    Eerola H, Vahteristo P, Sarantaus L, Kyyronen P, Pyrhonen S, Blomqvist C et al (2001) Survival of breast cancer patients in BRCA1, BRCA2, and non-BRCA1/2 breast cancer families: a relative survival analysis from Finland. Int J Cancer 93:368–372CrossRefPubMedGoogle Scholar
  25. 25.
    Goode EL, Dunning AM, Kuschel B, Healey CS, Day NE, Ponder BA et al (2002) Effect of germ-line genetic variation on breast cancer survival in a population-based study. Cancer Res 62:3052–3057PubMedGoogle Scholar
  26. 26.
    Robson M, Gilewski T, Haas B, Levin D, Borgen P, Rajan P et al (1998) BRCA-associated breast cancer in young women. J Clin Oncol 16:1642–1649PubMedGoogle Scholar
  27. 27.
    Robson M, Levin D, Federici M, Satagopan J, Bogolminy F, Heerdt A et al (1999) Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations. J Natl Cancer Inst 91:2112–2117CrossRefPubMedGoogle Scholar
  28. 28.
    Chappuis PO, Kapusta L, Begin LR, Wong N, Brunet JS, Narod SA et al (2000) Germline BRCA1/2 mutations and p27(Kip1) protein levels independently predict outcome after breast cancer. J Clin Oncol 18:4045–4052PubMedGoogle Scholar
  29. 29.
    Lee JS, Wacholder S, Struewing JP, McAdams M, Pee D, Brody LC et al (1999) Survival after breast cancer in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 91:259–263CrossRefPubMedGoogle Scholar
  30. 30.
    Foulkes WD, Wong N, Brunet JS, Begin LR, Zhang JC, Martinez JJ et al (1997) Germ-line BRCA1 mutation is an adverse prognostic factor in Ashkenazi Jewish women with breast cancer. Clin Cancer Res 3:2465–2469PubMedGoogle Scholar
  31. 31.
    Foulkes WD, Chappuis PO, Wong N, Brunet JS, Vesprini D, Rozen F et al (2000) Primary node negative breast cancer in BRCA1 mutation carriers has a poor outcome. Ann Oncol 11:307–313CrossRefPubMedGoogle Scholar
  32. 32.
    Stoppa-Lyonnet D, Ansquer Y, Dreyfus H, Gautier C, Gauthier-Villars M, Bourstyn E et al (2000) Familial invasive breast cancers: worse outcome related to BRCA1 mutations. J Clin Oncol 18:4053–4059PubMedGoogle Scholar
  33. 33.
    Moller P, Borg A, Evans DG, Haites N, Reis MM, Vasen H et al (2002) Survival in prospectively ascertained familial breast cancer: analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy. Int J Cancer 101:555–559CrossRefPubMedGoogle Scholar
  34. 34.
    Hamann U, Sinn HP (2000) Survival and tumor characteristics of German hereditary breast cancer patients. Breast Cancer Res Treat 59:185–192CrossRefPubMedGoogle Scholar
  35. 35.
    Veronesi A, De GC, Magri MD, Lombardi D, Zanetti M, Scuderi C et al (2005) Familial breast cancer: characteristics and outcome of BRCA 1–2 positive and negative cases. BMC Cancer 5:70CrossRefPubMedGoogle Scholar
  36. 36.
    Bonadona V, Dussart-Moser S, Voirin N, Sinilnikova OM, Mignotte H, Mathevet P et al (2007) Prognosis of early-onset breast cancer based on BRCA1/2 mutation status in a French population-based cohort and review. Breast Cancer Res Treat 101:233–245CrossRefPubMedGoogle Scholar
  37. 37.
    Vinodkumar B, Syamala V, Abraham EK, Balakrishnan R, Ankathil R (2007) Germline BRCA1 mutation and survival analysis in familial breast cancer patients in Kerala; South India. J Exp Clin Cancer Res 26:329–336PubMedGoogle Scholar
  38. 38.
    Robson ME, Chappuis PO, Satagopan J, Wong N, Boyd J, Goffin JR 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 6:R8–R17CrossRefPubMedGoogle Scholar
  39. 39.
    Rennert G, Bisland-Naggan S, Barnett-Griness O, Bar-Joseph N, Zhang S, Rennert HS et al (2007) Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med 357:115–123CrossRefPubMedGoogle Scholar
  40. 40.
    Goodwin PJ, Phillips KA, West DW (2007) Prognosis of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med 357:1555CrossRefPubMedGoogle Scholar
  41. 41.
    Roukos DH (2007) Prognosis of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med 357:1555–1556CrossRefPubMedGoogle Scholar
  42. 42.
    Brekelmans CT, Seynaeve C, Menke-Pluymers M, Bruggenwirth HT, Tilanus-Linthorst MM, Bartels CC et al (2006) Survival and prognostic factors in BRCA1-associated breast cancer. Ann Oncol 17:391–400CrossRefPubMedGoogle Scholar
  43. 43.
    Brekelmans CT, Tilanus-Linthorst MM, Seynaeve C, vd OA, Menke-Pluymers MB, Bartels CC et al (2007) Tumour characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, B. Eur J Cancer 43:867–876CrossRefPubMedGoogle Scholar
  44. 44.
    Kriege M, Seynaeve C, Meijers-Heijboer H, Collee JM, Menke-Pluymers MB, Bartels CC et al (2008) Distant disease-free interval, site of first relapse and post-relapse survival in B. Breast Cancer Res Treat 111:303–311CrossRefPubMedGoogle Scholar
  45. 45.
    Moller P, Evans DG, Reis MM, Gregory H, Anderson E, Maehle L et al (2007) Surveillance for familial breast cancer: differences in outcome according to BRCA mutation status. Int J Cancer 121:1017–1020CrossRefPubMedGoogle Scholar
  46. 46.
    Soerjomataram I, Louwman MW, Ribot JG, Roukema JA, Coebergh JW (2008) An overview of prognostic factors for long-term survivors of breast cancer. Breast Cancer Res Treat 107:309–330CrossRefPubMedGoogle Scholar
  47. 47.
    Mai PL, Chatterjee N, Hartge P, Tucker M, Brody L, Struewing JP et al (2009) Potential excess mortality in BRCA1/2 mutation carriers beyond breast, ovarian, prostate, and pancreatic cancers, and melanoma. PLoS One 4:e4812CrossRefPubMedGoogle Scholar
  48. 48.
    Haffty BG, Harrold E, Khan AJ, Pathare P, Smith TE, Turner BC et al (2002) Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status. Lancet 359:1471–1477CrossRefPubMedGoogle Scholar
  49. 49.
    Kirova YM, Stoppa-Lyonnet D, Savignoni A, Sigal-Zafrani B, Fabre N, Fourquet A (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 41:2304–2311CrossRefPubMedGoogle Scholar
  50. 50.
    Pierce LJ, Levin AM, Rebbeck TR, Ben-David MA, Friedman E, Solin LJ 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 24:2437–2443CrossRefPubMedGoogle Scholar
  51. 51.
    Narod SA, Brunet JS, Ghadirian P, Robson M, Heimdal K, Neuhausen SL et al (2000) Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case–control study. Hereditary Breast Cancer Clinical Study Group. Lancet 356:1876–1881CrossRefPubMedGoogle Scholar
  52. 52.
    Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, Warner E et al (2004) Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 22:2328–2335CrossRefPubMedGoogle Scholar
  53. 53.
    van Sprundel TC, Schmidt MK, Rookus MA, Brohet R, van Asperen CJ, Rutgers EJ et al (2005) Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers. Br J Cancer 93:287–292CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  1. 1.Juravinski Cancer Centre, Department of OncologyMcMaster UniversityHamiltonCanada
  2. 2.Department of Nursing OncologyMount Sinai HospitalTorontoCanada
  3. 3.Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity of TorontoTorontoCanada

Personalised recommendations