Epidemiology and Clinical Risk Factors

  • Mary B. Daly
Part of the Current Clinical Oncology book series (CCO)


Breast cancer remains the most common cancer among women in the United States, and the second leading cause of death due to cancer, with approximately 43,300 deaths expected a year. After decades of increasing incidence rates, data from the Surveillance, Epidemiology, and End Results (SEER) program indicate a plateau in rates of new cases between 1990 and 1996 and a shift in stage from regional and distant stages to more localized disease (1). Over the same period, breast cancer death rates have declined (on average) by 1.7% a year (2) (Fig. 1). Despite these recent promising trends, breast cancer represents a significant personal and societal burden that affects women in the prime of their lives and accounts for a large portion of the health care budget. A long history of classical epidemiologic studies, now coupled with the new information emerging from the field of molecular genetics, is beginning to elucidate the basic mechanisms of breast carcinogenesis and allow development of novel treatment and prevention strategies.


Breast Cancer Breast Cancer Risk Mammographic Density Breast Cancer Incidence Clinical Risk Factor 
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  1. 1.
    Chu KC, Tarone RE, Kessler LG, et al. (1996) Recent trends in U.S. breast cancer incidence, survival, and mortality rates. J. Natl. Cancer Inst. 88, 1571–1579.PubMedCrossRefGoogle Scholar
  2. 2.
    Wingo P, Ries L, Giovino G, et al. (1999) Annual report to the nation on the status of cancer, 1973–1996, with a special section on lung cancer and tobacco smoking. J. Natl. Cancer Inst. 91, 675–690.PubMedCrossRefGoogle Scholar
  3. 3.
    Hankey BF, Miller B, Curtis R, Kosary C (1994) Trends in breast cancer in younger women in contrast to older women. Monogr. Natl. Cancer Inst. 16, 7–14.PubMedGoogle Scholar
  4. 4.
    Winchester D, Osteen R, Menck H (1996) The national cancer data base report on breast carcinoma characteristics and outcome in relation to age. Cancer 78, 1838–1843.PubMedCrossRefGoogle Scholar
  5. 5.
    De La Rochefordiere A, Asselain B, Campana F, et al. (1993) Age as prognostic factor in premenopausal breast carcinoma. Lancet 341, 1039–1043.PubMedCrossRefGoogle Scholar
  6. 6.
    Stat Bite (1996) Breast cancer incidence by race/ethnicity. J. Natl. Cancer Inst. 88, 577.CrossRefGoogle Scholar
  7. 7.
    Krieger N (1990) Social class and the black/white crossover in the age-specific incidence of breast cancer: a study linking census-derived data to population-based registry records. Am. J. Epidemiol. 131, 804–814.PubMedGoogle Scholar
  8. 8.
    Eidson M, Becker T, Wiggins C, Key C, Samet J (1994) Breast cancer among Hispanics, American Indians and Non-Hispanic whites in New Mexico. Int. J. Epidemiol. 23, 231–237.PubMedCrossRefGoogle Scholar
  9. 9.
    Mettlin C (1999) Global breast cancer mortality statistics. CA 49, 138–144.PubMedGoogle Scholar
  10. 10.
    Berg J (1984) Clinical implications of risk factors for breast cancer. Cancer 53, 589–591.PubMedCrossRefGoogle Scholar
  11. 11.
    National Cancer Institute (1999) Atlas of Cancer Mortality in the United States, 1950–94. NIH Publication No. 99–4564. NIH, Bethesda, MD, pp. 211–212.Google Scholar
  12. 12.
    Sturgeon S, Schairer C, Gail M, McAdams M, Brinton L, Hoover R (1995) Geographic variation in mortality from breast cancer among white women in the United States. J. Natl. Cancer Inst. 87, 1846–1853.PubMedCrossRefGoogle Scholar
  13. 13.
    MacMahon B, Cole P, Brown J (1973) Etiology of human breast cancer: a review. J. Natl. Cancer Inst. 50, 21–42.PubMedGoogle Scholar
  14. 14.
    Henderson IC (1993) Risk factors for breast cancer development. Cancer (Suppl.) 71, 2127–2140.CrossRefGoogle Scholar
  15. 15.
    Colton T, Greenberg R, Noller K, et al. (1993) Breast cancer in mothers prescribed diethylstilbestrol in pregnancy. JAMA 269, 2096–2100.PubMedCrossRefGoogle Scholar
  16. 16.
    Rookus M, van Leeuwen F (1996) Induced abortion and risk for breast cancer: reporting (recall) bias in a Dutch case-control study. J. Natl. Cancer Inst. 88, 1759–1764.PubMedCrossRefGoogle Scholar
  17. 17.
    Melbye M, Wohlfahrt J, Olsen J, et al. (1997) Induced abortion and the risk of breast cancer. N. Engl. J. Med. 336, 81–85.PubMedCrossRefGoogle Scholar
  18. 18.
    Hankinson S, Willett W, Manson J, et al. (1998) Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. J. Natl. Cancer Inst. 90, 1292–1299.Google Scholar
  19. 19.
    Hankinson S, Willett W, Michaud D, et al. (1999) Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women. J. Natl. Cancer Inst. 91, 629–634.PubMedCrossRefGoogle Scholar
  20. 20.
    Michnovicz J, Bradlow H (1990) Induction of estradiol metabolism by dietary indole-3-carbinol in humans. J. Natl. Cancer Inst. 82, 947–949.PubMedCrossRefGoogle Scholar
  21. 21.
    Henderson IC (1990) What can a woman do about her risk of dying of breast cancer? Curr. Probl. Cancer 14, 165–229.CrossRefGoogle Scholar
  22. 22.
    Kelsey J, Berkowitz G (1988) Breast cancer epidemiology. Cancer Res. 48, 5615–5623.PubMedGoogle Scholar
  23. 23.
    Greenwald P, Kramer B, Weed D (1993) Expanding horizons in breast and prostate cancer prevention and early detection. J. Cancer Educ. 8, 91–107.PubMedCrossRefGoogle Scholar
  24. 24.
    Holmes MD, Hunter DJ, Colditz GA, et al. (1999) Association of dietary intake of fat and fatty acids with risk of breast cancer. JAMA 281, 914–920.PubMedCrossRefGoogle Scholar
  25. 25.
    Schatzkin A, Jones Y, Hoover R, et al. (1987) Alcohol consumption and breast cancer in the epidemiologic follow-up study of the first National Health and Nutrition Examination Survey. N. Engl. J. Med. 316, 1169–1173.PubMedCrossRefGoogle Scholar
  26. 26.
    Reed MJ, Beranek PA, Cheng RW, McNeill JM, James VH (1987) Peripheral oestrogen metabolism in postmenopausal women with or without breast cancer: the role of dietary lipids and growth factors. J. Steroid Biochem. 27, 985–989.PubMedCrossRefGoogle Scholar
  27. 27.
    Wu A, Pike M, Stram D (1999) Meta-analysis: dietary fat intake, serum estrogen levels, and the risk of breast cancer. J. Natl. Cancer Inst. 91, 529–534.PubMedCrossRefGoogle Scholar
  28. 28.
    Thune I, Brenn T, Lund E, Gaard M (1997) Physical activity and the risk of breast cancer. N. Engl. J. Med. 336, 1269–1275.PubMedCrossRefGoogle Scholar
  29. 29.
    Aisenberg A, Finkelstein D, Doppke K, Koerner F, Boivin J, Willett C (1997) High risk of breast carcinoma after irradiation of young women with Hodgkin’s disease. Cancer 79, 1203–1210.PubMedCrossRefGoogle Scholar
  30. 30.
    Miller A, Howe G, Sherman G, et al. (1989) Mortality from breast cancer after irradiation during fluoroscopic examinations in patients being treated for tuberculosis. N. Engl. J. Med. 321, 1285–1289.PubMedCrossRefGoogle Scholar
  31. 31.
    Hoffman D, Lonstein J, Morin M, Visscher W, Harris B, Boice J (1989) Breast cancer in women with scolio-sis exposed to multiple diagnostic X rays. J. Natl. Cancer Inst. 81, 1307–1312.PubMedCrossRefGoogle Scholar
  32. 32.
    Hildreth N, Shore R, Dvoretsky P (1989) The risk of breast cancer after irradiation of the thymus in infancy. N. Engl. J. Med. 321, 1281–1284.PubMedCrossRefGoogle Scholar
  33. 33.
    Anderson N, Lokich J (1990) Bilateral breast cancer after cured Hodgkin’s disease. Cancer 65, 221–223.PubMedCrossRefGoogle Scholar
  34. 34.
    Boice J, Mandel J, Doody M (1995) Breast cancer among radiologic technologists. JAMA 274, 394–401.PubMedCrossRefGoogle Scholar
  35. 35.
    Dupont W, Page D (1987) Breast cancer risk associated with proliferative disease, age at first birth, and a family history of breast cancer. Am. J. Epidemiol. 125, 769–779.PubMedGoogle Scholar
  36. 36.
    Jensen R, Page D, Dupont W, Rogers L (1989) Invasive breast cancer risk in women with sclerosing adenosis. Cancer 64, 1977–1983.PubMedCrossRefGoogle Scholar
  37. 37.
    Dupont W, Page D, Parl F, et al. (1994) Long-term risk of breast cancer in women with fibroadenoma. N. Engl. J. Med. 331, 10–15.PubMedCrossRefGoogle Scholar
  38. 38.
    Marshall L, Hunter D, Connolly J, et al. (1997) Risk of breast cancer associated with atypical hyperplasia of lobular and ductal types. Cancer Epidemiol. Biomarkers Prey. 6, 297–301.Google Scholar
  39. 39.
    Osborne M, Hoda S (1994) Current management of lobular carcinoma in situ of the breast. Oncology 8, 45–49.PubMedGoogle Scholar
  40. 40.
    Hutter R (1982) Lobular carcinoma in situ. CA 32, 231–2.Google Scholar
  41. 41.
    Bodian C, Perzin K, Lattes R (1996) Lobular neoplasia, long term risk of breast cancer and relation to other factors. Cancer 78, 1024–1034.PubMedCrossRefGoogle Scholar
  42. 42.
    Wolfe J (1976) Risk for breast cancer development determined by mammographic parenchymal pattern. Cancer 37, 2486–2492.PubMedCrossRefGoogle Scholar
  43. 43.
    Wolfe J (1976) Breast patterns as an index of risk for developing breast cancer. AJR 126, 1130–1139.PubMedCrossRefGoogle Scholar
  44. 44.
    Boyd N, Lockwood G, Byng J, Trichtler D, Yaffe M (1998) Mammographic densities and breast cancer risk. Cancer Epidemiol. Biomarkers Prey. 7, 1133–1144.Google Scholar
  45. 45.
    Byrne C, Schairer C, Wolfe J, et al. (1995) Mammographic features and breast cancer risk: effects with time, age, and menopause status. J. Natl. Cancer Inst. 87, 1622–1629.PubMedCrossRefGoogle Scholar
  46. 46.
    Boyd N, Jensen H, Cooke G, Han H (1992) Relationship between mammographic and histological risk factors for breast cancer. J. Nalt. Cancer Inst. 84, 1170–1179.CrossRefGoogle Scholar
  47. 47.
    Pankow J, Vachon C, Kuni C, et al. (1997) Genetic analysis of mammographic breast density in adult women: evidence of a gene effect. J. Natl. Cancer Inst. 89, 549–556.PubMedCrossRefGoogle Scholar
  48. 48.
    Knight J, Martin L, Greenberg C, et al. (1999) Macronutrient intake and change in mammographic density at menopause: results from a randomized trial. Cancer Epidemiol. Biomarkers Prey. 8, 123–128.Google Scholar
  49. 49.
    Zheng W, Shu X, McLaughlin J, Chow W, Gao Y, Blot W (1993) Occupational physical activity and the incidence of cancer of the breast, corpus uteri, and ovary in Shanghai. Cancer 71, 3620–3624.PubMedCrossRefGoogle Scholar
  50. 50.
    Helzlsouer K, Alberg A, Huang H, et al. (1999) Serum concentrations of organochlorine compounds and the subsequent development of breast cancer. Cancer Epidemiol. Biomarkers Prey. 8, 525–532.Google Scholar
  51. 51.
    Krieger N, Wolff M, Hiatt R, Rivera M, Vogelman J, Orentreich N (1994) Breast cancer and serum organochlorines: a prospective study among white, black and Asian women. J. Natl. Ganser Inst. 86, 589–599.CrossRefGoogle Scholar
  52. 52.
    Hunter D, Hankinson S, Laden F, et al. (1997) Plasma organochlorine levels and the risk of breast cancer. N. Engl. J. Med. 337, 1253–1258.PubMedCrossRefGoogle Scholar
  53. 53.
    Zheng T, Holford T, Mayne S, et al. (1999) Environmental exposure to hexachlorobenzene (HCB) and risk of female breast cancer in Connecticut. Cancer Epidemiol. Biomarkers Prey. 8, 407–411.Google Scholar
  54. 54.
    Zheng T, Holford T, Mayne S, et al. (1999) (3-Benzene hexachloride in breast adipose tissue and risk of breast carcinoma. Cancer 85, 2212–2218.Google Scholar
  55. 55.
    Horn-Ross PL (1993) Multiple primary cancers involving the breast. Epidemiol. Rev. 15, 169–176.PubMedGoogle Scholar
  56. 56.
    Thompson WD (1994) Genetic epidemiology of breast cancer. Cancer 74, 279–287.PubMedCrossRefGoogle Scholar
  57. 57.
    Colditz GA, Willett WC, Hunter DJ, et al. (1993) Family history, age, and risk of breast cancer. JAMA 270, 338–343.PubMedCrossRefGoogle Scholar
  58. 58.
    Colditz GA, Rosner BA, Speizer FE for the Nurses’ Health Study Research Group (1996) Risk factors for breast cancer according to family history of breast cancer. J. Natl. Cancer Inst. 88, 365–371.PubMedCrossRefGoogle Scholar
  59. 59.
    Chen P-L, Sellers TA, Rich SS, Potter JD, Folsom AR (1994) Examination of the effect of nongenetic risk factors on the familial risk of breast cancer among relatives of postmenopausal breast cancer patients. Cancer Epidemiol. Biomarkers Prey. 3, 549–555.Google Scholar
  60. 60.
    Claus EB, Risch N, Thompson WD, Carter D (1993) Relationship between breast histopathology and family history of breast cancer. Cancer 71, 147–153.PubMedCrossRefGoogle Scholar
  61. 61.
    Rosen PP, Lesser ML, Senie RT, Kinne DW (1982) Epidemiology of breast carcinoma III: relationship of family history to tumor type. Cancer 50, 171–179.PubMedCrossRefGoogle Scholar
  62. 62.
    DuPont W, Page D (1985) Risk factors for breast cancer in women with proliferative breast disease. N. Engl. J. Med. 312, 146.PubMedCrossRefGoogle Scholar
  63. 63.
    Claus EB, Risch N, Thompson WD (1991) Genetic analysis of breast cancer in the cancer and steroid hormone study. Am. J. Hum. Genet. 48, 232–242.PubMedGoogle Scholar
  64. 64.
    Narod S, Feunteun J, Lynch H, et al. (1991) Familial breast-ovarian locus on chromosome 17812–23. Lancet 338, 82.PubMedCrossRefGoogle Scholar
  65. 65.
    Phipps RF, Perry PM (1988) Familial breast cancer. Postgrad. Med. J. 64, 847–849.PubMedCrossRefGoogle Scholar
  66. 66.
    Sellers TA, Potter JD, Rich SS, et al. (1994) Familial clustering of breast and prostate cancers and risk of postmenopausal breast cancer. J. Natl. Cancer Inst. 86, 1860–1865.PubMedCrossRefGoogle Scholar
  67. 67.
    Hall J, Lee M, Newman B, et al. (1990) Linkage of early onset familial breast cancer to chromosome 17q21. Science 250, 1684–1689.PubMedCrossRefGoogle Scholar
  68. 68.
    Easton DF, Bishop DT, Ford D, Crockford GP, the Breast Cancer Linkage Consortium (1993) Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. Am. J. Hum. Genet. 52, 678–701.PubMedGoogle Scholar
  69. 69.
    Wooster R, Neuhausen SL, Mangion J, et al. (1994) Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13812–13. Science 265, 2088–2090.PubMedCrossRefGoogle Scholar
  70. 70.
    Gayther SA, Mangion J, Russell P, et al. (1997) Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene. Nat. Genet. 15, 103–105.PubMedCrossRefGoogle Scholar
  71. 71.
    Schubert EL, Lee MK, Mefford HC, et al. (1997) BRCA2 in American families with four or more cases of breast or ovarian cancer: recurrent and novel mutations, variable expression, penetrance, and the possibility of families whose cancer is not attributable to BRCA1 or BRCA2. Am. J. Hum. Genet. 60, 1031–1040.Google Scholar
  72. 72.
    Miki Y, Swensen J, Shattuck-Eidens D, et al. (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266, 66–71.CrossRefGoogle Scholar
  73. 73.
    Scully R, Chen J, Plug A (1997) Association of BRCAI with Rad51 in mitotic and meiotic cells. Cell 88, 265–275.PubMedCrossRefGoogle Scholar
  74. 74.
    Sharan SK, Morimatsu M, Albrecht U, et al. (1997) Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking BRCA2. Nature 386, 804–810.PubMedCrossRefGoogle Scholar
  75. 75.
    Blackwood A, Weber B (1998) BRCA1 and BRCA2. From molecular genetics to clinical medicine. J. Clin. Oncol. 16, 1969–1977.Google Scholar
  76. 76.
    Abbot D, Freeman M, Holt J (1998) Double-strand break repair deficiency and radiation sensitivity in BRCA2 mutant cancer cells. J. Natl. Cancer Inst. 90, 978–985.CrossRefGoogle Scholar
  77. 77.
    Biggs P, Bradley A (1998) A step toward genotype-based therapeutic regimens for breast cancer in patients with BRCA2 mutations? J. Natl. Cancer Inst. 90, 951–953.PubMedCrossRefGoogle Scholar
  78. 78.
    Neuhausen S, Gilewski T, Norton L, et al. (1998) Recurrent BRCA2 6174de1T mutations in Ashkenazi Jewish women affected by breast cancer. Nat. Genet. 13, 126–128.CrossRefGoogle Scholar
  79. 79.
    Peelen T, van Vliet M, Petrij-Bosch A, et al. (1997) A high proportion of novel mutations in BRCAI with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families. Am. J. Hum. Genet. 60, 1041–1049.PubMedGoogle Scholar
  80. 80.
    Thorlacius S, Olafsdottir G, Kryggvadottir L, et al. (1996) A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes. Nat. Genet. 13, 1 17–119.CrossRefGoogle Scholar
  81. 81.
    Greene MH (1997) Genetics of breast cancer. May. Clin. Proc. 72, 54–65.CrossRefGoogle Scholar
  82. 82.
    Malone KE, Daling JR, Weiss NS, McKnight B, White E, Voigt LF (1996) Family history and survival of young women with invasive breast carcinoma. Cancer 78, 1417–1425.PubMedCrossRefGoogle Scholar
  83. 83.
    Breast Cancer Linkage Consortium (1997) Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 and BRCA2 mutations and sporadic cases. Lancet 349, 1505–1510.CrossRefGoogle Scholar
  84. 84.
    Marcus JN, Page DL, Watson P, Narod SA, Lenoir GM, Lynch HT (1997) BRCAI and BRCA2 hereditary breast carcinoma phenotypes. Cancer 80, 543–556.Google Scholar
  85. 85.
    Marcus JN, Watson P, Page DL, et al. (1996) Hereditary breast cancer-pathobiology, prognosis, and BRCAI and BRCA2 gene linkage. Cancer 77, 697–709.PubMedCrossRefGoogle Scholar
  86. 86.
    Verhoog LC, Brekelmans CTM, Seynaeve C, et al. (1998) Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCAI. Lancet 351, 316–321.PubMedCrossRefGoogle Scholar
  87. 87.
    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, 397–404.PubMedGoogle Scholar
  88. 88.
    Garber JE, Goldstein AM, Kantor, AF, Dreyfus MG, Fraumeni JF Jr, Li FP (1991) Follow-up study of twenty-four families with Li-Fraumeni syndrome. Cancer Res. 51, 6094–6097.PubMedGoogle Scholar
  89. 89.
    Bottomley R, Condit P (1968) Cancer families. Cancer Bull. 20, 22.Google Scholar
  90. 90.
    Ford D, Easton DF (1995) The genetics of breast and ovarian cancer. Br. J. Cancer 72, 805–812.PubMedCrossRefGoogle Scholar
  91. 91.
    Tsou HC, Teng DHF, Ping XL, et al. (1997) The role of MMAC1 mutations in early-onset breast cancer: causative in association with Cowden syndrome and excluded in BRCAI-negative cases. Am. J. Hum. Genet. 61, 1036–1043.PubMedCrossRefGoogle Scholar
  92. 92.
    Lynch ED, Ostermeyer EA, Lee MK, et al. (1997) Inherited mutations in PTEN that are associated with breast cancer, Cowden disease, and juvenile polyposis. Am. J. Hum. Genet. 61, 1254–1260.PubMedCrossRefGoogle Scholar
  93. 93.
    Myers MP, Tonks NK (1997) Invited Editorial-PTEN: sometimes taking it off can be better than putting it on. Am. J. Hum. Genet. 61, 1234–1238.PubMedCrossRefGoogle Scholar
  94. 94.
    Savitsky K, Bar-Shira A, Gilad S, et al. (1995) A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268, 1749–1753.PubMedCrossRefGoogle Scholar
  95. 95.
    Gilad S, Chessa L, Khosravi R, et al. (1998) Genotype-phenotype relationships in ataxia-telangiectasia and variants. Am. J. Hum. Genet. 62, 551–561.PubMedCrossRefGoogle Scholar
  96. 96.
    Easton DF (1994) Cancer risks in A-T heterozygotes. Int. J. Radiat. Biol. 66 (suppl. 6), S 177–182.CrossRefGoogle Scholar

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  • Mary B. Daly

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