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Cancer Control Research

Abstract

APPLICANT?S DESCRIPTION This continuation proposes to follow-up 1,508 case women newly diagnosed with breast cancer who are participants in an ongoing population-based, case-control study of breast cancer among women on Long Island. The primary aims of the ongoing parent case-control study are to determine whether risk of developing breast cancer is increased among women with higher levels of serum organochlorine compounds, including DDT and PCBs, or higher levels of polycyclic aromatic hydrocarbons, assessed by PAH-DNA levels in blood samples. The proposed continuation will follow-up the case women 3- and 5-years after diagnosis of the primary breast cancer to identity environmental factors that affect the risk of disease-free and overall survival, including: (1) serum levels of DDT and PCBs, and PAH-DNA adducts based on blood samples collected at the parent case-control interview; and (2) cigarette smoking, physical activity, hormone replacement therapy, changes in weight as an adult, alcohol diet, and other factors assessed by structured questionnaire during the parent case-control interview. An additional aim is to explore whether the survival risk associated with these potential environmental risk factors is modified by known prognostic indicators in the tumor, including p53 and HER-2/neu. During the 3- and 5-year follow-up periods, medical treatment and outcomes (recurrence, second primary) will be assessed by telephone interview with the subject and by checking with physicians and medical records. Mortality will be determined by cross-checking the National Death Index, and by contacting next of kin and physicians. For the parent study, blood samples were successfully obtained for 1,087 case women and assays of DDT/PCBs and PAH-DNA adducts will be completed as planned for 643 and 577 cases, respectively. Blood samples for the remaining 444 and 320 case women, respectively, with sufficient blood volume will be assayed for these environmental compound as part of the proposed study. Assays for HER2/neu overexpression in case tumor tissue, assessed by immunohistochemisty, will be conducted for the proposed follow-up; funding for the immunohistochemical assays of p53 expression has already been obtained. Standard statistical techniques for the analysis of cohort data will be used to determine the risk of disease-free survival and overall survival, at the 3- and 5-year follow-up periods, associated with higher levels of environmental factors, with adjustments made for breast cancer treatment, breast tumor characteristics, and other clinical predictors of survival. Potential subgroup effects, with cases partitioned on p53 and HER-2/neu expression, the relation between environmental factors on breast cancer survival will be explored, where possible.