Anti-anginal efficacy and safety of ranolazine for angina were similar between diabetic and non-diabetic patients. Ranolazine significantly improved glycaemic control in diabetic patients.

RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit.

The NSABP B-20 prospective-retrospective study of the 21-gene Oncotype DX Breast Cancer Recurrence Score® test predicted benefit from addition of chemotherapy to tamoxifen in node-negative, estrogen-receptor positive breast cancer when recurrence score (RS) was ≥31. HER2 is a component of the RS algorithm with a positive coefficient and contributes to higher RS values. Accrual to B-20 occurred prior to routine testing for HER2, so questions have arisen regarding assay performance if HER2-positive patients were identified and excluded. We report an exploratory reanalysis of the B-20, 21-gene study following exclusion of such patients. Patients were considered HER2 positive if quantitative RT-PCR for HER2 was ≥11.5 units, and excluded from re-analyses performed using the original cutoffs: <18, 18–30, ≥31, and the TAILORx cutoffs: <11, 11–25, >25. The endpoint remained distant recurrence-free interval (DRFI) as in the original study. Distribution was estimated via the Kaplan–Meier method and compared via log-rank test. Multivariate Cox proportional hazards models estimated chemotherapy benefit in each group. In the RS < 18 and 18–30 groups, 1.7 and 6.7% were HER2 positive. In the RS ≥ 31 group, 41% were HER2 positive. Exclusion resulted in fewer events, with loss of significance for benefit from chemotherapy in the overall HER2-negative cohort (log-rank P = 0.06), but substantial benefit from chemotherapy remained in the RS ≥ 31 cohort (HR = 0.18; 95% CI: 0.07–0.47) and the RS > 25 cohort (HR = 0.28; 95% CI: 0.12–0.64). No benefit from chemotherapy was evident in the other RS groups. Following exclusion of HER2-positive patients based on RT-PCR expression, substantial benefit of chemotherapy remained for RS ≥ 31 as originally employed, and with RS > 25 employed in TAILORx.

PURPOSE The 21-gene recurrence score (RS) is prognostic for distant recurrence (DR) and predictive for chemotherapy benefit in early breast cancer, whereas clinical-pathological factors are only prognostic. Integration of genomic and clinical features offers the potential to guide adjuvant chemotherapy use with greater precision. METHODS We developed a new tool (RSClin) that integrates RS with tumor grade, tumor size, and age using a patient-specific meta-analysis including 10,004 women with hormone receptor–positive, human epidermal growth factor receptor 2–negative, and node-negative breast cancer who received endocrine therapy alone in the B-14 (n = 577) and TAILORx (n = 4,854) trials or plus chemotherapy in TAILORx (n = 4,573). Cox models for RSClin were compared with RS alone and clinical-pathological features alone using likelihood ratio tests. RSClin estimates of DR used a baseline risk with TAILORx event rates to reflect current medical practice. A patient-specific estimator of absolute chemotherapy benefit was computed using individualized relative chemotherapy effect from the randomized TAILORx and B-20 trials. External validation of risk estimation was performed by comparing RSClin estimated risk and observed risk in 1,098 women in the Clalit registry. RESULTS RSClin provides more prognostic information (likelihood ratio χ2) for DR than RS or clinical-pathological factors alone (both P < .001, likelihood ratio test). In external validation, the RSClin risk estimate was prognostic for DR risk in the Clalit registry ( P < .001) and the estimated risk closely approximated the observed 10-year risk (Lin concordance 0.962). The absolute chemotherapy benefit estimate ranges from 0% to 15% as the RS ranges from 11 to 50 using RSClin in a 55-year-old woman with a 1.5-cm intermediate-grade tumor. CONCLUSION The RSClin tool integrates clinical-pathological and genomic risk to guide adjuvant chemotherapy in node-negative breast cancer and provides more individualized information than clinical-pathological or genomic data alone.