Skip to main content

Advertisement

SpringerLink
Log in

Body mass index and risk of luminal, HER2-overexpressing, and triple negative breast cancer

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

Abstract

Triple negative (TN, tumors that do not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2)) and HER2-overexpressing (H2E, ER−/HER2+) tumors are two particularly aggressive subtypes of breast cancer. There is a lack of knowledge regarding the etiologies of these cancers and in particular how anthropometric factors are related to risk. We conducted a population-based case–case study consisting of 2659 women aged 20–69 years diagnosed with invasive breast cancer from 2004 to 2012. Four case groups defined based on joint ER/PR/HER2 status were included: TN, H2E, luminal A (ER+/HER2−), and luminal B (ER+/HER2+). Polytomous logistic regression was used to estimate odds ratios (ORs) and associated 95 % confidence intervals (CIs) where luminal A patients served as the reference group. Obese premenopausal women [body mass index (BMI) ≥30 kg/m2] had an 82 % (95 % CI 1.32–2.51) increased risk of TN breast cancer compared to women whose BMI <25 kg/m2, and those in the highest weight quartile (quartiles were categorized based on the distribution among luminal A patients) had a 79 % (95 % CI 1.23–2.64) increased risk of TN disease compared to those in the lowest quartile. Among postmenopausal women obesity was associated with reduced risks of both TN (OR = 0.74, 95 % CI 0.54–1.00) and H2E (OR = 0.47, 95 % CI 0.32–0.69) cancers. Our results suggest obesity has divergent impacts on risk of aggressive subtypes of breast cancer in premenopausal versus postmenopausal women, which may contribute to the higher incidence rates of TN cancers observed among younger African American and Hispanic women.

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

Similar content being viewed by others

References

  1. Perou CM, Sørlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752. doi:10.1038/35021093

    Article  CAS  PubMed  Google Scholar 

  2. Sørlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869–10874. doi:10.1073/pnas.191367098

    Article  PubMed  PubMed Central  Google Scholar 

  3. 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. doi:10.1001/jama.295.21.2492

    Article  CAS  PubMed  Google Scholar 

  4. 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. doi:10.3121/cmr.2009.825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Dawood S, Hu R, Homes MD et al (2011) Defining breast cancer prognosis based on molecular phenotypes: results from a large cohort study. Breast Cancer Res Treat 126:185–192. doi:10.1007/s10549-010-1113-7

    Article  PubMed  Google Scholar 

  6. Parise CA, Bauer KR, Brown MM, Caggiano V (2009) Breast cancer subtypes as defined by the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) among women with invasive breast cancer in California, 1999-2004. Breast J 15:593–602. doi:10.1111/j.1524-4741.2009.00822.x

    Article  PubMed  Google Scholar 

  7. Trentham-Dietz A, Newcomb PA, Storer BE et al (1997) Body size and risk of breast cancer. Am J Epidemiol 145:1011–1019. doi:10.1093/oxfordjournals.aje.a009057

    Article  CAS  PubMed  Google Scholar 

  8. Morimoto L, White E, Chen Z et al (2002) Obesity, body size, and risk of postmenopausal breast cancer: the Women’s Health Initiative (United States). Cancer Causes Control 13:741–751. doi:10.1023/A:1020239211145

    Article  PubMed  Google Scholar 

  9. van den Brandt PA, Spiegelman D, Yaun SS et al (2000) Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 152:514–527. doi:10.1093/aje/152.6.514

    Article  PubMed  Google Scholar 

  10. Ursin G, Longnecker MP, Haile RW, Greenland S (1995) A meta-analysis of body mass index and risk of premenopausal breast cancer on JSTOR. Epidemiology 6:137–141

    Article  CAS  PubMed  Google Scholar 

  11. Horn J, Alsaker MDK, Opdahl S et al (2014) Anthropometric factors and risk of molecular breast cancer subtypes among postmenopausal Norwegian women. Int J Cancer 135:2678–2686. doi:10.1002/ijc.28912

    Article  CAS  PubMed  Google Scholar 

  12. 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 Biomark Prev 16:439–443. doi:10.1158/1055-9965.EPI-06-0806

    Article  CAS  Google Scholar 

  13. Bandera EV, Chandran U, Hong C-C et al (2015) Obesity, body fat distribution, and risk of breast cancer subtypes in African American women participating in the AMBER Consortium. Breast Cancer Res Treat 150:655–666. doi:10.1007/s10549-015-3353-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Phipps AI, Malone KE, Porter PL et al (2008) Body size and risk of luminal, HER2-overexpressing, and triple-negative breast cancer in postmenopausal women. Cancer Epidemiol Biomark Prev 17:2078–2086. doi:10.1158/1055-9965.EPI-08-0206

    Article  CAS  Google Scholar 

  15. Gaudet MM, Press MF, Haile RW et al (2011) Risk factors by molecular subtypes of breast cancer across a population-based study of women 56 years or younger. Breast Cancer Res Treat 130:587–597. doi:10.1007/s10549-011-1616-x

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kwan ML, Kushi LH, Weltzien E et al (2009) Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors. Breast Cancer Res 11:R31. doi:10.1186/bcr2261

    Article  PubMed  PubMed Central  Google Scholar 

  17. Millikan RC, Newman B, Tse CK et al (2008) Epidemiology of basal-like breast cancer. Breast Cancer Res Treat 109:123–139. doi:10.1007/s10549-007-9632-6

    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 Biomark Prev 18:1157–1166. doi:10.1158/1055-9965.EPI-08-1005

    Article  Google Scholar 

  19. Bauer KR, Brown M, Cress RD et al (2007) Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer 109:1721–1728. doi:10.1002/cncr.22618

    Article  PubMed  Google Scholar 

  20. Li CI, Beaber EF, Tang MTC et al (2012) Effect of depo-medroxyprogesterone acetate on breast cancer risk among women 20 to 44 years of age. Cancer Res 72:2028–2035. doi:10.1158/0008-5472.CAN-11-4064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Li CI, Malone KE, Porter PL et al (2008) Relationship between menopausal hormone therapy and risk of ductal, lobular, and ductal-lobular breast carcinomas. Cancer Epidemiol Biomark Prev 17:43–50. doi:10.1158/1055-9965.EPI-07-0558

    Article  Google Scholar 

  22. Munsell MF, Sprague BL, Berry DA et al (2014) Body mass index and breast cancer risk according to postmenopausal estrogen-progestin use and hormone receptor status. Epidemiol Rev 36:114–136. doi:10.1093/epirev/mxt010

    Article  PubMed  PubMed Central  Google Scholar 

  23. Key TJ, Appleby PN, Reeves GK et al (2003) Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 95:1218–1226. doi:10.1093/jnci/djg022

    Article  CAS  PubMed  Google Scholar 

  24. Tchernof A, Després JP (1999) Sex steroid hormones, sex hormone-binding globulin, and obesity in men and women. Horm Metab Res 32:526–536. doi:10.1055/s-2007-978681

    Article  Google Scholar 

  25. Schmidt ME, Steindorf K, Mutschelknauss E et al (2008) Physical activity and postmenopausal breast cancer: effect modification by breast cancer subtypes and effective periods in life. Cancer Epidemiol Biomark Prev 17:3402–3410. doi:10.1158/1055-9965.EPI-08-0479

    Article  Google Scholar 

  26. Steindorf K, Ritte R, Eomois P-P et al (2013) Physical activity and risk of breast cancer overall and by hormone receptor status: the European prospective investigation into cancer and nutrition. Int J Cancer 132:1667–1678. doi:10.1002/ijc.27778

    Article  CAS  PubMed  Google Scholar 

  27. Phipps AI, Chlebowski RT, Prentice R et al (2011) Body size, physical activity, and risk of triple-negative and estrogen receptor-positive breast cancer. Cancer Epidemiol Biomark Prev 20:454–463. doi:10.1158/1055-9965.EPI-10-0974

    Article  CAS  Google Scholar 

  28. Fournier A, Dos Santos G, Guillas G et al (2014) Recent recreational physical activity and breast cancer risk in postmenopausal women in the E3N cohort. Cancer Epidemiol Biomark Prev 23:1893–1902. doi:10.1158/1055-9965.EPI-14-0150

    Article  Google Scholar 

  29. Zhang X, Eliassen AH, Tamimi RM et al (2015) Adult body size and physical activity in relation to risk of breast cancer according to tumor androgen receptor status. Cancer Epidemiol Biomark Prev 24:962–968. doi:10.1158/1055-9965.EPI-14-1429

    Article  CAS  Google Scholar 

  30. Enger S, Ross R, Paganini-Hill A et al (2000) Body size, physical activity, and breast cancer hormone receptor status: Results from two case-control studies. Cancer Epidemiol Biomark Prev 9:681

    CAS  Google Scholar 

  31. Lahmann PH, Hoffmann K, Allen N et al (2004) Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer And Nutrition (EPIC). Int J Cancer 111:762–771. doi:10.1002/ijc.20315

    Article  CAS  PubMed  Google Scholar 

  32. Huang Z, Hankinson SE, Colditz GA et al (1997) Dual effects of weight and weight gain on breast cancer risk. JAMA 278:1407–1411

    Article  CAS  PubMed  Google Scholar 

  33. Kato I, Toniolo P, Koenig KL et al (1999) Epidemiologic correlates with menstrual cycle length in middle aged women. Eur J Epidemiol 15:809–814

    Article  CAS  PubMed  Google Scholar 

  34. Gerber M (1997) Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status. J Natl Cancer Inst 89:661–662

    Article  CAS  PubMed  Google Scholar 

  35. Morris PG, Hudis CA, Giri D et al (2011) Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer. Cancer Prev Res 4:1021–1029. doi:10.1158/1940-6207.CAPR-11-0110

    Article  CAS  Google Scholar 

  36. Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4:579–591. doi:10.1038/nrc1408

    Article  CAS  PubMed  Google Scholar 

  37. Del Giudice ME, Fantus IG, Ezzat S et al (1998) Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Res Treat 47:111–120

    Article  PubMed  Google Scholar 

  38. Schernhammer ES, Holly JM, Pollak MN, Hankinson SE (2005) Circulating levels of insulin-like growth factors, their binding proteins, and breast cancer risk. Cancer Epidemiol Biomark Prev 14:699–704. doi:10.1158/1055-9965.EPI-04-0561

    Article  CAS  Google Scholar 

  39. Schernhammer ES, Holly JM, Hunter DJ et al (2006) Insulin-like growth factor-I, its binding proteins (IGFBP-1 and IGFBP-3), and growth hormone and breast cancer risk in The Nurses Health Study II. Endocr Relat Cancer 13:583–592. doi:10.1677/erc.1.01149

    Article  CAS  PubMed  Google Scholar 

  40. Howlader N, Altekruse SF, Li CI et al (2014) US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. doi:10.1093/jnci/dju055

    PubMed  PubMed Central  Google Scholar 

  41. Amirikia KC, Mills P, Bush J, Newman LA (2011) Higher population-based incidence rates of triple-negative breast cancer among young African-American women : implications for breast cancer screening recommendations. Cancer 117:2747–2753. doi:10.1002/cncr.25862

    Article  PubMed  PubMed Central  Google Scholar 

  42. Flegal KM, Carroll MD, Kit BK, Ogden CL (2012) Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA 307:491–497. doi:10.1001/jama.2012.39

    Article  PubMed  Google Scholar 

  43. Begg CB, Zhang ZF (1994) Statistical analysis of molecular epidemiology studies employing case-series. Cancer Epidemiol Biomark Prev 3:173–175

    CAS  Google Scholar 

Download references

Author contributions

Lu Chen had full access to all the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis. Study concept and design: L. Chen, L.S. Cook, C.I. Li. Acquisition, analysis, or interpretation of data: L.Chen, L.S. Cook, C.I. Li, M.C. Tang, P. Porter, D.A. Hill, C.L. Wiggins, L.S. Cook, C.I. Li. Drafting of the manuscript: L. Chen. Critical revision of the manuscript for important intellectual content: L.Chen, C.I. Li, M.C. Tang, P. Porter, D.A. Hill, C.L. Wiggins, L.S. Cook. Administrative, technical, or material support: M.C. Tang, P. Porter, D.A. Hill, C.L. Wiggins, L.S. Cook, C.I. Li. Study supervision: L.S. Cook, C.I. Li.

Author information

Authors and Affiliations

  1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Mail Stop M4-C308, P.O. Box 19024, Seattle, WA, 98109, USA

    Lu Chen, Mei-Tzu C. Tang, Peggy L. Porter & Christopher I. Li

  2. Department of Internal Medicine, University of New Mexico and the University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA

    Linda S. Cook, Deirdre A. Hill & Charles L. Wiggins

  3. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Peggy L. Porter

Authors
  1. Lu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Linda S. Cook
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mei-Tzu C. Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peggy L. Porter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Deirdre A. Hill
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Charles L. Wiggins
    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 Lu Chen.

Ethics declarations

Conflict of interest

No potential conflicts of interest were disclosed.

Funding/support

This study was supported by the National Cancer Institute 261201000029C (C.I. Li), P50 CA148143 (C.I. Li, L.S. Cook, D.A. Hill), and 261201000033C (C.L.Wiggins). The National Cancer Institute had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, L., Cook, L.S., Tang, MT.C. et al. Body mass index and risk of luminal, HER2-overexpressing, and triple negative breast cancer. Breast Cancer Res Treat 157, 545–554 (2016). https://doi.org/10.1007/s10549-016-3825-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-016-3825-9

Keywords

Search

Navigation