Introduction: Obesity is a risk factor for postmenopausal breast cancer and is independently associated with shorter disease-free and overall survival. Currently, in clinical settings, the combination of stage and grade of cancer at the initial presentation of the disease is the best prognostic indicator. Objective: To evaluate the association between body mass index (BMI) and risk of advanced stages and poorly differentiated grade of breast cancer. Design: A case-series study of women diagnosed with their first primary invasive breast cancer. Patients include a total of 831 women aged X40 years with a mean BMI of 29.6( ± 6.6) kg m À2 . Pathological, clinical and demographic data were retrieved from electronic medical records. Multinomial logistic regression analysis was preformed to estimate the risk of more advanced stages and poorly differentiated grade of cancer, adjusting for covariates. Results: Obese compared with normal weight women had an 80% increased risk of cancer with more advanced stages (III/IV) and poorly differentiated grade (odds ratio ¼ 1.80, 95% confidence interval 1.13-2.86, P ¼ 0.014). No significant increase in risk was observed for overweight women. Conclusion: Obesity at the time of diagnosis of breast cancer is associated with more advanced stages and poorly differentiated grade of cancers.

Campath-1H has been used successfully for induction and has resulted in a low rate of acute cellular rejection (ACR) in renal transplantation in combination with various postoperative immunosuppression regimens. This study was undertaken to investigate the extent of monocyte involvement in ACR, with or without Campath-1H induction. We found that monocytes represented the majority of inflammatory cells in grades Ib or higher ACR, but not with Ia type of ACR, regardless of the status of Campath-1H induction. Cases of ACR, following Campath-1H induction, appear to demonstrate a 'pure form' of monocytic ACR, whereas monocytes were mixed with many other types of inflammatory cells in the cases of ACR in the absence of Campath-1H induction. In addition with Campath-1H induction, the cases of monocytepredominant ACR were found to uniformly exhibit a good response to corticosteroid treatment. We conclude that monocyte-predominate ACR may represent a severe form of rejection, with or without Campath-1H treatment.

Chronic internal inflammation secondary to adiposity is a risk factor for sporadic breast cancer and Post-Menopausal Breast Cancer (PMBC) is largely defined as such. Adiposity is one of the clinical criteria for the diagnosis of Metabolic Syndrome (MetS) and is a risk factor for PMBC. We examined SNPs of eight genes implicated in adiposity, inflammation and cell proliferation in a Prospective-specimen-collection, Retrospective-Blinded-Evaluation (PRoBE) design approach. A total of 180 cases and 732 age-matched controls were identified from the MyCode prospective biobank database and then linked to the Clinical Decision Information System, an enterprise-wide data warehouse, to retrieve clinico-demographic data. Samples were analyzed in a core laboratory where the personnel were masked to their status. Results from multivariate logistic regression yielded one SNP (rs2922126) in the GHSR as protective against PMBC among homozygotes for the minor allele (A/A) (OR = 0.4, 95% CI 0.18-.89, P-value = .02); homozygosity for the minor allele (C/C) of the SNP (rs889312) of the gene MAP3K1 was associated with the risk of PMBC (OR = 2.41, 95% CI 1.25-4.63 P-value = .008). Advanced age was protective against PMBC (OR = 0.98, 95% CI 0.95-0.99, P-value = .02). Family history of breast cancer (OR = 2.22, 95% CI 1.14-4.43. P = .02), HRT (OR = 3.35; 95% CI 2.15-5.21, P < .001), and MetS (OR = 14.83, 95% CI 5.63-39.08, P < .001) and interaction between HRT and MetS (OR = 39.38, 95% CI 15.71-98.70, P < .001) were associated with the risk of PMBC. We did not detected significant interactions between SNPs or between the SNPs and the clinico-demographic risk factors. Our study further confirms that MetS increases the risk of PMBC and argues in favor of reducing exposure to HRT. Our findings are another confirmation that low penetrance genes involved in the inflammatory pathway, i.e. MAP3KI gene, may have a plausible causative role in PMBC. Given the fact that genetic constitutionality of individuals cannot be changed, efforts should be focused on life style modification.

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Mammography utilization gap has been significantly narrowed between urban and rural settings in recent years. Yet, evaluation of breast cancer incidence and mortality data suggest that women residing in rural areas in the US experience a higher incidence of breast cancer and shorter disease free and overall survival regardless of access to health care services. We have implemented a cohort study design to evaluate the pathologic prognostic indicators of breast cancer at the initial presentation of the disease and their association with shorter survival among women in rural PA. We identified women (n=550) diagnosed with their first primary invasive cancer between January 1, 2001 and December 31, 2007 from the Cancer Registry at Geisinger Health System (GHS). Pathologic, clinical and demographic data were retrieved from electronic health records. The mean age at the initial clinical presentation of the disease was 67(± 12.5). The majority, were diagnosed with either stages I and II, 58.6% and 26.8%, respectively. About 6.9% of women were diagnosed with stage III and 7.6% with stages IV. The proportions of women diagnosed with histologic grade 1, 2, and 3 were 31.8%, 41.7% and 26.5%, respectively. Assessment of the joint distribution of estrogen receptor (ER) and progesterone receptor (PR) yielded 58.6% as phenotypic positive for both receptors and, 26.8% as negative. The remaining 16.5% were discordant for the expression of hormone receptors. Sub-typing of breast cancer biomarkers by the three prognostic markers, ER, PR and HER 2/neu, yielded 69.7% as hormone receptor positive, epidermal growth factor negative; 7.5% as triple positive; 3.5% as hormone receptor negative, epidermal growth factor positive and 19.3% as triple negative. Preliminary findings from this ongoing research project suggest that the prevalence of triple negative breast cancer is higher in this population. Expression of other markers such as HER1, Viminetin, CK 5/6, P53 and E-Cadherin are also being evaluated. Context: Consensus guidelines recommend thiazides for first-line treatment in uncomplicated hypertension. Most patients require two or more drugs and little is known about the relative efficacy and outcomes of second-line treatments including thiazide. Objective: To compare differences in blood pressure, renal function and medical outcomes between commonly used two drug regimens, each including thiazide. Design: Retrospective cohort using data from a longitudinal electronic medical record. Setting: Large group medical practice. Patients: All patients >60 years treated for hypertension between 2001 and 2006. Main Outcome Measures: Changes in blood pressure and renal function, incident medical events, and time to failure indicated by an event or regimen change. Results: Of 47,419 patients, 6,534 received second -line therapy including thiazide for > 3 months. Thiazides + angiotensin converting enzyme inhibitors (ACE-I), and thiazides + potassium sparing diuretics (P S) were associated with the greatest reductions in systolic pressure, and t...