Skip to main content

Advertisement

SpringerLink
Log in

Breast cancer risk factors and second primary malignancies among women with breast cancer

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

Abstract

Purpose

To examine the association between breast cancer risk factors and second primary cancers (independent diagnoses occurring at least 12 months after the initial breast cancer diagnosis) among breast cancer survivors.

Methods

In this population-based study, cancer outcomes among breast cancer survivors first diagnosed during 1987–2000 were investigated. Invasive breast cancer cases were identified from the statewide tumor registry and interviewed regarding their pre-diagnosis risk factors, including reproductive and lifestyle characteristics, approximately 1 year after diagnosis. Data on second primary cancers (not recurrences) and deaths were obtained by linkage with tumor registry reports and death certificates through December 31, 2002. Hazard ratios (HR) were estimated using proportional hazards regression stratified by age and adjusted for stage and other factors.

Results

Among the 10,953 breast cancer cases, 10.8% experienced a second cancer diagnosis within an average of 7 years (including 488 breast, 132 colorectal, 113 endometrial, and 36 ovarian cancers). Risk of a second primary breast cancer increased according to low parity (P = 0.002), older age at menopause (P = 0.08), greater body mass index (P = 0.003) and adult weight gain (P = 0.02), and a family history of breast cancer-particularly among women with 2 or more first-degree affected relatives (HR = 1.8, 95% CI: 1.1–2.9). Reduced risk of colorectal cancer after breast cancer was observed in relation to older ages at menarche (P = 0.05), younger age at menopause (P = 0.04), postmenopausal hormone use (HR = 0.4, 95% CI: 0.3–0.7), normal body mass index (P = 0.07), and infrequent alcohol consumption (P = 0.01). Second endometrial cancer risk was associated with increasing body mass index (P < 0.01) and adult weight gain (P = 0.03). Risk of second ovarian cancer appeared related to recent alcohol intake and family history of breast cancer. Women who reported consuming any alcohol appeared to have a 55% reduction in ovarian cancer risk (95% CI: 0.2–1.0) compared to non-drinkers, while having 2 or more first-degree relatives with breast cancer was associated with an increased risk of ovarian cancer (HR = 4.3, 95% CI: 1.3–14.6).

Conclusion

This study suggests that family history of breast cancer as well as potentially modifiable characteristics including body weight, alcohol intake, and postmenopausal hormone use may be associated with risk of a second cancer diagnosis among breast cancer cases.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Travis LB, Rabkin CS, Brown LM et al (2006) Cancer survivorship – genetic susceptibility and second primary cancers: research strategies and recommendations. J Natl Cancer Inst 98(1):15–25

    Article  PubMed  Google Scholar 

  2. Horn-Ross PL (1993) Multiple primary cancers involving the breast. Epidemiol Rev 15(1):169–176

    PubMed  CAS  Google Scholar 

  3. Chen Y, Thompson W, Semenciw R, Mao Y (1999) Epidemiology of contralateral breast cancer. Cancer Epidemiol Biomarkers Prev 8(10):855–861

    PubMed  CAS  Google Scholar 

  4. Soerjomataram I, Louwman WJ, Lemmens VE et al (2005) Risks of second primary breast and urogenital cancer following female breast cancer in the south of The Netherlands, 1972–2001. Eur J Cancer 41(15):2331–2337

    Article  PubMed  CAS  Google Scholar 

  5. Mellemkjaer L, Friis S, Olsen JH et al (2006) Risk of second cancer among women with breast cancer. Int J Cancer 118(9):2285–2292

    Article  PubMed  CAS  Google Scholar 

  6. Harvey EB, Brinton LA (1985) Second cancer following cancer of the breast in Connecticut, 1935–82. Natl Cancer Inst Monogr 68:99–112

    PubMed  CAS  Google Scholar 

  7. Volk N, Pompe-Kirn V (1997) Second primary cancers in breast cancer patients in Slovenia. Cancer Causes Control 8(5):764–770

    Article  PubMed  CAS  Google Scholar 

  8. Soerjomataram I, Louwman WJ, de Vries E et al (2005) Primary malignancy after primary female breast cancer in the South of the Netherlands, 1972–2001. Breast Cancer Res Treat 93(1):91–95

    Article  PubMed  CAS  Google Scholar 

  9. Escobar PF, Patrick R, Rybicki L et al (2006) Primary gynecological neoplasms and clinical outcomes in patients diagnosed with breast carcinoma. Int J Gynecol Cancer 16(Suppl 1):118–122

    Article  PubMed  Google Scholar 

  10. Raymond JS, Hogue CJ (2006) Multiple primary tumours in women following breast cancer, 1973–2000. Br J Cancer 94(11):1745–1750

    PubMed  CAS  Google Scholar 

  11. Strom BL, Schinnar R, Weber AL et al (2006) Case–control study of postmenopausal hormone replacement therapy and endometrial cancer. Am J Epidemiol 164(8):775–786

    Article  PubMed  Google Scholar 

  12. Newcomb PA, Solomon C, White E (1999) Tamoxifen and risk of large bowel cancer in women with breast cancer. Breast Cancer Res Treat 53(3):271–277

    Article  PubMed  CAS  Google Scholar 

  13. Slomovitz BM, Sun CC, Ramirez PT et al (2004) Does tamoxifen use affect prognosis in breast cancer patients who develop endometrial cancer? Obstet Gynecol 104(2):255–260

    PubMed  CAS  Google Scholar 

  14. Matesich SM, Shapiro CL (2003) Second cancers after breast cancer treatment. Semin Oncol 30(6):740–748

    Article  PubMed  CAS  Google Scholar 

  15. Bernstein JL, Thompson WD, Risch N, Holford TR (1992) The genetic epidemiology of second primary breast cancer. Am J Epidemiol 136(8):937–948

    PubMed  CAS  Google Scholar 

  16. Trentham-Dietz A, Newcomb PA, Storer BE et al (1997) Body size and risk of breast cancer. Am J Epidemiol 145(11):1011–1019

    PubMed  CAS  Google Scholar 

  17. Trentham-Dietz A, Newcomb PA, Storer BE, Remington PL (2000) Risk factors for carcinoma in situ of the breast. Cancer Epidemiol Biomarkers Prev 9(7):697–703

    PubMed  CAS  Google Scholar 

  18. Wisconsin Cancer Incidence and Mortality (1999) Madison: Bureau of Health Information, Division of Health Care Financing, Wisconsin Department of Health and Family Services, 2002

  19. International Classification of Disease for Oncology, 3rd edn. World Health Organization, Geneva, 2000

  20. Gooley TA, Leisenring W, Crowley J, Storer BE (1999) Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 18(6):695–706

    Article  PubMed  CAS  Google Scholar 

  21. Trentham-Dietz A, Newcomb PA, Egan KM et al (2000) Weight change and risk of postmenopausal breast cancer (United States). Cancer Causes Control 11(6):533–542

    Article  PubMed  CAS  Google Scholar 

  22. Armstrong BK, White E, Saracci R (1995) Principles of exposure measurement in epidemiology. In: Monographs in epidemiology and biostatistics. Oxford, New York, pp 78–114

  23. Newcomb PA, Titus-Ernstoff L, Egan KM et al (2002) Postmenopausal estrogen and progestin use in relation to breast cancer risk. Cancer Epidemiol Biomarkers Prev 11(7):593–600

    PubMed  CAS  Google Scholar 

  24. Cole P, MacMahon B, Brown JB (1976) Oestrogen profiles of parous and nulliparous women. Lancet 2(7986):596–599

    Article  PubMed  CAS  Google Scholar 

  25. McMichael AJ, Potter JD (1980) Reproduction, endogenous and exogenous sex hormones, and colon cancer: a review and hypothesis. J Natl Cancer Inst 65(6):1201–1207

    PubMed  CAS  Google Scholar 

  26. Fowble B, Hanlon A, Freedman G, Nicolaou N, Anderson P (2001) Second cancers after conservative surgery and radiation for stages I–II breast cancer: identifying a subset of women at increased risk. Int J Radiat Oncol Biol Phys 51(3):679–690

    Article  PubMed  CAS  Google Scholar 

  27. Dignam JJ, Wieand K, Johnson KA et al (2003) Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer. J Natl Cancer Inst 95(19):1467–1476

    PubMed  CAS  Google Scholar 

  28. Hislop TG, Elwood JM, Coldman AJ et al (1984) Second primary cancers of the breast: incidence and risk factors. Br J Cancer 49(1):79–85

    PubMed  CAS  Google Scholar 

  29. Horn PL, Thompson WD (1988) Risk of contralateral breast cancer: associations with factors related to initial breast cancer. Am J Epidemiol 128(2):309–323

    PubMed  CAS  Google Scholar 

  30. Cook LS, White E, Schwartz SM et al (1996) A population-based study of contralateral breast cancer following a first primary breast cancer (Washington, United States). Cancer Causes Control 7(3):382–390

    Article  PubMed  CAS  Google Scholar 

  31. Vaittinen P, Hemminki K (2000) Risk factors and age-incidence relationships for contralateral breast cancer. Int J Cancer 88(6):998–1002

    Article  PubMed  CAS  Google Scholar 

  32. Li CI, Malone KE, Porter PL, Daling JR (2003) Epidemiologic and molecular risk factors for contralateral breast cancer among young women. Br J Cancer 89(3):513–158

    Article  PubMed  CAS  Google Scholar 

  33. Storm HH, Andersson M, Boice JD Jr et al (1992) Adjuvant radiotherapy and risk of contralateral breast cancer. J Natl Cancer Inst 84(16):1245–1250

    Article  PubMed  CAS  Google Scholar 

  34. Bernstein JL, Thompson WD, Risch N, Holford TR (1992) Risk factors predicting the incidence of second primary breast cancer among women diagnosed with a first primary breast cancer. Am J Epidemiol 136(8):925–936

    PubMed  CAS  Google Scholar 

  35. Weight Control and Physical Activity (2002) IARC Press, Lyon, France

  36. Kroenke CH, Chen WY, Rosner B, Holmes MD (2005) Weight, weight gain, and survival after breast cancer diagnosis. J Clin Oncol 23(7):1370–1378

    Article  PubMed  Google Scholar 

  37. Bernstein JL, Lapinski R, Lynch C, Holford T, Thompson WD (2002) Factors influencing mortality among young women with second primary breast carcinoma. Cancer 95(10):2051–2058

    Article  PubMed  Google Scholar 

  38. Willett WC (2001) Diet and breast cancer. J Intern Med 249(5):395–411

    Article  PubMed  CAS  Google Scholar 

  39. Gunnell DJ, Smith GD, Frankel SJ, Kemp M, Peters TJ (1998) Socio-economic and dietary influences on leg length and trunk length in childhood: a reanalysis of the Carnegie (Boyd Orr) survey of diet and health in prewar Britain (1937–39). Paediatr Perinat Epidemiol 12(Suppl 1):96–113

    Article  PubMed  Google Scholar 

  40. Gram IT, Braaten T, Terry PD et al (2005) Breast cancer risk among women who start smoking as teenagers. Cancer Epidemiol Biomarkers Prev 14(1):61–66

    PubMed  Google Scholar 

  41. Kurtz JM, Spitalier JM, Amalric R et al (1988) Mammary recurrences in women younger than forty. Int J Radiat Oncol Biol Phys 15(2):271–276

    Article  PubMed  CAS  Google Scholar 

  42. Boice JD Jr, Harvey EB, Blettner M, Stovall M, Flannery JT (1992) Cancer in the contralateral breast after radiotherapy for breast cancer. N Engl J Med 326(12):781–785

    Article  PubMed  Google Scholar 

  43. Kmet LM, Cook LS, Weiss NS, Schwartz SM, White E (2003) Risk factors for colorectal cancer following breast cancer. Breast Cancer Res Treat 79(2):143–147

    Article  PubMed  CAS  Google Scholar 

  44. Martinez ME, Grodstein F, Giovannucci E et al (1997) A prospective study of reproductive factors, oral contraceptive use, and risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 6(1):1–5

    PubMed  CAS  Google Scholar 

  45. Fernandez E, La Vecchia C, Franceschi S et al (1998) Oral contraceptive use and risk of colorectal cancer. Epidemiology 9(3):295–300

    Article  PubMed  CAS  Google Scholar 

  46. Nichols HB, Trentham-Dietz A, Hampton JM, Newcomb PA (2005) Oral contraceptive use, reproductive factors, and colorectal cancer risk: findings from Wisconsin. Cancer Epidemiol Biomarkers Prev 14(5):1212–1218

    Article  PubMed  CAS  Google Scholar 

  47. Rossouw JE, Anderson GL, Prentice RL et al (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results f rom the Women’s Health Initiative randomized controlled trial. JAMA 288(3):321–333

    Article  PubMed  CAS  Google Scholar 

  48. Metcalfe KA, Lynch HT, Ghadirian P et al (2005) The risk of ovarian cancer after breast cancer in BRCA1 and BRCA2 carriers. Gynecol Oncol 96(1):222–226

    Article  PubMed  CAS  Google Scholar 

  49. Estimated U.S. Cancer Prevalence [cited 2005 January 1]. Available from: http://www.dccps.nci.nih.gov/ocs/prevalence/prevalence.html#allsites

Download references

Acknowledgements

A preliminary version of this work was presented at the 37th Annual Meeting of the Society for Epidemiologic Research, June 17, 2004 in Salt Lake City, Utah, USA.

We thank Drs. Patrick Remington, Henry Anderson, and Jane McElroy for their advice and assistance during this project; Laura Stephenson, Robert Borchers and the rest of the staff of the Wisconsin Cancer Reporting System for providing data and technical support; and Jerry Phipps, Mary Pankratz, and the staff of the Wisconsin Women’s Health Study for their dedication. We are indebted to the generous participation of breast cancer survivors throughout Wisconsin.

This project was supported in part by grant CA47147 from the National Cancer Institute and faculty startup funds from the University of Wisconsin School of Medicine & Public Health.

Author information

Authors and Affiliations

  1. Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, WI, USA

    Amy Trentham-Dietz, Polly A. Newcomb, Hazel B. Nichols & John M. Hampton

  2. Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin, 610 Walnut St., WARF Room 701, Madison, WI, 53726, USA

    Amy Trentham-Dietz

  3. Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Polly A. Newcomb

Authors
  1. Amy Trentham-Dietz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Polly A. Newcomb
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hazel B. Nichols
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John M. Hampton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amy Trentham-Dietz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Trentham-Dietz, A., Newcomb, P.A., Nichols, H.B. et al. Breast cancer risk factors and second primary malignancies among women with breast cancer. Breast Cancer Res Treat 105, 195–207 (2007). https://doi.org/10.1007/s10549-006-9446-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-006-9446-y

Keywords

Search

Navigation