Abstract P6-08-11: Regional variation in de novo metastatic breast cancer survival improvement over time using an institutional registry to support SEER analysis: 1990-2010

Abstract Background: It is not known how much de novo MBC (dnMBC) survival varies by where one lives and receives treatment in the US. Variation could exist depending on access to care, insurance availability, geographic area, and treatment options (urban vs. rural). Our objective is to measure variance in survival by Surveillance, Epidemiology, and End Results (SEER) region and compared to a non-academic institutional cohort. Methods: We compared change in disease specific survival (DSS) over time intervals1990-1998, 1999-2004 and 2005-2010, following diagnosis of first primary dnMBC among women in the SEER 9 population-based cancer registry using SEER 9 without Seattle-Puget Sound (S-PS) (n = 11,139) and Seattle Puget Sound separately (n = 1787). In a separate analysis we calculated and compared dnMBC DSS in our community-based cancer center registry located in the Seattle-Puget Sound region (n = 247) for the same time intervals. For the institutional cohort time to event used the outcome death from breast cancer confirmed from the patient chart or death certificate if information on cause of death was not available in the chart. For SEER data we used the SEERstat calculation for cause-specific survival as equivalent for disease specific survival (DSS). We estimated 5-year DSS cumulative incidence with 95% confidence intervals using the Kaplan-Meier method and compared survivor function equality by diagnosis years with log-rank tests. SEER*stat 8.3.4 was used for the SEER regional comparison and SPSS 24 for the institutional. Results: Patient age in the SEER registry population ranged from 18-93 years. The institutional cohort patient age range was 24-94 years. DSS improved over time for SEER 9 without Seattle-Puget Sound [1990-1998: 18.8% (95% CI: 17.6%, 20.0%);1999-2004; 22.0% (95% CI: 20.5%, 23.4%); 2005-2010: 24.6% (95% CI: 23.2%, 26.0%) (log-rank test=61.59, p&amp;lt;0.001)]. DSS for SEER Seattle-Puget Sound had a similar significant improvement gradient over time [1990-1998: 20.1% (95% CI: 17.1%, 23.2%)]; 1999-2004: 25.6% (95% CI: 21.9%, 29.4%); 2005-2010: 33.4% (95% CI: 29.7%, 37.1%) (log-rank test=42.46, p&amp;lt;0.001)]. DSS was significantly better in the Seattle-Puget Sound region in 2005-2010 (33.4%) compared to SEER9 without Seattle-Puget Sound (24.6%) (p=.017). Among dnMBC cases at the non-academic community cancer center, five year dnMBC DSS improved over time as well and by a larger margin [1990-1998: 28%, 95% CI: 18.2%, 37.8%; 1999-2004: 48%, 95% CI: 33.9%, 58.9%; 2005-2010: 55%, 95% CI: 45.3%, 64.5% (log rank test=9.65, p=.008)]. Conclusions: The SEER regional comparison indicates a significant regional survival difference for breast cancer patients with de novo stage IV metastatic breast cancer. Better survival in the Seattle-Puget Sound region is supported by the retrospective cohort analysis results from a center with a more detailed registry and complete follow up in the same region. Supplementation of regional survival SEER analysis with detailed analysis from an embedded institutions' dedicated registry could be used to enhance evaluation of factors such as standard of care that impact survival improvement. Citation Format: Malmgren JA, Calip GS, Atwood MK, Kaplan HG. Regional variation in de novo metastatic breast cancer survival improvement over time using an institutional registry to support SEER analysis: 1990-2010 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-11.</jats:p

Risk of cancer-specific, cardiovascular, and all-cause mortality among Asian and Pacific Islander breast cancer survivors in the United States, 1991-2011.

Asian and Pacific Islander (API) women in the United States (U.S.) are a heterogeneous group reported to have better prognosis after breast cancer (BC) compared to their Non-Hispanic White (NHW) counterparts. Few studies have examined differences in BC survival between individual API ethnic groups. We conducted a retrospective cohort study of 462,005 NHW and 44,531 API women diagnosed with incident, stage I-III BC between 1991 and 2011 in the Surveillance, Epidemiology and End Results (SEER) 18 registries. SEER-reported API ethnicity was grouped as Chinese, Japanese, Filipino, Hawaiian, Korean, Vietnamese, Asian Indian and Pakistani, and Pacific Islander. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for risk of BC-specific, cardiovascular and all-cause mortality comparing API to NHW women. We also estimated mortality risk comparing U.S.-born to non-U.S.-born women. Compared to NHW women, API women overall had lower BC-specific, cardiovascular and all-cause mortality. BC-specific mortality risk was lowest among Japanese women (HR 0.69, 95 % CI 0.63-0.77). Other women had similar (Filipino, HR 0.93, 0.86-1.00; Hawaiian, HR 1.01, 0.89-1.17) or greater (Pacific Islander, HR 1.44, 1.17-1.78) risk of BC-specific death. Compared to non-U.S. born API women, findings were suggestive of increased cardiovascular (HR 1.12, 1.03-1.20) and all-cause mortality (HR 1.29, 1.08-1.54) among U.S.-born API women. Mortality risk varies greatly between BC survivors from different API backgrounds. Further research is warranted to understand these disparities in BC survivorship and the social and cultural factors that possibly contribute to greater mortality among later-generation API women born in the United States

Therapy-related Myelodysplastic Syndrome Following Primary Breast Cancer.

BACKGROUND: Therapy-related myelodysplastic syndrome (t-MDS) is a serious clinical disease occurring after breast cancer treatment. METHODS: A cohort of 11,684 invasive breast cancer (BC) patients from 1990-2014 were followed for incidence of t-MDS through institutional and the Surveillance, Epidemiology and End Results (SEER) Program registries. t-MDS cases were identified using ICD-O SEER registry codes, pathology and chart reports. Treatment, cytogenetics, and time from BC diagnosis to t-MDS and t-MDS diagnosis to last follow up or death were obtained. Incidence rate ratios were calculated using SEER national incidence rates for comparison. RESULTS: 27 cases of t-MDS post BC treatment were confirmed. 96% of cases were breast cancer stage I-II at diagnosis. All patients had received radiation treatment and 59% received adjuvant chemotherapy. Two patients were alive with no evidence of disease after treatment with stem cell transplantation (age 33 and 46). t-MDS incidence was 30 times the expected population rate among patients <55 years (RR 31.8, 95% CI 15.0, 60.8) with shorter time from t-MDS diagnosis to death (median survival time: <55: 8 months, 55-74: 26 months, 75+: 23 months). CONCLUSION: We found elevated t-MDS risk especially among younger BC patients with stem cell transplantation the only observed curative treatment

Therapy-related Myelodysplastic Syndrome Following Primary Breast Cancer.

BACKGROUND: Therapy-related myelodysplastic syndrome (t-MDS) is a serious clinical disease occurring after breast cancer treatment. METHODS: A cohort of 11,684 invasive breast cancer (BC) patients from 1990-2014 were followed for incidence of t-MDS through institutional and the Surveillance, Epidemiology and End Results (SEER) Program registries. t-MDS cases were identified using ICD-O SEER registry codes, pathology and chart reports. Treatment, cytogenetics, and time from BC diagnosis to t-MDS and t-MDS diagnosis to last follow up or death were obtained. Incidence rate ratios were calculated using SEER national incidence rates for comparison. RESULTS: 27 cases of t-MDS post BC treatment were confirmed. 96% of cases were breast cancer stage I-II at diagnosis. All patients had received radiation treatment and 59% received adjuvant chemotherapy. Two patients were alive with no evidence of disease after treatment with stem cell transplantation (age 33 and 46). t-MDS incidence was 30 times the expected population rate among patients <55 years (RR 31.8, 95% CI 15.0, 60.8) with shorter time from t-MDS diagnosis to death (median survival time: <55: 8 months, 55-74: 26 months, 75+: 23 months). CONCLUSION: We found elevated t-MDS risk especially among younger BC patients with stem cell transplantation the only observed curative treatment

Top-down versus Step-up Prescribing Strategies for Tumor Necrosis Factor Alpha Inhibitors in Children and Young Adults with Inflammatory Bowel Disease.

BACKGROUND: Early initiation of tumor necrosis factor-alpha inhibitor (TNFI) therapy for children and young adults with inflammatory bowel disease (IBD) is not well described. METHODS: We conducted a retrospective cohort study of children and young adults (≤24 yr) newly diagnosed with IBD using health insurance claims from 2009 to 2013. The conventional "step-up" approach was defined as TNFI initiation >30 days after first IBD medication prescription, whereas the "top-down" approach was defined as new TNFI prescription within 30 days of first IBD medication prescription. Switching rates, time to initiation, discontinuation, and adherence to TNFIs were compared between the 2 strategies. RESULTS: A total of 11,962 IBD patients were identified. Among 3300 TNFI users, 1298 (39.3%) were treated with the top-down approach, whereas 2002 (60.7%) were treated with the step-up approach. Top-down approach use increased from 31.4% to 49.8% during the 5-year period, and under this approach, most patients were treated with TNFIs alone. Time to TNFI initiation was shorter for patients diagnosed in more recent years. Patients treated with the top-down strategy had lower rates of corticosteroid use (32.5% versus 94.2%) compared with step-up treatment but presented a higher rate of TNFI discontinuation. The 2 strategies both exhibited high adherence (mean proportion of days covered: 83.7%-95.4%). CONCLUSIONS: Early TNFI initiation increased over time for children and young adults with IBD and was related to lower rates of corticosteroid use compared with the conventional approach. However, the higher rate of TNFI discontinuation under the top-down approach requires further examination

Top-down versus Step-up Prescribing Strategies for Tumor Necrosis Factor Alpha Inhibitors in Children and Young Adults with Inflammatory Bowel Disease.

BACKGROUND: Early initiation of tumor necrosis factor-alpha inhibitor (TNFI) therapy for children and young adults with inflammatory bowel disease (IBD) is not well described. METHODS: We conducted a retrospective cohort study of children and young adults (≤24 yr) newly diagnosed with IBD using health insurance claims from 2009 to 2013. The conventional "step-up" approach was defined as TNFI initiation >30 days after first IBD medication prescription, whereas the "top-down" approach was defined as new TNFI prescription within 30 days of first IBD medication prescription. Switching rates, time to initiation, discontinuation, and adherence to TNFIs were compared between the 2 strategies. RESULTS: A total of 11,962 IBD patients were identified. Among 3300 TNFI users, 1298 (39.3%) were treated with the top-down approach, whereas 2002 (60.7%) were treated with the step-up approach. Top-down approach use increased from 31.4% to 49.8% during the 5-year period, and under this approach, most patients were treated with TNFIs alone. Time to TNFI initiation was shorter for patients diagnosed in more recent years. Patients treated with the top-down strategy had lower rates of corticosteroid use (32.5% versus 94.2%) compared with step-up treatment but presented a higher rate of TNFI discontinuation. The 2 strategies both exhibited high adherence (mean proportion of days covered: 83.7%-95.4%). CONCLUSIONS: Early TNFI initiation increased over time for children and young adults with IBD and was related to lower rates of corticosteroid use compared with the conventional approach. However, the higher rate of TNFI discontinuation under the top-down approach requires further examination