Breast cancer is the most commonly diagnosed cancer and the second most common cause of cancer-related death among women in Ontario.1 More than 10 000 cases are diagnosed each year in the province.1 Several molecular subtypes of breast cancer have been identified b ased o n h ormone receptor and human epidermal growth factor receptor 2 (HER2) status.2 These molecular subtypes have been shown to affect survival: patients with hormone-receptor-negative tumours tend have greater mortality and lower survival than those with hormone-receptor-positive tumours. [3][4][5] Although the relation between breast cancer molecular subtype and survival has been studied in other jurisdictions, including British Columbia, 6,7 limited information is available for Ontario. The goal of this study was to determine how breast cancer molecular subtype affects survival among Ontario women and how survival for each subtype varies by selected demographic and tumour-based characteristics. Methods Setting and study populationThe study population included all cases of malignant breast cancer diagnosed in girls and women aged 15 years or more in Ontario between Jan. 1, 2010, and Dec. 31, 2012. We chose this period because data on molecular subtype were unavailable for cases diagnosed before 2010, and mortality data were unavailable for cases diagnosed after 2012. The relation between breast cancer molecular subtype and survival has been studied in several jurisdictions, but limited information is available for Ontario. The aim of this study was to determine breast cancer survival by molecular subtype and to assess the effect on survival of selected demographic and tumour-based characteristics.

The outcome of myelodysplastic syndrome (MDS) patients with uniformly higher-risk disease treated with azacitidine (AZA) in the 'real-world' remains largely unknown. We evaluated 1101 consecutive higher-risk MDS patients (International Prognostic Scoring System intermediate-2/high) and low-blast count acute myeloid leukaemia (AML; 21-30% blasts) patients treated in Ontario, Canada. By dosing schedule, 24·7% received AZA for seven consecutive days, 12·4% for six consecutive days and 62·9% by 5-2-2. Overall, median number of cycles was 6 (range 1-67) and 8 (range 6-14) when restricted to the 692 (63%) patients who received at least 4 cycles. The actuarial median survival was 11·6 months [95% confidence interval (CI) 10·7-12·4) for the entire cohort and 18·0 months (landmark analysis; 95% CI 16·6-19·1 months) for those receiving at least 4 cycles. There was no difference in overall survival (OS) between the 3 dosing schedules (P = 0·87). In our large 'real-world' evaluation of AZA in higher-risk MDS/low-blast count AML, we demonstrated a lower than expected OS. Reassuringly, survival did not differ by dosing schedules. The OS was higher in the 2/3 of patients who received at least 4 cycles of treatment, reinforcing the necessity of sustained administration until therapeutic benefits are realised. This represents the largest 'real-world' evaluation of AZA in higher-risk MDS/low-blast count AML.

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242 Background: There is uncertainty regarding the optimal systemic treatment for patients with SBA and AA due to the limited available evidence for these uncommon malignancies and conflicting recommendations in existing guidelines. However, on the basis of biologic similarities between SBA, AA and colorectal cancer (CRC), common practice is to use the same systemic therapies as for CRC. We compared the utilization of chemotherapeutic agents for SBA and AA to that of CRC patients in Ontario, Canada. Methods: The provincial tumour registry in Ontario, Canada was used to identify patients diagnosed with SBA, AA or CRC from 2010-2014. Subsequent chemotherapy utilization and costs were captured from single-payer government administrative databases. We studied the use of oxaliplatin, irinotecan, capecitabine, bevacizumab, cetuximab, panitumumab, and raltitrexed, which are funded for CRC treatment. Patients were excluded if they had multiple primary cancer sites, morphology codes inconsistent with adenocarcinomas, or missing identification data. Statistical analyses were used to report and test patterns of utilization and average costs per patient. Results: Our cohort consisted of 30,946 patients over a 5-year period. On average, 160 and 80 patients were diagnosed annually in Ontario with SBA and AA, respectively, together representing less than 4% of the total diagnoses each year. Among SBA and AA patients, 30-40% initiated therapy with the selected systemic therapies, similar to the proportion in CRC. SBA and AA patients were less likely to receive adjuvant oxaliplatin (SBA 9%, AA 13%) compared to CRC (18%) patients, but more likely to use first and second-line oxaliplatin or irinotecan for metastatic disease. Bevacizumab was added to first-line therapy for SBA and AA patients in fewer cases than CRC (SBA 29%, 45% AA, 72% CRC). Third-line EGFR inhibitors panitumumab and cetuximab were used infrequently in all groups ( < 2% of those diagnosed). Average per patient costs were similar across disease sites (p > 0.05). Conclusions: On a population level, SBA and AA patients appear to be managed similarly to CRC patients and at similar cost. Future research will evaluate survival outcomes.

Background: In the AZA-001 trial, azacitidine (AZA) altered the natural history of patients with higher-risk MDS (Fenaux et al., Lancet 2009) by significantly improving overall survival compared to conventional care regimens (24.5 months versus 15.0 months). Once approved for drug reimbursement by the provincial health ministry, Cancer Care Ontario (CCO) mandated that all eligible patients be enrolled in a prospective registry to ensure compliance with eligibility criteria and schedules of drug administration. Baseline characteristics were recorded and treatment response were to be submitted every 6 cycles of treatment. Our objectives were to audit this clinical program for results after 6 years and identify the prognostic markers for survival in a homogenous higher-risk MDS/low blast count AML patient population. Methods: Only higher-risk MDS patients (intermediate-2, high) as defined by the International Prognostic Scoring System (IPSS) and low blast count AML (20-30% blasts) treated with AZA in Ontario, Canada from June 1, 2010 to March 2, 2016 were eligible and included. Our primary outcome was overall survival (OS) from date of first AZA treatment. Our secondary outcomes were overall response rates and the predictors of OS including administration schedules, centre size or type (regional cancer versus community). Univariate and multivariable Cox proportional hazard model were used to determine the predictors of OS. Hazard ratios and generalized R2 (higher the R2, stronger association with OS) were also calculated. Results: 825 higher-risk MDS and 276 low blast count AML were included (n = 1101 total). Median age was 74 years (range 19 to 99), 65.2% were male and the IPSS scores were intermediate-2 (64.3%) and high-risk (35.7%). Sixty-six percent of patients were transfusion dependent (TD) at time of AZA initiation and 15.5% had received previous chemotherapy. By dosing schedule, 24.7% received AZA for 7 consecutive days (7d), 12.4% for 6 consecutive days (6d) and 62.9% by the 5-2-2 schedule. Overall, the median number of cycles received was 6 (range 1 to 67) and 8 (range 6 to 14) when restricted to the 692 (63%) patients who received at least 4 cycles of treatment. Dose reductions were seen in 33.3% of patients (mean 11.1 mg/m2 in those with reductions) and were more common over time (negative slope 0.178; p < .0001). Of those with repeat bone marrow (n = 293) best response was complete response (CR) in 16.7% and partial response (PR) in 10.6%. Of those without CR/PR/progressive disease on bone marrow (n = 814), 20.4% experienced hematologic improvement including those with marrow CR and marrow stable disease. The actuarial median survival was 11.6 months (95% CI 10.7- 12.4) with a significantly longer OS for MDS compared with low blast count AML (12.4 months vs. 9.6 months; p = .0002) and 16.7 months (95% CI 15.2-18.1) for those receiving at least 4 cycles. There was no difference in OS between the 3 dosing schedules (11.7 months (7d) vs. 10.2 months (6d) vs. 12.0 months (5-2-2); p = .87; figure 1A), regional cancer centre vs. community (11.3 months vs. 11.7 months; p = .19; figure 1B) or by centre volume (11.4 months < 50 patients vs. 11.6 months > 50 patients; p = .38; figure 1C). On univariate analysis, the following were predictive of OS: blast percentage, number of cytopenias, karyotype, IPSS, WHO classification, TD, greater transfusion burden and secondary MDS. The multivariate model with the highest R2 (13.5%) included blast percentage (p < .0001), karyotype (p < .0001), cytopenias (p = .038), TD (p < .0001) and secondary MDS (p = .0006) as summarized in the table below. Conclusions: In our large real world evaluation of AZA use in higher-risk MDS/low blast count AML, we validated the expected overall response rates to AZA but demonstrated a lower than expected OS compared to the AZA-001 trial. Reassuringly, survival did not differ by dosing schedules, centre volumes or center type (regional cancer vs. community). OS was higher in the 2/3 of patients who received at least 4 cycles of treatment, reinforcing the necessity of sustained administration until therapeutic benefits are realized. This represents the largest real world evaluation of AZA in higher-risk MDS/low blast count AML and additional analyses are underway. Table Table. Figure 1 Figure 1. Disclosures Mozessohn: Celgene: Honoraria. Buckstein:Celgene: Honoraria, Research Funding; Novartis: Honoraria.