Skip to main content

Advertisement

SpringerLink
Log in

Reproductive history and risk of three breast cancer subtypes defined by three biomarkers

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Breast cancer subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and HER2 expression are biologically distinct and thus, may have distinct etiologies. In particular, it is plausible that risk factors operating through hormonal mechanisms are differentially related to risk of such tumor subtypes. Using data from the Breast Cancer Surveillance Consortium, we explored associations between reproductive history and three breast cancer subtypes. Data on parity and age at first birth were collected from 743,623 women, 10,896 of whom were subsequently diagnosed with breast cancer. Cases were classified into three subtypes based on tumor maker expression: (1) ER positive (ER+, N = 8,203), (2) ER negative/PR negative/HER2 positive (ER−/PR−/HER2+, N = 288), or (3) ER-, PR-, and HER2-negative (triple-negative, N = 645). Associations with reproductive history, evaluated using Cox regression, differed significantly across tumor subtypes. Nulliparity was most strongly associated with risk of ER+ breast cancer [hazard ratio (HR) = 1.31, 95% confidence interval (CI): 1.23–1.39]; late age at first birth was most strongly associated with risk of ER-/PR-/HER2+ disease (HR = 1.83, 95% CI: 1.31–2.56). Neither parity nor age at first birth was associated with triple-negative breast cancer. In contrast to ER+ and ER−/PR−/HER2+ subtypes, reproductive history does not appear to be a risk factor for triple-negative breast cancer.

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

Similar content being viewed by others

References

  1. Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Article  CAS  PubMed  Google Scholar 

  2. Sorlie T, Tibshirani R, Parker J et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100:8418–8423

    Article  CAS  PubMed  Google Scholar 

  3. Sorlie T (2004) Molecular portraits of breast cancer: tumour subtypes as distinct disease entities. Eur J Cancer 40:2667–2675

    Article  CAS  PubMed  Google Scholar 

  4. Nielsen TO, Hsu FD, Jensen K et al (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10:5367–5374

    Article  CAS  PubMed  Google Scholar 

  5. Carey LA, Perou CM, Livasy CA et al (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295:2492–2502

    Article  CAS  PubMed  Google Scholar 

  6. Kim MJ, Ro JY, Ahn SH, Kim HH, Kim SB, Gong G (2006) Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. Hum Pathol 37:1217–1226

    Article  CAS  PubMed  Google Scholar 

  7. Lund MJ, Trivers KF, Porter PL et al (2009) Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA. Breast Cancer Res Treat 113:357–370

    Article  PubMed  Google Scholar 

  8. Onitilo AA, Engel JM, Greenlee RT, Mukesh BN (2009) Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res 7:4–13

    Article  CAS  PubMed  Google Scholar 

  9. Rakha EA, El-Rehim DA, Paish C et al (2006) Basal phenotype identifies a poor prognostic subgroup of breast cancer of clinical importance. Eur J Cancer 42:3149–3156

    Article  CAS  PubMed  Google Scholar 

  10. Potter JD, Cerhan JR, Sellers TA et al (1995) Progesterone and estrogen receptors and mammary neoplasia in the Iowa Women’s Health Study: how many kinds of breast cancer are there? Cancer Epidemiol Biomarkers Prev 4:319–326

    CAS  PubMed  Google Scholar 

  11. 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 Biomarkers Prev 13:1558–1568

    CAS  PubMed  Google Scholar 

  12. Rosenberg LU, Einarsdottir K, Friman EI et al (2006) Risk factors for hormone receptor-defined breast cancer in postmenopausal women. Cancer Epidemiol Biomarkers Prev 15:2482–2488

    Article  CAS  PubMed  Google Scholar 

  13. Ma H, Bernstein L, Pike MC, Ursin G (2006) Reproductive factors and breast cancer risk according to joint estrogen and progesterone receptor status: a meta-analysis of epidemiological studies. Breast Cancer Res 8:R43

    Article  PubMed  Google Scholar 

  14. Yang XR, Sherman ME, Rimm DL et al (2007) Differences in risk factors for breast cancer molecular subtypes in a population-based study. Cancer Epidemiol Biomarkers Prev 16:439–443

    Article  CAS  PubMed  Google Scholar 

  15. Millikan RC, Newman B, Tse CK et al (2008) Epidemiology of basal-like breast cancer. Breast Cancer Res Treat 109:123–139

    Article  PubMed  Google Scholar 

  16. Ma H, Wang Y, Sullivan-Halley J et al (2010) Use of four biomarkers to evaluate the risk of breast cancer subtypes in the women’s contraceptive and reproductive experiences study. Cancer Res 70:575–587

    Article  CAS  PubMed  Google Scholar 

  17. Phipps AI, Malone KE, Porter PL, Daling JR, Li CI (2008) Reproductive and hormonal risk factors for postmenopausal luminal, HER-2-overexpressing, and triple-negative breast cancer. Cancer 113:1521–1526

    Article  PubMed  Google Scholar 

  18. Dolle JM, Daling JR, White E et al (2009) Risk factors for triple-negative breast cancer in women under the age of 45 years. Cancer Epidemiol Biomarkers Prev 18:1157–1166

    Article  PubMed  Google Scholar 

  19. Trivers KF, Lund MJ, Porter PL et al (2009) The epidemiology of triple-negative breast cancer, including race. Cancer Causes Control 20:1071–1082

    Article  PubMed  Google Scholar 

  20. Xing P, Li J, Jin F (2010) A case-control study of reproductive factors associated with subtypes of breast cancer in Northeast China. Med Oncol 27(3):926–931

    Article  PubMed  Google Scholar 

  21. Ballard-Barbash R, Taplin SH, Yankaskas BC et al (1997) Breast cancer surveillance consortium: a national mammography screening and outcomes database. AJR Am J Roentgenol 169:1001–1008

    CAS  PubMed  Google Scholar 

  22. http://breastscreening.cancer.gov/data/elements.html

  23. http://breastscreening.cancer.gov/data/bcsc_data_definitions.pdf

  24. Kalbfleisch JD, Prentice RL (2002) The statistical analysis of failure time data, 2nd edition edn. Wiley, New York

    Google Scholar 

  25. Raghunathan TE, Lepkowski JM, Van Hoewyk J, Solenberger P (2001) A multivariate technique for multiply imputing missing values using a sequence of regression models. Surv Method 27:85–95

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  27. Clavel-Chapelon F, E3 N-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 86:723–727

    Article  CAS  PubMed  Google Scholar 

  28. Russo J, Russo IH (1997) Differentiation and breast cancer. Medicina (B Aires) 57(2):81–91

    CAS  Google Scholar 

Download references

Acknowledgments

We thank the participating women, mammography facilities, and radiologists for the data they have provided for this study. A list of the BCSC investigators and procedures for requesting BCSC data for research purposes are provided at: http://breastscreening.cancer.gov/. This work was supported by a NCI-funded Breast Cancer Surveillance Consortium co-operative agreement (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040). The collection of cancer data used in this study was supported in part by several state public health departments and cancer registries throughout the United States. For a full description of these sources, please see: http://breastscreening.cancer.gov/work/acknowledgment.html. This publication was supported by grant numbers T32 CA09168 and R25-CA94880 from the NCI, NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCI, NIH.

Author information

Authors and Affiliations

  1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M4-B402, Seattle, WA, 98109-1024, USA

    Amanda I. Phipps, Kathleen E. Malone, Peggy L. Porter & Christopher I. Li

  2. School of Public Health, University of Washington, Seattle, WA, USA

    Amanda I. Phipps, Diana S. M. Buist, Kathleen E. Malone, William E. Barlow & Christopher I. Li

  3. Group Health Research Institute, Seattle, WA, USA

    Diana S. M. Buist & William E. Barlow

  4. Cancer Research and Biostatistics, Seattle, WA, USA

    William E. Barlow

  5. School of Medicine, University of Washington, Seattle, WA, USA

    Peggy L. Porter

  6. Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

    Karla Kerlikowske

Authors
  1. Amanda I. Phipps
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diana S. M. Buist
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kathleen E. Malone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William E. Barlow
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peggy L. Porter
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Karla Kerlikowske
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christopher I. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amanda I. Phipps.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Phipps, A.I., Buist, D.S.M., Malone, K.E. et al. Reproductive history and risk of three breast cancer subtypes defined by three biomarkers. Cancer Causes Control 22, 399–405 (2011). https://doi.org/10.1007/s10552-010-9709-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-010-9709-0

Keywords

Search

Navigation