Nina Oestreicher

Mammographic density in a multiethnic cohort

Objectives:To compare mammographic density among premenopausal and early perimenopausal women from four racial/ethnic groups and to examine density and acculturation among Japanese and Chinese women. Design:The study included 391 white, 60 African American, 171 Japanese, and 179 Chinese participants in the Study of Womens Health Across the Nation, a multisite study of US women transitioning through menopause. Mammograms done when women were premenopausal or early perimenopausal were assessed for area of dense breast tissue and the percent of the breast occupied by dense tissue (percent density). Information on race/ethnicity, acculturation, and other factors was obtained from standardized instruments. Multiple linear regression modeling was used to examine the association between race/ethnicity or acculturation and density measures. Results:Age-adjusted mean percent density was highest for Chinese (52%) and lowest for African American (34%) women. After additional adjustment for body mass index, menopause status, age at first birth, breast-feeding duration, waist circumference, and smoking, African Americans had the highest mean percent density (51%) and Japanese women had the lowest (39%). In contrast, the area of dense tissue was highest for African Americans and similar for white, Japanese, and Chinese women. Less acculturated Chinese and Japanese women tended to have a larger area of density and a higher percent density. Conclusions:Neither the age-adjusted nor fully adjusted results for percent density or area of dense tissue reflected current differences in breast cancer incidence rates among similarly aged African American, Japanese, Chinese, and white women. In addition, mammographic density was higher in less acculturated Asian women.

Gene expression profiling and breast cancer care: what are the potential benefits and policy implications?

Purpose: Gene expression profiling has been proposed as an alternative to clinical guidelines to identify high-risk patients for adjuvant chemotherapy. However, the outcomes associated with gene expression profiling are not clear, and guidelines for the appropriate use of genomic technologies have not been established.Methods: We developed a decision analytic model to evaluate the incremental cost and quality-adjusted life years of gene expression profiling versus NIH clinical guidelines in a hypothetical cohort of premenopausal early stage breast cancer patients 44 years of age. We conducted empirical analyses and identified literature-based data to inform the model, and performed probabilistic sensitivity analyses to evaluate uncertainty in the results. We interpreted the implications of our findings for treatment guidelines and policies.Results: Use of gene expression profiling resulted in an absolute 5% decrease in the proportion of cases of distant recurrence prevented, 0.21 fewer quality-adjusted life years, and a cost savings of

Comparative clinical and economic outcomes of treatments for refractory non-small cell lung cancer (NSCLC)

2882. The chosen test cutoff value to identify a tumor as poor prognosis and the cost of adjuvant chemotherapy were the most influential parameters in the analysis, but our findings did not change substantially in sensitivity analyses. Regardless of the test cutoff used to identify a poor prognosis tumor, the gene expression profiling assay studied in our analysis, at its current level of performance, did not attain the threshold sensitivity (95%) necessary to produce equal or greater quality-adjusted life years than NIH guidelines.Conclusion: Although the use of gene expression profiling in breast cancer care holds great promise, our analysis suggests additional refinement and validation are needed before use in clinical practice.

Predicted quality-adjusted life years as a composite measure of the clinical value of diabetes risk factor control

BACKGROUND Various drug therapies are available for treatment of refractory stage IIIB/IV non-small cell lung cancer (NSCLC), but their comparative economic value is unclear. METHODS We developed a decision analytic model to evaluate the incremental costs and quality-adjusted life-years (QALYs) of erlotinib, docetaxel, or pemetrexed in a cohort of refractory advanced stage NSCLC patients 60 years of age from a US payer perspective. Mean progression-free and overall survival were assumed equal for the three treatments based on published clinical trials, from which adverse event rates were also derived. Costs and utilities were obtained from publicly available sources. We performed sensitivity analyses to evaluate uncertainty in the results. RESULTS Treatment with erlotinib, docetaxel, and pemetrexed yielded 0.42, 0.41, and 0.41 quality-adjusted life-years (QALYs), respectively. The slightly increased QALYs for erlotinib compared to docetaxel and pemetrexed resulted from less severe treatment complications and oral vs. IV administration. Total costs were US

Antibiotics and Risk of Breast Cancer: Up to 9 Years of Follow-up of 2.1 Million Women

37,000, US

Physical activity and mammographic density in a cohort of midlife women.

39,100 and US

Physical Activity and Change in Mammographic Density The Study of Women's Health Across the Nation

43,800 for erlotinib, docetaxel and pemetrexed, respectively. In the probabilistic sensitivity analyses, erlotinib was cost-saving in 65 and 87% of the simulations compared to docetaxel and pemetrexed, respectively, and had improved QALYs and decreased costs or was cost-effective in 42 and 55% of simulations. Estimates of treatment duration were among the most influential parameters in the analyses. CONCLUSIONS The results of our analysis suggest treatment of refractory NSCLC with erlotinib is less costly compared with alternative treatments, and suggested improvements in QALYs should be confirmed in controlled clinical trials.

Cost-Effectiveness Analysis of Patiromer and Spironolactone Therapy in Heart Failure Patients with Hyperkalemia

Background:Control of blood pressure, low-density lipoprotein cholesterol (LDL-c), and A1c can lower the risk for diabetes complications. These quality indicators often are examined separately and weighted equally in performance measurement, potentially discarding important information. Objectives:We sought to create a composite indicator of the clinical benefit, or value, of diabetes risk factor control that appropriately weights the clinical importance of A1c, LDL-c, and blood pressure, and to test its usability for quality measurement. Methods:The combined value of control for 3 diabetes risk factors, measured by predicted quality-adjusted life years (QALYs), was compared in diabetes patients (n = 129,236 in 2001; n = 185,006 in 2003) in Kaiser Permanente Northern California across 16 medical center populations in 2001 and 2003 using hierarchical linear regression to adjust for case-mix differences. Patient-level QALYs, simulated from risk factor and case-mix variables in a Markov model, was the main outcome variable. Results:There was significant cross-sectional variability in average case-mix adjusted QALYs for diabetes patients across centers in 2003. QALYs increased from 2001 to 2003 as the result of improved risk factor control; longitudinal improvements in QALYs also showed variation across centers. Regression analyses demonstrated the greater impact of blood pressure versus LDL-c or A1c control on QALYs, and the greater value of risk factor control in those with poor versus near or in-control blood pressure. Conclusion:Using predicted QALYs to measure value holds promise as a sensitive composite indicator for quality measurement. Complex, evidence-based quality indicators such as these can potentially provide accurate and useful information to health plans, providers, and consumers.

Menstrual and reproductive factors in relation to mammographic density: the Study of Women’s Health Across the Nation (SWAN)

Antibiotic use has been associated with risk of breast cancer in previous reports. Using Cox proportional hazards analysis, we evaluated this association in 2,130,829 adult female subscribers of a health care program according to their receipt of prescriptions of antibiotics from outpatient pharmacies. Hormone use was taken into account. Altogether, 18,521 women developed breast cancer in up to 9.4 years of follow-up. Use of any antibiotic was associated with slightly increased risk [hazard ratio (HR), 1.14; 95% confidence interval (95% CI), 1.10-1.18] but there was little, if any, evidence of dose response, with HR of 1.17 (95% CI, 0.97-1.42) for >1,000 days of use compared with no use. The only two weakly associated antibiotic groups (HR >1.10 for >100 days of use) were tetracyclines and macrolides with HRs (95% CI) of 1.23 (1.11-1.36) and 1.16 (0.98-1.36), respectively. An association of lincosamides with breast cancer in an earlier, smaller database was not confirmed, but follow-up was too short in the present data for adequate evaluation. Medical record review suggested that acne and/or rosacea could be the underlying factor, associated with long-term antibiotic therapy and found by others to be associated with risk of breast cancer. Although causality cannot be ruled out, the observed associations of antibiotics overall, tetracyclines, and macrolides with breast cancer were weak and could be explained by uncontrolled confounding by the diseases being treated or by other factors. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2102–6)

Active, but not passive cigarette smoking was inversely associated with mammographic density

PURPOSE Physical activity (PA) is one of few modifiable breast cancer risk factors. There have been few studies of the relation between PA and mammographic density, especially in multiethnic populations. METHODS In a cohort of pre- and early perimenopausal women of non-Hispanic white (N = 373), African American (N = 55), Chinese (N = 178), and Japanese (N = 166) ethnicity, we used multivariable linear regression to examine the association between two measures of mammographic density (percent density and area of density) and mutually exclusive components of recent physical activity (sports, household/caregiving and work activity, active living). RESULTS After adjusting for race/ethnicity, menopausal status, parity, past use of hormones, body mass index, waist circumference and education, we observed nonsignificant inverse associations for percent mammographic density and the highest versus the lowest category of each of our PA domains. For example, the adjusted beta for active living = -2.62, 95% confidence interval (CI) (-5.84, 0.60). Nonsignificant inverse associations also were observed for area of density and each PA domain except work activity. However, most associations were nonlinear. CONCLUSION Our results are consistent with a modest inverse association between multiple domains of PA and mammographic density, although findings may have been attributable to chance alone.