Metabolic syndrome and breast cancer recurrence within the 21-gene recurrence score assay.

Abstract

104 Background: The 21-gene recurrence score (RS) assay (OncotypeDX) is prognostic in stage I-II, ER+, HER2-, node negative breast cancer (BC). While RS reflects tumor gene expression its interaction with host factors including metabolic syndrome (MS) is unclear. MS conditions such as obesity have been associated with increased risk of BC and worse prognosis. The aim of this study is to determine correlations between MS conditions and RS group or BC outcomes in both pre- and post-menopausal women. Methods: We retrospectively reviewed women with stage I-II, ER+, HER2- node negative BC evaluated with RS assay treated at University of Michigan since 2005. Demographic, pathologic and treatment data, MS criteria and menopausal status were abstracted from medical records. MS was defined as ≥ 3 of the following within 6 months of diagnosis: BMI ≥ 27.7kg/m2; hypertension (HTN); impaired fasting glucose (IFG); HDL < 50mg/dL; hypertriglyceridemia (trig). RS groups were defined as low ( < 18), intermediate (18-30) and high ( > 31). Results: Of 533 eligible women 74% had stage I disease and 61% were postmenopausal at diagnosis. MS criteria prevalence was 43% BMI, 42% HTN, 34% trig, 14% IFG and 13% HDL. MS was present in 22% and more common in post- vs pre-menopausal women (30% vs 9%; p < 0.0001). RS groups were 55% low, 38% intermediate and 7% high. 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. Over the 4.2 year median follow-up there were 7 deaths and 20 events, including 5 DCIS, 3 local and 11 distant recurrences and 1 second primary BC. There was insufficient power to detect associations between event rate and MS status. Conclusions: MS and comprising conditions are present in many early stage breast cancer patients, especially postmenopausal women. We were unable to identify associations between RS group and MS criteria. Thus the known worse BC prognosis with MS is not reflected in the RS. Identification of factors underlying this higher risk will be important for optimizing management of patients with breast cancer and MS.