Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The role of BRCA mutation testing in determining breast cancer therapy

Abstract

Landmark discoveries in the field of breast cancer research include the identification of germline BRCA mutations as a cause of hereditary disease, and the use of gene-expression profiling to identify distinct subtypes of breast cancer. These findings, coupled with the availability of rapid germline testing, make it possible to identify a BRCA mutation carrier contemporaneous with a diagnosis of breast cancer. For the first time, testing for a germline mutation that predisposes to cancer has the potential to influence the immediate surgical, radiotherapeutic, and drug treatment choices of an individual with a new diagnosis of breast cancer. In this Review, we examine the implications of moving germline BRCA mutation testing from highly specialized family cancer clinics to mainstream settings.

Key Points

  • Germline mutations in the BRCA genes predispose carriers to early-onset breast and ovarian cancer

  • With modern technology, rapid BRCA mutation screens are now a possibility and are moving from highly specialized cancer clinics to the mainstream setting

  • A family history of cancer is an influential factor for performing a genetic test, but a test should also be considered in the presence of high-risk features and a triple-negative tumor phenotype

  • Knowledge of BRCA status may alter synchronous and metachronous cancer risk estimates, and influence the management of the patient, including decisions about specific systemic therapy

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Indications for germline testing in a patient presenting with breast cancer.
Figure 2: The implications for management of a BRCA mutation carrier newly diagnosed with breast cancer.

Similar content being viewed by others

References

  1. Ardern-Jones, A., Kenen, R. & Eeles, R. Too much, too soon? Patients and health professionals' views concerning the impact of genetic testing at the time of breast cancer diagnosis in women under the age of 40. Eur. J. Cancer Care (Engl.) 14, 272–281 (2005).

    CAS  Google Scholar 

  2. Antoniou, A. C. et al. The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br. J. Cancer 98, 1457–1466 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Berry, D. A. et al. BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes. J. Clin. Oncol. 20, 2701–2712 (2002).

    Article  CAS  PubMed  Google Scholar 

  4. Evans, D. G., Lalloo, F., Wallace, A. & Rahman, N. Update on the Manchester Scoring System for BRCA1 and BRCA2 testing. J. Med. Genet. 42, e39 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. [No authors listed] American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility. J. Clin. Oncol. 21, 2397–2406 (2003).

  6. Kang, H. H. et al. Evaluation of models to predict BRCA germline mutations. Br. J. Cancer 95, 914–920 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Møller, P. et al. Genetic epidemiology of BRCA mutations—family history detects less than 50% of the mutation carriers. Eur. J. Cancer 43, 1713–1717 (2007).

    PubMed  Google Scholar 

  8. de Sanjosé, S. et al. Prevalence of BRCA1 and BRCA2 germline mutations in young breast cancer patients: a population-based study. Int. J. Cancer 106, 588–593 (2003).

    PubMed  Google Scholar 

  9. Weitzel, J. N. et al. Limited family structure and BRCA gene mutation status in single cases of breast cancer. JAMA 297, 2587–2595 (2007).

    CAS  PubMed  Google Scholar 

  10. Malone, K. E. et al. Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases. Cancer 88, 1393–1402 (2000).

    CAS  PubMed  Google Scholar 

  11. Haffty, B. G., Silber, A., Matloff, E., Chung, J. & Lannin, D. Racial differences in the incidence of BRCA1 and BRCA2 mutations in a cohort of early onset breast cancer patients: African American compared to white women. J. Med. Genet. 43, 133–137 (2006).

    CAS  PubMed  Google Scholar 

  12. Hamann, U. et al. Similar contributions of BRCA1 and BRCA2 germline mutations to early-onset breast cancer in Germany. Eur. J. Hum. Genet. 11, 464–467 (2003).

    CAS  PubMed  Google Scholar 

  13. Robson, M. et al. Prevalence of recurring BRCA mutations among Ashkenazi Jewish women with breast cancer. Genet. Test. 1, 47–51 (1997).

    CAS  PubMed  Google Scholar 

  14. Górski, B. et al. A high proportion of founder BRCA1 mutations in Polish breast cancer families. Int. J. Cancer 110, 683–686 (2004).

    PubMed  Google Scholar 

  15. Verhoog, L. C. et al. Large regional differences in the frequency of distinct BRCA1/BRCA2 mutations in 517 Dutch breast and/or ovarian cancer families. Eur. J. Cancer 37, 2082–2090 (2001).

    CAS  PubMed  Google Scholar 

  16. Perou, C. M. et al. Molecular portraits of human breast tumours. Nature 406, 747–752 (2000).

    CAS  PubMed  Google Scholar 

  17. Sørlie, T. et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl Acad. Sci. USA 98, 10869–10874 (2001).

    PubMed  PubMed Central  Google Scholar 

  18. Reis-Filho, J. S. & Tutt, A. N. Triple negative tumours: a critical review. Histopathology 52, 108–118 (2008).

    CAS  PubMed  Google Scholar 

  19. Cleator, S., Heller, W. & Coombes, R. C. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 8, 235–244 (2007).

    PubMed  Google Scholar 

  20. Lakhani, S. R. et al. Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin. Cancer Res. 11, 5175–5180 (2005).

    CAS  PubMed  Google Scholar 

  21. Foulkes, W. D. et al. Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J. Natl Cancer Inst. 95, 1482–1485 (2003).

    CAS  PubMed  Google Scholar 

  22. Turner, N., Tutt, A. & Ashworth, A. Hallmarks of 'BRCAness' in sporadic cancers. Nat. Rev. Cancer 4, 814–819 (2004).

    CAS  PubMed  Google Scholar 

  23. Mavaddat, N., Rebbeck, T. R., Lakhani, S. R., Easton, D. F. & Antoniou, A. C. Incorporating tumour pathology information into breast cancer risk prediction algorithms. Breast Cancer Res. 12, R28 (2010).

    PubMed  PubMed Central  Google Scholar 

  24. Young, S. R. et al. The prevalence of BRCA1 mutations among young women with triple-negative breast cancer. BMC Cancer 9, 86 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Watson, P. et al. Detecting BRCA2 protein truncation in tissue biopsies to identify breast cancers that arise in BRCA2 gene mutation carriers. J. Clin. Oncol. 27, 3894–3900 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. James, P. A. et al. Optimal selection of individuals for BRCA mutation testing: a comparison of available methods. J. Clin. Oncol. 24, 707–715 (2006).

    CAS  PubMed  Google Scholar 

  27. Metcalfe, K. A. et al. Breast cancer risks in women with a family history of breast or ovarian cancer who have tested negative for a BRCA1 or BRCA2 mutation. Br. J. Cancer 100, 421–425 (2009).

    CAS  PubMed  Google Scholar 

  28. Kauff, N. D. et al. Risk of ovarian cancer in BRCA1 and BRCA2 mutation-negative hereditary breast cancer families. J. Natl Cancer Inst. 97, 1382–1384 (2005).

    CAS  PubMed  Google Scholar 

  29. Haffty, B. G. et al. Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status. Lancet 359, 1471–1477 (2002).

    PubMed  Google Scholar 

  30. Garcia-Etienne, C. A. et al. Breast-conserving surgery in BRCA1/2 mutation carriers: are we approaching an answer? Ann. Surg. Oncol. 16, 3380–3387 (2009).

    PubMed  Google Scholar 

  31. Chappuis, P. O. et al. Germline BRCA1/2 mutations and p27Kip1 protein levels independently predict outcome after breast cancer. J. Clin. Oncol. 18, 4045–4052 (2000).

    CAS  PubMed  Google Scholar 

  32. Robson, M. et al. Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations. J. Natl Cancer Inst. 91, 2112–2117 (1999).

    CAS  PubMed  Google Scholar 

  33. Brekelmans, C. T. et al. Survival and prognostic factors in BRCA1-associated breast cancer. Ann. Oncol. 17, 391–400 (2006).

    CAS  PubMed  Google Scholar 

  34. Haffty, B. G. & Lannin, D. Is breast-conserving therapy in the genetically predisposed breast cancer patient a reasonable and appropriate option? Eur. J. Cancer 40, 1105–1108 (2004).

    CAS  PubMed  Google Scholar 

  35. Pierce, L. J. et al. Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J. Clin. Oncol. 24, 2437–2443 (2006).

    PubMed  Google Scholar 

  36. Verhoog, L. C. et al. Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet 351, 316–321 (1998).

    CAS  PubMed  Google Scholar 

  37. Verhoog, L. C. et al. Survival in hereditary breast cancer associated with germline mutations of BRCA2. J. Clin. Oncol. 17, 3396–3402 (1999).

    CAS  PubMed  Google Scholar 

  38. Foulkes, W. D. et al. Primary node negative breast cancer in BRCA1 mutation carriers has a poor outcome. Ann. Oncol. 11, 307–313 (2000).

    CAS  PubMed  Google Scholar 

  39. Verhoog, L. C., Brekelmans, C. T., Seynaeve, C., Meijers-Heijboer, E. J. & Klijn, J. G. Contralateral breast cancer risk is influenced by the age at onset in BRCA1-associated breast cancer. Br. J. Cancer 83, 384–386 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Graeser, M. K. et al. Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J. Clin. Oncol. 27, 5887–5892 (2009).

    PubMed  Google Scholar 

  41. Robson, M. E. et al. 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–R17 (2004).

    CAS  PubMed  Google Scholar 

  42. Pierce, L. J. et al. Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations. J. Clin. Oncol. 18, 3360–3369 (2000).

    CAS  PubMed  Google Scholar 

  43. Robson, M. et al. Appropriateness of breast-conserving treatment of breast carcinoma in women with germline mutations in BRCA1 or BRCA2: a clinic-based series. Cancer 103, 44–51 (2005).

    PubMed  Google Scholar 

  44. Eccles, D. et al. Familial breast cancer: an investigation into the outcome of treatment for early stage disease. Fam. Cancer 1, 65–72 (2001).

    CAS  PubMed  Google Scholar 

  45. Kirova, Y. M. et al. 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 (2005).

    PubMed  Google Scholar 

  46. Metcalfe, K. et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J. Clin. Oncol. 22, 2328–2335 (2004).

    CAS  PubMed  Google Scholar 

  47. Gronwald, J. et al. Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int. J. Cancer 118, 2281–2284 (2006).

    CAS  PubMed  Google Scholar 

  48. Schwartz, G. F. et al. Proceedings of the international consensus conference on breast cancer risk, genetics, and risk management, April, 2007. Cancer 113, 2627–2637 (2008).

    PubMed  Google Scholar 

  49. Nieuwenhuis, B. et al. BRCA1 and BRCA2 heterozygosity and repair of X-ray-induced DNA damage. Int. J. Radiat. Biol. 78, 285–295 (2002).

    CAS  PubMed  Google Scholar 

  50. Lovelock, P. K. et al. Prediction of BRCA1 and BRCA2 mutation status using post-irradiation assays of lymphoblastoid cell lines is compromised by inter-cell-line phenotypic variability. Breast Cancer Res. Treat. 104, 257–266 (2007).

    CAS  PubMed  Google Scholar 

  51. Gaffney, D. K. et al. Response to radiation therapy and prognosis in breast cancer patients with BRCA1 and BRCA2 mutations. Radiother. Oncol. 47, 129–136 (1998).

    CAS  PubMed  Google Scholar 

  52. Shanley, S. et al. Late toxicity is not increased in BRCA1/BRCA2 mutation carriers undergoing breast radiotherapy in the United Kingdom. Clin. Cancer Res. 12, 7025–7032 (2006).

    CAS  PubMed  Google Scholar 

  53. Leong, T. et al. Mutation analysis of BRCA1 and BRCA2 cancer predisposition genes in radiation hypersensitive cancer patients. Int. J. Radiat. Oncol. Biol. Phys. 48, 959–965 (2000).

    CAS  PubMed  Google Scholar 

  54. Peralta, E. A. et al. Contralateral prophylactic mastectomy improves the outcome of selected patients undergoing mastectomy for breast cancer. Am. J. Surg. 180, 439–445 (2000).

    CAS  PubMed  Google Scholar 

  55. Lostumbo, L., Carbine, N., Wallace, J. & Ezzo, J. Prophylactic mastectomy for the prevention of breast cancer. Cochrane Database of Systematic Reviews, Issue 4. Art. No.: CD002748. doi:10.1002/14651858.CD002748.pub2 (2004).

  56. McDonnell, S. K. et al. Efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer. J. Clin. Oncol. 19, 3938–3943 (2001).

    CAS  PubMed  Google Scholar 

  57. van Sprundel, T. C. et al. Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers. Br. J. Cancer 93, 287–292 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Schwartz, M. D. et al. Impact of BRCA1/BRCA2 counseling and testing on newly diagnosed breast cancer patients. J. Clin. Oncol. 22, 1823–1829 (2004).

    PubMed  Google Scholar 

  59. Evans, D. G. et al. Surgical decisions made by 158 women with hereditary breast cancer aged <50 years. Eur. J. Surg. Oncol. 31, 1112–1118 (2005).

    CAS  PubMed  Google Scholar 

  60. Stolier, A. J., Fuhrman, G. M., Mauterer, L., Bolton, J. S. & Superneau, D. W. Initial experience with surgical treatment planning in the newly diagnosed breast cancer patient at high risk for BRCA-1 or BRCA-2 mutation. Breast J. 10, 475–480 (2004).

    PubMed  Google Scholar 

  61. Tuttle, T. M., Habermann, E. B., Grund, E. H., Morris, T. J. & Virnig, B. A. Increasing use of contralateral prophylactic mastectomy for breast cancer patients: a trend toward more aggressive surgical treatment. J. Clin. Oncol. 25, 5203–5209 (2007).

    PubMed  Google Scholar 

  62. McLaughlin, C. C., Lillquist, P. P. & Edge, S. B. Surveillance of prophylactic mastectomy: trends in use from 1995 through 2005. Cancer 115, 5404–5412 (2009).

    PubMed  Google Scholar 

  63. Anders, C. K. et al. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J. Clin. Oncol. 26, 3324–3330 (2008).

    PubMed  Google Scholar 

  64. Bauer, K. R. et al. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer 109, 1721–1728 (2007).

    PubMed  Google Scholar 

  65. Chetrit, A. et al. Effect of BRCA1/2 mutations on long-term survival of patients with invasive ovarian cancer: the national Israeli study of ovarian cancer. J. Clin. Oncol. 26, 20–25 (2008).

    PubMed  Google Scholar 

  66. Brekelmans, C. T. et al. 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 (2007).

    CAS  PubMed  Google Scholar 

  67. Budroni, M. et al. Role of BRCA2 mutation status on overall survival among breast cancer patients from Sardinia. BMC Cancer 9, 62 (2009).

    PubMed  PubMed Central  Google Scholar 

  68. Bonadona, V. et al. 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, 233–245 (2007).

    CAS  PubMed  Google Scholar 

  69. Eerola, H. et al. 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, 368–372 (2001).

    CAS  PubMed  Google Scholar 

  70. El-Tamer, M. et al. Survival and recurrence after breast cancer in BRCA1/2 mutation carriers. Ann. Surg. Oncol. 11, 157–164 (2004).

    PubMed  Google Scholar 

  71. Goffin, J. R. et al. Impact of germline BRCA1 mutations and overexpression of p53 on prognosis and response to treatment following breast carcinoma: 10-year follow up data. Cancer 97, 527–536 (2003).

    CAS  PubMed  Google Scholar 

  72. Rennert, G. et al. Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N. Engl. J. Med. 357, 115–123 (2007).

    CAS  PubMed  Google Scholar 

  73. Hamann, U. & Sinn, H. P. Survival and tumor characteristics of German hereditary breast cancer patients. Breast Cancer Res. Treat. 59, 185–192 (2000).

    CAS  PubMed  Google Scholar 

  74. Loman, N. et al. Prognosis and clinical presentation of BRCA2-associated breast cancer. Eur. J. Cancer 36, 1365–1373 (2000).

    CAS  PubMed  Google Scholar 

  75. Jóhannsson, O. T., Ranstam, J., Borg, A. & Olsson, H. Survival of BRCA1 breast and ovarian cancer patients: a population-based study from southern Sweden. J. Clin. Oncol. 16, 397–404 (1998).

    PubMed  Google Scholar 

  76. Seynaeve, C. et al. Ipsilateral breast tumour recurrence in hereditary breast cancer following breast-conserving therapy. Eur. J. Cancer 40, 1150–1158 (2004).

    CAS  PubMed  Google Scholar 

  77. Robson, M. et al. BRCA-associated breast cancer in young women. J. Clin. Oncol. 16, 1642–1649 (1998).

    CAS  PubMed  Google Scholar 

  78. Stoppa-Lyonnet, D. et al. Familial invasive breast cancers: worse outcome related to BRCA1 mutations. J. Clin. Oncol. 18, 4053–4059 (2000).

    CAS  PubMed  Google Scholar 

  79. Møller, P. et al. Survival in prospectively ascertained familial breast cancer: analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy. Int. J. Cancer 101, 555–559 (2002).

    PubMed  Google Scholar 

  80. Lee, E. H. et al. Effect of BRCA1/2 mutation on short-term and long-term breast cancer survival: a systematic review and meta-analysis. Breast Cancer Res. Treat. 122, 11–25 (2010).

    CAS  PubMed  Google Scholar 

  81. Eccles, D. et al. Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH): study protocol. BMC Cancer 7, 160 (2007).

    PubMed  PubMed Central  Google Scholar 

  82. Wang, W. Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins. Nat. Rev. Genet. 8, 735–748 (2007).

    CAS  PubMed  Google Scholar 

  83. Jasin, M. Homologous repair of DNA damage and tumorigenesis: the BRCA connection. Oncogene 21, 8981–8993 (2002).

    CAS  PubMed  Google Scholar 

  84. Taniguchi, T. & D'Andrea, A. D. Molecular pathogenesis of Fanconi anemia: recent progress. Blood 107, 4223–4233 (2006).

    CAS  PubMed  Google Scholar 

  85. Howlett, N. G. et al. Biallelic inactivation of BRCA2 in Fanconi anemia. Science 297, 606–609 (2002).

    CAS  PubMed  Google Scholar 

  86. Bhattacharyya, A., Ear, U. S., Koller, B. H., Weichselbaum, R. R. & Bishop, D. K. The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin. J. Biol. Chem. 275, 23899–23903 (2000).

    CAS  PubMed  Google Scholar 

  87. Evers, B. et al. Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281 and cisplatin. Clin. Cancer Res. 14, 3916–3925 (2008).

    CAS  PubMed  Google Scholar 

  88. Byrski, T. et al. Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers. Breast Cancer Res. Treat. 108, 289–296 (2008).

    CAS  PubMed  Google Scholar 

  89. Kurebayashi, J. et al. Loss of BRCA1 expression may predict shorter time-to-progression in metastatic breast cancer patients treated with taxanes. Anticancer Res. 26, 695–701 (2006).

    CAS  PubMed  Google Scholar 

  90. Quinn, J. E. et al. BRCA1 mRNA expression levels predict for overall survival in ovarian cancer after chemotherapy. Clin. Cancer Res. 13, 7413–7420 (2007).

    CAS  PubMed  Google Scholar 

  91. Lee, H. et al. Mitotic checkpoint inactivation fosters transformation in cells lacking the breast cancer susceptibility gene, Brca2. Mol. Cell 4, 1–10 (1999).

    CAS  PubMed  Google Scholar 

  92. Quinn, J. E. et al. BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis. Cancer Res. 63, 6221–6228 (2003).

    CAS  PubMed  Google Scholar 

  93. Byrski, T. et al. Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res. Treat. 115, 359–363 (2009).

    CAS  PubMed  Google Scholar 

  94. Chappuis, P. O. et al. A significant response to neoadjuvant chemotherapy in BRCA1/2 related breast cancer. J. Med. Genet. 39, 608–610 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Hubert, A. et al. Response to neo-adjuvant chemotherapy in BRCA1 and BRCA2 related stage III breast cancer. Fam. Cancer 8, 173–177 (2009).

    CAS  PubMed  Google Scholar 

  96. Wong Wong Keet, A. et al. Long-term outcome after neo-adjuvant chemotherapy for breast cancer in BRCA1/2 carriers. Int. J. Cancer 125, 2236–2238 (2009).

    PubMed  Google Scholar 

  97. Silva, E. & Lynch, H. Genetic counseling and management of newly diagnosed breast cancer patients at genetic risk for BRCA germline mutations. Breast J. 12, 280–281 (2006).

    PubMed  Google Scholar 

  98. Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917–921 (2005).

    CAS  PubMed  Google Scholar 

  99. Fong, P. C. et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N. Engl. J. Med. 361, 123–134 (2009).

    CAS  PubMed  Google Scholar 

  100. Tutt, A. et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 376, 235–244 (2010).

    CAS  PubMed  Google Scholar 

  101. Edwards, S. L. et al. Resistance to therapy caused by intragenic deletion in BRCA2. Nature 451, 1111–1115 (2008).

    CAS  PubMed  Google Scholar 

  102. Chen, S. & Parmigiani, G. Meta-analysis of BRCA1 and BRCA2 penetrance. J. Clin. Oncol. 25, 1329–1333 (2007).

    PubMed  Google Scholar 

  103. Antoniou, A. et al. 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, 1117–1130 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Metcalfe, K. A. et al. The risk of ovarian cancer after breast cancer in BRCA1 and BRCA2 carriers. Gynecol. Oncol. 96, 222–226 (2005).

    CAS  PubMed  Google Scholar 

  105. van der Velde, N. M. et al. Time to stop ovarian cancer screening in BRCA1/2 mutation carriers? Int. J. Cancer 124, 919–923 (2009).

    CAS  PubMed  Google Scholar 

  106. Mourits, M. J. & de Bock, G. H. Managing hereditary ovarian cancer. Maturitas 64, 172–176 (2009).

    CAS  PubMed  Google Scholar 

  107. Higgins, M. J. & Davidson, N. E. What is the current status of ovarian suppression/ablation in women with premenopausal early-stage breast cancer? Curr. Oncol. Rep. 11, 45–50 (2009).

    CAS  PubMed  Google Scholar 

  108. Bianco, A. R. et al. Prognostic role of amenorrhea induced by adjuvant chemotherapy in premenopausal patients with early breast cancer. Br. J. Cancer 63, 799–803 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Castiglione-Gertsch, M. et al. Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: a randomized trial. J. Natl Cancer Inst. 95, 1833–1846 (2003).

    PubMed  Google Scholar 

  110. Eisen, A. et al. Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J. Clin. Oncol. 23, 7491–7496 (2005).

    PubMed  Google Scholar 

  111. Kramer, J. L. et al. Prophylactic oophorectomy reduces breast cancer penetrance during prospective, long-term follow-up of BRCA1 mutation carriers. J. Clin. Oncol. 23, 8629–8635 (2005).

    PubMed  Google Scholar 

  112. Schlich-Bakker, K. J. et al. Short term psychological distress in patients actively approached for genetic counselling after diagnosis of breast cancer. Eur. J. Cancer 42, 2722–2728 (2006).

    PubMed  Google Scholar 

  113. Schlich-Bakker, K. J. et al. BRCA1/2 mutation testing in breast cancer patients: a prospective study of the long-term psychological impact of approach during adjuvant radiotherapy. Breast Cancer Res. Treat. 109, 507–514 (2008).

    CAS  PubMed  Google Scholar 

  114. Schlich-Bakker, K. J., ten Kroode, H. F., Wárlám-Rodenhuis, C. C., van den Bout, J. & Ausems, M. G. Barriers to participating in genetic counseling and BRCA testing during primary treatment for breast cancer. Genet. Med. 9, 766–777 (2007).

    PubMed  Google Scholar 

  115. Wárlám-Rodenhuis, C. C., Koot, V. C., van der Luijt, R. B., Vasen, H. F. & Ausems, M. G. A prospective study on predictive factors linked to the presence of BRCA1 and BRCA2 mutations in breast cancer patients. Eur. J. Cancer 41, 1409–1415 (2005).

    PubMed  Google Scholar 

  116. Weitzel, J. N. et al. Effect of genetic cancer risk assessment on surgical decisions at breast cancer diagnosis. Arch. Surg. 138, 1323–1328 (2003).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

A. H. Trainer, C. R. Lewis and R. L. Ward devised, wrote, and edited the article. B. Meiser, K. Tucker and M. Friedlander contributed substantially to the content of the article through numerous in-depth discussions.

Corresponding author

Correspondence to Alison H. Trainer.

Ethics declarations

Competing interests

M. Friedlander is on the advisory board of AstraZeneca and has also received grant/research support from this company. The other authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Trainer, A., Lewis, C., Tucker, K. et al. The role of BRCA mutation testing in determining breast cancer therapy. Nat Rev Clin Oncol 7, 708–717 (2010). https://doi.org/10.1038/nrclinonc.2010.175

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrclinonc.2010.175

This article is cited by

Search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer