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To assess the proportion of missed/misinterpreted imaging examinations of pancreatic ductal adenocarcinoma (PDAC), and their association with the diagnostic interval and survival. Two hundred fifty-seven patients (mean age, 71.8 years) diagnosed with PDAC in 2014–2015 were identified from the Nova Scotia Cancer Registry. Demographics, stage, tumor location, and dates of initial presentation, diagnosis, and, if applicable, surgery and death were recorded. US, CT, and MRI examinations during the diagnostic interval were independently graded by two radiologists using the RADPEER system; discordance was resolved in consensus. Mean diagnostic interval and survival were compared amongst RADPEER groups (one-way ANOVA). Kaplan-Meier analysis was performed for age (

To develop a breast cancer risk model to identify women at mammographic screening who are at higher risk of breast cancer within the general screening population. This retrospective nested case-control study used data from a population-based breast screening program (2009–2015). All women aged 40–75 diagnosed with screen-detected or interval breast cancer (n = 1882) were frequency-matched 3:1 on age and screen-year with women without screen-detected breast cancer (n = 5888). Image-derived risk factors from the screening mammogram (percent mammographic density [PMD], breast volume, age) were combined with core biopsy history, first-degree family history, and other clinical risk factors in risk models. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). Classifiers assigning women to low- versus high-risk deciles were derived from risk models. Agreement between classifiers was assessed using a weighted kappa. The AUC was 0.597 for a risk model including only image-derived risk factors. The successive addition of core biopsy and family history significantly improved performance (AUC = 0.660, p

The Diabetes Care Program of Nova Scotia (DCPNS)‘s mission is “to improve, through leadership and partnerships, the health of Nova Scotians living with, affected by, or at risk of developing diabetes.” Working together with local, provincial and national partners, the DCPNS has improved and standardized diabetes care in Nova Scotia over the past 25 years by developing and deploying a resourceful and collaborative program model. This article describes the model and highlights its key achievements. With balanced representation from frontline providers through to senior decision makers in health care, the DCPNS works across the age continuum, supporting the implementation of national clinical practice guidelines and, when necessary, developing provincial guidelines to meet local needs. The development and implementation of standardized documentation and data collection tools in all diabetes centres created a robust opportunity for the development and expansion of the DCPNS registry. This registry provides useful clinical and statistical information to staff, providers within the circle of care, management and senior leadership. Data are used to support individual care, program planning, quality improvement and business planning at both the local and the provincial levels. The DCPNS supports the sharing of new knowledge and advances through continuous education for providers. The DCPNS's ability to engage diabetes educators and key physician champions has ensured balanced perspectives in the creation of tools and resources that can be effective in real-world practice. The DCPNS has evolved to become an illustrative example of the chronic care model in action.

e12556 Background: Little is known about the association between mammographic breast density and the subtypes of breast cancer including HER2-positive breast cancers (HER2-BrCa). The objective of this study was to assess the strength of association between breast density and HER2-BrCa in a population-based screening program. Methods: This is a population-based case-control breast cancer study of women aged 40 to 75 who underwent digital breast screening from 2009 to 2015 in Nova Scotia, Canada. Cases included women diagnosed with HER2-BrCa at screen or before their next screen (interval); controls included women without screen-detected cancer matched to cases by age and year of screen. Measures of mammographic breast density (percent density, BI-RADS-4th and -5th edition) were obtained from automated software (densitasai) and linked with clinical risk factor data (age, parity, total breast volume, post-menopausal status, hormone replacement therapy, family history and history of core biopsy). The association between breast density and cancer risk was assessed by calculating the odds ratios [OR] with 95% confidence intervals using multivariable logistic regression. Results: A total of 209 cases (median age, 58.8 years) and 6812 controls (median age, 59.4 years) were included. The risk of HER2-BrCa increased with increasing levels of percent breast density. High breast density according to BIRADS-4th and -5th editions was significantly associated with HER2-BrCa: BIRADS -4th 3/4 vs 1: OR 2.50 (1.68 - 3.68); BIRADS-5th C/D vs A: OR 2.58 (1.71 - 4.01). The association between higher breast density and increased risk of HER2-BrCa remained after adjustment for clinical factors. Conclusions: The risk of HER2-BrCa was associated with progressively higher mammographic breast density, although to a lesser extent than breast cancer in general. Accurate risk models including breast density may support the development of more breast-screening protocols that can lead to more strategic use of healthcare resources.

Background Most investigations have compared triple-negative breast cancer (TNBC) to non-TNBC to elucidate clinical or epidemiologic differences between subtypes. We examined a contemporary cohort of patients with primary TNBC by detection and age at diagnosis within a population-based breast screening program to examine survival outcomes. Patients and Methods All women with a diagnosis of primary TNBC between January 1, 2005, and December 31, 2012, in Nova Scotia, Canada, were included. Clinicopathologic and detection variables were abstracted from the Nova Scotia Breast Screening Program. Patient charts were abstracted for adjuvant therapies and survival outcomes, supplemented by provincial vital statistical data. Results A total of 412 patients comprised the study population, with almost half aged over 60 years (46.3%) and 30.2% having screen-detected disease. There were no significant differences in prognostic variables between age groups. Younger patients were more likely to receive adjuvant chemotherapy (96.3% ≤ 49 years vs. 31.2% ≥ 70 years), but there were no differences in disease-free or breast cancer–specific survival between the age groups. For those with disease recurrence, median time to recurrence and death was shorter for younger patients (17 vs. 26 months, 16 vs. 33 months respectively; age 40-49 vs. 70+). Those with screen-detected disease had better disease-free, breast cancer–specific, and overall survival outcomes. Conclusion Detection method may play a role in TNBC survival outcomes, thus supporting novel screening strategies for TNBC. Shorter time to survival events in the younger patient groups suggests that TNBC is a clinically heterogeneous disease despite similarities in prognostic factors across age.

Lessons Learned Rate of progression-free survival at a particular point in time, i.e., a landmark analysis, is a difficult endpoint for a heterogenous malignancy such as neuroendocrine cancer. Landmark analyses can also be complicated by evolution in the standard of care during the conduct of a clinical trial. Improvements in biomarker development would be useful in developing future clinical trials in NET to better tailor individualized therapies and assess for possible efficacy endpoints. Background Neuroendocrine tumors (NETs) are rare malignancies of the gastrointestinal (GI) tract that are highly vascularized and overexpress vascular-endothelial growth factor (VEGF). Sunitinib has demonstrated efficacy in the pancreatic subset of NET. This study explored the activity of another oral VEGF inhibitor, AMG 706 or motesanib, a multikinase inhibitor that targets receptor tyrosine kinases, including VEGFR1, VEGFR2, VEGFR3, KIT, RET, and PDGFR (IC50s = 2, 3, 6, 8, 59, and 84 nM, respectively). Methods This was a single-arm, first-line, phase II study run through the Eastern Cooperative Oncology Group. Patients with low-grade NET (as defined by central confirmation of Ki-67 of 0%–2%) were administered a flat dose of 125 mg per day orally combined with octreotide long acting-repeatable (LAR) for patients who had been on a stable dose. The primary objective was to determine the 4-month progression-free survival (PFS). Results Forty-four patients were evaluated per protocol. The 4-month PFS was 78.5%. The partial response rate was 13.6% (6/44), stable disease was 54.5% (24/44), 9.1% (4/44) had progressive disease, and 10/44 were not evaluable for response. Common toxicities included fatigue, hypertension, nausea, and headache, and most were grade 1–2. Median PFS was 8.7 months, and overall survival was 27.5 months. Conclusion Motesanib (AMG 706) demonstrated a 4-month PFS that met the per-protocol definition of efficacy. Fatigue and hypertension were the most common toxicities, and few grade 3–4 toxicities were encountered. The progression-free survival of 8.7 months in all NETs merits further study.

Over a 10-year period (January 1993 to October 2002), 101 relapsed or refractory non-Hodgkin lymphoma patients were treated at our center with high-dose chemotherapy and autologous transplantation. The median patient age was 54 years (range, 25-70 years). Thirty-two patients had indolent (low-grade), 42 had aggressive (intermediate-grade), and 27 had very aggressive (high-grade) non-Hodgkin lymphoma. Thirty-six patients had primary refractory disease, 20 had a chemoresistant relapse, 35 patients had a chemosensitive relapse, and 10 patients were "initial high risk" patients. The median number of prior chemotherapy regimens was 2 (range, 1-5). The preparative regimen (BEP) was bischloroethylnitrosourea (BCNU) 600 mg/m 2 , etoposide 2400 mg/m 2 , and Platinol (cisplatin) 200 mg/m 2 given intravenously over 5 days. Within 3 weeks before transplantation, 70 patients received involved-field radiotherapy (IFR) 20 Gy to sites of currently active (2 cm) or prior bulky (5 cm) disease. Most patients (n = 93) received mobilized peripheral blood stem cells (median CD34 + cell dose, 6.7 x 10 6 /kg). Median neutrophil (500/microL) and platelet (20 000/microL, untransfused) recoveries were 11 days (range, 7-19 days) and 14 days (range, 7-36 days), respectively. At a median follow-up of 41 months (range, 4 to 118 months) for survivors, Kaplan-Meier 5-year probabilities of overall survival (OS) and disease-free survival (DFS) were 58.6% and 51.1%, respectively. Four patients (4%) died within 30 days of stem cell infusion (1 pulmonary embolism, 2 septicemias with multiorgan failure, and 1 progressive lymphoma). Two patients (2%) developed interstitial pneumonitis most likely secondary to high-dose BCNU. Three cases (3%) of secondary acute myelogenous leukemia occurred. On multivariate analysis, age (60 oror =60 years), histologic grade (low versus intermediate or high), the use of IFR, and chemotherapy response at baseline did not affect OS or DFS. Of 70 patients given IFR, 27 relapsed: 10 (37%) within and 17 (63%) outside the radiation field. The use of IFR did not affect either OS or DFS, probably because IFR was offered to patients with bulky or chemoresistant disease. BEP with or without IFR is a highly effective and well-tolerated regimen in the relapsed/refractory lymphoma setting. It has low morbidity and transplant-related mortality and a low incidence (3%) of posttransplantation malignancy.

Glut 5 is a member of a family of facilitative glucose transporter proteins that are involved in the transportation of glucose and/or fructose across plasma membranes. Glut 5 is one of three isoforms expressed in brain. Using immunocytochemical and immunoblotting techniques in formalin fixed tissue, we have shown that Glut 5 is exclusively expressed in microglial cells of the human and rat brain. Our data demonstrate that unlike other microglial markers, Glut 5 can be used as a microglial marker in formalin fixed tissue.

Various clinical risk factors, including high breast density, have been shown to be associated with breast cancer. The utility of using relative and absolute area-based breast density-related measures was evaluated as an alternative to clinical risk factors in cancer risk assessment at the time of screening mammography.Contralateral mediolateral oblique digital mammography images from 392 females with unilateral breast cancer and 817 age-matched controls were analysed. Information on clinical risk factors was obtained from the provincial breast-imaging information system. Breast density-related measures were assessed using a fully automated breast density measurement software. Multivariable logistic regression was conducted, and area under the receiver-operating characteristic (AUROC) curve was used to evaluate the performance of three cancer risk models: the first using only clinical risk factors, the second using only density-related measures and the third using both clinical risk factors and density-related measures.The risk factor-based model generated an AUROC of 0.535, while the model including only breast density-related measures generated a significantly higher AUROC of 0.622 (p 0.001). The third combined model generated an AUROC of 0.632 and performed significantly better than the risk factor model (p 0.001) but not the density-related measures model (p = 0.097).Density-related measures from screening mammograms at the time of screen may be superior predictors of cancer compared with clinical risk factors.Breast cancer risk models based on density-related measures alone can outperform risk models based on clinical factors. Such models may support the development of personalized breast-screening protocols.

Background Previous analyses of interval breast cancers have been limited because of a lack of control for screening interval length and patient age, failure to restrict the interval group to ‘true' intervals, and incomplete descriptions of pathology, adjuvant therapies and clinical outcomes. Patients and Methods A nested case-control study within the population-based Nova Scotia Breast Screening Program was performed. All true interval cases between 1991 and 2004 were identified, matched 1:2 to screen-detected cases (age, screening interval, time period), and compared in terms of pathologic characteristics and adjuvant therapies via logistic regression. Disease-free and overall survival was estimated, controlling for pathology and adjuvant chemotherapy receipt. Results A total of 241 true interval invasive cases were matched to 481 screen-detected cases. Interval cases were more likely to be > 1 cm (odds ratio [OR] = 1.76; 95% CI, 1.10-2.83), grade 3 (OR = 2.71; 95% CI, 1.49-4.92), and have lymphovascular invasion (OR = 3.06; 95% CI, 1.85-5.07). Interval cases received more adjuvant chemotherapy (OR = 4.37; 95% CI, 3.03-6.30) and radiation (OR = 1.43; 95% CI, 1.02-2.00). The 5-year Kaplan-Meier estimates of disease-free and overall survival rates for true intervals and screens were 0.830 (95% CI, 0.770-0.875) versus 0.926 (95% CI, 0.898-0.947) and 0.860 (95% CI, 0.804-0.901) versus 0.937 (95% CI, 0.910-0.956), respectively. Conclusion True interval breast cancers have more adverse prognostic factors compared with screen-detected cases and, despite receiving more adjuvant chemotherapy, are associated with significantly poorer survival outcomes.

e12530 Background: Triple Negative Breast Cancer (TNBC) accounts for approximately 10% of invasive breast malignancies and is characterized by a relative lack of adjuvant systemic therapeutic optio...

s / Can J Diabetes 37 (2013) S6eS11 S11 immigration records for 592376 immigrants to Ontario, Canada. We used Cox-Proportional Hazard models to generate adjusted incidence rates by ethnicity, sex and age and to determine the age cutoffs at which different ethnicities experienced equivalent risk of developing diabetes. Findings: South Asians had the highest overall incidence rate (agesex adjusted rate of 15.7 per 1000 person years), which was 3.3 times higher than in Western Europeans (p

We examined the expression of platelet-derived growth factor (PDGF)-A and the PDGF alpha-receptor in pre-implantation and early post-implantation mouse embryos. At two-cell and blastocyst stages, all cells express mRNA and protein for both ligand and receptor. In contrast, early post-implantation embryos express PDGF-A chain mRNA in both embryonic ectoderm and in the ectoderm lining the ectoplacental cavity, while mRNA for PDGF alpha-receptor is localized to the mesoderm layers of both embryonic and extra-embryonic membranes. At days 3.5 and 7.5, receptors are demonstrably functional in response to exogenous PDGF-AA. We propose that chronic autostimulation of PDGF alpha-receptors occurs in pre-implantation embryos, whereas, following implantation, early mesoderm development is dependent on stimulation by ectodermally produced PDGF-A.

6528 Background: It has been hypothesized that, compared to screen-detected breast cancer (Scr), true interval breast cancers (Int) are associated with adverse prognostic factors and outcomes. Data has remained controversial due to failure to control for age at diagnosis and screening interval as well as lack of information regarding adjuvant therapies and inclusion of other categories of interval cancers (e.g., missed or noncompliant). Methods: A case-control study nested among participants of the population-based Nova Scotia Breast Screening Program diagnosed with invasive disease between the ages 40–69 in the period 1991–2006 was performed. Ints were validated by blinded review of the pre-diagnostic screening mammogram by 3 mammographers, 2 or 3 of whom had to agree that it was negative for inclusion as a true Int. Scrs were matched to Ints on a 2:1 basis by 5 year age group at diagnosis and screening interval (40–49 yo, annual; 50–69 yo + family history, annual; 50–69 yo - family history, biennial). Results: 243 true Ints were observed and matched to 485 Scrs. The Table presents (i) univariate analysis of selected pathology variables for the entire cohort of Ints vs Scrs (ii) multivariate analysis of these selected variables. In addition to standard adjuvant hormonal, radiation and trastuzumab therapies, 62.4% of Ints received standard adjuvant chemotherapy (adjC) vs. 30.6% of Scrs. 5 year disease-free (DFS) and overall (OS) survival rates for Int vs Scr were 82.6% vs 92.3% and 87.2% vs 93.3% respectively. Cox proportional hazards modeling for (i) DFS shows HR=1.96 (p=0.0024) for Int vs Scr, dropping to HR=1.57 (p=0.0556) after adjusting for adjC received and (ii) OS shows HR=1.99 (p=0.0028) for Int vs Scr, dropping to 1.61 (p=0.0487) after adjusting for adjC received. Conclusions: True Ints present with more adverse prognostic factors compared to Scrs. Despite more use of adjC, outcomes are significantly poorer. [Table: see text] No significant financial relationships to disclose.

638 Background: The interpretation of clinical and biologic differences between screen-detected and interval breast cancers has been limited by the failure to control for factors known to influence...