Skip to main content

Advertisement

Log in

Reproductive factors and breast cancer risk among older women

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Reproductive factors have been shown to affect pre- and postmenopausal breast cancer risk differently, but whether there are additional age-specific differences among menopausal women as they age has not been clarified. We analyzed data from a large population-based case–control study that included 1,508 breast cancer cases and 1,556 controls, aged 20–98 years, who completed an in-home interviewer-administered questionnaire. The following subgroups were created to examine if the associations between reproductive factors and breast cancer risk varied by age- and menopausal-status: premenopausal (n = 968), postmenopausal <65 years (n = 1,045), postmenopausal ≥65 years (n = 958). Among postmenopausal women ≥65 years, ever having breastfed decreased risk (odds ratio (OR) = 0.67, 95% confidence interval (CI) = 0.48, 0.92), and a strong dose–response relationship was observed for longer durations of breastfeeding (P trend = 0.02), with the most pronounced protective effect observed for ≥14 months of breastfeeding (OR = 0.40, 95% CI = 0.21,0.76). Late age at first birth (AFB) and older age at last birth (ALB) were associated with non-statistically significant increases in breast cancer risk in this older group, while late age at menarche and surgical menopause decreased risk. ORs for multiparity were close to the null. Among premenopausal women and postmenopausal women <65 years, multiparity significantly decreased risk, and older AFB nonsignificantly increased risk. Our findings suggest that the well-known protective effect of multiparity attenuates with older age. Moreover, breastfeeding, one of the few potentially modifiable risk factors for breast cancer, was an important factor in decreasing risk among older parous postmenopausal women.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Alberg AJ, Singh S (2001) Epidemiology of breast cancer in older women: implications for future healthcare. Drugs Aging 18(10):761–772

    Article  PubMed  CAS  Google Scholar 

  2. Edwards BK et al (2002) Annual report to the nation on the status of cancer, 1973–1999, featuring implications of age and aging on U.S. cancer burden. Cancer 94(10):2766–2792

    Article  PubMed  Google Scholar 

  3. Ries LAG et al (2000) SEER cancer statistics review. National Cancer Institute, Bethesda(MD) pp 1973–1997

    Google Scholar 

  4. KelseyJL, Bernstein L (2001) Epidemiology and prevention of breast cancer. Annu Rev Public Health 17:47–67

    Article  Google Scholar 

  5. Key TJ, Verkasalo PK, Banks E (2001) Epidemiology of breast cancer. Lancet Oncol 2(3):133–140

    Article  PubMed  CAS  Google Scholar 

  6. Kelsey JL, Horn-Ross PL (1993) Breast cancer: magnitude of the problem and descriptive epidemiology. Epidemiol Rev 15(1):7–16

    PubMed  CAS  Google Scholar 

  7. Key TJ, Pike MC (1988) The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. Eur J Cancer Clin Oncol 24(1):29–43

    Article  PubMed  CAS  Google Scholar 

  8. Clemons M, Goss P (2001) Estrogen and the risk of breast cancer. N Engl J Med 344(4):276–285

    Article  PubMed  CAS  Google Scholar 

  9. Kelsey J, Gammon MD, John EM (1993) Reproductive factors and breast cancer. Epidemiol Rev 15(1):36–47

    PubMed  CAS  Google Scholar 

  10. 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(9328):187–195

    Google Scholar 

  11. Clavel-Chapelon F, E3N-EPIC Group (2002) Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women. Br J Cancer 86(5):723–727

    Article  PubMed  CAS  Google Scholar 

  12. Gammon M, Neugut AI, Santella RM, Teitelbaum SL, Britton JA, Terry MB, Eng SM, Wolff MS, Stellman SD, Kabat GC, Levin B, Bradlow HL, Hatch M, Beyea J, Camann D, Trent M, Senie RT, Garbowski GC, Maffeo C,␣Montalvan P, Berkowitz GS, Kemeny M, Citron M, Schnabe F, Schuss A, Hajdu S, Vincguerra V, Collman GW, Obrams GI (2002) The Long Island breast cancer study project: description of a multi-institutional collaboration to identify environmental risk factors for breast cancer. Breast Cancer Res Treat 3:235–254

    Article  Google Scholar 

  13. Waksberg J (1978) Sampling methods for random digit dialing. J Am Stat Assoc 73:40–46

    Article  Google Scholar 

  14. Hosmer D, Lemeshow S (1989) Applied logistic regression. John Wiley and Sons Inc, New York

    Google Scholar 

  15. Lubin J, 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(2):211–217

    PubMed  CAS  Google Scholar 

  16. Byers T, Graham S, Rzepka T, Marshall J (1985) Lactation and breast cancer. Evidence for a negative association in premenopausal women. Am J Epidemiol 121(5):664–674

    Article  PubMed  CAS  Google Scholar 

  17. McTiernan A, Thomas DB (1989) Evidence for a protective effect of lactation on risk of breast cancer in young women. Results from a case-control study. Am J Epidemiol 124(3):353–358

    Google Scholar 

  18. Layde P, Webster LA, Baughman AL, Wingo PA, Rubin GL, Ory HW (1989) The independent associations of parity, age at first full term pregnancy, and duration of breastfeeding with the risk of breast cancer. Cancer and steroid hormone study group. J Clin Epidemiol 42(10):963–973

    Article  PubMed  CAS  Google Scholar 

  19. Yoo K, Tajima K, Kuroishi T, Hirose K, Yoshida M, Miura S, Murai H (1992) Independent protective effect of lactation against breast cancer: a case–control study in Japan. Am J Epidemiol 135(7):726–733

    PubMed  CAS  Google Scholar 

  20. United Kingdom National Case–Control Study Group (1993) Breast feeding and risk of breast cancer in young women. Br Med J 307(6895):17–20

    Google Scholar 

  21. Newcomb P, 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(2):81–87

    Article  PubMed  CAS  Google Scholar 

  22. Brinton L, Potischman NA, Swanson CA, Schoenberg JB, Coates RJ, Gammon MD, Malone KE, Stanford JL, Daling JR (1995) Breastfeeding and breast cancer risk. Cancer Causes Control 6(3):199–208

    Article  PubMed  CAS  Google Scholar 

  23. Chang-Claude J, Eby N, Kiechle M, Bastert G, Becher H (2000) Breastfeeding and breast cancer risk by age 50 among women in Germany. Cancer Causes Control 11(8):687–695

    Article  PubMed  CAS  Google Scholar 

  24. Enger S, Ross RK, Paganini-Hill A, Bernstein L (1998) Breastfeeding experience and breast cancer risk among postmenopausal women. Cancer Epidemiol Biomarkers Prev 7(5):365–369

    PubMed  CAS  Google Scholar 

  25. Petrakis N, Wrensch MR, Ernster VL, Miike R, Murai J, Simberg N, Siiteri PK (1987) Influence of pregnancy and lactation on serum and breast fluid estrogen levels: implications for breast cancer risk. Int J Cancer 40(5):587–591

    Article  PubMed  CAS  Google Scholar 

  26. Musey V, Collins DC, Musey PI, Martino-Saltzman D, Preedy JR (1987) Long-term effect of a first pregnancy on the secretion of prolactin. N Engl J Med 316(5):229–234

    Article  PubMed  CAS  Google Scholar 

  27. Russo J, Russo IH (1994) Toward a physiological approach to breast cancer prevention. Cancer Epidemiology Biomarkers Prev 3(4):353–364

    CAS  Google Scholar 

  28. Gruenke L, Wrensch MR, Petrakis NL, Miike R, Ernster VL, Craig JC (1987) Breast fluid cholesterol and cholesterol epoxides: relationship to breast cancer risk factors and other characteristics. Cancer Res 47(20):5483–5487

    PubMed  CAS  Google Scholar 

  29. Cassoni P, Sapino A, Papotti M, Bussolati G (1996) Oxytocin and oxytocin-analogue F314 inhibit cell proliferation and tumor growth of rat and mouse mammary carcinomas. Int J Cancer 66(6):817–820

    Article  PubMed  CAS  Google Scholar 

  30. Pike MC, et al (1993) Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 15(1):17–35

    PubMed  CAS  Google Scholar 

  31. Henderson BE, Bernstein L (1991) The international variation in breast cancer rates: an epidemiological assessment. Breast Cancer Res Treat 18(Suppl 1):S11–S17

    PubMed  Google Scholar 

  32. La Vecchia C, Negri E, Bruzzi P et al (1992) The role of age at menarche and at menopause on breast cancer risk: combined evidence from four case–control studies. Ann Oncol 3:625–629

    PubMed  CAS  Google Scholar 

  33. Paganini-Hill A, Krailo MD, Pike MC (1984) Age at natural menopause and breast cancer risk: the effect of errors in recall. Am J Epidemiol 119(1):81–85

    PubMed  CAS  Google Scholar 

  34. Cook LS, White JL, Stuart GC, Magliocco AM (2003) The reliability of telephone interviews compared with in-person interviews using memory aids. Ann Epidemiol 13(7):495–501

    Article  PubMed  Google Scholar 

  35. Apter D (1996) Hormonal events during female puberty in relation to breast cancer risk. Eur J Cancer Prev 5(6):476–482

    PubMed  CAS  Google Scholar 

  36. Henderson B, Pike MC, Casagrande JT (1981) Breast cancer and the oestrogen window hypothesis. Lancet 2(8242):363–364

    Article  PubMed  CAS  Google Scholar 

  37. Windham G, Elkin E, Fenster L, Waller K, Anderson M, Mitchell PR, Lasley B, Swan SH (2002) Ovarian hormones in premenopausal women: variation by demographic, reproductive and menstrual cycle characteristics. Epidemiology 13(6):675–684

    Article  PubMed  Google Scholar 

  38. MacMahon B et al (1982) Age at menarche, probability of ovulation and breast cancer risk. Int J Cancer 29(1):13–16

    Article  PubMed  CAS  Google Scholar 

  39. Henderson BE et al (1985) Do regular ovulatory cycles increase breast cancer risk? Cancer 56(5):1206–1208

    Article  PubMed  CAS  Google Scholar 

  40. Brinton L, Schairer C, Hoover RN, Fraumeni JF Jr (1988) Menstrual factors and risk of breast cancer. Cancer Invest 6(3):245–254

    PubMed  CAS  Google Scholar 

  41. Clavel-Chapelon F, Launoy G, Auquier A, Gairard B, Bremond A, Piana L, Lansac J, Renaud R (1995) Reproductive factors and breast cancer risk. Effect of age at diagnosis. Ann Epidemiol 5(4):315–320

    Article  PubMed  CAS  Google Scholar 

  42. Clavel-Chapelon F, Gerber M (2002) Reproductive factors and breast cancer risk. Do they differ according to age at diagnosis? Breast Cancer Res Treat 72(2):107–115

    Article  PubMed  CAS  Google Scholar 

  43. Russo J, Moral R, Balogh GA, Mailo D, Russo IH (2005) The protective role of pregnancy in breast cancer. Breast Cancer Res 7(3):131–142

    Article  PubMed  Google Scholar 

  44. Moorman P, Newman B, Millikan RC, Tse CK, Sandler DP (1999) Participation rates in a case–control study: the impact of age, race, and race of interviewer. Am J Epidemiol 9(3):188–195

    Article  CAS  Google Scholar 

  45. Hoffman S, Grisso JA, Kelsey JL, Gammon MD, O’Brien LA (1993) Parity, lactation and hip fracture. Osteoporos Int 3(4):171–176

    Article  PubMed  CAS  Google Scholar 

  46. Guralnik JM, LaCroix AZ, Everett DF, Kovar MG (1989) Aging in the eighties: the prevalence of comorbidity, its association with disability. National Center for Health Statistics, Advanced Data from Vital and Health Statistics. MD, Hyattsville,. p. 179

  47. Yancik R, Havlik RJ, Wesley MN, Ries L, Long S, Rossi WK, Edwards BK (1996) Cancer and comorbidity in older patients: a descriptive profile. Ann Epidemiol 6(5)(5):399–412

    Article  Google Scholar 

  48. Havlik RJ, Yancik R, Long S, Ries L, Edwards B (1994) The National Institue on Aging and the National Cancer Institute SEER collaborative study on comorbidity and early diagnosis of cancer in the elderly. Cancer 74(Suppl):2101–2106

    Article  PubMed  CAS  Google Scholar 

  49. Tomeo C, Rich-Edwards JW, Michels KB, Berkey CS, Hunter DJ, Frazier AL, Willett WC, Buka SL (1999) Reproducibility and validity of maternal recall of pregnancy-related events. Epidemiology 10(6):774–777

    Article  PubMed  CAS  Google Scholar 

  50. Albain KS, Allred DC, Clark GM (1994) Breast cancer outcome and predictors of outcome: are there age differentials? J Natl Cancer Inst Monogr 16:35–42

    PubMed  Google Scholar 

  51. Walker RA et al (1996) Breast carcinomas occurring in young women (<35 years) are different. Br J Cancer 315:1796–1800

    Google Scholar 

  52. Yancik R, Ries LG, Yates JW (1989) Breast cancer in aging women. A population-based study of contrasts in stage, surgery, and survival. Cancer 63:976–981

    Article  PubMed  CAS  Google Scholar 

  53. Balducci L, Schapira DV, Cox CE, Greenberg HM, Lyman GH (1991) Breast cancer of the older woman: an annotated review. J Am Geriatr Soc 39:1113–1123

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants from the National Cancer Institute and the National Institute of Environmental Health Sciences (Grant nos. UO1CA/ES66572, T32CA09330, P30ES09089, and P30ES10126). For their valuable contributions to the Long Island Breast Cancer Study Project the authors thank: members of the Long Island Breast Cancer Network; the 31 participating institutions on Long Island and in New York City, NY; our National Institutes of Health collaborators, Gwen Collman, Ph.D., National Institutes of Environmental Health Sciences; G. Iris Obrams, M.D., Ph.D. formerly of the National Cancer Institute; members of the External Advisory Committee: Leslie Bernstein, Ph.D., (Committee chair); Gerald Akland, M.S.; Barbara Balaban, MSW; Blake Cady, M.D.; Dale Sandler, Ph.D.; Roy Shore, Ph.D.; and Gerald Wogan, Ph.D.; as well as other collaborators who assisted with various aspects of our data collection efforts including Mary Wolff, Ph.D.; Geoff Kabat, Ph.D.; Steve Stellman, Ph.D.; Maureen Hatch, Ph.D.; Gail Garbowski, MPH; H. Leon Bradlow, Ph.D.; Martin Trent, B.S.; Ruby Senie, Ph.D.; Carla Maffeo, Ph.D.; Pat Montalvan; Gertrud Berkowitz, Ph.D.; Margaret Kemeny, M.D.; Mark Citron, M.D.; Freya Schnabel, M.D.; Allen Schuss, M.D.; Steven Hajdu, M.D.; and Vincent Vinciguerra, M.D. For their careful review of the manuscript, the authors would also like to thank Andrew Olshan, Ph.D., and Stephen Kritchevsky, Ph.D.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sumitra Shantakumar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shantakumar, S., Terry, M.B., Teitelbaum, S.L. et al. Reproductive factors and breast cancer risk among older women. Breast Cancer Res Treat 102, 365–374 (2007). https://doi.org/10.1007/s10549-006-9343-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-006-9343-4

Keywords

Navigation