Citations

Abstract Background: Many newly diagnosed breast cancer patients undergo preoperative breast MRI which includes visualization of some degree of the axilla. The impact of patient characteristics and tumor biology on the fidelity of MRI imaging of the axilla in these cases is not well-studied. We sought to examine the correlation between nodal findings on breast MRI and pathologic nodal status in newly diagnosed breast cancer patients. Methods: With IRB approval, we identified 1868 consecutive breasts with invasive cancer in 1803 patients undergoing primary operation with axillary surgery from 1/2010-7/2013. Patients undergoing neoadjuvant chemotherapy (348) were excluded leaving 1510 breasts with cancer in 1455 patients. Preoperative MRI was performed in 763 patients (52%). We evaluated patient, imaging and pathology data. Results: Patients evaluated with MRI were median age 57 years. The majority of tumors were T1 (63%) and T2 (28%). MRI identified suspicious axillary nodes in 240 cases (31%), of which 123 (51%) were node positive at operation. Suspicious axillary findings on MRI predicted both nodal status and pN stage at operation (both p<0.0001). The sensitivity, specificity, accuracy, positive (PPV) and negative predictive value (NPV) of MRI for nodal disease across tumor types is shown. Pathologic Node PositiveSensitivity (95% CI)Specificity (95% CI)NPV (95% CI)PPV (95% CI)Accuracy (95% CI)All Cases (n=763)234 (31%)52.6 (46-59.1)77.9 (74.1-81.3)78.8 (75-82.1)51.3 (44.8-57.7)70.1 (66.7-73.3)Approximated Biologic Subtype (missing=24)ER+/HER2- (n=609)194 (32%)51.0 (43.8-58.2)80.0 (75.8-83.7)77.8 (73.4-81.5)54.4 (46.9-61.7)70.8 (67-74.3)HER2+ (n=69)20 (29%)65.0 (40.9-83.7)71.4 (56.5-83)83.3 (68-92.5)48.1 (29.2-67.6)69.6 (57.2-79.8)ER-/HER2- (n=61)17 (28%)58.8 (33.5-80.6)75.0 (59.4-86.3)82.5 (66.6-92.1)47.6 (26.4-70)70.5 (57.3-81.1)p value0.740.430.330.560.730.98Tumor Grade (missing=5)1 (n=259)58 (22%)32.8 (21.4-46.5)79.6 (73.2-84.8)80.4 (74.1-85.5)31.7 (20.6-45.1)69.1 (63.0-74.6)2 (n=351)124 (35%)55.6 (46.5-64.5)79.7 (73.8-84.6)76.7 (70.7-81.8)60.0 (50.4-68.9)71.2 (66.1-75.9)3 (n=148)51 (34%)66.7 (52.0-79.0)70.1 (59.8-78.8)80.0 (69.6-87.6)54.0 (41.0-66.4)68.9 (60.7-76.1)p value0.0010.00030.110.720.020.93 Diagnostic performance did not vary significantly based on patient body mass index (BMI) or approximated biologic subtype, but specificity was better for patients >age 50 (p=0.007) and sensitivity and PPV both were worse for grade 1 vs grade 2/3 tumors. Node positivity rate at operation was 48% (51/106) for patients with a solitary abnormal node on MRI and 54% (72/134) when >1 suspicious node was seen (p=0.39). However, multiple vs solitary MRI suspicious nodes correlated with ≥3 positive nodes at operation (40 [30%] vs 19 [18%], p=0.03) and pN2/pN3 disease (29 [22%] vs 12 [11%], p=0.03). Conclusion: Axillary lymph node findings on MRI for breast cancer predict nodal status and disease volume in invasive breast cancer patients. Tumor biologic subtype did not affect performance characteristics of preoperative MRI, but tumor grade did influence the sensitivity and PPV of MRI. When MRI is performed in the evaluation of newly diagnosed breast cancer, axillary findings inform pathologic nodal stage at operation regardless of tumor subtype. Citation Format: Sean C Dupont, Judy C Boughey, Tanya L Hoskin, Katrina N Glazebrook, Tina J Hieken. Value of breast MRI for preoperative axillary assessment of breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-01-03.

Abstract Background: Tumor features such as stage, grade, and microsatellite instability (MSI) status have relevance for colorectal cancer survival whereas the prognostic role of body mass index (BMI) is unclear. We assessed the association of BMI and adult weight gain on colorectal cancer survival, overall and by strata of sex and MSI. Methods: Participants were identified from a multi-center cohort that includes 6,763 colorectal cancer patients with invasive colorectal cancer who were enrolled into the Colon Cancer Family Registry from 1997 to 2008. Vital status was updated through direct contact with patients/next-of-kin and/or linkage with mortality records. BMI 2 years before diagnosis, BMI at age 20 years, and adult weight gain were derived from self-reports of height and weight (i.e., weight 2 years before diagnosis and weight at age 20 years). Tumor MSI status was available for 4,987 patients. Multivariable, two-sided hazard ratios (HR) and 95% confidence intervals (CIs) were estimated from delayed-entry Cox proportional hazards models, controlling for age at diagnosis, TNM summary stage (i.e., I, II, III, IV or missing), smoking (current, former, never), and study center. Results: After a maximum of 13.7 years of follow-up from enrollment to end-of-study (median: 5.3 years), 2,335 patients had died. Higher BMI 2 years before cancer diagnosis (per 5-kg/m2) was associated with higher risk of all-cause mortality overall (HR, 1.10; 95% CI, 1.05 to 1.14), with similar associations when stratified by sex (men: HR, 1.07; 95% CI, 1.02 to 1.14; women: HR, 1.11: 95% CI, 1.05 to 1.17; p-interaction: 0.18) and MSI status (MS-stable/MSI-low: HR, 1.08; 95% CI, 1.03 to 1.14; MSI-high, HR: 1.19; 95% CI, 1.02 to 1.40; p-interaction: 0.88). In joint models, with MS-stable/MSI-low and normal BMI as the referent group, risk of death was lower for those with MSI-high and normal BMI (HR: 0.77; 95% CI: 0.59 to 1.00), higher for MS-stable/MSI-low and high (≥30) BMI (HR: 1.23; 95% CI: 1.07 to 1.42), and essentially the same for MSI-high and high BMI (HR: 0.97; 95% CI: 0.72 to 1.30). Similar patterns of association were observed for BMI at age 20 years and when the outcome was colorectal cancer-specific mortality, although not all associations remained statistically significant for some of the smaller sub-group analyses. After controlling for BMI at age 20 years, adult weight gain was only modestly associated with all-cause mortality (per 5 kg HR: 1.01; 95% CI: 1.00 to 1.02; p-trend: 0.07). Conclusion: High pre-diagnosis BMI was associated with increased mortality after colorectal cancer diagnosis; this association was consistent for men and women and by tumor MSI status. These results also suggest that obesity attenuates the survival advantage observed with MSI-high tumors. Citation Format: Peter T. Campbell, Christina Newton, Polly A. Newcomb, Dennis Ahnen, John Baron, Sean Cleary, Michelle Cotterchio, A. Brad Farris, Jane Figueiredo, Roger C. Green, Loic Le Marchand, John McLaughlin, Amanda Phipps, John D. Potter, Andrew Renehan, Aung Ko Win, Noralane Lindor, Paul Limburg. Prospective study of body mass index and adult weight change with colorectal cancer survival, overall and by tumor microsatellite instability status. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-276. doi:10.1158/1538-7445.AM2014-LB-276

Abstract An ovarian cancer Genome Wide Association Study (GWAS) identified 9p22.2 as a novel susceptibility locus with the most statistically significant single nucleotide polymorphisms (SNPs) located in an intergenic region near the Basonuclin 2 (BNC2) gene, which codes for a putative transcription regulator containing three pairs of zinc finger (ZF) domains. The minor alleles are protective in terms of ovarian cancer susceptibility. However, the molecular mechanisms by which these SNPs modify susceptibility remain largely unknown. The significant SNPs in the 9p22.2 locus lie in non-coding regions and therefore are hypothesized to affect the activity of regulatory elements and modify the expression of a target gene(s). In order to test this hypothesis we conducted fine mapping for the locus which delimited a ∼74kb region containing SNPs with a p-value less than 10-8. FAIRE-Seq and ChIP-Seq experiments for histone markers conducted in immortalized ovarian surface epithelial cells (IOSE) and fallopian tube epithelial cells (IFTE) were used to prioritize functional SNP candidates which overlap with regulatory elements. Luciferase assays tested the ability of these regulatory elements to activate transcription. Chromosome conformation capture (3C) experiments demonstrate a physical interaction between the BNC2 promoter and candidate regulatory elements containing risk-associated SNPs. Methylation Quantification at Trait Loci (mQTL) revealed an association between decreased methylation at the BNC2 promoter and the protective minor alleles. Expression analysis shows decreased expression of BNC2 in cancer versus normal tissue implicating tumor suppressor function of BNC2. Therefore the protective minor allele likely increases expression of BNC2 which in turn contains tumor suppressing properties that decrease ovarian cancer risk. BNC2 protein is in complex with transcriptional regulatory proteins, in particular the NURD complex components. Moreover, BNC2 acts as a transcriptional repressor in in vitro transfection assays indicating that it functions in transcriptional repression. We then used protein binding microarrays and CHIP-Seq experiments to identify its putative DNA binding motifs and its downstream target genes. Analysis of this data suggests that BNC2 functions in a regulatory transcription network that impacts on genes implicated in ovarian cancer with enrichment for genes in the TGF-beta response pathway. Citation Format: Melissa A. Buckley, Howard C. Shen, Gustavo A. Mendoza-Fandino, Nicholas T. Woods, Anxhela Gjyshi, Juliet French, Kate Lawrenson, Honglin Song, Jonathan Tyrer, Renato S. Carvalho, Alexandra Valle, Ann Chen, Sean Yoder, Gregory Bloom, Ya-Yu Tsai, Ally Yang, Timothy R. Hughes, Xiaotao Qu, Mine Cicek, Melissa Larson, Ellen Goode, Brooke Fridley, Susan Ramus, Georgia Chenevix-Trench, Paul Pharoah, Thomas A. Sellers, Simon Gayther, Alvaro N.A. Monteiro, Ovarian Cancer Association Consortium. Functional analysis of the 9p22 locus implicates the transcriptional regulation of BNC2 as a mechanism in ovarian cancer predisposition. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3285. doi:10.1158/1538-7445.AM2014-3285

AbstractObjectivesChest pain is a common complaint to emergency departments (EDs) and clinical risk factors are used to predict which patients are at risk for worse outcomes and mortality. The goal was to assess the novel biomarker midregional proadrenomedullin (MR‐proADM) in prediction of mortality and major adverse cardiac events (MACE).MethodsThis was a subanalysis of the CHOPIN study, a 16‐center prospective trial that enrolled 2,071 patients presenting with chest pain within 6 hours of onset. The primary endpoint was 6‐month all‐cause mortality and the secondary endpoint was 30‐day and 6‐month MACE: ED visits or hospitalization for acute myocardial infarction, unstable angina, reinfarction, revascularization, and heart failure.ResultsMR‐proADM performed similarly to troponin (cTnI; c‐statistic = 0.845 and 0.794, respectively) for mortality prediction in all subjects and had similar results in those with noncardiac diagnoses. MR‐proADM concentrations were stratified by decile, and the cohort in the top decile had a 9.8% 6‐month mortality risk versus 0.9% risk for those in the bottom nine deciles (p < 0.0001). MR‐proADM, history of coronary artery disease (CAD), and hypertension were predictors of short‐term MACE, while history of CAD, hypertension, cTnI, and MR‐proADM were predictors of long‐term MACE.ConclusionsIn patients with chest pain, MR‐proADM predicts mortality and MACE in all‐comers with chest pain and has similar prediction in those with a noncardiac diagnosis. This exploratory analysis is primarily hypotheses‐generating and future prospective studies to identify its utility in risk stratification should be considered.

We sought to obtain high resolution 3D contrast-enhanced MR angiograms of the carotid arteries, vertebral arteries and aortic arch with venous signal suppression utilizing novel timing techniques. A secondary purpose was to compare contrast-enhanced MR angiograms with 2D time-of-flight MR angiograms of the carotid arteries.

BACKGROUNDThe current study was performed to determine whether patient characteristics, including race/ethnicity, were associated with patient‐reported care coordination for patients with colorectal cancer (CRC) who were treated in the Veterans Affairs (VA) health care system, with the goal of better understanding potential goals of quality improvement efforts aimed at improving coordination.METHODSThe nationwide Cancer Care Assessment and Responsive Evaluation Studies survey involved VA patients with CRC who were diagnosed in 2008 (response rate, 67%). The survey included a 4‐item scale of patient‐reported frequency (“never,” “sometimes,” “usually,” and “always”) of care coordination activities (scale score range, 1‐4). Among 913 patients with CRC who provided information regarding care coordination, demographics, and symptoms, multivariable logistic regression was used to examine odds of patients reporting optimal care coordination.RESULTSVA patients with CRC were found to report high levels of care coordination (mean scale score, 3.50 [standard deviation, 0.61]). Approximately 85% of patients reported a high level of coordination, including the 43% reporting optimal/highest‐level coordination. There was no difference observed in the odds of reporting optimal coordination by race/ethnicity. Patients with early‐stage disease (odds ratio [OR], 0.60; 95% confidence interval [95% CI], 0.45‐0.81), greater pain (OR, 0.97 for a 1‐point increase in pain scale; 95% CI, 0.96‐0.99), and greater levels of depression (OR, 0.97 for a 1‐point increase in depression scale; 95% CI, 0.96‐0.99) were less likely to report optimal coordination.CONCLUSIONSPatients with CRC in the VA reported high levels of care coordination. Unlike what has been reported in settings outside the VA, there appears to be no racial/ethnic disparity in reported coordination. However, challenges remain in ensuring coordination of care for patients with less advanced disease and a high symptom burden. Cancer 2015;121:2207–2213. © 2015 American Cancer Society.

Epithelial stromal cells represent a major cellular component of human uterine endometrium that is subject to tight hormonal regulation. Through cell-cell contacts and/or paracrine mechanisms, stromal cells play a significant role in the malignant transformation of epithelial cells. We isolated stromal cells from normal human endometrium and investigated the morphological and transcriptional changes induced by estrogen, progesterone and tamoxifen. We demonstrated that stromal cells express appreciable levels of estrogen and progesterone receptors and undergo different morphological changes upon hormonal stimulation. Microarray analysis indicated that both estrogen and progesterone induced dramatic alterations in a variety of genes associated with cell structure, transcription, cell cycle, and signaling. However, divergent patterns of changes, and in some genes opposite effects, were observed for the two hormones. A large number of genes are identified as novel targets for hormonal regulation. These hormone-responsive genes may be involved in normal uterine function and the development of endometrial malignancies.

Summary The objective of this study was to critically review the empirical evidence from all relevant disciplines regarding obesity stigma in order to (i) determine the implications of obesity stigma for healthcare providers and their patients with obesity and (ii) identify strategies to improve care for patients with obesity. We conducted a search of M edline and PsychInfo for all peer‐reviewed papers presenting original empirical data relevant to stigma, bias, discrimination, prejudice and medical care. We then performed a narrative review of the existing empirical evidence regarding the impact of obesity stigma and weight bias for healthcare quality and outcomes. Many healthcare providers hold strong negative attitudes and stereotypes about people with obesity. There is considerable evidence that such attitudes influence person‐perceptions, judgment, interpersonal behaviour and decision‐making. These attitudes may impact the care they provide. Experiences of or expectations for poor treatment may cause stress and avoidance of care, mistrust of doctors and poor adherence among patients with obesity. Stigma can reduce the quality of care for patients with obesity despite the best intentions of healthcare providers to provide high‐quality care. There are several potential intervention strategies that may reduce the impact of obesity stigma on quality of care.