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Obesity and related conditions and risk of inflammatory breast cancer: a nested case–control study

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

Abstract

Purpose

Inflammatory breast cancer (IBC) is a rare, poorly understood and aggressive tumor. We extended prior findings linking high body mass index (BMI) to substantial increased IBC risk by examining BMI associations before and after adjustment for well-characterized comorbidities using medical record data for diabetes, insulin resistance, and disturbances of cholesterol metabolism in a general community healthcare setting.

Methods

We identified 247 incident IBC cases diagnosed at Kaiser Permanente Northern California between 2005 and 2017 and 2470 controls matched 10:1 on birth year and geographic area and with ≥ 13 months of continuous enrollment prior to diagnosis/index date. We assessed exposures from 6 years up to one year prior to the diagnosis/index date, using logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs).

Results

Before adjustment for comorbidities, ORs (95% CIs) for BMI of 25–< 30, 30–< 35, and ≥ 35 compared to < 25 kg/m2 were 1.5 (0.9–2.3), 2.0 (1.2–3.1), and 2.5 (1.4–4.4), respectively. After adjustment for pre-diabetes/diabetes, HDL-C and triglyceride levels, and dyslipidemia, corresponding ORs were 1.3 (0.8–2.1), 1.6 (0.9–2.9), and 1.9 (1.0–3.5). The OR for HDL-C levels < 50 mg/dL compared to ≥ 65 mg/dL was 2.0 (1.2–3.3) in the adjusted model. In a separate model the OR for a triglyceride/HDL-C ratio ≥ 2.50 compared to < 1.62 was 1.7 (1.1–2.8) after adjustment for BMI, pre-diabetes/diabetes, and dyslipidemia. Results did not differ significantly by estrogen receptor status.

Conclusions

Obesity and measures of insulin resistance independently increased IBC risk as did obesity and low HDL-C levels. These findings, if confirmed, have implications for IBC prevention.

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Data availability

The data in this manuscript were sourced from electronic health records and related clinical and administrative data sources from Kaiser Permanente Northern California, and are not generally available to the public. These data may be made available through scientific collaborations under IRB-approved protocols and data use agreements.

Abbreviations

IBC:

Inflammatory breast cancer

KPNC:

Kaiser Permanente Northern California

KPNCCR:

Kaiser Permanente Northern California Cancer Registry

BMI:

Body mass index

ER:

Estrogen receptor

ICD:

International Classification of Disease

OR:

Odds ratio

CI:

Confidence interval

HDL-C:

High-density lipoprotein cholesterol

VEGF:

Vascular endothelial growth factor

References

  1. Anderson WF, Schairer C, Chen BE, Hance KW, Levine PH (2005) Epidemiology of inflammatory breast cancer (IBC). Breast Dis 22:9–23

    Article  Google Scholar 

  2. Greene FL, Page DL, Fritz A, Balch CM, Haller DG, Morrow M (2002) Breast. AJCC cancer staging manual, 6th edn. Springer-Verlag, New York, pp 225–226

    Chapter  Google Scholar 

  3. Hance KW, Anderson WF, Devesa SS, Young HA, Levine PH (2005) Trends in inflammatory breast cancer incidence and survival: the Surveillance, Epidemiology, and End Results Program at the National Cancer Institute. J Natl Cancer Inst 97:966–974

    Article  Google Scholar 

  4. Amiri-Kordestani L, Kamangar F, Zujewski JA (2013) Inflammatory breast cancer: yet another risk of the obesity epidemic? J Natl Cancer Inst 105:1340–1342

    Article  Google Scholar 

  5. Schairer C, Li Y, Frawley P, Graubard BI, Wellman RD, Buist DS, Kerlikowske K, Onega TL, Anderson WF, Miglioretti DL (2013) Risk factors for inflammatory breast cancer and other invasive breast cancers. J Natl Cancer Inst 105:1373–1384

    Article  CAS  Google Scholar 

  6. Chang S, Buzdar AU, Hursting SD (1998) Inflammatory breast cancer and body mass index. J Clin Oncol 16:3731–3735

    Article  CAS  Google Scholar 

  7. Atkinson RL, El-Zein R, Valero V, Lucci A, Bevers TB, Fouad T, Liao W, Ueno NT, Woodward WA, Brewster AM (2016) Epidemiological risk factors associated with inflammatory breast cancer subtypes. Cancer Causes Control 27:359–366

    Article  Google Scholar 

  8. Suzuki R, Orsini N, Saji S, Key TJ, Wolk A (2009) Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status – A meta-analysis. Int J Cancer 124:698–712

    Article  CAS  Google Scholar 

  9. Varmus H, Harlow E (2012) Provocative questions in cancer research. Nature 481:436–437

    Article  CAS  Google Scholar 

  10. Matthews SB, Thompson HJ (2016) The obesity-breast cancer conundrum: an analysis of the issues. Int J Mol Sci 17:989

    Article  Google Scholar 

  11. Rose DP, Gracheck PJ, Vona-Davis L (2015) The interactions of obesity, inflammation and insulin resistance in breast cancer. Cancers 7:2147–2168

    Article  CAS  Google Scholar 

  12. Ni H, Liu H, Gao R (2015) Serum lipids and breast cancer risk: a meta-analysis of prospective cohort studies. PLoS ONE 10(11):e0142669. https://doi.org/10.1371/journal.pone.0142669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. De Bruijn KM, Arends LR, Hansen BE, Leeflang S, Ruiter R, van Eijck CH (2013) Systematic review and meta-analysis of the association between diabetes mellitus and incidence and mortality in breast and colorectal cancer. Br J Surg 100:1421–1429

    Article  Google Scholar 

  14. Huang Y, Cai X, Qiu M, Chen P, Tang H, Hu Y, Huang Y (2014) Prediabetes and the risk of cancer: a meta-analysis. Diabetologia 57:2261–2269

    Article  CAS  Google Scholar 

  15. Boyle P, Koechlin A, Pizot C, Boniol M, Robertson C, Mullie P, Bolli G, Rosenstock J, Autier P (2013) Blood glucose concentrations and breast cancer risk in women without diabetes: a meta-analysis. Eur J Nutr 52:1533–1540

    Article  CAS  Google Scholar 

  16. Esposito K, Chiodini P, Capuano A, Bellastella G, Maiorino MI, Rafaniello C, Giugliano D (2013) Metabolic syndrome and postmenopausal breast cancer: systematic review and meta-analysis. Menopause 20:1301–1309

    Article  Google Scholar 

  17. Touvier M, Fassier P, His M, Norat T, Chan DS, Blacher J, Hercberg S, Galan P, Druesne-Pecollo N, Latino-Martel P (2015) Cholesterol and breast cancer risk: a systematic review and meta-analysis of prospective studies. Br J Nutr 114:347–357

    Article  CAS  Google Scholar 

  18. Autier P, Koechlin A, Boniol M, Mullie P, Bolli G, Rosenstock J, Boyle P (2013) Serum insulin and c-peptide concentration and breast cancer: a meta-analysis. Cancer Causes Control 24:873–883

    Article  Google Scholar 

  19. Hernandez AV, Guarnizo M, Miranda Y, Pasupuleti V, Deshpande A, Paico S, Lenti H, Ganoza S, Montalvo L, Thota P, Lazaro H (2014) Association between insulin resistance and breast carcinoma: a systematic review and meta-analysis. PLoS ONE 9(6):e99317. https://doi.org/10.1371/journal.pone.0099317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Schairer C, Gadalla SM, Pfeiffer RM, Moore SC, Engels EA (2017) Diabetes, abnormal glucose, dyslipidemia, hypertension, and risk of inflammatory and other breast cancer. Cancer Epidemiol Biomark Prev 26:862–868

    Article  CAS  Google Scholar 

  21. Nichols GA, Desai J, Lafata JE, Lawrence JM, O’Connor PJ, Pathak RD, Raebel MA, Reid RJ, Selby JV, Silverman BG, Steiner JF, Stewart WF, Vupputuri S, Waitzfelder B, SUPREME-DM Study Group (2012) Construction of a multisite datalink using electronic health records for the identification, surveillance, prevention, and management of diabetes mellitus: the SUPREME-DM Project. Prev Chronic Dis. https://doi.org/10.5888/pcd9.110311

    Article  PubMed  PubMed Central  Google Scholar 

  22. Koebnick C, Smith N, Huang K, Martinez MP, Clancy HA, Kushi LH (2012) The prevalence of obesity and obesity-related health conditions in a large, multiethnic cohort of young adults in California. Ann Epidemiol 22:609–616

    Article  Google Scholar 

  23. McKeever K, Saydah SH, Imperatore G, Cowie CC, Gregg EW, Geiss LS, Cheng YJ, Rolka DB, Williams DE, Caspersen CJ (2013) Secular changes in U.S. prediabetes prevalence defined by hemoglobin A1c and fasting plasma glucose. Diabetes Care 36:2286–2293

    Article  Google Scholar 

  24. Schmittdiel JA, Dyer WT, Marshall CJ, Bivins R (2018) Using neighborhood-level census data to predict diabetes progression in patients with laboratory-defined prediabetes. Perm J 22:18–096

    PubMed  PubMed Central  Google Scholar 

  25. Raghunathan TE, Lepkowski JM, van Hoewyk M, Solenberger PW (2001) A multivariate technique for multiply imputing missing values using a sequence of regression models. Survey Methodol 27:85–95

    Google Scholar 

  26. Priya G, Kalra S (2018) A review of insulin resistance in type I diabetes: is there a place for adjunctive metformin? Diabetes Ther 9:341–361

    Article  Google Scholar 

  27. Hostalek U, Gwilt M, Hildemann S (2015) Therapeutic use of metformin in prediabetes and diabetes prevention. Drugs 75:1071–1094

    Article  CAS  Google Scholar 

  28. Ojha A, Ojha U, Mohammed R, Chandrashekar A, Ojha H (2019) Current perspective on the role of insulin and glucagon in the pathogenesis and treatment of type 2 diabetes. Clin Pharm 11:57–65

    CAS  Google Scholar 

  29. Scappaticcio L, Maiorino MI, Bellastella G, Giugliano D, Esposito K (2017) Insights into the relationships between diabetes, prediabetes, and cancer. Endocrine 56:231–239

    Article  CAS  Google Scholar 

  30. https://ncbi.nlm.nih.gov/books/NBK507839

  31. Garcia-Estevez L, Moreno-Bueno G (2019) Updating the role of obesity and cholesterol in breast cancer. Breast Cancer Res 21:35

    Article  Google Scholar 

  32. Vermeulen PB, van Golen KL, Dirix LY (2010) Angiogenesis, lymphangiogenesis, growth pattern, and tumor emboli in inflammatory breast cancer: a review of current knowledge. Cancer 116(Suppl 11):2748–2754

    Article  CAS  Google Scholar 

  33. Morrow RJ, Etemadi N, Yeo B, Ernst M (2017) Challenging a misnomer? The role of inflammatory pathways in inflammatory breast cancer. Mediators Inflamm. https://doi.org/10.1155/2017/4754827

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kolb R, Sutterwala FS, Weizhou Z (2016) Obesity and cancer: inflammation bridges the two. Curr Opin Pharmacol 29:77–89

    Article  CAS  Google Scholar 

  35. Ahmadieh H, Azar ST (2013) Type 2 diabetes mellitus, oral diabetic medications, insulin therapy, and overall breast cancer risk. ISRN Endocrinol. https://doi.org/10.1155/181240

    Article  PubMed  PubMed Central  Google Scholar 

  36. Schairer C, Freedman DM, Gadalla SM, Pfeiffer RM (2018) Dyslipidemia, lipid-lowering drug use and breast cancer risk in the SEER-Medicare database. Breast Cancer Res Treat 169:607–614

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Cancer Institute at the National Institutes of Health Intramural Research Program and in part by NCI Grant U24 CA171524.

Funding

Division of Cancer Epidemiology and Genetics, National Cancer Institute. Division of Cancer Prevention, National Cancer Institute (U24).

Author information

Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Rm 7E142, Bethesda, MD, 20892, USA

    Catherine Schairer, Gretchen L. Gierach, Neil E. Caporaso & Ruth M. Pfeiffer

  2. Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA

    Cecile A. Laurent, Lisa M. Moy & Lawrence H. Kushi

Authors
  1. Catherine Schairer
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  2. Cecile A. Laurent
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  3. Lisa M. Moy
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  4. Gretchen L. Gierach
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  5. Neil E. Caporaso
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  6. Ruth M. Pfeiffer
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  7. Lawrence H. Kushi
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Corresponding author

Correspondence to Ruth M. Pfeiffer.

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The authors declare that they have no competing interests.

Ethical approval

This project was reviewed and approved by the KPNC Institutional Review Board (Protocol number: 1285916).

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The requirement to obtain informed consent for this data-only project was waived.

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Schairer, C., Laurent, C.A., Moy, L.M. et al. Obesity and related conditions and risk of inflammatory breast cancer: a nested case–control study. Breast Cancer Res Treat 183, 467–478 (2020). https://doi.org/10.1007/s10549-020-05785-1

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  • DOI: https://doi.org/10.1007/s10549-020-05785-1

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