Epidemiology, Risk Factors, and Prevention

  • Soley Bayraktar
  • Banu K. Arun


Breast cancer is the most frequently diagnosed cancer in women in the United States, with an estimated 296,000 new cases and more than 40,000 deaths in 2013. Age, family history, and both endogenous and exogenous ovarian hormone exposure have important effects on risk and have been incorporated into models that predict individual risk of breast cancer; diet, alcohol use, and other factors play smaller roles. Inherited mutations in BRCA1, BRCA2, and CHEK2 play a role in the development of hereditary breast cancer, and high-risk individuals can be directly tested. BRCA mutation-associated breast cancer differs from sporadic breast cancer in that BRCA mutation carriers have a higher risk of breast and ovarian cancer and differential sensitivity to chemotherapeutic agents. As BRCA genetic testing is readily available, BRCA mutation status should be evaluated in high-risk women, including women who were diagnosed with breast cancer at an early age, who have a strong family history, or whose tumors were triple negative (TN). Given the high rate of contralateral breast cancer and ovarian cancer, mutation carriers with newly diagnosed breast cancer may choose to undergo contralateral prophylactic mastectomy or bilateral salpingo-oophorectomy. In addition, two selective estrogen receptor modulators, tamoxifen and raloxifene, and aromatase inhibitors can be used to decrease the incidence of invasive breast cancer in women who are at high risk of this condition.


Breast cancer Prevention Risk factors BRCA Hereditary breast cancer Risk models Prophylactic mastectomy Prophylactic oophorectomy 


  1. 1.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.PubMedCrossRefGoogle Scholar
  2. 2.
    Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. Lancet Oncol. 2001;2:133–40.PubMedCrossRefGoogle Scholar
  3. 3.
    Global Cancer Facts and Figures.
  4. 4.
    Ziegler RG, Hoover RN, Pike MC, Hildesheim A, Nomura AM, West DW, et al. Migration patterns and breast cancer risk in Asian-American women. J Natl Cancer Inst. 1993;85:1819–27.PubMedCrossRefGoogle Scholar
  5. 5.
    King SE, Schottenfeld D. The “epidemic” of breast cancer in the U.S. – determining the factors. Oncology. 1996;10:453–62; discussion 62, 64, 70–2.PubMedGoogle Scholar
  6. 6.
  7. 7.
  8. 8.
    Percent of new breast cancer cases by age group surveillance, epidemiology, and end results [SEER]. 2011. Accessed 26 June 2015.
  9. 9.
    Incidence rates of female breast cancer by race and ethnicity, U.S., 1999–2011. Accessed 26 June 2015.
  10. 10.
    Death rates by race and ethnicity, U.S., 1999–2011. Accessed 26 June 2015.
  11. 11.
    Zhang SM, Lee IM, Manson JE, Cook NR, Willett WC, Buring JE. Alcohol consumption and breast cancer risk in the women’s health study. Am J Epidemiol. 2007;165:667–76.PubMedCrossRefGoogle Scholar
  12. 12.
    Tretli S. Height and weight in relation to breast cancer morbidity and mortality. A prospective study of 570,000 women in Norway. Int J Cancer. 1989;44:23–30.PubMedCrossRefGoogle Scholar
  13. 13.
    Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. Postmenopausal hormone replacement therapy: scientific review. JAMA. 2002;288:872–81.PubMedCrossRefGoogle Scholar
  14. 14.
    Boice JD Jr, Preston D, Davis FG, Monson RR. Frequent chest X-ray fluoroscopy and breast cancer incidence among tuberculosis patients in Massachusetts. Radiat Res. 1991;125:214–22.PubMedCrossRefGoogle Scholar
  15. 15.
    Clemons M, Loijens L, Goss P. Breast cancer risk following irradiation for Hodgkin’s disease. Cancer Treat Rev. 2000;26:291–302.PubMedCrossRefGoogle Scholar
  16. 16.
    Brinton LA, Schairer C, Hoover RN, Fraumeni JF Jr. Menstrual factors and risk of breast cancer. Cancer Investig. 1988;6:245–54.CrossRefGoogle Scholar
  17. 17.
    Trichopoulos D, MacMahon B, Cole P. Menopause and breast cancer risk. J Natl Cancer Inst. 1972;48:605–13.PubMedGoogle Scholar
  18. 18.
    Brinton LA, Hoover R, Fraumeni JF Jr. Reproductive factors in the aetiology of breast cancer. Br J Cancer. 1983;47:757–62.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Brinton LA, Hoover R, Fraumeni JF Jr. Epidemiology of minimal breast cancer. JAMA. 1983;249:483–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Ries LAG EM, Kosary CL, et al., editors. SEER cancer statistics, review. Bethesda: National Cancer Institute. NIH Pub. No. 00–2789; 2000.Google Scholar
  21. 21.
    Hankey BF, Curtis RE, Naughton MD, Boice JD Jr, Flannery JT. A retrospective cohort analysis of second breast cancer risk for primary breast cancer patients with an assessment of the effect of radiation therapy. J Natl Cancer Inst. 1983;70:797–804.PubMedGoogle Scholar
  22. 22.
    Page DL, Dupont WD, Rogers LW, Landenberger M. Intraductal carcinoma of the breast: follow-up after biopsy only. Cancer. 1982;49:751–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Dupont WD, Parl FF, Hartmann WH, Brinton LA, Winfield AC, Worrell JA, et al. Breast cancer risk associated with proliferative breast disease and atypical hyperplasia. Cancer. 1993;71:1258–65.PubMedCrossRefGoogle Scholar
  24. 24.
    Fabian CJ, Kimler BF, Zalles CM, Klemp JR, Kamel S, Zeiger S, et al. Short-term breast cancer prediction by random periareolar fine-needle aspiration cytology and the Gail risk model. J Natl Cancer Inst. 2000;92:1217–27.Google Scholar
  25. 25.
    Pharoah PD, Day NE, Duffy S, Easton DF, Ponder BA. Family history and the risk of breast cancer: a systematic review and meta-analysis. Int J Cancer. 1997;71:800–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Easton DF, Ford D, Bishop DT. Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast cancer linkage consortium. Am J Hum Genet. 1995;56:265–71.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Singletary SE. Rating the risk factors for breast cancer. Ann Surg. 2003;237(4):474–82.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Litton JK, Eralp Y, Gonzalez-Angulo AM, Broglio K, Uyei A, Hortobagyi GN, et al. Multifocal breast cancer in women < or =35 years old. Cancer. 2007;110:1445–50.PubMedCrossRefGoogle Scholar
  29. 29.
    Inskip PD, Curtis RE. New malignancies following childhood cancer in the United States, 1973–2002. Int J Cancer. 2007;121:2233–40.PubMedCrossRefGoogle Scholar
  30. 30.
    Buist DS, Abraham LA, Barlow WE, Krishnaraj A, Holdridge RC, Sickles EA, et al. Diagnosis of second breast cancer events after initial diagnosis of early stage breast cancer. Breast Cancer Res Treat. 2010;124:863–73.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Cote ML, Ruterbusch JJ, Alosh B, Bandyopadhyay S, Kim E, Albashiti B, et al. Benign breast disease and the risk of subsequent breast cancer in African American women. Cancer Prev Res. 2012;5:1375–80.CrossRefGoogle Scholar
  32. 32.
    Hartmann LC, Sellers TA, Frost MH. Benign breast disease and the risk of breast cancer. N Engl J Med. 2005;353:229–37.PubMedCrossRefGoogle Scholar
  33. 33.
    Colditz GA, Kaphingst KA, Hankinson SE, Rosner B. Family history and risk of breast cancer: nurses’ health study. Breast Cancer Res Treat. 2012;133:1097–104.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58 wwbca, 986 women without the disease. Lancet. 2001;358:1389–99.CrossRefGoogle Scholar
  35. 35.
    Hsieh CC, Trichopoulos D, Katsouyanni K, Yuasa S. Age at menarche, age at menopause, height and obesity as risk factors for breast cancer: associations and interactions in an international case–control study. Int J Cancer. 1990;46:796–800.PubMedCrossRefGoogle Scholar
  36. 36.
    Ritte R, Lukanova A, Berrino F. Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study. Breast Cancer Res. 2012;14:R76.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Bayraktar S, Amendola L, Gutierrez-Barrera AM, Hashmi SS, Amos C, Gambello M, et al. Clinicopathologic characteristics of breast cancer in BRCA-carriers and non-carriers in women 35 years of age or less. Breast. 2014;23:770–4.PubMedCrossRefGoogle Scholar
  38. 38.
    Rosner B, Colditz GA, Willett WC. Reproductive risk factors in a prospective study of breast cancer: the nurses’ health study. Am J Epidemiol. 1994;139:819–35.PubMedCrossRefGoogle Scholar
  39. 39.
    Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease. Lancet. 2002;360:187–95.CrossRefGoogle Scholar
  40. 40.
    Sieri S, Krogh V, Bolelli G. Sex hormone levels, breast cancer risk, and cancer receptor status in postmenopausal women: the ORDET cohort. Cancer Epidemiol Biomark Prev. 2009;18:169–76.CrossRefGoogle Scholar
  41. 41.
    Kelsey JL, Gammon MD, John EM. Reproductive factors and breast cancer. Epidemiol Rev. 1993;15:36–47.PubMedCrossRefGoogle Scholar
  42. 42.
    Lahmann PH, Hoffmann K, Allen N. Body size and breast cancer risk: findings from the European prospective investigation into cancer and nutrition (EPIC). Int J Cancer. 2004;111:762–71.PubMedCrossRefGoogle Scholar
  43. 43.
    Breast cancer and hormone replacement. therapy: collaborative reanalysis of data from 51 epidemiological studies of 52 wwbca, 411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet. 1997;350:1047–59.CrossRefGoogle Scholar
  44. 44.
    Anderson GL, Manson J, Wallace R, Lund B, Hall D, Davis S, et al. Implementation of the women’s health initiative study design. Ann Epidemiol. 2003;13:S5–17.PubMedCrossRefGoogle Scholar
  45. 45.
    Colditz GA, Rosner B. Cumulative risk of breast cancer to age 70 years according to risk factor status: data from the nurses’ health study. Am J Epidemiol. 2000;152:950–64.PubMedCrossRefGoogle Scholar
  46. 46.
    Chlebowski RT, Manson JE, Anderson GL, Cauley JA, Aragaki AK, Stefanick ML, et al. Estrogen plus progestin and breast cancer incidence and mortality in the women’s health initiative observational study. J Natl Cancer Inst. 2013;105:526–35.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Danaei G, Vander Hoorn S, Lopez AD, Murray CJ, Ezzati M, Comparative Risk Assessment Collaborating Group. Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors. Lancet. 2005;366:1784–93.PubMedCrossRefGoogle Scholar
  48. 48.
    Chen WY, Rosner B, Hankinson SE, Colditz GA, Willett WC. Moderate alcohol consumption during adult life, drinking patterns, and breast cancer risk. JAMA. 2011;306:1884–90.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Wu Y, Zhang D, Kang S. Physical activity and risk of breast cancer: a meta-analysis of prospective studies. Breast Cancer Res Treat. 2013;137:869–82.PubMedCrossRefGoogle Scholar
  50. 50.
    Milazzo G, Giorgino F, Damante G, Sung C, Stampfer MR, Vigneri R, et al. Insulin receptor expression and function in human breast cancer cell lines. Cancer Res. 1992;52:3924–30.PubMedGoogle Scholar
  51. 51.
    Gunter MJ, Hoover DR, Yu H. Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 2009;101:48–60.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    TO H, Amsterdam A, Bhatia S. Systematic review: surveillance for breast cancer in women treated with chest radiation for childhood, adolescent, or young adult cancer. Ann Intern Med. 2010;152:444–55. W144-54.CrossRefGoogle Scholar
  53. 53.
    Guibout C, Adjadj E, Rubino C, Shamsaldin A, Grimaud E, Hawkins M, et al. Malignant breast tumors after radiotherapy for a first cancer during childhood. J Clin Oncol. 2005;23:197–204.PubMedCrossRefGoogle Scholar
  54. 54.
    Preston DL, Cullings H, Suyama A. Solid cancer incidence in atomic bomb survivors exposed in utero or as young children. J Natl Cancer Inst. 2008;100:428–36.PubMedCrossRefGoogle Scholar
  55. 55.
    Pukkala E, Kesminiene A, Poliakov S. Breast cancer in Belarus and Ukraine after the Chernobyl accident. Int J Cancer. 2006;119:651–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Barlow WE, White E, Ballard-Barbash R. Prospective breast cancer risk prediction model for women undergoing screening mammography. J Natl Cancer Inst. 2006;98:1204–14.PubMedCrossRefGoogle Scholar
  57. 57.
    Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007;356:227–36.PubMedCrossRefGoogle Scholar
  58. 58.
    McCormack VA, dos Santos Silva I. Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev. 2006;15:1159–69.CrossRefGoogle Scholar
  59. 59.
    Pettersson A, Hankinson SE, Willett WC, Lagiou P, Trichopoulos D, Tamimi RM. Nondense mammographic area and risk of breast cancer. Breast Cancer Res. 2011;13:R100.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Rauh C, Hack CC, Häberle L, Hein A, Engel A, Schrauder MG, et al. Percent mammographic density and dense area as risk factors for breast cancer. Geburtshilfe Frauenheilkd. 2012;72:727–33.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Lynch HT, Lynch JF. Breast cancer genetics in an oncology clinic: 328 consecutive patients. Cancer Genet Cytogenet. 1986;22:369–71.PubMedCrossRefGoogle Scholar
  62. 62.
    Margolin S, Johansson H, Rutqvist LE, Lindblom A, Fornander T. Family history, and impact on clinical presentation and prognosis, in a population-based breast cancer cohort from the Stockholm County. Familial Cancer. 2006;5:309–21.PubMedCrossRefGoogle Scholar
  63. 63.
    Lalloo F, Evans DG. Familial breast cancer. Clin Genet. 2012;82:105–14.PubMedCrossRefGoogle Scholar
  64. 64.
    Sharif S, Moran A, Huson SM, Iddenden R, Shenton A, Howard E, et al. Women with neurofibromatosis 1 are at a moderately increased risk of developing breast cancer and should be considered for early screening. J Med Genet. 2007;44:481–4.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 1998;62:676–89.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Antoniou A, Pharoah PD, Narod S. 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. 2003;72:1117–30.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    King MC, Marks JH, Mandell JB, New York Breast Cancer Study Group. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003;302:643–6.PubMedCrossRefGoogle Scholar
  68. 68.
    Thompson D, Duedal S, Kirner J, McGuffog L, Last J, Reiman A, et al. Cancer risks and mortality in heterozygous ATM mutation carriers. J Natl Cancer Inst. 2005;97:813–22.PubMedCrossRefGoogle Scholar
  69. 69.
    Seal S, Thompson D, Renwick A, Elliott A, Kelly P, Barfoot R, et al. Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat Genet. 2006;38:1239–41.PubMedCrossRefGoogle Scholar
  70. 70.
    Wong MW, Nordfors C, Mossman D. BRIP1, PALB2, and RAD51C mutation analysis reveals their relative importance as genetic susceptibility factors for breast cancer. Breast Cancer Res Treat. 2011;127:853–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Melhem-Bertrandt A, Bojadzieva J, Ready KJ, Obeid E, Liu DD, Gutierrez-Barrera AM, et al. Early onset HER2-positive breast cancer is associated with germline TP53 mutations. Cancer. 2012;118:908–13.PubMedCrossRefGoogle Scholar
  72. 72.
    Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer. 2012;12:68–78.CrossRefGoogle Scholar
  73. 73.
    Yuan SS, Lee SY, Chen G, Song M, Tomlinson GE, Lee EY. BRCA2 is required for ionizing radiation-induced assembly of Rad51 complex in vivo. Cancer Res. 1999;59:3547–51.PubMedGoogle Scholar
  74. 74.
    Zhong Q, Chen CF, Li S. Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response. Science. 1999;285:747–50.PubMedCrossRefGoogle Scholar
  75. 75.
    Rajan JV, Wang M, Marquis ST, Chodosh LA. Brca2 is coordinately regulated with Brca1 during proliferation and differentiation in mammary epithelial cells. Proc Natl Acad Sci USA. 1996;93:13078–83.PubMedCrossRefGoogle Scholar
  76. 76.
    Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev. 2000;14:927–39.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Narod SA, Foulkes WD. BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer. 2004;4:665–76.PubMedCrossRefGoogle Scholar
  78. 78.
    Collins N, McManus R, Wooster R. Consistent loss of the wild type allele in breast cancers from a family linked to the BRCA2 gene on chromosome 13q12-13. Oncogene. 1995;10:1673–5.PubMedGoogle Scholar
  79. 79.
    Cornelis RS, Neuhausen SL, Johansson O. High allele loss rates at 17q12-q21 in breast and ovarian tumors from BRCAl-linked families. The Breast Cancer Linkage Consortium. Genes Chromosomes Cancer. 1995;13:203–10.PubMedCrossRefGoogle Scholar
  80. 80.
    Khoo US, Ozcelik H, Cheung AN. Somatic mutations in the BRCA1 gene in Chinese sporadic breast and ovarian cancer. Oncogene. 1999;18:4643–6.PubMedCrossRefGoogle Scholar
  81. 81.
    Esteller M, Silva JM, Dominguez G, Bonilla F, Matias-Guiu X, Lerma E, et al. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst. 2000;92:564–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Tapia T, Smalley SV, Kohen P, Muñoz A, Solis LM, Corvalan A, et al. Promoter hypermethylation of BRCA1 correlates with absence of expression in hereditary breast cancer tumors. Epigenetics. 2008;3:157–63.PubMedCrossRefGoogle Scholar
  83. 83.
    Dworkin AM, Spearman AD, Tseng SY, Sweet K, Toland AE. Methylation not a frequent “second hit” in tumors with germline BRCA mutations. Familial Cancer. 2009;8:339–46.PubMedCrossRefGoogle Scholar
  84. 84.
    Collins N, Wooster R, Stratton MR. Absence of methylation of CpG dinucleotides within the promoter of the breast cancer susceptibility gene BRCA2 in normal tissues and in breast and ovarian cancers. Br J Cancer. 1997;76:1150–6.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Rich TA, Woodson AH, Litton J, Arun B. Hereditary breast cancer syndromes and genetic testing. J Surg Oncol. 2015;111(1):66–80.PubMedCrossRefGoogle Scholar
  86. 86.
    Foulkes WD. Inherited susceptibility to common cancers. N Engl J Med. 2008;359:2143–53.PubMedCrossRefGoogle Scholar
  87. 87.
    Honrado E, Benitez J, Palacios J. The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications. Mod Pathol. 2005;18:1305–20.PubMedCrossRefGoogle Scholar
  88. 88.
    Gerdes AM, Cruger DG, Thomassen M, Kruse TA. Evaluation of two different models to predict BRCA1 and BRCA2 mutations in a cohort of Danish hereditary breast and/or ovarian cancer families. Clin Genet. 2006;69:171–8.PubMedCrossRefGoogle Scholar
  89. 89.
    Melchor L, Benitez J. The complex genetic landscape of familial breast cancer. Hum Genet. 2013;132:845–63.PubMedCrossRefGoogle Scholar
  90. 90.
    Thompson D, Easton D. The genetic epidemiology of breast cancer genes. J Mammary Gland Biol Neoplasia. 2004;9:221–36.PubMedCrossRefGoogle Scholar
  91. 91.
    Diez O, Osorio A, Duran M. Analysis of BRCA1 and BRCA2 genes in Spanish breast/ovarian cancer patients: a high proportion of mutations unique to Spain and evidence of founder effects. Hum Mutat. 2003;22:301–12.PubMedCrossRefGoogle Scholar
  92. 92.
    Mavaddat N, Barrowdale D, Andrulis IL. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomark Prev. 2012;21:134–47.CrossRefGoogle Scholar
  93. 93.
    Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007;25:1329–33.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Atchley DP, Albarracin CT, Lopez A, Valero V, Amos CI, Gonzalez-Angulo AM, et al. Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer. J Clin Oncol. 2008;26:4282–8.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Marcus JN, Watson P, Page DL, Narod SA, Lenoir GM, Tonin P, et al. Hereditary breast cancer: pathobiology, prognosis, and BRCA1 and BRCA2 gene linkage. Cancer. 1996;77:697–709.PubMedCrossRefGoogle Scholar
  96. 96.
    Eisinger F, Jacquemier J, Charpin C, Stoppa-Lyonnet D, Bressac-de Paillerets B, Peyrat JP, et al. Mutations at BRCA1: the medullary breast carcinoma revisited. Cancer Res. 1998;58:1588–92.PubMedGoogle Scholar
  97. 97.
    Lakhani SR, Gusterson BA, Jacquemier J, Sloane JP, Anderson TJ, van de Vijver MJ, et al. The pathology of familial breast cancer: histological features of cancers in families not attributable to mutations in BRCA1 or BRCA2. Clin Cancer Res. 2000;6:782–9.PubMedGoogle Scholar
  98. 98.
    Lakhani SR, Gusterson BA, Jacquemier J, Sloane JP, Anderson TJ, van de Vijver MJ, et al. The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol. 2002;20:2310–8.PubMedCrossRefGoogle Scholar
  99. 99.
    Arun B, Vogel KJ, Lopez A, Hernandez M, Atchley D, Broglio KR, et al. High prevalence of preinvasive lesions adjacent to BRCA1/2-associated breast cancers. Cancer Prev Res. 2009;2:122–7.CrossRefGoogle Scholar
  100. 100.
    Kennedy RD, Quinn JE, Johnston PH, Harkin DP. BRCA1: mechanisms of inactivation and implications for management of patients. Lancet. 2002;360:1007–14.PubMedCrossRefGoogle Scholar
  101. 101.
    Verhoog LC, Brekelmans CT, Seynaeve C, Dahmen G, van Geel AN, Bartels CC. Survival in hereditary breast cancer associated with germline mutations of BRCA2. J Clin Oncol. 1999;17:3396–402.PubMedCrossRefGoogle Scholar
  102. 102.
    Rennert G, Bisland-Naggan S, Barnett-Griness O, Bar-Joseph N, Zhang S, Rennert HS, et al. Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med. 2007;357:115–23.PubMedCrossRefGoogle Scholar
  103. 103.
    Brekelmans CT, Tilanus-Linthorst MM, Seynaeve C, vd Ouweland A, Menke-Pluymers MB, Bartels CC. Tumour characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, B. Eur J Cancer. 2007;43:867–76.PubMedCrossRefGoogle Scholar
  104. 104.
    Kriege M, Seynaeve C, Meijers-Heijboer H, Collee JM, Menke-Pluymers MB, Bartels CC. Distant disease-free interval, site of first relapse and post-relapse survival in B. Breast Cancer Res Treat. 2008;111:303–11.PubMedCrossRefGoogle Scholar
  105. 105.
    Bonadona V, Dussart-Moser S, Voirin N, Sinilnikova OM, Mignotte H, Mathevet P, 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. 2007;101:233–45.PubMedCrossRefGoogle Scholar
  106. 106.
    Bordeleau L, Panchal S, Goodwin P. Prognosis of BRCA-associated breast cancer: a summary of evidence. Breast Cancer Res Treat. 2010;119:13–24.PubMedCrossRefGoogle Scholar
  107. 107.
    Robson M, Levin D, Federici M, Satagopan J, Bogolminy F, Heerdt A, et al. Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations. J Natl Cancer Inst. 1999;91:2112–7.PubMedCrossRefGoogle Scholar
  108. 108.
    Chappuis PO, Kapusta L, Bégin LR, Wong N, Brunet JS, Narod SA, et al. Germline BRCA1/2 mutations and p27(Kip1) protein levels independently predict outcome after breast cancer. J Clin Oncol. 2000;18:4045–52.PubMedCrossRefGoogle Scholar
  109. 109.
    Stoppa-Lyonnet D, Ansquer Y, Dreyfus H, Gautier C, Gauthier-Villars M, Bourstyn E, The Institute Curie Breast Cancer Group, et al. Familial invasive breast cancer: worse outcome related to BRCA1 mutations. J Clin Oncol. 2000;18:4053–9.Google Scholar
  110. 110.
    Moller P, Evans DG, Reis MM, Gregory H, Anderson E, Maehle L, et al. Surveillance for familial breast cancer: differences in outcome according to BRCA mutation status. Int J Cancer. 2007;121:1017–20.PubMedCrossRefGoogle Scholar
  111. 111.
    Lee EH, Park SK, Park B. Effect of BRCA1/2 mutation on short-term and long-term breast cancer survival: a systematic review and meta-analysis. Breast Cancer Res Treat. 2010;122:11–25.PubMedCrossRefGoogle Scholar
  112. 112.
    Lee LJ, Alexander B, Schnitt SJ, Comander A, Gallagher B, Garber JE, et al. Clinical outcome of triple negative breast cancer in BRCA1 mutation carriers and noncarriers. Cancer. 2011;117:3093–100.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Bayraktar S, Gutierrez-Barrera AM, Liu D, Tasbas T, Akar U, Litton JK, et al. Outcome of triple-negative breast cancer in patients with or without deleterious BRCA mutations. Breast Cancer Res Treat. 2011;130:145–53.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Riley BD, Culver JO, Skrzynia C. Essential elements of genetic cancer risk assessment, counseling, and testing: updated recommendations of the National Society of Genetic Counselors. J Genet Couns. 2012;21:151–61.PubMedCrossRefGoogle Scholar
  115. 115.
    Genetic/familial high-risk assessment: breast and ovarian. NCCN guidelines. 2015.;
  116. 116.
    Kwon JS, Gutierrez-Barrera AM, Young D, Sun CC, Daniels MS, Lu KH, et al. Expanding the criteria for BRCA mutation testing in breast cancer survivors. J Clin Oncol. 2010;28:4214–20.PubMedCrossRefGoogle Scholar
  117. 117.
    Bayraktar S, Elsayegh N, Gutierrez Barrera AM, Lin H, Kuerer H, Tasbas T, et al. Predictive factors for BRCA1/BRCA2 mutations in women with ductal carcinoma in situ. Cancer. 2012;118:1515–22.PubMedCrossRefGoogle Scholar
  118. 118.
    Elsayegh N, Kuerer HM, Lin H, Gutierrez Barrera AM, Jackson M, Muse KI, et al. Predictors that influence contralateral prophylactic mastectomy election among women with ductal carcinoma in situ who were evaluated for BRCA genetic testing. Ann Surg Oncol. 2014;21:3466–72.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Claus EB, Risch N, Thompson WD. Autosomal dominant inheritance of early-onset breast cancer. Implications for risk prediction. Cancer. 1994;73:643–51.PubMedCrossRefGoogle Scholar
  120. 120.
    Saslow D, Boetes C, Burke W. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75–89.PubMedCrossRefGoogle Scholar
  121. 121.
    Hollingsworth AB, Stough RG. An alternative approach to selecting patients for high-risk screening with breast MRI. Breast J. 2014;20:192–7.PubMedCrossRefGoogle Scholar
  122. 122.
    Gail MH, Brinton LA, Byar DP. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst. 1989;81:1879–86.PubMedCrossRefGoogle Scholar
  123. 123.
    Pastor-Barriuso R, Ascunce N, Ederra M. Recalibration of the Gail model for predicting invasive breast cancer risk in Spanish women: a population-based cohort study. Breast Cancer Res Treat. 2013;138:249–59.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Tyrer J, Duffy SW, Cuzick J. A breast cancer prediction model incorporating familial and personal risk factors. Stat Med. 2004;23:1111–30.PubMedCrossRefGoogle Scholar
  125. 125.
    Antoniou AC, Pharoah PP, Smith P, Easton DF. The BOADICEA model of genetic susceptibility to breast and ovarian cancer. Br J Cancer. 2004;91:1580–90.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Antoniou AC, Durocher F, Smith P, Simard J, Easton DF. BRCA1 and BRCA2 mutation predictions using the BOADICEA and BRCAPRO models and penetrance estimation in high-risk French-Canadian families. Breast Cancer Res. 2006;8:R3.PubMedCrossRefGoogle Scholar
  127. 127.
    Antoniou AC, Cunningham AP, Peto J, Evans DG, Lalloo F, Narod SA, et al. The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br J Cancer. 2008;98:1457–66.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Powell M, Jamshidian F, Cheyne K, Nititham J, Prebil LA, Ereman R. Assessing breast cancer risk models in Marin County, a population with high rates of delayed childbirth. Clin Breast Cancer. 2014;14:212–20 e1.PubMedCrossRefGoogle Scholar
  129. 129.
    Laitman Y, Simeonov M, Keinan-Boker L, Liphshitz I, Friedman E. Breast cancer risk prediction accuracy in Jewish Israeli high-risk women using the BOADICEA and IBIS risk models. Genet Res. 2013;95:174–7.CrossRefGoogle Scholar
  130. 130.
    Berry DA, Parmigiani G, Sanchez J, Schildkraut J, Winer E. Probability of carrying a mutation of breast-ovarian cancer gene BRCA1 based on family history. J Natl Cancer Inst. 1997;89:227–38.PubMedCrossRefGoogle Scholar
  131. 131.
    Parmigiani G, Berry D, Aguilar O. Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2. Am J Hum Genet. 1998;62:145–58.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Antoniou AC, Cunningham AP, Peto J, Evans DG, Lalloo F, Narod SA, et al. Predicting the likelihood of carrying a BRCA1 or BRCA2 mutation: validation of BOADICEA, BRCAPRO, IBIS, Myriad and the Manchester scoring system using data from UK genetics clinics. J Med Genet. 2008;45:425–31.PubMedCrossRefGoogle Scholar
  133. 133.
    Berry DA, Iversen ES Jr, Gudbjartsson DF. BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes. J Clin Oncol. 2002;20:2701–12.PubMedCrossRefGoogle Scholar
  134. 134.
    Vogel KJ, Atchley DP, Erlichman J, Broglio KR, Ready KJ, Valero V, et al. BRCA1 and BRCA2 genetic testing in Hispanic patients: mutation prevalence and evaluation of the BRCAPRO risk assessment model. J Clin Oncol. 2007;25:4635–41.PubMedCrossRefGoogle Scholar
  135. 135.
    Daniels MS, Babb SA, King RH, Urbauer DL, Batte BA, Brandt AC, et al. Underestimation of risk of a BRCA1 or BRCA2 mutation in women with high-grade serous ovarian cancer by BRCAPRO: a multi-institution study. J Clin Oncol. 2014;32:1249–55.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Varesco L, Viassolo V, Viel A, Gismondi V, Radice P, Montagna M, et al. Performance of BOADICEA and BRCAPRO genetic models and of empirical criteria based on cancer family history for predicting BRCA mutation carrier probabilities: a retrospective study in a sample of Italian cancer genetics clinics. Breast. 2013;22:1130–5.PubMedCrossRefGoogle Scholar
  137. 137.
    Fischer C, Kuchenbacker K, Engel C. Evaluating the performance of the breast cancer genetic risk models BOADICEA, IBIS, BRCAPRO and Claus for predicting BRCA1/2 mutation carrier probabilities: a study based on 7352 families from the German Hereditary Breast and Ovarian Cancer Consortium. J Med Genet. 2013;50:360–7.PubMedCrossRefGoogle Scholar
  138. 138.
    Ready KJ, Vogel KJ, Atchley DP, Broglio KR, Solomon KK, Amos C, et al. Accuracy of the BRCAPRO model among women with bilateral breast cancer. Cancer. 2009;115:725–30.PubMedCrossRefGoogle Scholar
  139. 139.
    Pfeiffer RM, Park Y, Kreimer AR. Risk prediction for breast, endometrial, and ovarian cancer in white women aged 50 y or older: derivation and validation from population-based cohort studies. PLoS Med. 2013;10:e1001492.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Warner E, Plewes DB, Hill KA, Causer PA, Zubovits JT, Jong RA, et al. Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA. 2004;292:1317–25.PubMedCrossRefGoogle Scholar
  141. 141.
    Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, Warner E, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2004;22:2328–35.PubMedCrossRefGoogle Scholar
  142. 142.
    van Sprundel TC, Schmidt MK, Rookus MA. Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers. Br J Cancer. 2005;93:287–92.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Metcalfe KA, Lubinski J, Ghadirian P. Predictors of contralateral prophylactic mastectomy in women with a BRCA1 or BRCA2 mutation: the Hereditary Breast Cancer Clinical Study Group. J Clin Oncol. 2008;26:1093–7.PubMedCrossRefGoogle Scholar
  144. 144.
    Metcalfe K, Lynch HT, Ghadirian P, Tung N, Kim-Sing C, Olopade OI, et al. Risk of ipsilateral breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2011;127:287–96.PubMedCrossRefGoogle Scholar
  145. 145.
    Graeser MK, Engel C, Rhiem K, Gadzicki D, Bick U, Kast K, et al. Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2009;27:5887–92.PubMedCrossRefGoogle Scholar
  146. 146.
    Malone KE, Begg CB, Haile RW, Borg A, Concannon P, Tellhed L, et al. Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2. J Clin Oncol. 2010;28:2404–10.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Reding KW, Bernstein JL, Langholz BM, Bernstein L, Haile RW, Begg CB, et al. Adjuvant systemic therapy for breast cancer in BRCA1/BRCA2 mutation carriers in a population-based study of risk of contralateral breast cancer. Breast Cancer Res Treat. 2010;123:491–8.PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Narod SA, Brunet JS, Ghadirian P. Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case–control study. Hereditary Breast Cancer Clinical Study Group. Lancet. 2000;356:1876–81.PubMedCrossRefGoogle Scholar
  149. 149.
    Robson M, Svahn T, McCormick B. Appropriateness of breast-conserving treatment of breast carcinoma in women with germline mutations in BRCA1 or BRCA2: a clinic-based series. Cancer. 2005;103:44–51.PubMedCrossRefGoogle Scholar
  150. 150.
    Pierce LJ, Levin AM, Rebbeck TR. Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol. 2006;24:2437–43.PubMedCrossRefGoogle Scholar
  151. 151.
    Gronwald J, Tung N, Foulkes WD, Offit K, Gershoni R, Daly M, et al. Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer. 2006;118:2281–4.PubMedCrossRefGoogle Scholar
  152. 152.
    Robson ME, Chappuis PO, Satagopan J, Wong N, Boyd J, Goffin JR, 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. 2004;6:R8–17.PubMedCrossRefGoogle Scholar
  153. 153.
    Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304:967–75.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Struewing JP, Hartge P, Wacholder S. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med. 1997;336:1401–8.PubMedCrossRefGoogle Scholar
  155. 155.
    Satagopan JM, Boyd J, Kauff ND, Robson M, Scheuer L, Narod S, et al. Ovarian cancer risk in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations. Clin Cancer Res. 2002;8:3776–81.PubMedGoogle Scholar
  156. 156.
    Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, Van’t Veer L, Garber JE, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346:1616–22.PubMedCrossRefGoogle Scholar
  157. 157.
    Finch A, Beiner M, Lubinski J, Lynch HT, Moller P, Rosen B, et al. Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation. JAMA. 2006;296:185–92.PubMedCrossRefGoogle Scholar
  158. 158.
    Kramer JVI, Chen BS. Prophylactic oophorectomy reduces breast cancer penetrance during prospective, long-term follow-up of BRCA1 mutation carriers. J Clin Oncol. 2005;23:8629–35.PubMedCrossRefGoogle Scholar
  159. 159.
    Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101:80–7.PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Visvanathan K, Hurley P, Bantug E. Use of pharmacologic interventions for breast cancer risk reduction: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2013;31(23):2942–62.PubMedCrossRefGoogle Scholar
  161. 161.
    Eisen A, Lubinski J, Klijn J. Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case–control study. J Clin Oncol. 2005;23:7491–6.PubMedCrossRefGoogle Scholar
  162. 162.
    Kurian AW, Sigal BM, Plevritis SK. Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers. J Clin Oncol. 2010;28:222–31.PubMedCrossRefGoogle Scholar
  163. 163.
    Finch A, Narod SA. Quality of life and health status after prophylactic salpingo-oophorectomy in women who carry a BRCA mutation: a review. Maturitas. 2011;70:261–5.PubMedCrossRefGoogle Scholar
  164. 164.
    Heemskerk-Gerritsen BA, Rookus MA, Aalfs CM, Ausems MG, Collée JM, Jansen L, et al. 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. 2015;136(3):668–77.PubMedGoogle Scholar
  165. 165.
    Ready K, Gutierrez-Barrera AM, Amos C, Meric-Bernstam F, Lu K, Hortobagyi G, Arun B. Cancer risk management decisions of women with BRCA1 or BRCA2 variants of uncertain significance. Breast J. 2011;17:210–2.Google Scholar
  166. 166.
    Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, et al. Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat. 2009;115:359–63.PubMedCrossRefGoogle Scholar
  167. 167.
    Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, et al. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol. 2010;28:375–9.PubMedCrossRefGoogle Scholar
  168. 168.
    Arun B, Bayraktar S, Liu DD, Gutierrez Barrera AM, Atchley D, Pusztai L, et al. Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers: a single-institution experience. J Clin Oncol. 2011;29:3739–46.PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, Juul N, et al. Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. J Clin Oncol. 2010;28:1145–53.PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Wen J, Li R, Lu Y, Shupnik MA. Decreased BRCA1 confers tamoxifen resistance in breast cancer cells by altering estrogen receptor-coregulator interactions. Oncogene. 2009;28:575–86.PubMedCrossRefGoogle Scholar
  171. 171.
    Fong PC, Boss DS, Yap TA. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361:123–34.PubMedCrossRefGoogle Scholar
  172. 172.
    Iglehart JD, Silver DP. Synthetic lethality – a new direction in cancer-drug development. N Engl J Med. 2009;361:189–91.PubMedCrossRefGoogle Scholar
  173. 173.
    Carey LA, Sharpless NE. PARP and cancer – if it’s broke, don’t fix it. N Engl J Med. 2011;364:277–9.PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Kennedy RD, Quinn JE, Mullan PB, Johnston PG, Harkin DP. The role of BRCA1 in the cellular response to chemotherapy. J Natl Cancer Inst. 2004;96:1659–68.PubMedCrossRefGoogle Scholar
  175. 175.
    Tassone P, Tagliaferri P, Perricelli A, Blotta S, Quaresima B, Martelli ML, et al. BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells. Br J Cancer. 2003;88:1285–91.PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Chabalier C, Lamare C, Racca C, Privat M, Valette A, Larminat F. BRCA1 downregulation leads to premature inactivation of spindle checkpoint and confers paclitaxel resistance. Cell Cycle. 2006;5:1001–7.PubMedCrossRefGoogle Scholar
  177. 177.
    Kriege M, Jager A, Hooning MJ, Huijskens E, Blom J, van Deurzen CH, et al. The efficacy of taxane chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers. Cancer. 2012;118:899–907.PubMedCrossRefGoogle Scholar
  178. 178.
    Gholam D, Chebib A, Hauteville D, Bralet MP, Jasmin C. Combined paclitaxel and cetuximab achieved a major response on the skin metastases of a patient with epidermal growth factor receptor-positive, estrogen receptor-negative, progesterone receptor-negative and human epidermal growth factor receptor-2-negative (triple-negative) breast cancer. Anti-Cancer Drugs. 2007;18:835–7.PubMedCrossRefGoogle Scholar
  179. 179.
    Petrelli F, Cabiddu M, Ghilardi M, Barni S. Current data of targeted therapies for the treatment of triple-negative advanced breast cancer: empiricism or evidence-based? Expert Opin Investig Drugs. 2009;18:1467–77.PubMedCrossRefGoogle Scholar
  180. 180.
    Ame JC, Spenlehauer C, de Murcia G. The PARP superfamily. BioEssays. 2004;26:882–93.PubMedCrossRefGoogle Scholar
  181. 181.
    Dantzer F, de La Rubia G, Menissier-De Murcia J, Hostomsky Z, de Murcia G, Schreiber V. Base excision repair is impaired in mammalian cells lacking Poly(ADP-ribose) polymerase-1. Biochemistry. 2000;39:7559–69.PubMedCrossRefGoogle Scholar
  182. 182.
    McCabe N, Turner NC, Lord CJ, Kluzek K, Bialkowska A, Swift S, et al. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res. 2006;66:8109–15.Google Scholar
  183. 183.
    Ashworth A. A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol. 2008;26:3785–90.PubMedCrossRefGoogle Scholar
  184. 184.
    Farmer H, McCabe N, Lord CJ. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917–21.PubMedCrossRefGoogle Scholar
  185. 185.
    Bryant HE, Schultz N, Thomas HD. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434:913–7.PubMedCrossRefGoogle Scholar
  186. 186.
    Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, 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. 2010;376:235–44.PubMedCrossRefGoogle Scholar
  187. 187.
    Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010;376:245–51.PubMedCrossRefGoogle Scholar
  188. 188.
    O’Shaughnessy J, Danso MA. A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). Chicago: ASCO; 2011.Google Scholar
  189. 189.
    O’Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, et al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med. 2011;364:205–14.PubMedCrossRefGoogle Scholar
  190. 190.
    Metcalfe K, Lynch H, Gadirian P. Tamoxifen may reduce contralateral cancers in BRCA mutation carriers. ASCO Chicago: J Clin Oncol. 2011;29.Google Scholar
  191. 191.
    Wesolowski R Shealy AG, Tao J, Moore HC. Differential outcomes in patients treated with endocrine therapy for early or locally advanced breast cancer based on BRCA mutation status. In: Oncol JC, editor. Chicago: ASCO; 2009.Google Scholar
  192. 192.
  193. 193.
    Lee CH, Dershaw DD, Kopans D. Breast cancer screening with imaging: recommendations from the society of breast imaging and the ACR on the use of mammography, breast MRI, breast ultrasound, and other technologies for the detection of clinically occult breast cancer. J Am Coll Radiol. 2010;7:18–27.PubMedCrossRefGoogle Scholar
  194. 194.
    Le-Petross HT, Whitman GJ, Atchley DP. Effectiveness of alternating mammography and magnetic resonance imaging for screening women with deleterious BRCA mutations at high risk of breast cancer. Cancer. 2011;117:3900–7.PubMedCrossRefGoogle Scholar
  195. 195.
  196. 196.
    Brentnall TA. Cancer surveillance of patients from familial pancreatic cancer kindreds. Med Clin North Am. 2000;84:707–18.PubMedCrossRefGoogle Scholar
  197. 197.
    Canto MI, Goggins M, Yeo CJ. Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol. 2004;2:606–21.PubMedCrossRefGoogle Scholar
  198. 198.
  199. 199.
    Gabriel EM, Jatoi I. Breast cancer chemoprevention. Expert Rev Anticancer Ther. 2012;12:223–8.PubMedCrossRefGoogle Scholar
  200. 200.
    Fisher B, Costantino JP, Wickerham DL. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90:1371–88.PubMedPubMedCentralCrossRefGoogle Scholar
  201. 201.
    Fisher B, Costantino JP, Wickerham DL. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 2005;97:1652–62.PubMedCrossRefGoogle Scholar
  202. 202.
    Veronesi U, Maisonneuve P, Costa A. Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study. Lancet. 1998;352:93–7.PubMedCrossRefGoogle Scholar
  203. 203.
    Decensi A, Robertson C, Rotmensz N. Effect of tamoxifen and transdermal hormone replacement therapy on cardiovascular risk factors in a prevention trial. Italian Chemoprevention Group. Br J Cancer. 1998;78:572–8.PubMedPubMedCentralCrossRefGoogle Scholar
  204. 204.
    Powles T, Eeles R, Ashley S. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet. 1998;352:98–101.PubMedCrossRefGoogle Scholar
  205. 205.
    Powles TJ, Ashley S, Tidy A, Smith IE, Dowsett M. Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial. J Natl Cancer Inst. 2007;99:283–90.PubMedCrossRefGoogle Scholar
  206. 206.
    Cuzick J, Forbes J, Edwards R. First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. Lancet. 2002;360:817–24.PubMedCrossRefGoogle Scholar
  207. 207.
    Cuzick J, Forbes JF, Sestak I. International Breast Cancer Intervention Study I investigators. Long-term results of tamoxifen prophylaxis for breast cancer – 96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst. 2007;99(4):272–82.PubMedCrossRefGoogle Scholar
  208. 208.
    Cuzick J, Powles T, Veronesi U, Forbes J, Edwards R, Ashley S, et al. Overview of the main outcomes in breast-cancer prevention trials. Lancet. 2003;361:296–300.Google Scholar
  209. 209.
    Atkinson C, Warren R, Bingham SA, Day NE. Mammographic patterns as a predictive biomarker of breast cancer risk: effect of tamoxifen. Cancer Epidemiol Biomark Prev. 1999;8:863–6.Google Scholar
  210. 210.
    Brisson J, Brisson B, Cote G, Maunsell E, Berube S, Robert J. Tamoxifen and mammographic breast densities. Cancer Epidemiol Biomark Prev. 2000;9:911–5.Google Scholar
  211. 211.
    Cuzick J, Warwick J, Pinney E, Warren RM, Duffy SW. Tamoxifen and breast density in women at increased risk of breast cancer. J Natl Cancer Inst. 2004;96:621–8.PubMedCrossRefGoogle Scholar
  212. 212.
    Cuzick J, Warwick J, Pinney E. Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case–control study. J Natl Cancer Inst. 2011;103:744–52.PubMedCrossRefGoogle Scholar
  213. 213.
    Raloxifene hydrochloride. 2007.
  214. 214.
    Ettinger B, Black DM, Mitlak BH. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA. 1999;282:637–45.PubMedCrossRefGoogle Scholar
  215. 215.
    Cauley JA, Norton L, Lippman ME. Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple Outcomes of Raloxifene Evaluation. Breast Cancer Res Treat. 2001;65:125–34.PubMedCrossRefGoogle Scholar
  216. 216.
    Cummings SR, Eckert S, Krueger KA. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA. 1999;281:2189–97.PubMedCrossRefGoogle Scholar
  217. 217.
    Martino S, Cauley JA, Barrett-Connor E. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst. 2004;96:1751–61.PubMedCrossRefGoogle Scholar
  218. 218.
    Vogel VG, Costantino JP, Wickerham DL. 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. 2006;295:2727–41.PubMedPubMedCentralCrossRefGoogle Scholar
  219. 219.
    Vogel VG, Costantino JP, Wickerham DL. Update of the national surgical adjuvant breast and bowel project study of tamoxifen and raloxifene (STAR) P-2 trial: preventing breast cancer. Cancer Prev Res. 2010;3:696–706.CrossRefGoogle Scholar
  220. 220.
    Goldstein SR, Neven P, Cummings S. Postmenopausal evaluation and risk reduction with lasofoxifene (PEARL) trial: 5-year gynecological outcomes. Menopause. 2011;18:17–22.PubMedCrossRefGoogle Scholar
  221. 221.
    Cummings SR, McClung M, Reginster JY. Arzoxifene for prevention of fractures and invasive breast cancer in postmenopausal women. J Bone Miner Res. 2011;26:397–404.PubMedCrossRefGoogle Scholar
  222. 222.
    Powles TJ, Diem SJ, Fabian CJ. Breast cancer incidence in postmenopausal women with osteoporosis or low bone mass using arzoxifene. Breast Cancer Res Treat. 2012;134:299–306.PubMedCrossRefGoogle Scholar
  223. 223.
    Goss PE, Strasser K. Aromatase inhibitors in the treatment and prevention of breast cancer. J Clin Oncol. 2001;19:881–94.PubMedCrossRefGoogle Scholar
  224. 224.
    Litton JK, Bevers TB, Arun BK. Exemestane in the prevention setting. Ther Adv Med Oncol. 2012;4:107–12.PubMedPubMedCentralCrossRefGoogle Scholar
  225. 225.
    Baum M, Buzdar A, Cuzick J. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer. 2003;98:1802–10.PubMedCrossRefGoogle Scholar
  226. 226.
    Coombes RC, Hall E, Gibson LJ. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004;350:1081–92.PubMedCrossRefGoogle Scholar
  227. 227.
    Goss PE, Ingle JN, Martino S. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003;349:1793–802.PubMedCrossRefGoogle Scholar
  228. 228.
    Goss PE, Ingle JN, Ales-Martinez JE. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364:2381–91.PubMedCrossRefGoogle Scholar
  229. 229.
    Cuzick J, Sestak I, Forbes JF. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet. 2014;383:1041–8.PubMedPubMedCentralCrossRefGoogle Scholar
  230. 230.
    Cuzick J, Sestak I, Bonanni B. Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data. Lancet. 2013;381:1827–34.PubMedPubMedCentralCrossRefGoogle Scholar
  231. 231.
    Arun B, Valero V, Liu D. Short-term biomarker modulation prevention study of anastrozole in women at increased risk for second primary breast cancer. Cancer Prev Res. 2012;5:276–82.CrossRefGoogle Scholar
  232. 232.
    King MC, Wieand S, Hale K. 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. 2001;286:2251–6.PubMedCrossRefGoogle Scholar
  233. 233.
    Arun B, Dunn BK, Ford LG, Ryan A. Breast cancer prevention trials: large and small trials. Semin Oncol. 2010;37:367–83.PubMedCrossRefGoogle Scholar
  234. 234.
    World Cancer Research Fund/American Institute for Cancer Research. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Washington, DC: AICR; 2007.Google Scholar
  235. 235.
    Mahoney MC, Bevers T, Linos E, Willett WC. Opportunities and strategies for breast cancer prevention through risk reduction. CA Cancer J Clin. 2008;58:347–71.PubMedCrossRefGoogle Scholar
  236. 236.
    Hamajima N, Hirose K, Tajima K. Alcohol, tobacco and breast cancer – collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer. 2002;87:1234–45.PubMedCrossRefGoogle Scholar
  237. 237.
    Smith-Warner SA, Spiegelman D, Yaun SS. Alcohol and breast cancer in women: a pooled analysis of cohort studies. JAMA. 1998;279:535–40.PubMedCrossRefGoogle Scholar
  238. 238.
    Larsson SC, Bergkvist L, Wolk A. Folate intake and risk of breast cancer by estrogen and progesterone receptor status in a Swedish cohort. Cancer Epidemiol Biomark Prev. 2008;17:3444–9.CrossRefGoogle Scholar
  239. 239.
    Zhang SM, Willett WC, Selhub J. Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. J Natl Cancer Inst. 2003;95:373–80.PubMedCrossRefGoogle Scholar
  240. 240.
    Prentice RL, Caan B, Chlebowski RT. Low-fat dietary pattern and risk of invasive breast cancer: the women’s health initiative randomized controlled dietary modification trial. JAMA. 2006;295:629–42.PubMedCrossRefGoogle Scholar
  241. 241.
    Boyd NF, Stone J, Vogt KN, Connelly BS, Martin LJ, Minkin S. Dietary fat and breast cancer risk revisited: a meta-analysis of the published literature. Br J Cancer. 2003;89:1672–85.PubMedPubMedCentralCrossRefGoogle Scholar
  242. 242.
    Missmer SA, Smith-Warner SA, Spiegelman D. Meat and dairy food consumption and breast cancer: a pooled analysis of cohort studies. Int J Epidemiol. 2002;31:78–85.PubMedCrossRefGoogle Scholar
  243. 243.
    Taylor EF, Burley VJ, Greenwood DC, Cade JE. Meat consumption and risk of breast cancer in the UK Women’s Cohort Study. Br J Cancer. 2007;96:1139–46.PubMedPubMedCentralCrossRefGoogle Scholar
  244. 244.
    Willett WC. Nurses’ Health, Study II (NHS II): risk factors for breast cancer among younger nurses. Bethesda: National Cancer Institute. Accessed Dec 2013.

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Soley Bayraktar
    • 1
    • 2
  • Banu K. Arun
    • 1
  1. 1.Department of Breast Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Medical OncologyMercy Cancer CenterArdmoreUSA

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