Breast Cancer Research and Treatment

, Volume 145, Issue 1, pp 165–175 | Cite as

Modification of breast cancer risk according to age and menopausal status: a combined analysis of five population-based case–control studies

  • Amy Trentham-Dietz
  • Brian L. Sprague
  • John M. Hampton
  • Diana L. Miglioretti
  • Heidi D. Nelson
  • Linda J. Titus
  • Kathleen M. Egan
  • Patrick L. Remington
  • Polly A. Newcomb


While several risk factors for breast cancer have been identified, studies have not consistently shown whether these factors operate more strongly at certain ages or for just pre- or postmenopausal women. We evaluated whether risk factors for breast cancer differ according to age or menopausal status. Data from five population-based case–control studies conducted during 1988–2008 were combined and analyzed. Cases (N = 23,959) and population controls (N = 28,304) completed telephone interviews. Logistic regression was used to estimate adjusted odds ratios and 95 % confidence intervals and tests for interaction by age and menopausal status. Odds ratios for first-degree family history of breast cancer were strongest for younger women—reaching twofold elevations—but were still statistically significantly elevated by 58–69 % among older women. Obesity was inversely associated with breast cancer among younger women and positively associated with risk for older women (interaction P < 0.0001). Recent alcohol intake was more strongly related to breast cancer risk among older women, although consumption of 3 or more drinks/day among younger women also was associated with elevated odd ratios (P < 0.0001). Associations with benign breast disease and most reproductive/menstrual factors did not vary by age. Repeating analysis stratifying by menopausal status produced similar results. With few exceptions, menstrual and lifestyle factors are associated with breast cancer risk regardless of age or menopausal status. Variation in the association of family history, obesity, and alcohol use with breast cancer risk by age and menopausal status may need to be considered when determining individual risk for breast cancer.


Case–control studies Breast neoplasms Alcohol drinking Obesity Risk factors Menopause Age factors 



Breast imaging-reporting and data system


Body mass index


Confidence interval


Estrogen receptor


Human epidermal growth factor receptor 2


International Classification of Diseases-Oncology


Odds ratio


Standard error


Surveillance, Epidemiology and End-Results


  1. 1.
    Collaborative Group on Hormonal Factors in Breast Cancer (1996) Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Lancet 347:1713–1727Google Scholar
  2. 2.
    Althuis MD, Fergenbaum JH, Garcia-Closas M, Brinton LA, Madigan MP, Sherman ME (2004) Etiology of hormone receptor-defined breast cancer: a systematic review of the literature. Cancer Epidemiol Biomark Prev 13:1558–1568Google Scholar
  3. 3.
    Anderson WF, Chatterjee N, Ershler WB, Brawley OW (2002) Estrogen receptor breast cancer phenotypes in the Surveillance, Epidemiology, and End Results database. Breast Cancer Res Treat 76:27–36PubMedCrossRefGoogle Scholar
  4. 4.
    Anderson WF, Chen BE, Brinton LA, Devesa SS (2007) Qualitative age interactions (or effect modification) suggest different cancer pathways for early-onset and late-onset breast cancers. Cancer Causes Control 18:1187–1198. doi:10.1007/s10552-007-9057-x PubMedCrossRefGoogle Scholar
  5. 5.
    Andrieu N, Prevost T, Rohan TE, Luporsi E, Le MG, Gerber M, Zaridze DG, Lifanova Y, Renaud R, Lee HP, Duffy SW (2000) Variation in the interaction between familial and reproductive factors on the risk of breast cancer according to age, menopausal status, and degree of familiality. Int J Epidemiol 29:214–223PubMedCrossRefGoogle Scholar
  6. 6.
    Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, Jong RA, Hislop G, Chiarelli A, Minkin S, Yaffe MJ (2007) Mammographic density and the risk and detection of breast cancer. New Engl J Med 356:227–236. doi:10.1056/NEJMoa062790 PubMedCrossRefGoogle Scholar
  7. 7.
    Boyd NF, Rommens JM, Vogt K, Lee V, Hopper JL, Yaffe MJ, Paterson AD (2005) Mammographic breast density as an intermediate phenotype for breast cancer. Lancet Oncol 6:798–808. doi:10.1016/S1470-2045(05)70390-9 PubMedCrossRefGoogle Scholar
  8. 8.
    Byrne C, Brinton LA, Haile RW, Schairer C (1991) Heterogeneity of the effect of family history on breast cancer risk. Epidemiology 2:276–284PubMedCrossRefGoogle Scholar
  9. 9.
    Calle EE, Martin LM, Thun MJ, Miracle HL, Heath CW Jr (1993) Family history, age, and risk of fatal breast cancer. Am J Epidemiol 138:675–681PubMedGoogle Scholar
  10. 10.
    Chie W-C, Hsieh C–C, Newcomb PA, Longnecker MP, Mittendorf R, Greenberg ER, Clapp RW, Burke KP, Titus-Ernstoff L, Trentham-Dietz A, MacMahon B (2000) Age at any full-term pregnancy and breast cancer risk. Am J Epidemiol 151:715–722PubMedCrossRefGoogle Scholar
  11. 11.
    Chun J, Pocock B, Joseph KA, El-Tamer M, Klein L, Schnabel F (2009) Breast cancer risk factors in younger and older women. Ann Surg Oncol 16:96–99. doi:10.1245/s10434-008-0176-8 PubMedCrossRefGoogle Scholar
  12. 12.
    Claus EB, Risch NJ, Thompson WD (1990) Age at onset as an indicator of familial risk of breast cancer. Am J Epidemiol 131:961–972PubMedGoogle Scholar
  13. 13.
    Colditz GA, Rosner B (2000) Cumulative risk of breast cancer to age 70 years according to risk factor status: data from the Nurses’ Health Study. Am J Epidemiol 152:950–964PubMedCrossRefGoogle Scholar
  14. 14.
    Collaborative Group on Hormonal Factors in Breast Cancer (2002) 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 360:187–195. doi:10.1016/S0140-6736(02)09454-0 CrossRefGoogle Scholar
  15. 15.
    Dorgan JF, Baer DJ, Albert PS, Judd JT, Brown ED, Corle DK, Campbell WS, Hartman TJ, Tejpar AA, Clevidence BA, Giffen CA, Chandler DW, Stanczyk FZ, Taylor PR (2001) Serum hormones and the alcohol-breast cancer association in postmenopausal women. J Natl Cancer Inst 93:710–715PubMedCrossRefGoogle Scholar
  16. 16.
    Egan KM, Stampfer MJ, Rosner BA, Trichopoulos D, Newcomb PA, Trentham-Dietz A, Longnecker MP, Mittendorf R, Greenberg ER, Willett WC (1998) Risk factors for breast cancer in women with a breast cancer family history. Cancer Epidemiol Biomark Prev 7:359–364Google Scholar
  17. 17.
    Hamajima N, Hirose K, Tajima K, Rohan T, Calle EE, Heath CW Jr, Coates RJ, Liff JM, Talamini R, Chantarakul N, Koetsawang S, Rachawat D, Morabia A, Schuman L, Stewart W, Szklo M, Bain C, Schofield F, Siskind V, Band P, Coldman AJ, Gallagher RP, Hislop TG, Yang P, Kolonel LM, Nomura AM, Hu J, Johnson KC, Mao Y, De Sanjose S, Lee N, Marchbanks P, Ory HW, Peterson HB, Wilson HG, Wingo PA, Ebeling K, Kunde D, Nishan P, Hopper JL, Colditz G, Gajalanski V, Martin N, Pardthaisong T, Silpisornkosol S, Theetranont C, Boosiri B, Chutivongse S, Jimakorn P, Virutamasen P, Wongsrichanalai C, Ewertz M, Adami HO, Bergkvist L, Magnusson C, Persson I, Chang-Claude J, Paul C, Skegg DC, Spears GF, Boyle P, Evstifeeva T, Daling JR, Hutchinson WB, Malone K, Noonan EA, Stanford JL, Thomas DB, Weiss NS, White E, Andrieu N, Bremond A, Clavel F, Gairard B, Lansac J, Piana L, Renaud R, Izquierdo A, Viladiu P, Cuevas HR, Ontiveros P, Palet A, Salazar SB, Aristizabel N, Cuadros A, Tryggvadottir L, Tulinius H, Bachelot A, Le MG, Peto J, Franceschi S, Lubin F, Modan B, Ron E, Wax Y, Friedman GD, Hiatt RA, Levi F, Bishop T, Kosmelj K et al (2002) 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 87:1234–1245PubMedCrossRefGoogle Scholar
  18. 18.
    Hankinson S, Tamimi R, Hunter D (2008) Breast Cancer. In: Adami HO, Hunter D, Trichopoulos D (eds) Textbook of cancer epidemiology. Oxford University Press, New York, pp 403–445CrossRefGoogle Scholar
  19. 19.
    Jacobsen BK, Heuch I, Kvale G (2003) Age at natural menopause and all-cause mortality: a 37-year follow-up of 19,731 Norwegian women. Am J Epidemiol 157:923–929PubMedCrossRefGoogle Scholar
  20. 20.
    Kato I, Toniolo P, Akhmedkhanov A, Koenig KL, Shore R, Zeleniuch-Jacquotte A (1998) Prospective study of factors influencing the onset of natural menopause. J Clin Epidemiol 51:1271–1276PubMedCrossRefGoogle Scholar
  21. 21.
    Key J, Hodgson S, Omar RZ, Jensen TK, Thompson SG, Boobis AR, Davies DS, Elliott P (2006) Meta-analysis of studies of alcohol and breast cancer with consideration of the methodological issues. Cancer Causes Control 17:759–770. doi:10.1007/s10552-006-0011-0 PubMedCrossRefGoogle Scholar
  22. 22.
    Key TJ, Appleby PN, Reeves GK, Roddam A, Dorgan JF, Longcope C, Stanczyk FZ, Stephenson HE Jr, Falk RT, Miller R, Schatzkin A, Allen DS, Fentiman IS, Wang DY, Dowsett M, Thomas HV, Hankinson SE, Toniolo P, Akhmedkhanov A, Koenig K, Shore RE, Zeleniuch-Jacquotte A, Berrino F, Muti P, Micheli A, Krogh V, Sieri S, Pala V, Venturelli E, Secreto G, Barrett-Connor E, Laughlin GA, Kabuto M, Akiba S, Stevens RG, Neriishi K, Land CE, Cauley JA, Kuller LH, Cummings SR, Helzlsouer KJ, Alberg AJ, Bush TL, Comstock GW, Gordon GB, Miller SR (2003) Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 95:1218–1226PubMedCrossRefGoogle Scholar
  23. 23.
    Kruk J (2007) Association of lifestyle and other risk factors with breast cancer according to menopausal status: a case–control study in the Region of Western Pomerania (Poland). Asian Pac J Cancer Prev 8:513–524PubMedGoogle Scholar
  24. 24.
    Lambe M, Hsieh C, Trichopoulos D, Ekbom A, Pavia M, Adami HO (1994) Transient increase in the risk of breast cancer after giving birth. N Engl J Med 331:5–9. doi:10.1056/NEJM199407073310102 PubMedCrossRefGoogle Scholar
  25. 25.
    Li CI, Anderson BO, Daling JR, Moe RE (2003) Trends in incidence rates of invasive lobular and ductal breast carcinoma. JAMA 289:1421–1424PubMedCrossRefGoogle Scholar
  26. 26.
    Li CI, Chlebowski RT, Freiberg M, Johnson KC, Kuller L, Lane D, Lessin L, O’Sullivan MJ, Wactawski-Wende J, Yasmeen S, Prentice R (2010) Alcohol consumption and risk of postmenopausal breast cancer by subtype: the women’s health initiative observational study. J Natl Cancer Inst 102:1422–1431. doi:10.1093/jnci/djq316 PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Longnecker MP (1994) Alcoholic beverage consumption in relation to risk of breast cancer: meta-analysis and review. Cancer Causes Control 5:73–82PubMedCrossRefGoogle Scholar
  28. 28.
    Longnecker MP, Newcomb PA, Mittendorf R, Greenberg ER, Clapp RW, Bogdan G, Willett WC, MacMahon B (1992) The reliability of self-reported alcohol consumption in the remote past. Epidemiology 3:535–539PubMedCrossRefGoogle Scholar
  29. 29.
    Lubin JH, Burns PE, Blot WJ, Lees AW, May C, Morris LE, Fraumeni JF Jr (1982) Risk factors for breast cancer in women in northern Alberta, Canada, as related to age at diagnosis. J Natl Cancer Inst 68:211–217PubMedGoogle Scholar
  30. 30.
    Munsell MF, Sprague BL, Berry DA, Chisholm G, Trentham-Dietz A (2014) Body mass index and breast cancer risk according to postmenopausal estrogen–progestin use and hormone receptor status. Epidemiol Rev 36:114–136. doi:10.1093/epirev/mxt010 PubMedCrossRefGoogle Scholar
  31. 31.
    Nelson SE, Gould MN, Hampton JM, Trentham-Dietz A (2005) A case–control study of the HER2 Ile655Val polymorphism in relation to risk of invasive breast cancer. Breast Cancer Res 7:R357–R364PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Newcomb PA, Egan KM, Titus-Ernstoff L, Trentham-Dietz A, Greenberg ER, Baron JA, Willett WC, Stampfer MJ (1999) Lactation in relation to postmenopausal breast cancer. Am J Epidemiol 150:174–182PubMedCrossRefGoogle Scholar
  33. 33.
    Newcomb PA, Longnecker MP, Storer BE, Mittendorf R, Baron JA, Clapp RW, Bogdan G, Willett WC (1995) Long-term hormone replacement therapy and risk of breast cancer in postmenopausal women. Am J Epidemiol 142:788–795PubMedGoogle Scholar
  34. 34.
    Newcomb PA, Storer BE, Longnecker MP, Mittendorf R, Greenberg ER, Clapp RW, Burke KP, Willett WC, MacMahon B (1994) Lactation and a reduced risk of premenopausal breast cancer. N Engl J Med 330:81–87PubMedCrossRefGoogle Scholar
  35. 35.
    Newcomb PA, Trentham-Dietz A, Hampton JM (2010) Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk. Br J Cancer 102:799–802. doi:10.1038/sj.bjc.6605555 PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Newcomer LM, Newcomb PA, Potter JD, Yasui Y, Trentham-Dietz A, Storer BE, Longnecker MP, Baron JA, Daling JR (2003) Postmenopausal hormone therapy and risk of breast cancer by histologic type (United States). Cancer Causes Control 14:225–233PubMedCrossRefGoogle Scholar
  37. 37.
    Newcomer LM, Newcomb PA, Trentham-Dietz A, Longnecker MP, Greenberg ER (2003) Oral contraceptive use and risk of breast cancer by histologic type. Int J Cancer 106:961–964PubMedCrossRefGoogle Scholar
  38. 38.
    Nichols HB, Trentham-Dietz A, Hampton JM, Titus-Ernstoff L, Egan KM, Willett WC, Newcomb PA (2006) From menarche to menopause: trends among US Women born from 1912 to 1969. Am J Epidemiol 164:1003–1011PubMedCrossRefGoogle Scholar
  39. 39.
    Pathak DR, Speizer FE, Willett WC, Rosner B, Lipnick RJ (1986) Parity and breast cancer risk: possible effect on age at diagnosis. Int J Cancer 37:21–25PubMedCrossRefGoogle Scholar
  40. 40.
    Phipps AI, Buist DS, Malone KE, Barlow WE, Porter PL, Kerlikowske K, Li CI (2011) Family history of breast cancer in first-degree relatives and triple-negative breast cancer risk. Breast Cancer Res Treat 126:671–678. doi:10.1007/s10549-010-1148-9 PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Phipps AI, Buist DS, Malone KE, Barlow WE, Porter PL, Kerlikowske K, Li CI (2011) Reproductive history and risk of three breast cancer subtypes defined by three biomarkers. Cancer Causes Control 22:399–405. doi:10.1007/s10552-010-9709-0 PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Phipps AI, Chlebowski RT, Prentice R, McTiernan A, Stefanick ML, Wactawski-Wende J, Kuller LH, Adams-Campbell LL, Lane D, Vitolins M, Kabat GC, Rohan TE, Li CI (2011) Body size, physical activity, and risk of triple-negative and estrogen receptor-positive breast cancer. Cancer Epidemiol Biomark Prev 20:454–463. doi:10.1158/1055-9965.EPI-10-0974 CrossRefGoogle Scholar
  43. 43.
    Ramsey SD, Yoon P, Moonesinghe R, Khoury MJ (2006) Population-based study of the prevalence of family history of cancer: implications for cancer screening and prevention. Genet Med 8:571–575. doi:10.109701.gim.0000237867.34011.12 PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371:569–578. doi:10.1016/S0140-6736(08)60269-X PubMedCrossRefGoogle Scholar
  45. 45.
    Roseman DL, Straus AK, Shorey W (1990) A positive family history of breast cancer. Does it effect diminish with age? Arch Intern Med 150:191–194PubMedCrossRefGoogle Scholar
  46. 46.
    Rosenberg L, Metzger LS, Palmer JR (1993) Alcohol consumption and risk of breast cancer: a review of the epidemiologic evidence. Epidemiol Rev 15:133–144PubMedGoogle Scholar
  47. 47.
    Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results. From the Women’s Health Initiative randomized controlled trial. JAMA 288:321–333PubMedCrossRefGoogle Scholar
  48. 48.
    Smith-Warner SA, Spiegelman D, Yaun SS, van den Brandt PA, Folsom AR, Goldbohm RA, Graham S, Holmberg L, Howe GR, Marshall JR, Miller AB, Potter JD, Speizer FE, Willett WC, Wolk A, Hunter DJ (1998) Alcohol and breast cancer in women: a pooled analysis of cohort studies. JAMA 279:535–540PubMedCrossRefGoogle Scholar
  49. 49.
    Sowers MR, La Pietra MT (1995) Menopause: its epidemiology and potential association with chronic diseases. Epidemiol Rev 17:287–302PubMedGoogle Scholar
  50. 50.
    Sprague BL, Trentham-Dietz A, Hampton JM, Egan KM, Titus-Ernstoff L, Remington PL, Newcomb PA (2011) Variation in breast cancer risk factors by mode of detection. Am J Epidemiol 173:S251Google Scholar
  51. 51.
    Sprague BL, Trentham-Dietz A, Newcomb PA, Titus-Ernstoff L, Hampton JM, Egan KM (2007) Lifetime recreational and occupational physical activity and risk of in situ and invasive breast cancer. Cancer Epidemiol Biomark Prev 16:236–243CrossRefGoogle Scholar
  52. 52.
    Surveillance Epidemiology and End Results (SEER) Program (April 2011 (updated 10/28/2011), based on the November 2010 submission) SEER*Stat Database: Incidence—SEER 9 Regs Research Data, Nov 2010 Sub (1973–2008) <Katrina/Rita Population Adjustment>-Linked to County Attributes—Total U.S., 1969–2009 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics BranchGoogle Scholar
  53. 53.
    Suzuki R, Orsini N, Mignone L, Saji S, Wolk A (2008) Alcohol intake and risk of breast cancer defined by estrogen and progesterone receptor status—a meta-analysis of epidemiological studies. Int J Cancer 122:1832–1841. doi:10.1002/ijc.23184 PubMedCrossRefGoogle Scholar
  54. 54.
    Suzuki R, Orsini N, Saji S, Key TJ, Wolk A (2009) Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status—a meta-analysis. Int J Cancer 124:698–712. doi:10.1002/ijc.23943 PubMedCrossRefGoogle Scholar
  55. 55.
    Trentham-Dietz A, Newcomb PA, Storer BE, Longnecker MP, Baron JA, Greenberg ER, Willett WC (1997) Body size and risk of breast cancer. Am J Epidemiol 145:1011–1019PubMedCrossRefGoogle Scholar
  56. 56.
    WHO (2000) Obesity: preventing and managing the global epidemic. Report of a WHO Consulation. In: WHO Technical Report Series 894. World Health Organization, GenevaGoogle Scholar
  57. 57.
    World Cancer Research Fund/American Institute for Cancer Research (2007) 7.10 Breast Cancer. In: Food, nutrition, physical activity, and the prevention of cancer: a global perspective. AICR, Washington, DC, pp. 289–295Google Scholar
  58. 58.
    World Cancer Research Fund/American Institute for Cancer Research (2007) Food, nutrition, physical activity, and the prevention of cancer: a global perspective. AICR, Washington DCGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Amy Trentham-Dietz
    • 1
  • Brian L. Sprague
    • 2
  • John M. Hampton
    • 9
  • Diana L. Miglioretti
    • 3
    • 4
  • Heidi D. Nelson
    • 5
  • Linda J. Titus
    • 6
  • Kathleen M. Egan
    • 7
  • Patrick L. Remington
    • 1
  • Polly A. Newcomb
    • 8
    • 9
  1. 1.Department of Population Health Sciences, University of Wisconsin Carbone Cancer CenterUniversity of WisconsinMadisonUSA
  2. 2.Department of Surgery and Vermont Cancer CenterUniversity of VermontBurlingtonUSA
  3. 3.Department of Public Health SciencesUniversity of CaliforniaDavisUSA
  4. 4.Group Health Research InstituteSeattleUSA
  5. 5.Department of Medical Informatics and Clinical Epidemiology and Medicine, Oregon Health & Sciences University, and Providence Cancer CenterProvidence Health and ServicesPortlandUSA
  6. 6.Geisel School of Medicine at DartmouthHanoverUSA
  7. 7.Moffitt Cancer CenterTampaUSA
  8. 8.Fred Hutchinson Cancer Research CenterSeattleUSA
  9. 9.Carbone Cancer CenterUniversity of WisconsinMadisonUSA

Personalised recommendations