Clinical outcomes in patients with node-negative breast cancer treated based on the recurrence score results: evidence from a large prospectively designed registry.

The 21-gene Recurrence Score® (RS) assay is a validated prognostic/predictive tool in ER + early-stage breast cancer. However, clinical outcome data from prospective studies in RS ≥ 11 patients are lacking, as are relevant real-life clinical practice data. In this retrospective analysis of a prospectively designed registry, we evaluated treatments/clinical outcomes in patients undergoing RS-testing through Clalit Health Services. The analysis included N0 ER + HER2-negative breast cancer patients who were RS-tested from 1/2006 through 12/2010. Medical records were reviewed to verify treatments/recurrences/survival. The cohort included 1801 patients (median follow-up, 6.2 years). Median age was 60 years, 50.4% were grade 2 and 81.1% had invasive ductal carcinoma; 48.9% had RS < 18, 40.7% RS 18-30, and 10.4% RS ≥ 31, with chemotherapy use of 1.4, 23.7, and 87.2%, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 0.8, 3.0, and 8.6%, for patients with RS < 18, RS 18-30 and RS ≥ 31, respectively; the corresponding 5-year Kaplan-Meier estimates for breast cancer death were 0.0, 0.9, and 6.2%. Chemotherapy-untreated patients with RS < 11 (n = 304) and 11-25 (n = 1037) (TAILORx categorization) had 5-year Kaplan-Meier estimates for distant recurrence risk/breast cancer death of 1.0%/0.0% and 1.3%/0.4%, respectively. Our results extend those of the prospective TAILORx trial: the 5-year Kaplan-Meier estimates for distant recurrence and breast cancer death rate for the RS < 18 patients were very low supporting the use of endocrine therapy alone. Furthermore, in chemotherapy-untreated patients with RS 11-25 (where TAILORx patients were randomized to chemoendocrine or endocrine therapy alone), 5-year distant recurrence rates were also very low, suggesting that chemotherapy would not have conferred clinically meaningful benefit.

Community pharmacists' support improves antidepressant adherence in the community.

The treatment goal of major depressive disorder (MDD) is achieving and maintaining remission. One of the major obstacles in attaining remission is poor adherence to the medication regimen. Community pharmacists (CPs) are accessible to primary care patients and are in a unique position to help improve adherence. The aim was to compare the effectiveness of pharmacist intervention with standard care for patients with MDD. This was an exploratory controlled trial conducted in 17 general pharmacies with clinical pharmacists in Israel. Participants were patients with MDD prescribed escitalopram by their general practitioner. CP medication review was initiated at enrollment, with face-to-face pharmacist adherence support at treatment initiation and every month throughout the study. Treatment as usual (TAU) was derived from computerized medical charts for the same pharmacies during the same time period. Comparison with published 'historical' controls was also carried out. No blinding was possible. Continuous antidepressant treatment at 6 months as reflected in computerized pharmacy records was the primary outcome. Within a 1-year period, 173 patients were enrolled. There were 49 men (28%) and 124 women (72%) in the CP group, mean age 53.9 ± 18.9 years. There were 4079 men (32%) and 8667 women (68%) in the TAU group, mean age 50.4 ± 17.8 years. Ninety-six patients (55%) completed 6 months of antidepressant treatment. At 1 month, the adherence rate was 71% in the CP arm and at 6 months, the rates were 55% versus published norms of 42% (P=0.004). At 1 month, the adherence rate was 57% (N=7256) in the TAU arm and at 6 months, the rate was 15.2% (N=1934) (compared with CP rates: P<0.0001). There were no differences between sites in adherence rates. CPs participating in this study reported higher levels of confidence in supporting MDD patients at the end of the study. This is the first trial of pharmacist adherence support in Israel, and shows benefits for patients in the community with MDD.

The impact of the 21-gene Recurrence Score assay on clinical decision-making in node-positive (up to 3 positive nodes) estrogen receptor-positive breast cancer patients.

Oncotype DX testing is reimbursed in Israel for node-negative and node-positive (N1+; up to 3 positive nodes including micrometastases), estrogen receptor positive (ER+), breast cancer patients. This retrospective study evaluated the impact of Oncotype DX testing on treatment decisions in N1+/ER+ breast cancer patients. To this end, we compared treatments for all N+ patients for whom testing had been ordered with treatments for patients with similar characteristics where the test had not been available. The retrospective analysis included 951 patients (282 Oncotype DX, 669 controls), all of whom received endocrine therapy with or without chemotherapy. In Oncotype DX patients, 7.1, 37.0, and 100 % of those with low, intermediate, and high Recurrence Score results (Oncotype DX summary score) received chemotherapy, respectively (P < 0.0001, all comparisons). Chemotherapy use was lower in Oncotype DX patients versus controls (24.5 vs. 70.1 %). In a multivariate logistic regression analysis in which the probability of receiving chemotherapy was modeled as a function of Oncotype DX testing, age, tumor size, tumor grade, nodal status, and the interactions between Oncotype DX testing and the other covariates, Oncotype DX testing was associated with significantly lower odds of receiving chemotherapy (odds ratio 0.16; 95 % CI 0.11-0.24; P < 0.0001). In summary, our findings suggest that Oncotype DX testing has a significant impact on reducing chemotherapy use in N1+/ER+ breast cancer patients in Israel.

Economic implications of 21-gene breast cancer risk assay from the perspective of an Israeli-managed health-care organization.

OBJECTIVE: Oncotype DX, a 21-gene assay, was clinically validated as a predictor of 10-year recurrence-free survival and treatment response in patients with early-stage estrogen-receptor-positive, lymph-node negative breast cancer (ER+ LN- ESBC). This study determined "real-life" alteration in treatment decision and economic implications of Oncotype DX use in women with ER+ LN- ESBC. METHODS: Clalit Health Services (CHS, Tel Aviv, Israel), determined the proportion of women in low, intermediate and high-risk groups in the first 368 Oncotype DX assays performed, the change of adjuvant therapy recommendation following the recurrence (RS) results from Oncotype DX use, and associated chemotherapy costs. The risk of recurrence-free survival was derived from prespecified statistical protocols of NCI-sponsored trials conducted by NSABP (B-14 and B-20). Utilities were literature based. A 3% discount rate was employed. RESULTS: Oncotype DX altered recommendations of 40% of patients, 84% of whom were changed from hormone + chemotherapy to hormonal therapy alone. Among high-risk women, 8% switched actual treatment from hormonal therapy to hormone + chemotherapy. By reducing the chemotherapy disutility, quality-adjusted life-years (QALY) increased 0.170 years. Use of Oncotype DX costs $10,770 per QALY gained. Sensitivity analyses revealed that risk reduction in the low-risk population, the cost of adverse events, and the relative risk reduction of recurrence were the most influential variables. CONCLUSION: Oncotype DX resulted in net QALY gain and increased overall costs, with an incremental cost-effectiveness ratio of $10,770. For CHS, Oncotype DX represents an effective and affordable approach to favorably affect the lives of women with ESBC.

Antipsychotics and diabetes: an age-related association.

BACKGROUND: Previous studies have reported an association between anti-psychotic medications and diabetes. OBJECTIVE: To explore the association between antipsychotic medications and diabetes in patients of different ages. METHODS: A retrospective analysis of a large health maintenance organization's drug claim database (3.7 million members) was performed. All patients treated with antipsychotic drugs during 1998-2004 were identified. Patients with diabetes were defined by a record of antidiabetic drug use during 2004. The prevalence of diabetes in different age groups treated with antipsychotics was compared with the prevalence of diabetes among enrollees in the same age groups not treated with antipsychotics. RESULTS: Among 82,754 patients treated with antipsychotics, the association between diabetes and consumption of antipsychotics was strongest in the younger age groups and decreased with increasing age: for patients aged 0-24 years, OR 8.9 (95% CI 7.0 to 11.3); 25-44 years, OR 4.2 (95% CI 3.8 to 4.5); 45-54 years, OR 1.9 (95% CI 1.8 to 2.1); 55-64 years, OR 1.3 (95% CI 1.2 to 1.4); and 65 years or older, OR 0.93 (95% CI 0.9 to 1.0). However, the risk associated with atypical antipsychotics was lower than the risk associated with typical antipsychotics, with ORs ranging from 0.7 in patients 0-24 years old to 0.3 in those 65 years or older. CONCLUSIONS: Antipsychotic drug use was associated with diabetes mellitus. This association was stronger in younger patients. In older adults, the difference was much smaller and, in some cases, there was no association. A lower risk was associated with atypical agents, as compared with typical antipsychotics. Clinicians should be aware that young adults treated with antipsychotics are at increased risk for diabetes.