Body size measures, hemostatic and inflammatory markers and risk of venous thrombosis: The Longitudinal Investigation of Thromboembolism Etiology

Obesity is an important venous thrombosis (VT) risk factor but the reasons for this are unclear

Multilevel factors associated with long-term adherence to screening mammography in older women in the U.S.

In the U.S., guidelines recommend that women continue mammography screening until at least age 74, but recent evidence suggests declining screening rates in older women. We estimated adherence to screening mammography and multilevel factors associated with adherence in a longitudinal cohort of older women. Women aged 66–75 years receiving screening mammography within the Breast Cancer Surveillance Consortium were linked to Medicare claims (2005–2010). Claims data identified baseline adherence, defined as receiving subsequent mammography within approximately 2 years, and length of time adherent to guidelines. Characteristics associated with adherence were investigated using logistic and Cox proportional hazards regression models. Analyses were stratified by age to investigate variation in relationships between patient factors and adherence. Among 49,775 women, 89% were adherent at baseline. Among women 66–70 years, those with less than a high school education were more likely to be non-adherent at baseline (odds ratio [OR] 1.96; 95% confidence interval [CI] 1.65–2.33) and remain adherent for less time (hazard ratio [HR] 1.41; 95% CI 1.11–1.80) compared to women with a college degree. Women with ≥1 versus no Charlson co-morbidities were more likely to be non-adherent at baseline (OR 1.46; 95% CI 1.31–1.62) and remain adherent for less time (HR 1.44; 95% CI 1.24–1.66). Women aged 71–75 had lower adherence overall, but factors associated with non-adherence were similar. In summary, adherence to guidelines is high among Medicare-enrolled women in the U.S. receiving screening mammography. Efforts are needed to ensure that vulnerable populations attain these same high levels of adherence

The contribution of a 9p21.3 variant, a KIF6 variant, and C-reactive protein to predicting risk of myocardial infarction in a prospective study

<p>Abstract</p> <p>Background</p> <p>Genetic risk factors might improve prediction of coronary events. Several variants at chromosome 9p21.3 have been widely reported to be associated with coronary heart disease (CHD) in prospective and case-control studies. A variant of <it>KIF6 </it>(719Arg) has also been reported to be associated with increased risk of CHD in large prospective studies, but not in case-control studies. We asked whether the addition of genetic information (the 9p21.3 or <it>KIF6 </it>variants) or a well-established non-genetic risk factor (C-reactive protein [CRP]) can improve risk prediction by the Framingham Risk Score (FRS) in the Cardiovascular Health Study (CHS)--a prospective observational study of risk factors for cardiovascular disease among > 5,000 participants aged 65 or older.</p> <p>Methods</p> <p>Improvement of risk prediction was assessed by change in the area under the receiver-operator characteristic curve (AUC) and by net reclassification improvement (NRI).</p> <p>Results</p> <p>Among white participants the FRS was improved by addition of <it>KIF6 </it>719Arg carrier status among men as assessed by the AUC (from 0.581 to 0.596, P = 0.03) but not by NRI (NRI = 0.027, P = 0.32). Adding both CRP and 719Arg carrier status to the FRS improved risk prediction by the AUC (0.608, P = 0.02) and NRI (0.093, P = 0.008) in men, but not women (P ≥ 0.24).</p> <p>Conclusions</p> <p>While none of these risk markers individually or in combination improved risk prediction among women, a combination of <it>KIF6 </it>719Arg carrier status and CRP levels modestly improved risk prediction among white men; although this improvement is not significant after multiple-testing correction. These observations should be investigated in other prospective studies.</p

Factors Associated With Rates of False-Positive and False-Negative Results From Digital Mammography Screening: An Analysis of Registry Data.

BackgroundWomen screened with digital mammography may receive false-positive and false-negative results and subsequent imaging and biopsies. How these outcomes vary by age, time since the last screening, and individual risk factors is unclear.ObjectiveTo determine factors associated with false-positive and false-negative digital mammography results, additional imaging, and biopsies among a general population of women screened for breast cancer.DesignAnalysis of registry data.SettingParticipating facilities at 5 U.S. Breast Cancer Surveillance Consortium breast imaging registries with linkages to pathology databases and tumor registries.Patients405,191 women aged 40 to 89 years screened with digital mammography between 2003 and 2011. A total of 2963 were diagnosed with invasive cancer or ductal carcinoma in situ within 12 months of screening.MeasurementsRates of false-positive and false-negative results and recommendations for additional imaging and biopsies from a single screening round; comparisons by age, time since the last screening, and risk factors.ResultsRates of false-positive results (121.2 per 1000 women [95% CI, 105.6 to 138.7]) and recommendations for additional imaging (124.9 per 1000 women [CI, 109.3 to 142.3]) were highest among women aged 40 to 49 years and decreased with increasing age. Rates of false-negative results (1.0 to 1.5 per 1000 women) and recommendations for biopsy (15.6 to 17.5 per 1000 women) did not differ greatly by age. Results did not differ by time since the last screening. False-positive rates were higher for women with risk factors, particularly family history of breast cancer; previous benign breast biopsy result; high breast density; and, for younger women, low body mass index.LimitationsConfounding by variation in patient-level characteristics and outcomes across registries and regions may have been present. Some factors, such as numbers of first- and second-degree relatives with breast cancer and diagnoses associated with previous benign biopsy results, were not examined.ConclusionFalse-positive mammography results and additional imaging are common, particularly for younger women and those with risk factors, whereas biopsies occur less often. Rates of false-negative results are low.Primary funding sourceAgency for Healthcare Research and Quality and National Cancer Institute

Breast cancer detection with short-interval follow-up compared with return to annual screening in patients with benign stereotactic or US-guided breast biopsy results.

PurposeTo compare the cancer detection rate and stage after benign stereotactic or ultrasonography (US)-guided core breast biopsy between patients with short-interval follow-up (SIFU) and those who return to annual screening.Materials and methodsThe Breast Cancer Surveillance Consortium (BCSC) registry and the BCSC Statistical Coordinating Center received institutional review board approval for active and passive consent processes and a waiver of consent. All procedures were HIPAA compliant. BCSC data for 1994-2010 were used to compare ipsilateral breast cancer detection rates and tumor characteristics for diagnoses within 3 months after SIFU (3-8 months) versus return to annual screening (RTAS) mammography (9-18 months) after receiving a benign pathology result from image-guided breast biopsy.ResultsIn total, 17 631 biopsies with benign findings were identified with SIFU or RTAS imaging. In the SIFU group, 27 ipsilateral breast cancers were diagnosed in 10 715 mammographic examinations (2.5 cancers per 1000 examinations) compared with 16 cancers in 6916 mammographic examinations in the RTAS group (2.3 cancers per 1000 examinations) (P = .88). Sixteen cancers after SIFU (59%; 95% confidence interval [CI]: 39%, 78%) were invasive versus 12 after RTAS (75%; 95% CI: 48%, 93%). The invasive cancer rate was 1.5 per 1000 examinations after SIFU (95% CI: 0.9, 2.4) and 1.7 per 1000 examinations (95% CI: 0.9, 3.0) after RTAS (P = .70). Among invasive cancers, 25% were late stage (stage 2B, 3, or 4) in the SIFU group (95% CI: 7%, 52%) versus 27% in the RTAS group (95% CI: 6%, 61%). Positive lymph nodes were found in seven (44%; 95% CI: 20%, 70%) invasive cancers after SIFU and in three (25%; 95% CI: 5%, 57%) invasive cancers after RTAS.ConclusionSimilar rates of cancer detection were found between SIFU and RTAS after benign breast biopsy with no significant differences in stage, tumor size, or nodal status, although the present study was limited by sample size. These findings suggest that patients with benign radiologic-pathologic-concordant percutaneous breast biopsy results could return to annual screening

Mammographic screening interval in relation to tumor characteristics and false‐positive risk by race/ethnicity and age

BackgroundBiennial screening mammography retains most of the benefits of annual breast cancer screening with reduced harms. Whether screening guidelines based on race/ethnicity and age would be more effective than age-based guidelines is unknown.MethodsMammography data from the Breast Cancer Surveillance Consortium were linked to pathology and tumor databases. The authors identified women aged 40 to 74 years who underwent annual, biennial, or triennial screening mammography between 1994 and 2008. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI) of adverse tumor characteristics among 14,396 incident breast cancer cases and 10-year cumulative risks of false-positive recall and biopsy recommendation among 1,276,312 noncases.ResultsNo increased risk of adverse tumor characteristics associated with biennial versus annual screening were noted in white women, black women, Hispanic women aged 40 to 49 years, or Asian women aged 50 to 74 years. Hispanic women aged 50 to 74 years who screened biennially versus annually were found to have an increased risk of late-stage disease (OR, 1.6; 95% CI, 1.0-2.5) and large tumors (OR, 1.6; 95% CI, 1.1-2.4). Asian women aged 40 to 49 years who underwent biennial screening had an elevated risk of positive lymph nodes (OR, 3.1; 95% CI, 1.3-7.1). No elevated risks were associated with triennial versus biennial screening. Cumulative false-positive risks decreased markedly with a longer screening interval.ConclusionsThe authors found limited evidence of elevated risks of adverse tumor characteristics with biennial versus annual screening, whereas cumulative false-positive risks were lower. However, elevated risks of late-stage disease in Hispanic women and lymph node-positive disease in younger Asian women who screened less often than annually warrant consideration and replication

Outcomes of screening mammography by frequency, breast density, and postmenopausal hormone therapy.

ImportanceControversy exists about the frequency women should undergo screening mammography and whether screening interval should vary according to risk factors beyond age.ObjectiveTo compare the benefits and harms of screening mammography frequencies according to age, breast density, and postmenopausal hormone therapy (HT) use.DesignProspective cohort.SettingData collected January 1994 to December 2008 from mammography facilities in community practice that participate in the Breast Cancer Surveillance Consortium (BCSC) mammography registries.ParticipantsData were collected prospectively on 11,474 women with breast cancer and 922,624 without breast cancer who underwent mammography at facilities that participate in the BCSC.Main outcomes and measuresWe used logistic regression to calculate the odds of advanced stage (IIb, III, or IV) and large tumors (&gt;20 mm in diameter) and 10-year cumulative probability of a false-positive mammography result by screening frequency, age, breast density, and HT use. The main predictor was screening mammography interval.ResultsMammography biennially vs annually for women aged 50 to 74 years does not increase risk of tumors with advanced stage or large size regardless of women's breast density or HT use. Among women aged 40 to 49 years with extremely dense breasts, biennial mammography vs annual is associated with increased risk of advanced-stage cancer (odds ratio [OR], 1.89; 95% CI, 1.06-3.39) and large tumors (OR, 2.39; 95% CI, 1.37-4.18). Cumulative probability of a false-positive mammography result was high among women undergoing annual mammography with extremely dense breasts who were either aged 40 to 49 years (65.5%) or used estrogen plus progestogen (65.8%) and was lower among women aged 50 to 74 years who underwent biennial or triennial mammography with scattered fibroglandular densities (30.7% and 21.9%, respectively) or fatty breasts (17.4% and 12.1%, respectively).Conclusions and relevanceWomen aged 50 to 74 years, even those with high breast density or HT use, who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of false-positive results than those who undergo annual mammography. When deciding whether to undergo mammography, women aged 40 to 49 years who have extremely dense breasts should be informed that annual mammography may minimize their risk of advanced-stage disease but the cumulative risk of false-positive results is high