Impact of Genomics and Exposures on Disparities in Breast Cancer Radiosensitivity
- To develop and validate prediction biomarkers for radiation therapy (RT)-induced acute
and chronic skin reactions and quality of life in five racial/ethnic groups of breast
cancer patients, Whites*, Black/African Americans, Hispanic/Latinos, Asians/Native
Hawaiians/Pacific Islanders, and American Indians/Alaskan Natives. NOTE: *This stratum
is closed as of April 25, 2012.
- To develop polygenic models of RT-induced skin reactions with a comprehensive
evaluation of genome-wide nonsynonymous single nucleotide polymorphisms (nsSNPs).
- To evaluate the levels of DNA damage (Comet assay) and radiosensitivity (Cell Cycle G2
Delay assay) in lymphocytes before and after RT.
- To test the effect of gene-gene and gene-smoking interactions on RT-induced skin
- To assess race-ethnic differences in RT-induced skin reactions, DNA damage, and
radiosensitivity and to determine if the gene effects are consistent across
race-ethnicity (gene-race/ethnic interactions).
OUTLINE: This is a multicenter study. Patients are stratified according to race/ethnicity
(Whites* vs Black/African Americans vs Hispanic/Latinos vs Asians/Native Hawaiians/Pacific
Islanders vs American Indians/Alaskan Natives). NOTE: *This stratum is closed as of April
Patients undergo adjuvant radiotherapy after breast-conserving surgery.
Blood and urine samples are collected at baseline and last day of radiotherapy for
genotyping, DNA damage, cell cycle assays, urine cotinine, inflammatory immune response
biomarkers, and tumor-killing activity by BeadArray System, Comet assay, flow
cytometry-based assay, Cell-Cycle G2 Delay Assay, Oxygen Radical Absorbance Capacity (ORAC)
assay, and ELISA.
Patients are assessed for acute toxicity by research staff using the ONS Criteria for
Radiation-Induced Acute Skin Toxicity at baseline, week 3, and at 1 and 2 months after
radiotherapy. Patients are also assessed for chronic toxicity by research staff using the
Chronic skin toxicity questionnaire (RTOG SOMA Criteria for RT- Induced Breast/Chest Wall
Late Skin Toxicity) at 6 and 12 months after completion of radiotherapy. Photographs of the
breast, chest wall, and contralateral breast are also taken at baseline, week 3, last day of
radiotherapy, and at 1, 2, 6, and 12 months after completion of radiotherapy.
Patients complete the Breast Cancer Risk Study Questionnaire, the Functional Assessment of
Cancer Therapy Breast (FACT-B), the Modified Skindex, and the B39 Quality-of-Life (QOL)
Questionnaire at baseline, last day of radiotherapy, and at 1, 2, 6, and 12 months after
Time Perspective: Prospective
Occurrence of RT-induced early adverse skin reaction (EASR)
The primary endpoint is RT-related skin reactions which for consistency and clarity across the study we will use the term "Early Adverse Skin Reaction" (EASR). Skin reactions will be assessed at 4 time points from the start of radiotherapy through 2 months of the post radiotherapy follow-up period. The Modified ONS Criteria for Radiation-Induced Acute Skin Toxicity will be used for classification of EASRs related to the skin. The primary outcome variable will be the occurrence (or not) of RT-induced EASR defined as a grade 4 or higher toxicity (based on the ONS criteria) during the 2 months of the follow-up period of the study.
James J. Urbanic, MD
Comprehensive Cancer Center of Wake Forest University
United States: Institutional Review Board
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|