Citations

Abstract Purpose: This phase II trial evaluated the efficacy and safety of cixutumumab, a human anti–insulin-like growth factor receptor 1 (IGF-1R) monoclonal IgG1 antibody, and explored potential biomarkers in postmenopausal women with hormone receptor–positive breast cancer. Experimental Design: Patients with hormone receptor–positive breast cancer that progressed on antiestrogen therapy received (2:1 randomization) cixutumumab 10 mg/kg and the same antiestrogen (arm A) or cixutumumab alone (arm B) every 2 weeks (q2w). Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and safety. Correlative analyses of IGF-1R, total insulin receptor (IR), and IR isoforms A (IR-A) and B (IR-B) expression in tumor tissue were explored. Results: Ninety-three patients were randomized (arm A, n = 62; arm B, n = 31). Median PFS was 2.0 and 3.1 months for arm A and arm B, respectively. Secondary efficacy measures were similar between the arms. Overall, cixutumumab was well tolerated. IGF-1R expression was not associated with clinical outcomes. Regardless of the treatment, lower IR-A, IR-B, and total IR mRNA expression in tumor tissue was significantly associated with longer PFS [IR-A: HR, 2.62 (P = 0.0062); IR-B: HR, 2.21 (P = 0.0202); and total IR: HR, 2.18 (P = 0.0230)] and OS [IR-A: HR, 2.94 (P = 0.0156); IR-B: HR, 2.69 (P = 0.0245); and total IR: HR, 2.72 (P = 0.0231)]. Conclusions: Cixutumumab (10 mg/kg) with or without antiestrogen q2w had an acceptable safety profile, but no significant clinical efficacy. Patients with low total IR, IR-A, and IR-B mRNA expression levels had significantly longer PFS and OS, independent of the treatment. The prognostic or predictive value of IR as a biomarker for IGF-1R–targeted therapies requires further validation. Clin Cancer Res; 22(2); 301–9. ©2015 AACR.

Previously, the biological factors were weighed by the expert opinions. In this paper, we evaluate the risk factors proposed by the expert opinions. We use fuzzy logic techniques for predicting risk for development of carotid intima–medial thickness (CIMT) using expert opinion and various factors associated with CIMT in recently menopausal women. Study participants were enrolled in the Kronos Early Estrogen Prevention Study (KEEPS), a four-year study where participants were assigned to either oral or transdermal hormone treatments or to placebo. We use preference modeling techniques to determine the consensus winner of the causal factors. We use a measure to determine the degree to which one factor is preferred to another. We also determine the extent to which a factor is preferred to another by "most" experts. We determine the degree to which the experts agree. We consider a model concerning social networks and the effects of these networks on persons' opinions.

Purpose: This project examined potential changes in health behaviors following wellness coaching. Design: In a single cohort study design, wellness coaching participants were recruited in 2011, data were collected through July 2012, and were analyzed through December 2013. Items in the study questionnaire used requested information about 11 health behaviors, self-efficacy for eating, and goalsetting skills. Setting: Worksite wellness center. Participants: One-hundred employee wellness center members with an average age of 42 years; 90% were female and most were overweight or obese. Intervention: Twelve weeks of in-person, one-on-one wellness coaching. Method: Participants completed study questionnaires when they started wellness coaching (baseline), after 12 weeks of wellness coaching, and at a 3-month follow-up. Results: From baseline to week 12, these 100 wellness coaching participants improved their self-reported health behaviors (11 domains, 0- to 10-point scale) from an average of 6.4 to 7.7 ( p < .001), eating selfefficacy from an average of 112 to 142 (on a 0- to 180-point scale; p < .001), and goal-setting skills from an average of 49 to 55 (on a 16- to 80-point scale; p < .001). Conclusion: These results suggest that participants improved their current health behaviors and learned skills for continued healthy living. Future studies that use randomized controlled trials are needed to establish causality for wellness coaching.

ABSTRACTNeither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established forCandidaspp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable.Candidaspecies wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007Candida albicans, 186C. dubliniensis, 3,188C. glabratacomplex, 119C. guilliermondii, 493C. krusei, 205C. lusitaniae, 3,136C. parapsilosiscomplex, and 1,016C. tropicalisisolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing ≥97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 μg/ml forC. albicans, 0.12, 0.25, and 0.03 μg/ml forC. glabratacomplex, 4, 2, and 4 μg/ml forC. parapsilosiscomplex, 0.5, 0.25, and 0.06 μg/ml forC. tropicalis, 0.25, 1, and 0.25 μg/ml forC. krusei, 0.25, 1, and 0.12 μg/ml forC. lusitaniae, 4, 2, and 2 μg/ml forC. guilliermondii, and 0.25, 0.25, and 0.12 μg/ml forC. dubliniensis. Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81Candidaisolates with identifiedfksmutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities ofCandidaspp. to caspofungin by reference methodologies is not recommended.

Abstract Introduction: Increased levels of circulating estrogens are associated with elevated risks of postmenopausal breast cancer. Previously, we showed that levels of sex steroid hormones in breast adipose tissue are positively correlated with circulating hormones. Further evaluation of hormone levels in breast tissues may help to explain the relationship between estrogens and breast cancer risk. Specifically, data suggest that focal breast lesions consisting of macrophages encircling dying adipocytes, referred to as “crown-like structures (CLS)”, are associated with increased aromatase activity, which could increase conversion of androgens to estrogens locally in the breast. Therefore, we assessed whether the presence of CLS affects the correlations between blood and breast adipose tissue hormone levels. Methods: Participants included 84 postmenopausal women with invasive breast cancer in the Polish Breast Cancer Study, a population based case-control study conducted from 2000 to 2003. We previously reported sex steroid hormone levels in cancer-free breast adipose tissue removed as part of breast excisions performed for cancer. Here, using immunohistochemical stains, we evaluated the number of CD68 positive macrophages and the presence of full CLS (i.e., complete adipocyte encirclement) in benign breast tissue sections prepared from surgical pathology specimens containing breast cancer. The relationship between the number of CD68 positive macrophages per unit area of fat and hormone levels was examined using Spearman rank correlations (rs). We assessed potential effect modification of the association between blood and tissue hormone levels by presence or absence of CLS by including an interaction term in linear regression models. Results: The number of CD68 positive macrophages per unit area of fat was not significantly correlated with levels of estrone, estradiol, androstenedione or testosterone measured in blood (rs = 0.001, -0.04, -0.07, and -0.09, respectively; p&gt;0.05) or breast adipose tissue (rs = -0.15, 0.06, -0.06, and -0.08, respectively; p&gt;0.05). Correlations between serum and adipose tissue hormones did not statistically significantly differ between women with CLS (n = 30) compared to those without CLS (n = 54). CLS were found more frequently in breast adipose tissue from overweight (i.e., women with a body mass index (BMI) between 25 and 29.9) (43%) and obese women (BMI &gt;30) (30%) versus normal weight women, with (BMI between 18.5 and 24.9), (27%); (p = 0.04, χ2 test). The number of CD68 positive macrophages per unit area of fat was not significantly related to BMI (p = 0.31). Conclusion: Among postmenopausal women with invasive breast cancer, the presence of CLS was more common among overweight and obese women, but CLS did not influence the correlation between circulating and breast adipose tissue sex steroid hormone levels. Citation Format: Maeve Mullooly, Hannah P. Yang, Roni T. Falk, Sarah Nyante, Renata Cora, Ruth M. Pfeiffer, Derek C. Radisky, Daniel W. Visscher, Lynn C. Hartmann, Amy C. Degnim, Frank Z. Stanczyk, Jonine F. Figueroa, Montserrat Garcia-Closas, Jolanta Lissowska, Melissa T. Troester, Louise A. Brinton, Mark E. Sherman, Gretchen L. Gierach. Investigation of the relationship between crown-like structures and adipose tissue hormone levels among postmenopausal women with breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2767. doi:10.1158/1538-7445.AM2015-2767

Background: Carbohydrate counting may improve glycemic control in hospitalized cardiology patients by providing individualized insulin doses tailored to meal consumption. The purpose of this study was to compare glycemic outcomes with mealtime insulin dosed by carbohydrate counting versus fixed dosing in the inpatient setting. Materials and Methods: This single-center retrospective cohort study included 225 adult medical cardiology patients who received mealtime, basal, and correction-scale insulin concurrently for at least 72 h and up to 7 days in the interval March 1, 2010–November 7, 2013. Mealtime insulin was dosed by carbohydrate counting or with fixed doses determined prior to meal intake. An inpatient diabetes consult service was responsible for insulin management. Exclusion criteria included receipt of an insulin infusion. The primary end point compared mean daily postprandial glucose values, whereas secondary end points included comparison of preprandial glucose values and mean daily rates of hypoglycemia. Results: Mean postprandial glucose level on Day 7 was 204 and 183 mg/dL in the carbohydrate counting and fixed mealtime dose groups, respectively (unadjusted P =0.04, adjusted P =0.12). There were no statistical differences between groups on Days 2–6. Greater rates of preprandial hypoglycemia were observed in the carbohydrate counting cohort on Day 5 (8.6% vs. 1.5%, P =0.02), Day 6 (1.7% vs. 0%, P =0.01), and Day 7 (7.1% vs. 0%, P =0.008). No differences in postprandial hypoglycemia were seen. Conclusions: Mealtime insulin dosing by carbohydrate counting was associated with similar glycemic outcomes as fixed mealtime insulin dosing, except for a greater incidence of preprandial hypoglycemia. Additional comparative studies that include hospital outcomes are needed.

Objective To evaluate the outcome of patients after surgical resection of isolated retroperitoneal lymph node ( RPLN ) recurrence of renal cell carcinoma ( RCC ) using a multicentre international cohort. Patients and Methods In all, 50 patients were identified who underwent resection of isolated RPLN recurrence of RCC at four institutions after nephrectomy for pT any N any M0 disease. Progression‐free ( PFS ) and cancer‐specific survival ( CSS ) were estimated using the Kaplan–Meier method. Cox proportional hazards regression models were used to assess the association of clinicopathological characteristics with disease progression. Results The median (interquartile range, IQR ) age at resection was 57.0 (50.0–62.5) years. The median ( IQR ) time to RPLN recurrence after nephrectomy was 12.6 (6.9–39.5) months, with no significant difference in median time to RPLN recurrence between patients with N+ disease at nephrectomy (10.7 [6.5–24.6] months) and those with Nx/pN0 disease at nephrectomy (13.7 [8.7–44.2] months) ( P = 0.66). The median ( IQR ) size of the RPLN recurrence before resection was 2.6 (1.9–5) cm. The most common site for RPLN recurrence was within the interaortocaval region (34%). The median ( IQR ) follow‐up after RPLN resection for patients alive at last follow‐up was 28.0 (13.7–51.2) months. During follow‐up, 26 patients developed RCC recurrence, at a median ( IQR ) of 9.9 (4.0–18.5) months after RPLN resection. Of those who developed a secondary recurrence, disease was again isolated to the retroperitoneum in seven patients. In all, 11 patients subsequently died, including 10 who died from disease. The median PFS after RPLN resection was 19.5 months, with a 3‐ and 5‐year PFS of 40.5% and 35.4%, respectively. We also found that RPLN recurrence at ≤12 months after nephrectomy was associated with a significantly inferior median PFS (12.3 months) compared with RPLN recurrence at >12 months after nephrectomy (47.6 months; P = 0.003). Moreover, on multivariate analysis, a shorter time to recurrence remained associated with a significantly increased risk for subsequent disease progression (hazard ratio 3.51; P = 0.005). Conclusion Surgical resection of isolated RPLN recurrence from RCC may result in durable cancer control in appropriately selected patients. Recurrence at ≤12 months after nephrectomy was associated with a significantly increased risk of progression after resection, underscoring the importance of this variable for risk stratification. Thus, we recommend that, in the setting of isolated RPLN recurrence of RCC (in patients without precluding comorbidities), careful consideration with the patients and medical oncology colleagues be undertaken about the relative and individualised benefits of surgical resection, systemic therapy, and surveillance.