Abstract PD10-02: Metabolic syndrome and recurrence within the 21-gene recurrence score assay risk categories in lymph node negative breast cancer
Authors: Lakhani A , Guo R , Duan X , Ersahin C , Gaynor ER , Godellas C , Kay C , Lo SS , Mai H , Perez C , Albain K , Robinson P 
Published: August 2014

Abstract
Background: The incidence of the metabolic syndrome (MS) has been increasing in the United States and elsewhere. The interaction of MS with breast cancer (BC) incidence, tumor biology and outcomes are under study. We hypothesized that the presence of MS would predict BC recurrence to a variable degree across the diverse BC biology as defined by the risk categories of the 21-gene recurrence score (RS) assay.
Patients and Methods: We studied consecutive patients (pts) with newly diagnosed, estrogen receptor (ER) positive, lymph node (LN) negative BC treated in our institution between 2006–2011 who had a 21-gene RS assay done on their tumors. All pts were treated with standard systemic and local therapy. The electronic medical record was queried for key diagnoses including MS and its constituent parts. The WHO definition was used to categorize pts as having MS defined as diabetes mellitus (DM) or glucose intolerance, plus at least 2 of the following: hypertension (HTN), dyslipidemia (HL), central obesity and microalbuminemia. Tumor characteristics including Ki67 index, grade, tumor size, HER2/neu status; and pt characteristics including age, race, menopausal status, body mass index were recorded. The association of MS and the tumor and patient characteristics with the RS tertiles of low, intermediate and high risk was analyzed.
Results: We identified 332 pts, median age 62 years, of whom 88 (27%) had MS. There was no significant association between the MS and any of the patient or tumor variables including the 21-gene RS assay, except for race (p = 0.004). Eleven of 21 (52%) African-American women had MS, 68 of 284 (24%) Caucasian women had MS, and 9 of 21 (43%) others including Hispanic and Asian women had MS. However, there was a significant association between recurrence and MS (p = 0.0002) independent of other factors. Of the 21 pts who recurred, 13 (61.9%) had MS. There was an association of recurrence and MS within RS tertiles. For pts with low risk scores, 7/44 (15.9%) with MS vs. 1/126 (0.79%) without MS had recurrence (p = 0.0003). For pts with intermediate risk scores, 5/30 (16.67%) with MS vs. 4/83 (4.82%) without MS had recurrence (p = 0.05). For patients with high risk scores, 1/9 (11.11%) with MS vs. 2/15 (13.33%) without MS had recurrence (p = 1).
Conclusion: MS is an independent risk factor for BC recurrence among women with LN negative, ER positive BC treated with standard adjuvant therapy. There is a striking impact of MS on recurrence in pts with tumor biologies defined by low (and to a lesser degree) intermediate risk 21-gene RS assay scores. However, there is no difference in recurrence risk by MS among those pts with high RS. This implies that interventions directed at modifying MS in newly diagnosed pts with early BC may potentially favorably impact survival in those with specific tumor biologies as defined by multigene assays. Thus, long-term prospective studies should be conducted to further evaluate both the short and long term effects of MS on BC outcomes.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD10-02.