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.
Breast cancer Triple negative Obesity BMI
This is a preview of subscription content, log in to check access.
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.
Compliance with ethical standards
Conflict of interest
No potential conflicts of interest were disclosed.
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.
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.xCrossRefPubMedGoogle Scholar
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 6:137–141CrossRefPubMedGoogle Scholar
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.28912CrossRefPubMedGoogle Scholar
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-08-0206CrossRefGoogle Scholar
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.22618CrossRefPubMedGoogle Scholar
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-08-0479CrossRefGoogle Scholar
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.27778CrossRefPubMedGoogle Scholar
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-14-1429CrossRefGoogle Scholar
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 9:681Google Scholar
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.20315CrossRefPubMedGoogle Scholar
Huang Z, Hankinson SE, Colditz GA et al (1997) Dual effects of weight and weight gain on breast cancer risk. JAMA 278:1407–1411CrossRefPubMedGoogle Scholar
Kato I, Toniolo P, Koenig KL et al (1999) Epidemiologic correlates with menstrual cycle length in middle aged women. Eur J Epidemiol 15:809–814CrossRefPubMedGoogle Scholar
Gerber M (1997) Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status. J Natl Cancer Inst 89:661–662CrossRefPubMedGoogle Scholar
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.1.01149CrossRefPubMedGoogle Scholar
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.25862CrossRefPubMedPubMedCentralGoogle Scholar