Breast Cancer Research and Treatment

, Volume 158, Issue 2, pp 351–359 | Cite as

Reproductive factors related to childbearing and mammographic breast density

  • Lusine Yaghjyan
  • Graham A. Colditz
  • Bernard Rosner
  • Kimberly A. Bertrand
  • Rulla M. Tamimi
Epidemiology

Abstract

We investigated the associations of reproductive factors related to childbearing with percent breast density, absolute dense and nondense areas, by menopausal status. This study included 4110 cancer-free women within the Nurses’ Health Study and Nurses’ Health Study II cohorts. Percent breast density, absolute dense and nondense areas were measured from digitized mammography film images with computerized techniques. All density measures were square root-transformed in all the analyses to improve normality. The data on reproductive variables and other breast cancer risk factors were obtained from biennial questionnaires, at the time of the mammogram date. As compared to nulliparous women, parous postmenopausal women had lower percent density (β = −0.60, 95 % CI −0.84; −0.37), smaller absolute dense area (β = −0.66, 95 % CI −1.03; −0.29), and greater nondense area (β = 0.72, 95 % CI 0.27; 1.16). Among parous women, number of children was inversely associated with percent density in pre- (β per one child = −0.12, 95 % CI −0.20; −0.05) and postmenopausal women (β per one child = −0.07, 95 % CI −0.12; −0.02). The positive associations of breastfeeding with absolute dense and nondense areas were limited to premenopausal women, while the positive association of the age at first child’s birth with percent density and the inverse association with nondense area were limited to postmenopausal women. Women with greater number of children and younger age at first child’s birth have more favorable breast density patterns that could explain subsequent breast cancer risk reduction.

Keywords

Parity Breastfeeding Age at first child Breast density Risk prediction 

References

  1. 1.
    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(10):798–808PubMedCrossRefGoogle Scholar
  2. 2.
    Ginsburg OM, Martin LJ, Boyd NF (2008) Mammographic density, lobular involution, and risk of breast cancer. Br J Cancer 99(9):1369–1374PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Tamimi RM, Byrne C, Colditz GA, Hankinson SE (2007) Endogenous hormone levels, mammographic density, and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst 99(15):1178–1187PubMedCrossRefGoogle Scholar
  4. 4.
    Harvey JA, Bovbjerg VE (2004) Quantitative assessment of mammographic breast density: relationship with breast cancer risk. Radiology 230(1):29–41PubMedCrossRefGoogle Scholar
  5. 5.
    Boyd NF, Byng JW, Jong RA, Fishell EK, Little LE, Miller AB, Lockwood GA, Tritchler DL, Yaffe MJ (1995) Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. J Natl Cancer Inst 87(9):670–675PubMedCrossRefGoogle Scholar
  6. 6.
    Byrne C, Schairer C, Wolfe J, Parekh N, Salane M, Brinton LA, Hoover R, Haile R (1995) Mammographic features and breast cancer risk: effects with time, age, and menopause status. J Natl Cancer Inst 87(21):1622–1629PubMedCrossRefGoogle Scholar
  7. 7.
    Pettersson A, Hankinson S, Willett W, Lagiou P, Trichopoulos D, Tamimi R (2011) Nondense mammographic area and risk of breast cancer. Breast Cancer Res 13(5):R100PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Aitken Z, McCormack VA, Highnam RP, Martin L, Gunasekara A, Melnichouk O, Mawdsley G, Peressotti C, Yaffe M, Boyd NF, dos Santos Silva I (2010) Screen-film mammographic density and breast cancer risk: a comparison of the volumetric standard mammogram form and the interactive threshold measurement methods. Cancer Epidemiol Biomark Prev 19(2):418–428CrossRefGoogle Scholar
  9. 9.
    Stone J, Ding J, Warren RM, Duffy SW, Hopper JL (2010) Using mammographic density to predict breast cancer risk: dense area or percentage dense area. Breast Cancer Res 12(6):R97PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Ursin G, Ma H, Wu AH, Bernstein L, Salane M, Parisky YR, Astrahan M, Siozon CC, Pike MC (2003) Mammographic density and breast cancer in three ethnic groups. Cancer Epidemiol Biomark Prev 12(4):332–338Google Scholar
  11. 11.
    Maskarinec G, Pagano I, Lurie G, Wilkens LR, Kolonel LN (2005) Mammographic density and breast cancer risk. Am J Epidemiol 162(8):743–752PubMedCrossRefGoogle Scholar
  12. 12.
    Boyd N, Martin L, Gunasekara A, Melnichouk O, Maudsley G, Peressotti C, Yaffe M, Minkin S (2009) Mammographic density and breast cancer risk: evaluation of a novel method of measuring breast tissue volumes. Cancer Epidemiol Biomark Prev 18(6):1754–1762CrossRefGoogle Scholar
  13. 13.
    Vachon CM, Brandt KR, Ghosh K, Scott CG, Maloney SD, Carston MJ, Pankratz VS, Sellers TA (2007) Mammographic breast density as a general marker of breast cancer risk. Cancer Epidemiol Biomark Prev 16(1):43–49CrossRefGoogle Scholar
  14. 14.
    Lokate M, Peeters PH, Peelen LM, Haars G, Veldhuis WB, van Gils CH (2011) Mammographic density and breast cancer risk: the role of the fat surrounding the fibroglandular tissue. Breast Cancer Res 13(5):R103PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Pettersson A, Graff RE, Ursin G, Santos Silva ID, McCormack V, Baglietto L, Vachon C, Bakker MF, Giles GG, Chia KS, Czene K, Eriksson L, Hall P, Hartman M, Warren RM, Hislop G, Chiarelli AM, Hopper JL, Krishnan K, Li J, Li Q, Pagano I, Rosner BA, Wong CS, Scott C, Stone J, Maskarinec G, Boyd NF, van Gils CH, Tamimi RM (2014) Mammographic Density Phenotypes and Risk of Breast Cancer: A Meta-analysis. J Natl Cancer Inst 106(5):dju078PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Britt K, Ashworth A, Smalley M (2007) Pregnancy and the risk of breast cancer. Endocr Relat Cancer 14(4):907–933PubMedCrossRefGoogle Scholar
  17. 17.
    Morris GJ (2009) Breastfeeding, parity, and reduction of breast cancer risk. Breast J 15(5):562–563PubMedCrossRefGoogle Scholar
  18. 18.
    MacMahon B, Cole P, Lin TM, Lowe CR, Mirra AP, Ravnihar B, Salber EJ, Valaoras VG, Yuasa S (1970) Age at first birth and breast cancer risk. Bull World Health Organ 43:209–221PubMedPubMedCentralGoogle Scholar
  19. 19.
    Trichopoulos D, Hsieh CC, MacMahon B, Lin TM, Lowe CR, Mirra AP, Ravnihar B, Salber EJ, Valaoras VG, Yuasa S (1983) Age at any birth and breast cancer risk. Int J Cancer 31:701–704PubMedCrossRefGoogle Scholar
  20. 20.
    Kelsey JL, Gammon MD, John EM (1993) Reproductive factors and breast cancer. Epidemiol Rev 15(1):36–47PubMedGoogle Scholar
  21. 21.
    Vachon CM, Kuni CC, Anderson K, Anderson VE, Sellers TA (2000) Association of mammographically defined percent breast density with epidemiologic risk factors for breast cancer (United States). Cancer Causes Control 11(7):653–662PubMedCrossRefGoogle Scholar
  22. 22.
    Yaghjyan L, Mahoney MC, Succop P, Wones R, Buckholz J, Pinney SM (2012) Relationship between breast cancer risk factors and mammographic breast density in the Fernald Community Cohort. Br J Cancer 106(5):996–1003PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Prebil L, Ereman R, Powell M, Jamshidian F, Kerlikowske K, Shepherd J, Hurlbert M, Benz C (2014) First pregnancy events and future breast density: modification by age at first pregnancy and specific VEGF and IGF1R gene variants. Cancer Causes Control 25(7):859–868PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Li CI, Malone KE, Daling JR, Potter JD, Bernstein L, Marchbanks PA, Strom BL, Simon MS, Press MF, Ursin G, Burkman RT, Folger SG, Norman S, McDonald JA, Spirtas R (2008) Timing of menarche and first full-term birth in relation to breast cancer risk. Am J Epidemiol 167(2):230–239PubMedCrossRefGoogle Scholar
  25. 25.
    Ritte R, Tikk K, Lukanova A, Tjonneland A, Olsen A, Overvad K, Dossus L, Fournier A, Clavel-Chapelon F, Grote V, Boeing H, Aleksandrova K, Trichopoulou A, Lagiou P, Trichopoulos D, Palli D, Berrino F, Mattiello A, Tumino R, Sacerdote C, Quiros JR, Buckland G, Molina-Montes E, Chirlaque MD, Ardanaz E, Amiano P, Bueno-de-Mesquita HB, van Gils CH, Peeters PH, Wareham N, Khaw KT, Key TJ, Travis RC, Weiderpass E, Dumeaux V, Lund E, Sund M, Andersson A, Romieu I, Rinaldi S, Vineis P, Merritt MA, Riboli E, Kaaks R (2013) Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study. BMC Cancer 13:584PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Rosner B, Colditz GA (1996) Nurses’ health study: log-incidence mathematical model of breast cancer incidence. J Natl Cancer Inst 88(6):359–364PubMedCrossRefGoogle Scholar
  27. 27.
    Pike MC, Krailo MD, Henderson BE, Casagrande JT, Hoel DG (1983) ‘Hormonal’ risk factors, ‘breast tissue age’ and the age-incidence of breast cancer. Nature 303(5920):767–770PubMedCrossRefGoogle Scholar
  28. 28.
    Hankinson SE, Colditz GA, Willett WC (2004) Towards an integrated model for breast cancer etiology: the lifelong interplay of genes, lifestyle, and hormones. Breast Cancer Res 6(5):213–218PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Russo J, Moral R, Balogh GA, Mailo D, Russo IH (2005) The protective role of pregnancy in breast cancer. Breast Cancer Res 7(3):131–142PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Colditz GA, Bohlke K (2014) Priorities for the primary prevention of breast cancer. CA Cancer J Clin 64(3):186–194PubMedCrossRefGoogle Scholar
  31. 31.
    Biro FM, Deardorff J (2013) Identifying opportunities for cancer prevention during preadolescence and adolescence: puberty as a window of susceptibility. J adolesc health: off publ Soc Adolesc Med 52(5 Suppl):S15–S20CrossRefGoogle Scholar
  32. 32.
    Colditz GA, Hankinson SE (2005) The Nurses’ Health Study: lifestyle and health among women. Nat Rev Cancer 5(5):388–396PubMedCrossRefGoogle Scholar
  33. 33.
    Bertrand KA, Rosner B, Eliassen AH, Hankinson SE, Rexrode KM, Willett W, Tamimi RM (2015) Premenopausal plasma 25-hydroxyvitamin D, mammographic density, and risk of breast cancer. Breast Cancer Res Treat 149(2):479–487PubMedCrossRefGoogle Scholar
  34. 34.
    Byng JW, Boyd NF, Little L, Lockwood G, Fishell E, Jong RA, Yaffe MJ (1996) Symmetry of projection in the quantitative analysis of mammographic images. Eur J Cancer Prev 5(5):319–327PubMedCrossRefGoogle Scholar
  35. 35.
    Bertrand K, Eliassen AH, Hankinson S, Gierach G, Xu X, Rosner B, Ziegler R, Tamimi R (2012) Urinary estrogens and estrogen metabolites and mammographic density in premenopausal women. Breast Cancer Res Treat 136(1):277–287PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Willett W, Stampfer MJ, Bain C, Lipnick R, Speizer FE, Rosner B, Cramer D, Hennekens CH (1983) Cigarette smoking, relative weight, and menopause. Am J Epidemiol 117(6):651–658PubMedGoogle Scholar
  37. 37.
    Stampfer MJ, Willett WC, Colditz GA, Rosner B, Speizer FE, Hennekens CH (1985) A prospective study of postmenopausal estrogen therapy and coronary heart disease. N Engl J Med 313(17):1044–1049PubMedCrossRefGoogle Scholar
  38. 38.
    Modugno F, Ngo DL, Allen GO, Kuller LH, Ness RB, Vogel VG, Costantino JP, Cauley JA (2006) Breast cancer risk factors and mammographic breast density in women over age 70. Breast Cancer Res Treat 97(2):157–166PubMedCrossRefGoogle Scholar
  39. 39.
    Meier-Abt F, Bentires-Alj M, Rochlitz C (2015) Breast cancer prevention: lessons to be learned from mechanisms of early pregnancy-mediated breast cancer protection. Cancer Res 75(5):803–807PubMedCrossRefGoogle Scholar
  40. 40.
    Isfoss B, Holmqvist B, Jernström H, Alm P, Olsson H (2013) Women with familial risk for breast cancer have an increased frequency of aldehyde dehydrogenase expressing cells in breast ductules. BMC Clin Pathol 13(1):1–9CrossRefGoogle Scholar
  41. 41.
    Savarese TM, Low HP, Baik I, Strohsnitter WC, Hsieh CC (2006) Normal breast stem cells, malignant breast stem cells, and the perinatal origin of breast cancer. Stem Cell Rev 2(2):103–110PubMedCrossRefGoogle Scholar
  42. 42.
    Kordon EC, Smith GH (1998) An entire functional mammary gland may comprise the progeny from a single cell. Development 125(10):1921–1930PubMedGoogle Scholar
  43. 43.
    Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE (2006) Generation of a functional mammary gland from a single stem cell. Nature 439(7072):84–88PubMedCrossRefGoogle Scholar
  44. 44.
    Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ (2006) Purification and unique properties of mammary epithelial stem cells. Nature 439(7079):993–997PubMedGoogle Scholar
  45. 45.
    Cobaleda C, Cruz JJ, Gonzalez-Sarmiento R, Sanchez-Garcia I, Perez-Losada J (2008) The emerging picture of human breast cancer as a stem cell-based disease. Stem Cell Rev 4(2):67–79PubMedCrossRefGoogle Scholar
  46. 46.
    Dontu G (2008) Breast cancer stem cell markers - the rocky road to clinical applications. Breast Cancer Res 10(5):110PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Radisky DC, Hartmann LC (2009) Mammary involution and breast cancer risk: transgenic models and clinical studies. J Mammary Gland Biol Neoplasia 14(2):181–191PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    O’Brien J, Martinson H, Durand-Rougely C, Schedin P (2012) Macrophages are crucial for epithelial cell death and adipocyte repopulation during mammary gland involution. Development 139(2):269–275PubMedCrossRefGoogle Scholar
  49. 49.
    Must A, Phillips SM, Naumova EN, Blum M, Harris S, Dawson-Hughes B, Rand WM (2002) Recall of early menstrual history and menarcheal body size: after 30 years, how well do women remember? Am J Epidemiol 155(7):672–679PubMedCrossRefGoogle Scholar
  50. 50.
    Koprowski C, Coates RJ, Bernstein L (2001) Ability of young women to recall past body size and age at menarche. Obes Res 9(8):478–485PubMedCrossRefGoogle Scholar
  51. 51.
    Cooper R, Blell M, Hardy R, Black S, Pollard TM, Wadsworth MEJ, Pearce MS, Kuh D (2006) Validity of age at menarche self-reported in adulthood. J Epidemiol Community Health 60(11):993–997PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Promislow JH, Gladen BC, Sandler DP (2005) Maternal recall of breastfeeding duration by elderly women. Am J Epidemiol 161(3):289–296PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Lusine Yaghjyan
    • 1
  • Graham A. Colditz
    • 2
    • 3
  • Bernard Rosner
    • 4
  • Kimberly A. Bertrand
    • 5
  • Rulla M. Tamimi
    • 4
  1. 1.Department of Epidemiology, College of Public Health and Health Professions and College of MedicineUniversity of FloridaGainesvilleUSA
  2. 2.Department of SurgeryWashington University in St. Louis School of MedicineSt. LouisUSA
  3. 3.Institute for Public HealthWashington University in St. LouisSt. LouisUSA
  4. 4.Channing Division of Network Medicine, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  5. 5.Slone Epidemiology Center at Boston UniversityBostonUSA

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