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Grant Details

Grant Number: 5R01CA116395-04 Interpret this number
Primary Investigator: Ambrosone, Christine
Organization: Roswell Park Cancer Institute Corp
Project Title: Antioxidant Supplements, Genetics, and Chemotherapy Outcomes
Fiscal Year: 2009
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Abstract

DESCRIPTION (provided by applicant): Cancer patients report widespread use of antioxidant supplements during chemotherapy, despite the recommendations by the American Institute for Cancer Research and others that supplements not be used during treatment. These guidelines are based upon the fact that numerous chemotherapeutic agents, including those used to treat breast cancer, exert their cytotoxic effects by generation of reactive oxygen species (ROS), which cause massive damage to DNA and proteins and trigger apoptosis, resulting in tumor and normal cell death. Thus, there is the concern that antioxidants may block the ROS-generated effects of therapy on tumor cells. There are no data based on sound epidemiological or clinical studies to support this hypothesis, however. In fact, some experimental studies have shown that antioxidants may potentiate the effects of chemotherapeutic drugs, while also lessening treatment-related toxicities. We will investigate the question of whether or not use of antioxidant supplements during adjuvant chemotherapy has any impact on toxicities and disease-free, as well as overall, survival, and also evaluate the role of polymorphisms in genes related to oxidative stress in relation to treatment outcomes in the context of a newly activated Southwest Oncology Group (SWOG) clinical trial. In the ongoing Phase III Intergroup parent study chaired by SWOG, S0221, patients are randomized onto one of four arms that test different doses/intensities/intervals of cyclophosphamide, adriamycin, and paclitaxel. Blood specimens are being collected and banked. All patients upon enrollment in the treatment trial will be asked to be contacted for participation in this ancillary study. Telephone interviews will be conducted at the initiation of therapy, and at completion of treatment, regarding use of antioxidant supplements and other lifestyle factors. DNA will be genotyped for polymorphisms in a number of oxidative stress-related genes. Data will be analyzed at the SWOG Statistical Center, and supplement use and genetic variability will be evaluated in relation to toxicities, as well as to disease-free and overall survival. We will also explore the potential modification of antioxidant use on treatment outcomes by genetic variability. Because of the expected large size of this study, and the homogeneity of the study population and treatments given, the proposed study will have the capabilities to answer an extremely important question in the care of cancer patients today, and provide data that may lead to reduced treatment toxicities and increased disease-free survival.

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Publications

Germline genetic variants in ABCB1, ABCC1 and ALDH1A1, and risk of hematological and gastrointestinal toxicities in a SWOG Phase III trial S0221 for breast cancer.
Authors: Yao S, Sucheston LE, Zhao H, Barlow WE, Zirpoli G, Liu S, Moore HC, Thomas Budd G, Hershman DL, Davis W, Ciupak GL, Stewart JA, Isaacs C, Hobday TJ, Salim M, Hortobagyi GN, Gralow JR, Livingston RB, Albain KS, Hayes DF, Ambrosone CB
Source: Pharmacogenomics J, 2014 Jun;14(3), p. 241-7.
EPub date: 2013 Sep 3.
PMID: 23999597
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Supplement use during an intergroup clinical trial for breast cancer (S0221).
Authors: Zirpoli GR, Brennan PM, Hong CC, McCann SE, Ciupak G, Davis W, Unger JM, Budd GT, Hershman DL, Moore HC, Stewart J, Isaacs C, Hobday T, Salim M, Hortobagyi GN, Gralow JR, Albain KS, Ambrosone CB
Source: Breast Cancer Res Treat, 2013 Feb;137(3), p. 903-13.
EPub date: 2013 Jan 10.
PMID: 23306462
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Parity and lactation in relation to estrogen receptor negative breast cancer in African American women.
Authors: Palmer JR, Boggs DA, Wise LA, Ambrosone CB, Adams-Campbell LL, Rosenberg L
Source: Cancer Epidemiol Biomarkers Prev, 2011 Sep;20(9), p. 1883-91.
EPub date: 2011 Aug 16.
PMID: 21846820
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Genetic predictors of taxane-induced neurotoxicity in a SWOG phase III intergroup adjuvant breast cancer treatment trial (S0221).
Authors: Sucheston LE, Zhao H, Yao S, Zirpoli G, Liu S, Barlow WE, Moore HC, Thomas Budd G, Hershman DL, Davis W, Ciupak GL, Stewart JA, Isaacs C, Hobday TJ, Salim M, Hortobagyi GN, Gralow JR, Livingston RB, Albain KS, Hayes DF, Ambrosone CB
Source: Breast Cancer Res Treat, 2011 Dec;130(3), p. 993-1002.
EPub date: 2011 Jul 16.
PMID: 21766209
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