ABSTRACT
Oncotype-DX assay has never been validated for BRCA mutation carriers. This study compares the recurrence score (RS) distribution in BRCA-positive breast cancer patients with that of a general population (GP) of patients and reports their outcomes. Eligible patients were BRCA carriers who performed the Oncotype-DX assay. Two sets of databases were cross-linked: BRCA carriers at Rabin Medical Center and Sheba Medical Center with Oncotype-DX tests performed through Clalit Health Services HMO, from 2003 to 2015. Fifty-eight BRCA patients were included (20 BRCA1, 38 BRCA2). The GP included 1020 patients. Compared to the GP, BRCA1 patients were younger, had higher rate of grade three tumors, and higher Ki67. BRCA2 patients had lower PR index, higher rate of grade three tumors, and higher Ki67. Among the GP, 52.9, 37.9, and 9.1 % had low, intermediate, and high risk RS, respectively. Corresponding rates were 15, 35, and 50 % in BRCA1 patients, and 18.4, 52.6, and 29 % in BRCA2 patients. Subgroup analysis revealed a similar RS distribution pattern regardless of the nodal status. Median follow-up was 45 months. Four BRCA patients (7 %) developed disease recurrence. RS of these patients were in the intermediate and low range. All recurrences occurred in chemo-naïve patients who had not undergone bilateral oophorectomy. This study revealed significantly different RS distributions between BRCA patients and the GP. RS values shifted toward high and intermediate risk categories. This pattern held regardless of the nodal status and was more pronounced in the BRCA1 group.
Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/genetics , Mutation , Neoplasm Recurrence, Local/diagnosis , Adult , Aged , Aged, 80 and over , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Databases, Genetic , Female , Gene Expression Regulation, Neoplastic , Humans , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/metabolism , Prognosis , Receptors, Estrogen/metabolism , Risk AssessmentABSTRACT
OBJECTIVE: To examine the hypothesis that transition from creatine kinase MB subunits (CK-MB) to troponin as a more sensitive biomarker of myocardial necrosis reduced the 1 year mortality of non-ST elevation acute coronary syndrome (ACS) patients. DESIGN: Retrospective population based cohort study performed in seven tertiary care hospitals in Israel. The patient population comprised all non-ST elevation ACS admissions during a 5 year period (1999-2004). CK-MB was the biomarker for the diagnosis of myocardial infarction (MI) at the time of admission in 14 037 patients (group 1), while 11 643 patients were admitted after the individual hospital laboratory switched to troponin (group 2). Incidence of ACS types, in-hospital management and 1 year survival was assessed. RESULTS: Group 2 patients had a higher frequency of non-ST elevation MI diagnosis (27.9% vs 17.7%, p<0.001) and were more likely to undergo coronary catheterisation during hospitalisation (44.5% vs 37.5%, p<0.001). One year mortality in non-ST elevation MI was lower in group 2 compared to group 1 (24.6% vs 28.1%, p = 0.002). Similarly, the 1 year death rate in the unstable angina group decreased in group 2 compared to group 1 (7.7% vs 8.5%, p = 0.04). However, the overall non-ST elevation ACS 1 year mortality rate did not change (12.4% vs 11.9%, p = 0.27). In multivariate Cox proportional hazard analysis the transition from CK-MB to troponin had no significant effect on overall 1 year mortality (hazard ratio 0.95, 95% confidence interval 0.89 to 1.03). CONCLUSIONS: Transition to troponin as a diagnostic marker of MI led to an increase in the incidence of non-ST elevation MI. This transition was not associated with a decrease in the 1 year non-ST elevation ACS mortality rate.
