Relationship between Topoisomerase 2A RNA Expression and Recurrence after Adjuvant Chemotherapy for Breast Cancer

Purpose: To perform an exploratory analysis of the relationship between gene expression and recurrence in operable hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–normal breast cancer patients treated with adjuvant doxorubicin-containing chemotherapy. Experimental Design: RNA was extracted from archived tumor samples derived from 378 patients with stage I to III HR-positive, HER2-normal breast cancer and analyzed by reverse transcription-PCR for a panel of 374 genes, including the 21-gene recurrence score (RS). Patients were randomized to receive adjuvant doxorubicin plus cyclophosphamide or docetaxel in trial E2197, with no difference in recurrence seen in the treatment arms. All available recurrent cases were selected plus a nonrecurrent cohort. Cox proportional hazard models were used to identify relationships between gene expression and recurrence. Results: TOP2A expression exhibited the strongest association with increased recurrence risk ( P = 0.01), and was significantly associated with recurrence ( P = 0.008) in a multivariate analysis adjusted for clinicopathologic features. Elevated TOP2A expression above the median was associated with a 2.6-fold increase (95% confidence interval, 1.3-5.2; P = 0.008) in risk of recurrence if the RS was