Skip to main content Accessibility help

Prenatal smoke exposure and mammographic density in mid-life

  • M. B. Terry (a1) (a2) (a3), C. A. Schaefer (a4), J. D. Flom (a1), Y. Wei (a2) (a5), P. Tehranifar (a1) (a2), Y. Liao (a1), S. Buka (a6) and K. B. Michels (a7) (a8) (a9)...


Tobacco smoke has both carcinogenic effects and anti-estrogenic properties and its inconsistent association with breast cancer risk in observational studies may be because of these competing effects across the lifecourse. We conducted a prospective study of prenatal smoke exposure, childhood household smoke exposure, and adult active smoke exposure and mammographic density, a strong intermediate marker of breast cancer risk, in an adult follow-up of existing US birth cohorts. Specifically, we followed up women who were born between 1959 and 1967 and whose mothers participated in either the Collaborative Perinatal Project (Boston and Providence sites) or the Childhood Health and Development Study in California. Of the 1134 women interviewed in adulthood (ranging in age from 39 to 49 years at interview), 79% had a screening mammogram. Cigarette smoking was reported by mothers at the time of their pregnancy; 40% of mothers smoked while pregnant. Women whose mothers smoked during pregnancy had a 3.1% (95% confidence interval (CI) = −6.0%, −0.2%) lower mammographic density than women whose mothers did not smoke during pregnancy. When we further accounted for adult body mass index and adult smoking status, the association remained (β = −2.7, 95% CI = −5.0, −0.3). When we examined patterns of smoking, prenatal smoke exposure without adult smoke exposure was associated with a 5.6% decrease in mammographic density (β = −5.6, 95% CI = −9.6, −1.6). Given the strength of mammographic density as an intermediate marker for breast cancer, the inverse associations between mammographic density and smoking patterns across the lifecourse may help explain the complex association between cigarette smoking and breast cancer risk.


Corresponding author

*Address for correspondence: Dr M. B. Terry, Department of Epidemiology, Columbia University, Mailman School of Public Health, 722 West 168th Street, Room 724 A, New York, NY 10032, USA. (Email


Hide All
1. Terry, PD, Miller, AB, Rohan, TE. Cigarette smoking and breast cancer risk: a long latency period? Int J Cancer. 2002; 100, 723728.
2. Johnson, KC, Miller, AB, Collishaw, NE, et al. Active smoking and secondhand smoke increase breast cancer risk: the report of the Canadian Expert Panel on Tobacco Smoke and Breast Cancer Risk (2009). Tob Control. 2011; 20, e2, 16.
3. Terry, PD, Goodman, M. Is the association between cigarette smoking and breast cancer modified by genotype? A review of epidemiologic studies and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2006; 15, 602611.
4. Shen, J, Gammon, MD, Terry, MB, et al. Polymorphisms in XRCC1 modify the association between polycyclic aromatic hydrocarbon–DNA adducts, cigarette smoking, dietary antioxidants, and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2005; 14, 336342.
5. Shen, J, Terry, MB, Gammon, MD, et al. MGMT genotype modulates the associations between cigarette smoking, dietary antioxidants and breast cancer risk. Carcinogenesis. 2005; 26, 21312137.
6. Terry, MB, Gammon, MD, Zhang, FF, et al. Polymorphism in the DNA repair gene XPD, polycyclic aromatic hydrocarbon–DNA adducts, cigarette smoking, and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2004; 13, 20532058.
7. Breast Cancer Family Registry, Kathleen Cuningham Consortium for Research into Familial Breast Cancer (Australasia) and Ontario Cancer Genetics Network (Canada). Smoking and risk of breast cancer in carriers of mutations in BRCA1 or BRCA2 aged less than 50 years. Breast Cancer Res Treat. 2008; 109, 6775.
8. Bissonauth, V, Shatenstein, B, Fafard, E, et al. Weight history, smoking, physical activity and breast cancer risk among French–Canadian women non-carriers of more frequent BRCA1/2 mutations. J Cancer Epidemiol. 2009; 2009, 111.
9. Baron, JA, La Vecchia, C, Levi, F. The antiestrogenic effect of cigarette smoking in women. Am J Obstet Gynecol. 1990; 162, 502514.
10. Band, PR, Le, ND, Fang, R, Deschamps, M. Carcinogenic and endocrine disrupting effects of cigarette smoke and risk of breast cancer. Lancet. 2002; 360, 10441049.
11. Xue, F, Willett, WC, Rosner, BA, Hankinson, SE, Michels, KB. Cigarette smoking and the incidence of breast cancer. Arch Intern Med. 2011; 171, 125133.
12. Xue, F, Michels, KB. Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence. Lancet Oncol. 2007; 8, 10881100.
13. Forman, MR, Cantwell, MM, Ronckers, C, Zhang, Y. Through the looking glass at early-life exposures and breast cancer risk. Cancer Invest. 2005; 23, 609624.
14. Herbst, AL, Ulfelder, H, Poskanzer, DC. Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. 1971; 284, 878881.
15. Giusti, RM, Iwamoto, K, Hatch, EE. Diethylstibestrol revisted: a review of the long-term health effects. Ann Intern Med. 1995; 122, 778788.
16. Hatch, EE, Palmer, JR, Titus-Ernstoff, L, Noller, KL, et al. Cancer risk in women exposed to diethylstilbestrol in utero. JAMA. 1998; 280, 630634.
17. Anbazhagan, R, Nathan, B, Gusterson, BA. Prenatal influences and breast cancer [letter; comment]. Lancet. 1992; 340, 14771478.
18. Anbazhagan, R, Gusterson, BA. Prenatal factors may influence predisposition to breast cancer. Eur J Cancer. 1994; 30A, 13.
19. Standfast, SJ. Birth characteristics of women dying from breast cancer. J Natl Cancer Inst. 1967; 39, 3342.
20. Rothman, KJ, MacMahon, B, Lin, TM, et al. Maternal age and birth rank of women with breast cancer. J Natl Cancer Inst. 1980; 65, 719722.
21. Thompson, WD, Janerich, DT. Maternal age at birth and risk of breast cancer in daughters. Epidemiology. 1990; 1, 101106.
22. Janerich, DT, Hayden, CL, Thompson, WD, Selenskas, SL, Mettlin, C. Epidemiologic evidence of the perinatal influence in the etiology of adult cancers. Clin Epidemiol. 1989; 42, 151158.
23. Hsieh, CC, Tzonou, A, Trichopoulos, D. Birth order and breast cancer risk. Cancer Causes Control. 1991; 2, 9598.
24. Weiss, HA, Potischman, NA, Brinton, LA, et al. Prenatal and perinatal risk factors for breast cancer in young women. Epidemiology. 1997; 8, 181187.
25. Swerdlow, AJ, De Stavola, BL, Swanwick, MA, Maconochie, NES. Risks of breast and testicular cancer in young adult twins in England and Wales: evidence on prenatal and genetic aetilogy. Lancet. 1997; 350, 17231728.
26. Ekbom, A, Trichopoulos, D, Adami, HO, Hsieh, CC, Lan, SJ. Evidence of prenatal influences on breast cancer risk. Lancet. 1992; 340, 10151018.
27. Ekbom, A. Growing evidence that several human cancers may originate in utero. Semin Cancer Biol. 1997; 8, 237244.
28. Braun, MM, Ahlbom, A, Floderus, B, Brinton, LA, Hoover, RN. Effect of twinship on incidence of cancer of the testis, breast, and other sites (Sweden). Cancer Causes Control. 1995; 6, 519524.
29. Verkasalo, PK, Kaprio, J, Pukkala, E, Koskenvuo, M. Breast cancer risk in monozygotic and dizygotic female twins: a 20-year population-based cohort study in Finland from 1976 to 1995. Cancer Epidemiol Biomarkers Prev. 1999; 8, 271274.
30. Michels, KB, Trichopoulos, D, Robins, JM, et al. Birthweight as a risk factor for breast cancer. Lancet. 1996; 348, 15421546.
31. Sanderson, M, Williams, MA, Malone, KE, et al. Perinatal factors and risk of breast cancer. Epidemiology. 1996; 7, 3437.
32. Mogren, I, Damber, L, Tavelin, B, Hogberg, U. Characteristics of pregnancy and birth and malignancy in the offspring (Sweden). Cancer Causes Control. 1999; 10, 8594.
33. Tehranifar, P, Liao, Y, Flom, JD, Terry, MB. Validity of self-reported birth weight by adult women: sociodemographic influences and implications for life-course studies. Am J Epidemiol. 2009; 170, 910917.
34. Liu, T, Gatsonis, CA, Baylin, A, Buka, SL. Prenatal exposure to cigarette smoke and benign breast disease. Epidemiology. 2010; 21, 736743.
35. Sanderson, M, Williams, MA, Daling, JR, et al. Maternal factors and breast cancer risk among young women. Paediatr Perinat Epidemiol. 1998; 12, 397407.
36. Sandler, DP, Everson, RB, Wilcox, AJ, Browder, JP. Cancer risk in adulthood from early life exposure to parents’ smoking. Am J Public Health. 1985; 75, 487492.
37. Boyd, NF, Guo, H, Martin, LJ, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007; 356, 227236.
38. Boyd, NF, Lockwood, GA, Byng, JW, Tritchler, DL, Yaffe, MJ. Mammographic densities and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1998; 7, 11331144.
39. Boyd, NF, Byng, JW, Jong, RA, et al. Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. J Natl Cancer Inst. 1995; 87, 670675.
40. Ciatto, S, Zappa, M. A prospective study of the value of mammographic patterns as indicators of breast cancer risk in a screening experience. Eur J Radiol. 1993; 17, 122125.
41. Byrne, C, Schairer, C, Wolfe, J, et al. Mammographic features and breast cancer risk: effects with time, age, and menopause status. J Natl Cancer Inst. 1995; 87, 16221629.
42. Kato, I, Beinart, C, Bleich, A, et al. A nested case–control study of mammographic patterns, breast volume, and breast cancer (New York City, NY, United States). Cancer Causes Control. 1995; 6, 431438.
43. Oza, AM, Boyd, NF. Mammographic parencymal patterns: a marker of breast cancer risk. Epidemiol Rev. 1993; 15, 196208.
44. Butler, LM, Gold, EB, Conroy, SM, et al. Active, but not passive cigarette smoking was inversely associated with mammographic density. Cancer Causes Control. 2010; 21, 301311.
45. Bremnes, Y, Ursin, G, Bjurstam, N, Gram, IT. Different measures of smoking exposure and mammographic density in postmenopausal Norwegian women: a cross-sectional study. Breast Cancer Res. 2007; 9(5), R73. 18.
46. Jeffreys, M, Warren, R, Gunnell, D, McCarron, P, Smith, GD. Life course breast cancer risk factors and adult breast density (United Kingdom). Cancer Causes Control. 2004; 15, 947955.
47. Van den Berg, BJ. The California child health and development studies. In Hanbook of Longitudinal Studies (eds. Mednick SA, Harway M, Finello KM), 1984 pp. 166179. New York, Praeger.
48. Broman, S. The Collaborative Perinatal Project: an overview. In Handbook of Longitudinal Research, Vol. I (eds. Mednick SA, Harway M, Finello KM), 1984, pp. 185227. Praeger Publishers: New York.
49. Susser, E, Buka, SL, Schaefer, CA, et al. The Early Determinants of Adult Health (EDAH) Study, 2011. DOHAD.
50. Benirschke, K. Examination of the placenta. Obstet Gynecol. 1961; 18, 309333.
51. Byng, JW, Boyd, NF, Fishell, E, Jong, RA, Yaffe, MJ. The quantitative analysis of mammographic densities. Phys Med Biol. 1994; 39, 16291638.
52. Byng, JW, Boyd, NF, Little, L, et al. Symmetry of projection in the quantitative analysis of mammographic images. Eur J Cancer Prev. 1996; 5, 319327.
53. Strohsnitter, WC, Noller, KL, Titus-Ernstoff, L, et al. Breast cancer incidence in women prenatally exposed to maternal cigarette smoke. Epidemiology. 2005; 16, 342345.
54. Ferris, JS, Flom, JD, Tehranifar, P, Mayne, ST, Terry, MB. Prenatal and childhood environmental tobacco smoke exposure and age at menarche. Paediatr Perinat Epidemiol. 2010; 24, 515523.
55. MacMahon, B, Trichopoulos, D, Cole, P, Brown, J. Cigarette smoking and urinary estrogens. N Engl J Med. 1982; 307, 10621065.
56. Evans, P, Wheeler, T, Anthony, F, Osmond, C. Maternal serum vascular endothelial growth factor during early pregnancy. Clin Sci. 1997; 92, 567571.
57. Kandel, DB, Udry, JR. Prenatal effects of maternal smoking on daughters’ smoking: nicotine or testosterone exposure? Am J Public Health. 1999; 89, 13771383.
58. Martin, LJ, Minkin, S, Boyd, NF. Hormone therapy, mammographic density, and breast cancer risk. Maturitas. 2009; 64, 2026.
59. Galobardes, B, Shaw, M, Lawlor, DA, Lynch, JW, Davey Smith, G. Indicators of socioeconomic position (part 1). J Epidemiol Community Health. 2006; 60, 712.
60. Giovino, GA. Epidemiology of tobacco use in the United States. Oncogene. 2002; 21, 73267340.
61. Giovino, GA, Schooley, MW, Zhu, BP, et al. Surveillance for selected tobacco-use behaviors – United States, 1900–1994. MMWR CDC Surveill Summ. 1994; 43, 143.
62. Link, BG, Phelan, J. The social shaping of health and smoking. Drug Alcohol Depend. 2009; 104, S6S10.
63. Link, BG. Epidemiological sociology and the social shaping of population health. J Health Soc Behav. 2008; 49, 367384.
64. Mortensen, LH, Diderichsen, F, Smith, GD, Andersen, AM. The social gradient in birthweight at term: quantification of the mediating role of maternal smoking and body mass index. Hum Reprod. 2009; 24, 26292635.
65. Terry, MB, Flom, J, Tehranifar, P, Susser, E. The role of birth cohorts in studies of adult health: the New York women's birth cohort. Paediatr Perinat Epidemiol. 2009; 23, 431445.
66. Susser, E, Terry, MB, Matte, T. The birth cohorts grow up: new opportunities for epidemiology. Paediatr Perinat Epidemiol. 2000; 14, 98100.
67. Susser, E, Terry, MB. A conception-to-death cohort. Lancet. 2003; 361, 797798.
68. Hemachandra, AH, Howards, PP, Furth, SL, Klebanoff, MA. Birth weight, postnatal growth, and risk for high blood pressure at 7 years of age: results from the Collaborative Perinatal Project. Pediatrics. 2007; 119, e1264e1270.
69. Klebanoff, MA, Zemel, BS, Buka, S, Zierler, S. Long-term follow-up of participants in the Collaborative Perinatal Project: tracking the next generation. Paediatr Perinat Epidemiol. 1998; 12, 334346.


Prenatal smoke exposure and mammographic density in mid-life

  • M. B. Terry (a1) (a2) (a3), C. A. Schaefer (a4), J. D. Flom (a1), Y. Wei (a2) (a5), P. Tehranifar (a1) (a2), Y. Liao (a1), S. Buka (a6) and K. B. Michels (a7) (a8) (a9)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed