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Associations between metabolic syndrome, breast cancer recurrence, and the 21-gene recurrence score assay

  • Epidemiology
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Abstract

The 21-gene recurrence score (RS) assay is prognostic in estrogen receptor-positive (HR+), HER2-negative, node-negative breast cancer (BC). The interaction between RS and host factors including metabolic syndrome (MS) is unclear. MS conditions such as obesity have been associated with worse BC prognosis. The aim of this study was to identify associations between presence of MS conditions and RS group or breast cancer recurrence. Demographic, pathologic, and treatment data, MS criteria, and menopausal status were abstracted from medical records of women with stage I–II, HR+, HER2-negative BC evaluated with the RS assay at a single institution since 2005. MS was defined as presence of ≥3 of the following within 2 years of diagnosis: body mass index ≥27.7 kg/m2; hypertension; impaired fasting glucose; HDL <50 mg/dL; hypertriglyceridemia. Of 533 eligible women, 22 % had MS. MS was more common in post- vs premenopausal women (30 vs 9 %; P < 0.0001). There was no significant association between RS group and overall MS status or any individual criterion, controlling for stage, and no association after stratification by menopausal status. Postmenopausal status was associated with higher RS group (P = 0.039), independent of stage. With 4.2-year median follow-up, no association between disease recurrence and MS was identified. Although MS has been associated with worse BC outcomes, we were unable to identify associations between RS group and MS criteria. Identification of prognostic factors other than RS that underlie this higher risk will be important for optimizing breast cancer treatment decision-making in patients with MS.

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References

  1. Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE, Dees EC, Perez EA, Olson JA, Zujewski J, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin P, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Atkins JN, Berenberg JL, Sledge GW (2015) Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med 373:2005–2014. doi:10.1056/NEJMoa1510764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W, Fisher ER, Wickerham DL, Bryant J, Wolmark N (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351:2817–2826

    Article  CAS  PubMed  Google Scholar 

  3. Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, Cronin M, Baehner FL, Watson D, Bryant J, Costantino JP, Geyer CE Jr, Wickerham DL, Wolmark N (2006) Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 24:3726–3734

    Article  CAS  PubMed  Google Scholar 

  4. Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT, Ravdin P, Bugarini R, Baehner FL, Davidson NE, Sledge GW, Winer EP, Hudis C, Ingle JN, Perez EA, Pritchard KI, Shepherd L, Gralow JR, Yoshizawa C, Allred DC, Osborne CK, Hayes DF (2010) Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol 11:55–65. doi:10.1016/S1470-2045(09)70314-6

    Article  CAS  PubMed  Google Scholar 

  5. Lakhani A, Guo A, Duan X, Ersahin C, Gaynor ER, Godellas C, Kay C, Lo SS, Mai H, Perez C, Albain K, Robinson P (2012) Metabolic syndrome and recurrence within the 21-gene recurrence score assay risk categories in lymph node negative breast cancer. Cancer Res 72(24 Supplement):Abstract PD10-02

  6. Hanauer DA, Mei Q, Law J, Khanna R, Zheng K (2015) Supporting information retrieval from electronic health records: a report of University of Michigan’s nine-year experience in developing and using the Electronic Medical Record Search Engine (EMERSE). J Biomed Inform 55:290–300. doi:10.1016/j.jbi.2015.05.003

    Article  PubMed  PubMed Central  Google Scholar 

  7. National Cholesterol Education Program (2002) Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 106:3143–3421. doi:10.1001/jama.285.19.2486

    Google Scholar 

  8. Protani M, Coory M, Martin JH (2010) Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 123:627–635. doi:10.1007/s10549-010-0990-0

    Article  PubMed  Google Scholar 

  9. Chlebowski RT (2012) Obesity and breast cancer outcome: adding to the evidence. J Clin Oncol 30:126–128. doi:10.1200/JCO.2011.39.7877

    Article  PubMed  Google Scholar 

  10. Ligibel JA, Goodwin PJ (2012) NEW and RENEW: building the case for weight loss in breast cancer. J Clin Oncol 30:2294–2296. doi:10.1200/JCO.2012.42.5496

    Article  CAS  PubMed  Google Scholar 

  11. Chen S, Chen CM, Zhou Y, Zhou RJ, Yu KD, Shao ZM (2012) Obesity or overweight is associated with worse pathological response to neoadjuvant chemotherapy among Chinese women with breast cancer. PLoS One 7:e41380. doi:10.1371/journal.pone.0041380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ewertz M, Gray KP, Regan MM, Ejlertsen B, Price KN, Thürlimann B, Bonnefoi H, Forbes JF, Paridaens RJ, Rabaglio M, Gelber RD, Colleoni M, Láng I, Smith IE, Coates AS, Goldhirsch A, Mouridsen HT (2012) Obesity and risk of recurrence or death after adjuvant endocrine therapy with letrozole or tamoxifen in the Breast International Group 1–98 trial. J Clin Oncol 30:3967–3975. doi:10.1200/JCO.2011.40.8666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kroenke CH, Chen WY, Rosner B, Holmes MD (2005) Weight, weight gain, and survival after breast cancer diagnosis. J Clin Oncol 23:1370–1378. doi:10.1200/JCO.2005.01.079

    Article  PubMed  Google Scholar 

  14. Loi S, Milne RL, Friedlander ML, McCredie MR, Giles GG, Hopper JL, Phillips KA (2005) Obesity and outcomes in premenopausal and postmenopausal breast cancer. Cancer Epidemiol Biomark Prev 14:1686–1691. doi:10.1158/1055-9965.EPI-05-0042

    Article  Google Scholar 

  15. Healy LA, Ryan AM, Carroll P, Ennis D, Crowley V, Boyle T, Kennedy MJ, Connolly E, Reynolds JV (2010) Metabolic syndrome, central obesity and insulin resistance are associated with adverse pathological features in postmenopausal breast cancer. Clin Oncol (R Coll Radiol) 22:281–288. doi:10.1016/j.clon.2010.02.001

    Article  CAS  Google Scholar 

  16. Bhandari R, Kelley GA, Hartley TA, Rockett IR (2014) Metabolic syndrome is associated with increased breast cancer risk: a systematic review with meta-analysis. Int J Breast Cancer 2014:189384. doi:10.1155/2014/189384

    Article  PubMed  PubMed Central  Google Scholar 

  17. 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. doi:10.1097/GME.0b013e31828ce95d

    Article  PubMed  Google Scholar 

  18. Rosato V, Bosetti C, Talamini R, Levi F, Montella M, Giacosa A, Negri E, La Vecchia C (2011) Metabolic syndrome and the risk of breast cancer in postmenopausal women. Ann Oncol 22:2687–2692. doi:10.1093/annonc/mdr025

    Article  CAS  PubMed  Google Scholar 

  19. Calip GS, Malone KE, Gralow JR, Stergachis A, Hubbard RA, Boudreau DM (2014) Metabolic syndrome and outcomes following early-stage breast cancer. Breast Cancer Res Treat 148:363–377. doi:10.1007/s10549-014-3157-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chun J, Refinetti AP, Schnabel F, Price A, Billig J, Cimeno A, Schwartz S, Guth A, Axelrod D (2012) Tumor characteristics in obese women with breast cancer. J Clin Oncol 30(suppl 27; abstr 179)

  21. Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717. doi:10.1016/s0140-6736(05)66544-0

    Article  Google Scholar 

  22. Magliano DJ, Shaw JE, Zimmet PZ (2006) How to best define the metabolic syndrome. Ann Med 38:34–41. doi:10.1080/07853890500300311

    Article  CAS  PubMed  Google Scholar 

  23. Huang PL (2009) A comprehensive definition for metabolic syndrome. Dis Model Mech 2:231–237. doi:10.1242/dmm.001180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Holmes MD, Chen WY, Li L, Hertzmark E, Spiegelman D, Hankinson SE (2010) Aspirin intake and survival after breast cancer. J Clin Oncol 28:1467–1472. doi:10.1200/JCO.2009.22.7918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Goodwin PJ, Parulekar WR, Gelmon KA, Shepherd LE, Ligibel JA, Hershman DL, Rastogi P, Mayer IA, Hobday TJ, Lemieux J, Thompson AM, Pritchard KI, Whelan TJ, Mukherjee SD, Chalchal HI, Oja CD, Tonkin KS, Bernstein V, Chen BE, Stambolic V (2015) Effect of metformin vs placebo on and metabolic factors in NCIC CTG MA.32. J Natl Cancer. doi:10.1093/jnci/djv006

    Google Scholar 

  26. NCIC Clinical Trials Group. A phase III randomized trial of metformin vs placebo in early stage breast cancer. https://clinicaltrials.gov/ct2/show/NCT01101438. Accessed 25 May 2016

  27. Chlebowski RT, Blackburn GL, Thomson CA, Nixon DW, Shapiro A, Hoy MK, Goodman MT, Giuliano AE, Karanja N, McAndrew P, Hudis C, Butler J, Merkel D, Kristal A, Caan B, Michaelson R, Vinciguerra V, Del Prete S, Winkler M, Hall R, Simon M, Winters BL, Elashoff RM (2006) Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women’s Intervention Nutrition Study. J Natl Cancer Inst 98:1767–1776. doi:10.1093/jnci/djj494

    Article  PubMed  Google Scholar 

  28. Pierce JP, Faerber S, Wright FA, Rock CL, Newman V, Flatt SW, Kealey S, Jones VE, Caan BJ, Gold EB, Haan M, Hollenbach KA, Jones L, Marshall JR, Ritenbaugh C, Stefanick ML, Thomson C, Wasserman L, Natarajan L, Thomas RG, Gilpin EA (2002) A randomized trial of the effect of a plant-based dietary pattern on additional breast cancer events and survival: the Women’s Healthy Eating and Living (WHEL) Study. Control Clin Trials 23:728–756

    Article  PubMed  Google Scholar 

  29. Chlebowski RT, Aiello E, McTiernan A (2002) Weight loss in breast cancer patient management. J Clin Oncol 20:1128–1143

    Article  PubMed  Google Scholar 

  30. Ligibel JA, Alfano CM, Hershman D, Ballard RM, Bruinooge SS, Courneya KS, Daniels EC, Demark-Wahnefried W, Frank ES, Goodwin PJ, Irwin ML, Levit LA, McCaskill-Stevens W, Minasian LM, O’Rourke MA, Pierce JP, Stein KD, Thomson CA, Hudis CA (2015) Recommendations for obesity clinical trials in cancer survivors: American Society of Clinical Oncology Statement. J Clin Oncol 33:3961–3967. doi:10.1200/jco.2015.63.1440

    Article  PubMed  Google Scholar 

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Acknowledgments

NLH was supported in part by a National Cancer Institute Clinical Cancer Investigator Team Leadership Award (supplement to 3-P30-CA046592, PI M Wicha).

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Authors and Affiliations

  1. Department of Internal Medicine, University of Michigan Medical School, 1500 E. Medical Center Dr, Med Inn Bldg C450, Ann Arbor, MI, 48109-5843, USA

    Jeanette Muniz & N. Lynn Henry

  2. Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, USA

    Kelley M. Kidwell

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  1. Jeanette Muniz
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Correspondence to N. Lynn Henry.

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Muniz, J., Kidwell, K.M. & Henry, N.L. Associations between metabolic syndrome, breast cancer recurrence, and the 21-gene recurrence score assay. Breast Cancer Res Treat 157, 597–603 (2016). https://doi.org/10.1007/s10549-016-3846-4

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