Abstract P6-08-42: Association of metabolic syndrome, its components and multigene assays for recurrence risk
Authors: Mai Hanh P , Kliethermes Stephanie , Jain Shikha , Lo Shelly S , Gaynor Ellen R , Albain Kathy S , Robinson Patricia 
Published: May 2015

Background:

There is an association of metabolic syndrome (MS) and its constituents (obesity; diabetes mellitus, DM; hypertension, HTN; hyperlipidemia, HL) with breast cancer (BC) causation and outcomes. Previously we showed an impact of obesity on tumor biology as defined by a multigene assay. Our objective was to study the association between MS, its components and tumor biology, as determined by the 70 gene signature (70-GS) and the 21-gene Recurrence Score (RS).

Methods:

Consecutive patients with newly diagnosed ER+, lymph node-negative BC from 2005-2012 were studied. A 70-GS was done for those pts with tumors that had either low or intermediate RS. Pearson’s Chi-square tests for univariate analyses and logistic regression for multivariate analysis were used.

Results:

Low or intermediate RS were found on tumors from 151 pts of which 133 had a 70-GS. The MS was present in 23/104 (22%) pts with intermediate RS and 21/46 (46%) pts with low RS (p=0.004). DM, HTN, and obesity were each inversely associated with 21-gene RS in univariate analyses (p=0.002, p=0.003, p=0.004 respectively, see Table). However, MS and its individual components were not significantly associated with the 70-GS. Upon adjustment for age and race, the association between MS and RS was not significant (OR=0.64; p=0.28); however, DM (OR=0.35; p=0.01), HTN (OR=0.44; p=0.05) and obesity (OR=0.35; p=0.01) remained significantly inversely associated with RS. Independent of age and race, patients with DM, HTN, or obesity were more likely to be in the low-risk 21-gene RS group.

[Table] High Risk 70-GSLow Risk 70-GSp-valueIntermediate 21-gene RSLow 21-gene RSp-valueMetabolic Syndrome  0.30  0.004Yes14(24%)24(32%) 23(22%)21(46%) No44(76%)50(68%) 81(78%)25(54%) Diabetes  0.24  0.002Yes12(21%)22(30%) 18(17%)19(41%) No46(79%)52(70%) 86(83%)27(59%) Hypertension  0.28  0.003Yes36(62%)39(53%) 52(50%)35(76%) No22(38%)35(47%) 52(50%)11(24%) Obesity  0.27  0.004Yes35(60%)38(51%) 51(49%)34(74%) No23(40%)37(49%) 54(51%)12(26%) 

Conclusions and Implications:

The association of MS and its components differs for the 70-GS and RS assays. There is significant association between MS (and DM, HTN, obesity) and RS, but no association with 70-GS. Patients with MS (and components) are more likely to have a biology (low RS) known to have less chemotherapy benefit. Given the reported impact of MS on BC incidence and outcomes along with the global increased MS incidence, the MS may have profound impact on BC biology and treatment outcomes in the coming years. It is also possible that multigene assays currently in use for prognosis and prediction may need refinement in the presence of MS and/or its components.

Citation Format: Hanh P Mai, Stephanie Kliethermes, Shikha Jain, Shelly S Lo, Ellen R Gaynor, Kathy S Albain, Patricia Robinson. Association of metabolic syndrome, its components and multigene assays for recurrence risk [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-42.