Importance Time to surgery (TTS) is of concern to patients and clinicians, but controversy surrounds its impact on breast cancer survival. There remains little national data evaluating the association. Objective To investigate the relationship between the time from diagnosis to breast cancer surgery and survival, using separate analyses of two of the largest cancer databases in the United States. Design Two independent population-based studies of prospectively-collected national data utilizing the Surveillance Epidemiology and End Results (SEER)-Medicare-linked database (SMDB), and the National Cancer Database (NCDB). Setting The SMDB cohort included Medicare patients >65 years of age, and the NCDB cohort included patients cared for at Commission on Cancer-accredited facilities throughout the United States. Each analysis assessed overall survival as a function of time between diagnosis and surgery by evaluating intervals encompassing ≤30, 31–60, 61–90, 91–120, and 121–180 days in length, and disease-specific survival at 60-day intervals. Participants All patients were diagnosed with noninflammatory, nonmetastatic, invasive breast cancer and underwent surgery as initial treatment. Main Outcomes and Measures Overall and disease-specific survival as a function of time between diagnosis and surgery, after adjusting for patient, demographic and tumor-related factors. Results The SMDB cohort had 94,544 patients ≥66 years old, diagnosed 1992 – 2009. With each interval delay increase, overall survival was lower overall (hazard ratio [HR] 1.09, p<0.001), and in stage I (HR 1.13, p<0.001) and II (HR 1.06, p=0.010) patients. Breast cancer-specific mortality increased with each 60-d interval (subhazard ratio [sHR] 1.26, p= 0.03). The NCDB study evaluated 115,790 patients ≥18 years old, diagnosed 2003 – 2005. The overall mortality HR was 1.10 (p<0.001) for each increasing interval, significant in stages I (HR 1.16, p<0.001) and II (1.09, p<0.001) only, adjusting for demographic, tumor and treatment factors. Conclusions and Relevance Greater TTS confers lower overall and disease-specific survival, and a shortened delay is associated with benefits comparable to some standard therapies. Although time is required for preoperative evaluation and consideration of some options such as reconstruction, efforts to reduce TTS should be pursued where possible to enhance survival.

Setting: Comprehensive cancer center.Patients: Fifty-one patients (21 men and 30 women) with biopsy-proven skin metastases and correlative clinical data.Interventions: Four dermatopathologists reviewed a random mixture of metastases and primary skin tumors. Immunohistochemical studies for 12 markers were performed on the metastases, with skin adnexal tumors as controls.Main Outcome Measures: Clinical characteristics of cutaneous lesions, clinical outcomes, histologic features, and immunohistochemical markers.Results: Eighty-six percent (43 of 50) of the patients had known stage IV cancer, and skin metastasis was the pre-

The authors studied associations between ankle-brachial index (ABI) and subclinical atherosclerosis in the Multi-Ethnic Study of Atherosclerosis. Participants included 3,458 women (average age = 62.6 years) and 3,112 men (average age = 62.8 years) who were free of clinically evident cardiovascular disease. Measurements included ABI, carotid artery intima-media thickness, and coronary artery calcium assessed with computed tomography. Five ABI categories were defined: <0.90 (definite peripheral arterial disease (PAD)), 0.90-0.99 (borderline ABI), 1.00-1.09 (low-normal ABI), 1.10-1.29 (normal ABI), and > or =1.30 (high ABI). Compared with that in men with normal ABI, significantly higher internal carotid artery intima-media thickness was observed in men with definite PAD (1.58 vs. 1.09; p < 0.001), borderline ABI (1.33 vs. 1.09; p < 0.001), and low-normal ABI (1.18 vs. 1.09; p < 0.001) after adjustment for confounders. Fully adjusted odds ratios for a coronary artery calcium score greater than 20 decreased across progressively higher ABI categories in both women (2.85 (definite PAD), 1.27 (borderline ABI), 1.11 (low-normal ABI), 1.00 (normal ABI; referent), and 0.78 (high ABI); p for trend = 0.0002) and men (3.26 (definite PAD), 1.72 (borderline ABI), 1.14 (low-normal ABI), 1.00 (normal ABI; referent), and 1.43 (high ABI); p for trend = 0.0002). These findings indicate excess coronary and carotid atherosclerosis at ABI values below 1.10 (men) and 1.00 (women) and may imply increased risk of cardiovascular events in persons with borderline and low-normal ABI.

A B S T R A C T PurposeAlthough no specific delay threshold after diagnosis of breast cancer has been demonstrated to affect outcome, delays can cause anxiety, and surgical waiting time has been suggested as a quality measure. This study was performed to determine the interval from presentation to surgery in Medicare patients with nonmetastatic invasive breast cancer who did not receive neoadjuvant chemotherapy and factors associated with a longer time to surgery. MethodsMedicare claims linked to Surveillance, Epidemiology, and End Results data were reviewed for factors associated with delay between the first physician claim for a breast problem and first therapeutic surgery. 1992 and 2005, 72,586 Medicare patients with breast cancer had a median interval (delay) between first physician visit and surgery of 29 days, increasing from 21 days in 1992 to 32 days in 2005. Women (29 days v 24 days for men; P Ͻ .001), younger patients (29 days; P Ͻ .001), blacks and Hispanics (each 37 days; P Ͻ .001), patients in the northeast (33 days; P Ͻ .001), and patients in large metropolitan areas (32 days; P Ͻ .001) had longer delays. Patients having breast conservation and mastectomies had adjusted median delays of 28 and 30 days, respectively, with simultaneous reconstruction adding 12 days. Preoperative components, including imaging modalities, biopsy type, and clinician visits, were also each associated with a specific additional delay. Results Between ConclusionWaiting times for breast cancer surgery have increased in Medicare patients, and measurable delays are associated with demographics and preoperative evaluation components. If such increases continue, periodic assessment may be required to rule out detrimental effects on outcomes.

Purpose Low absolute lymphocyte count (ALC), a likely index of poor systemic immunity, may be associated with aggressive features and inferior survival in clear cell renal cell carcinoma (CCRCC). Materials and Methods We retrospectively analyzed preoperative blood cell counts in 430 patients (mean age 60 years) undergoing primary surgical resection for CCRCC at Fox Chase Cancer Center. ALC values as a continuous variable and at a level below 1300/μl (our lowest reference value) were correlated with nuclear grade, pathologic stage (pT), and (TNM) stage. We used Kaplan-Meier method to estimate the overall survival (OS) stratified by ALC status. Results As a continuous variable, low ALC was associated with higher grade (p=0.009), higher pT stage (p =0.034), and TNM stage (p<0.0001). Lymphopenia below 1300/μl was associated with high grade (p=0.0043), pT stage (p =0.051) and TNM stage (p<0.0001). After a median follow-up of 33.5 months, lymphopenia was associated with inferior OS in univariate model (p<0.0001), and independent of pT, N, and M stages, age, grade, smoking history and comorbidities in multivariable analysis (p=0.0102). Lymphopenia was also associated with inferior OS in a subset of young patients (≤60) with no distant metastasis (p=0.014). Conclusions In 430 CCRC patients lymphopenia was associated with lower OS independent of pT and TNM stages, nuclear grade, age, tobacco smoking, and comorbidity index.

Background To report associations between p16 status, clinicopathologic characteristics, and outcomes for unknown primary head and neck squamous cell carcinoma (SCCUPS). Methods Specimens of SCCUPS were re-analyzed. HPV status was determined by p16 stain. A tissue microarray (TMA) was constructed to evaluate biomarkers potentially prognostic in HNSCC. Results A majority of the population (n = 26, 74%) was p16+. Prognostic factors benefitting survival were p16+ status (p < 0.0001), absence of macroscopic extracapsular extension [ECE] (p = 0.004), younger age (p = 0.01), and higher grade (p = 0.007). The prognostic implication of worse OS with macroscopic ECE (p = 0.009) remained significant when limited to p16+ patients (p=0.002). Exploratory TMA between unknown primary and controls suggested a biomolecular difference between SCCUPS and known-primary cancer. Conclusions The majority of SCCUPS patients were p16+, indicative of HPV association. p16 staining and ECE appear to be the most prognostic features in SCCUPS.

Abstract-Relationships of nutrients, alcohol intake, and change in weight to change in blood pressure over 8 years in 1714 employed middle-aged men from the Chicago Western Electric Study were explored. At first and second annual examinations, 2 in-depth interviews were performed to assess usual intake of foods and beverages during the preceding 28 days. Annual follow-up data through examination year 9 were used to determine change in weight and blood pressure. Averages of nutrients from 2 interviews were related to annual blood pressure change from baseline by use of the Generalized Estimating Equation, with control for confounders. In analyses of dietary variables considered individually, total and animal protein; total, saturated, monounsaturated, and polyunsaturated fatty acids; cholesterol; Keys dietary lipid score; calcium; alcohol; and average annual change in weight were positively and significantly related to average annual change in systolic pressure; vegetable protein, total carbohydrate, beta-carotene, and an antioxidant vitamin score based on vitamin C and beta-carotene were inversely and significantly related to average annual change in systolic pressure. In analyses of combinations of dietary factors, cholesterol, Keys score, and alcohol were positively related to change in systolic pressure (eg, Z-scores 2.21, 2.05, and 2.50); vegetable protein and antioxidant index were inversely related to change in systolic and diastolic pressure. Change in weight was directly related to change in systolic and diastolic pressure. These findings support the concept that multiple macro-and micronutrients, alcohol intake, and calorie imbalance relate prospectively to blood pressure change. Key Words: blood pressure Ⅲ diet Ⅲ nutrition Ⅲ alcohol Ⅲ body weight Ⅲ population Ⅲ prospective studies D espite progress in the detection, evaluation, and treatment of high blood pressure (BP), adverse BP levels remain the rule nationally and internationally among adults age Ն35 years. 1-10 Prevalence rates of optimal BP (systolic BP [SBP]/diastolic BP [DBP] Յ120/Յ80 mm Hg) are low, whereas rates of high-normal BP and hypertension are epidemic, resulting in markedly increased risks of major cardiovascular diseases. In contrast, this is not the pattern among young adults, who on average have SBP/DBP within the optimal range. 5,9 Thus, the root of the epidemic of adverse BP levels is the increase in SBP/DBP that most people experience (in varying degrees) during the decades from youth through middle age. 10 Improved understanding of the causes of this common rise in BP during adulthood-and the application of that understanding for its prevention and control-are essential to end the mass BP problem and the vast burden it engenders. Despite the importance of this problem, prevention of the rise in BP with age was for decades a neglected research area. Few intervention trials were performed, and few population studies measured BP repeatedly for years to assess factors accounting for BP rise. 1,2,6,10 By 1993, data from these and fr...

Background This study reports a randomized clinical trial evaluating the efficacy of an intervention to prepare individuals to communicate BRCA1/BRCA2 results to family members. Methods Women aged 18 years and older, who had genetic testing, and who had adult first-degree relatives (FDRs), were randomly assigned to a communication skills-building intervention or a wellness control session. Primary outcomes were the percentage of probands sharing test results, and the level of distress associated with sharing. The ability of the Theory of Planned Behavior variables to predict the outcomes was explored. Results Four hundred twenty-two women were enrolled in the study, 219 (intervention) and 203 (control). Data from 137 in the intervention group and 112 in the control group were analyzed. Two hundred forty-nine probands shared test results with 838 relatives (80.1%). There were no significant differences between study groups in the primary outcomes. Combining data from both arms revealed that perceived control and specific social influence were associated with sharing. Probands were more likely to share genetic test results with their children, female relatives and relatives who they perceived had a favorable opinion about learning the results. Conclusion The communication skills intervention did not impact sharing of test results. The proband’s perception of her relative’s opinion of genetic testing and her sense of control in relaying this information influenced sharing. Communication of test results is selective, with male relatives and parents less likely to be informed. Impact Prevalent psychosocial factors play a role in the communication of genetic test results within families.