Project Summary The destruction of the World Trade Center (WTC) towers on September 11, 2001 resulted in the massive release of dust and fumes with exposure of local community members (“survivors”) to carcinogenic compounds (asbestos, metals, and dioxins). It is well known that environmental exposures can cause somatic mutations and aberrant DNA methylation which, in turn, are known to be associated with cancer initiation and progression. There have been a rapid increased of the number of cancers among community members affected by the terrorist attack on the WTC towers on September 11, 2001. Studies of cancers from the FDNY and General Responders’ group report elevated cancer incidence in prostate cancers and other solid tumors among men. Importantly, there are also several studies of WTC Responders enrolled in WTCHP medical monitoring and treatment programs (MMTP) that find significantly lower mortality rates compared to national peer groups mortality rate. These are important findings, however, the members of the FDNY and general responders are predominately limited to white males thus lack the necessary diversity in gender, socioeconomic and race/ethnicity to fully understand breast cancers and other leading cancers in the affected urban community. Studies performed by the NYCDOH WTC Health Registry report increased cancer incidence rate in women’s breast cancers among community members, but are based on epidemiological data from survey questionnaires thus lack of individual level clinical information. Moreover, there has been no investigation on the link between the complex WTC exposures and the phenotypes and mortality of cancers in WTC Survivors enrolled in the WTC Environmental Health Center (EHC), Williams Street Clinic (WSC) and National Provider Network (NPN), the CDC/NIOSH designated treatment and monitoring program for affected community members (i.e. survivors). In particular, the enrollees of WTC EHC include about 50% women and have diverse social-economic status and racial/ethnic background. To fill the important knowledge gaps and to improve disease surveillance, diagnosis and treatment activities for cancer among affected community, we propose to conduct integrated analyses of individual-level patient data to investigate the link between WTC exposures and certified WTC cancers at the WTC EHC and to measure cancer mortality in survivors. We will systematically examine WTC exposures and other risk factors and associations with breast cancer characteristics and cancer survival outcomes. Successful completion of this project will establish the link between elevated WTC exposures with combination of other risk factors and characteristics of breast cancers, and characterize effects of risk factors associated with breast cancer stage, subtypes, and overall survival among community members affected by the WTC terrorist attack, which can inform subsequent studies and improve surveillance and treatment of the WTC-exposed population.