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Purpose Prior studies examining cost effectiveness of the 21-gene assay (Oncotype DX [ODX]) for women with hormone receptor-positive, early-stage breast cancer have yielded disparate results. We aimed to explore why these analyses may have yielded different conclusions. Methods We conducted a systematic literature review of cost-effectiveness analyses (CEAs) of ODX. We examined the extent to which the structure of CEA modeling, the assumptions of the models, and the selection of input parameters influenced cost-effectiveness estimates. We also explored the prevalence of industry funding and whether industry funding was associated with study designs favoring ODX. Results We identified 27 analyses, 15 of which received industry funding. In 18 studies, the clinical characteristics (eg, tumor size and grade) commonly used to make chemotherapy decisions were not incorporated into simulation modeling; thus, these studies would favor ODX being cost effective and might not reflect clinical practice. Most studies ignored the heterogeneous effect of ODX on chemotherapy use; only five studies assumed that ODX would increase chemotherapy use for clinically low-risk patients but decrease chemotherapy use for clinically high-risk patients. No study used population-based joint distributions of ODX recurrence score and tumor characteristics, and 12 studies inappropriately assumed that chemotherapy would increase distant recurrence for the low recurrence score group; both approaches overestimated the benefits of ODX. Industry-funded studies tended to favor ODX; all five studies that reported ODX as being cost saving were industry funded. In contrast, two studies that reported an incremental cost-effectiveness ratio > $50,000 per quality-adjusted life-year were not funded by industry. Conclusion Although a majority of published analyses indicated that ODX is cost effective, they incorporated study designs that can increase the risk of bias.

Objective African Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than SLE patients of European descent. We investigated whether European genetic ancestry protects against the development of lupus nephritis and explored genetic and socioeconomic factors that might explain this effect. Methods This was a cross-sectional study of 1906 adults with SLE. Participants were genotyped for 126 single nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. We used logistic regression to test the association between European ancestry and renal disease. Analyses adjusted for continental ancestries, socioeconomic status, and candidate genes. Results Participants (n=1906) had on average 62.4% European, 15.8% African, 11.5% East Asian, 6.5% Amerindian, and 3.8% South Asian ancestry. Among participants, 34% (n=656) had renal disease. A 10% increase in European ancestry was associated with a 15% reduction in the odds of having renal disease after adjustment for disease duration and sex (OR 0.85, 95% CI 0.82-0.87, p=1.9 × 10−30). Adjusting for other genetic ancestries, measures of socioeconomic status, or SNPs in genes most associated with renal disease (IRF5 (rs4728142), BLK (rs2736340), STAT4 (rs3024912), ITGAM (rs9937837) and HLA-DRB1*0301 and DRB1*1501, p<0.05) did not substantively alter this relationship. Conclusion European ancestry is protective against the development of renal disease in SLE, an effect independent of other genetic ancestries, common risk alleles, and socioeconomic status.

IMPORTANCE Among high-risk patients with hypertension, targeting a systolic blood pressure of 120 mm Hg reduces cardiovascular morbidity and mortality compared with a higher target. However, intensive blood pressure management incurs additional costs from treatment and from adverse events. OBJECTIVE To evaluate the incremental cost-effectiveness of intensive blood pressure management compared with standard management. DESIGN, SETTING, AND PARTICIPANTS This cost-effectiveness analysis conducted from September 2015 to August 2016 used a Markov cohort model to estimate cost-effectiveness of intensive blood pressure management among 68-year-old high-risk adults with hypertension but not diabetes. We used the Systolic Blood Pressure Intervention Trial (SPRINT) to estimate treatment effects and adverse event rates. We used Centers for Disease Control and Prevention Life Tables to project age- and cause-specific mortality, calibrated to rates reported in SPRINT. We also used population-based observational data to model development of heart failure, myocardial infarction, stroke, and subsequent mortality. Costs were based on published sources, Medicare data, and the National Inpatient Sample. INTERVENTIONS Treatment of hypertension to a systolic blood pressure goal of 120 mm Hg (intensive management) or 140 mm Hg (standard management). MAIN OUTCOMES AND MEASURES Lifetime costs and quality-adjusted life-years (QALYs), discounted at 3% annually. RESULTS Standard management yielded 9.6 QALYs and accrued $155 261 in lifetime costs, while intensive management yielded 10.5 QALYs and accrued $176 584 in costs. Intensive blood pressure management cost $23 777 per QALY gained. In a sensitivity analysis, serious adverse events would need to occur at 3 times the rate observed in SPRINT and be 3 times more common in the intensive management arm to prefer standard management. CONCLUSIONS AND RELEVANCE Intensive blood pressure management is cost-effective at typical thresholds for value in health care and remains so even with substantially higher adverse event rates.

BACKGROUND: To date, 38 states have enacted dense breast notification (DBN) laws mandating that mammogram reports include language informing women of risks related to dense breast tissue. OBJECTIVE: Nationally representative survey to assess the association between residing in a state with a DBN law and women's awareness and knowledge about breast density, and breast cancer anxiety. DESIGN: Internet survey conducted in 2018 with participants in KnowledgePanel®, an online research panel. PARTICIPANTS: English-speaking US women ages 40-59 years without a personal history of breast cancer who had received at least one screening mammogram (N = 1928; survey completion rate 68.2%). MAIN MEASURES: (1) Reported history of increased breast density, (2) knowledge of the increased risk of breast cancer with dense breasts, (3) knowledge of the masking effect of dense breasts on mammography, and (4) breast cancer anxiety. KEY RESULTS: Women residing in DBN states were more likely to report increased breast density (43.6%) compared with women residing in non-DBN states (32.7%, p < 0.01, adjusted odds ratio, 1.70, 95% CI,1.34-2.17). Interaction effect between DBN states and education status showed that the impact of DBN on women's reporting of dense breasts was significant for women with greater than high school education, but not among women with a high school education or less (p value = 0.01 for interaction). Only 23.0% of women overall knew that increased breast density was associated with a higher risk of breast cancer, and 68.0% of women understood that dense breasts decreased the sensitivity of mammography. There were no significant differences between women in DBN states and non-DBN states for these outcomes, or for breast cancer-related anxiety. CONCLUSIONS: State DBN laws were not associated with increased understanding of the clinical implications of breast density. DBN laws were associated with a higher likelihood of women reporting increased breast density, though not among women with lower education.

had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

BACKGROUND:The Affordable Care Act (ACA) eliminated cost-sharing for evidence-based preventive services in an effort to encourage use. OBJECTIVE: To evaluate use of colorectal cancer (CRC) screening in a national population-based sample before and after implementation of the ACA. DESIGN: Repeated cross-sectional analysis of the Medical Expenditure Panel Survey (MEPS) between 2009 and 2012 comparing CRC screening rates before and after implementation of the ACA. PARTICIPANTS: Adults 50-64 with private health insurance and adults 65-75 with Medicare. MAIN MEASURES: Self-reported receipt of screening colonoscopy, sigmoidoscopy, or fecal occult blood test (FOBT) within the past year among those eligible for screening. KEY RESULTS: Our study included 8617 adults aged 50-64 and 3761 adults aged 65-75. MEPS response rates ranged from 58 to 63%. Among adults aged 50-64, 18.9-20.9% received a colonoscopy in the survey year, 0.59-2.1% received a sigmoidoscopy, and 7.9-10.4% received an FOBT. For adults aged 65-75, 23.6-27.7% received a colonoscopy, 1.3-3.2% a sigmoidoscopy, and 13.5-16.4% an FOBT. In adjusted analyses, among participants aged 50-64, there was no increase in yearly rates of colonoscopy (−0.28 percentage points, 95% CI −2.3 to 1.7, p=0.78), sigmoidoscopy (−1.1%, 95% CI −1.7 to −0.46, p=<0.001), or FOBT (−1.6%, 95% CI −3.2 to −0.03, p=0.046) post-ACA. For those aged 65-75, rates of colonoscopy (+2.3%, 95% CI −1.4 to 6.0, p=0.22), sigmoidoscopy (+0.34%, 95% CI 0.88 to 1.6, p=0.58) and FOBT (−0.65, 95% CI −4.1 to 2.8, p=0.72) did not increase. Among those aged 65-75 with Medicare and no additional insurance, the use of colonoscopy rose by 12.0% (95% CI 3.3 to 20.8, p = 0.007). Among participants with Medicare living in poverty, colonoscopy use also increased (+5.7%, 95% CI 0.18 to 11.3, p=0.043). CONCLUSIONS: Eliminating cost-sharing for CRC screening has not resulted in changes in the use of CRC screening services for many Americans, although use may have increased in the post-ACA period among some Medicare beneficiaries.KEY WORDS: colorectal cancer; health care reform; health insurance; preventive care.

Breast density notification legislation in Connecticut was associated with a small increase in the proportion of women diagnosed with localized invasive breast cancer in individual-level but not county-level analyses. Whether this finding reflects potentially beneficial early detection or potentially harmful overdiagnosis is not known. Legislation was not associated with changes in regional or metastatic disease.