Myeloperoxidase Genotypes and Enhanced Efficacy of Chemotherapy for Early-Stage Breast Cancer in SWOG-8897. Export

@article{citeulike:5961435, abstract = {PURPOSE: Myeloperoxidase (MPO) generates reactive oxygen species and also activates xenobiotics. In a rigorous clinical trial (Southwest Oncology Group SWOG-8897), we examined relationships between genotypes and disease-free survival (DFS) among women treated for breast cancer, as well as those who did not receive adjuvant chemotherapy. PATIENTS AND METHODS: Patients were assigned to risk groups according to standard prognostic features; the low-risk group (n = 753 genotyped) received follow-up only, and the high-risk group (n = 401 genotyped) was randomly assigned to adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) or cyclophosphamide, doxorubicin, and fluorouracil (CAF), with or without tamoxifen. DNA from archived normal lymph node tissue was genotyped, and Cox proportional hazard models were used to calculate DFS associated with MPO genotypes. RESULTS: Among women in the treatment arm, those with MPO G alleles had more than a two-fold reduction in hazard of recurrence (adjusted hazard ratio [HR] for GA genotypes, 0.51; 95\% CI, 0.21 to 0.99; HR for GG genotypes, 0.41; 95\% CI, 0.21 to 0.77). Effects were greatest among women who were further randomly assigned to tamoxifen (HR for GA genotypes, 0.28; 95\% CI, 0.12 to 0.69; HR for GG genotypes, 0.19; 95\% CI, 0.08 to 0.45). There were no significant associations between genotypes and DFS among women in the untreated arm, and relationships between genotypes and DFS did not differ by CAF or CMF. CONCLUSION: These results, observed in two independent study populations, indicate that high-activity MPO genotypes are associated with better survival among women receiving cyclophosphamide-containing therapy, particularly when followed by tamoxifen therapy. MPO can be inhibited and/or upregulated by commonly used drugs; thus, our findings merit further investigation for optimization of therapeutics for breast cancer.}, author = {Ambrosone, Christine B. and Barlow, William E. and Reynolds, Wanda and Livingston, Robert B. and Yeh, I-Tien T. and Choi, Ji-Yeob Y. and Davis, Warren and Rae, James M. and Tang, Li and Hutchins, Laura R. and Ravdin, Peter M. and Martino, Silvana and Osborne, C. Kent and Lyss, Alan P. and Hayes, Daniel F. and Albain, Kathy S.}, citeulike-article-id = {5961435}, citeulike-linkout-0 = {http://dx.doi.org/10.1200/JCO.2009.21.8669}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19752340}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19752340}, day = {14}, doi = {10.1200/JCO.2009.21.8669}, issn = {1527-7755}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, keywords = {ambrosone, breast, cancer, mpo, pharmacogenetics}, month = {September}, posted-at = {2009-10-18 18:10:53}, priority = {2}, title = {Myeloperoxidase Genotypes and Enhanced Efficacy of Chemotherapy for Early-Stage Breast Cancer in SWOG-8897.}, url = {http://dx.doi.org/10.1200/JCO.2009.21.8669}, year = {2009} }

TY - JOUR ID - citeulike:5961435 L3 - citeulike-article-id:5961435 N2 - PURPOSE: Myeloperoxidase (MPO) generates reactive oxygen species and also activates xenobiotics. In a rigorous clinical trial (Southwest Oncology Group SWOG-8897), we examined relationships between genotypes and disease-free survival (DFS) among women treated for breast cancer, as well as those who did not receive adjuvant chemotherapy. PATIENTS AND METHODS: Patients were assigned to risk groups according to standard prognostic features; the low-risk group (n = 753 genotyped) received follow-up only, and the high-risk group (n = 401 genotyped) was randomly assigned to adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) or cyclophosphamide, doxorubicin, and fluorouracil (CAF), with or without tamoxifen. DNA from archived normal lymph node tissue was genotyped, and Cox proportional hazard models were used to calculate DFS associated with MPO genotypes. RESULTS: Among women in the treatment arm, those with MPO G alleles had more than a two-fold reduction in hazard of recurrence (adjusted hazard ratio [HR] for GA genotypes, 0.51; 95% CI, 0.21 to 0.99; HR for GG genotypes, 0.41; 95% CI, 0.21 to 0.77). Effects were greatest among women who were further randomly assigned to tamoxifen (HR for GA genotypes, 0.28; 95% CI, 0.12 to 0.69; HR for GG genotypes, 0.19; 95% CI, 0.08 to 0.45). There were no significant associations between genotypes and DFS among women in the untreated arm, and relationships between genotypes and DFS did not differ by CAF or CMF. CONCLUSION: These results, observed in two independent study populations, indicate that high-activity MPO genotypes are associated with better survival among women receiving cyclophosphamide-containing therapy, particularly when followed by tamoxifen therapy. MPO can be inhibited and/or upregulated by commonly used drugs; thus, our findings merit further investigation for optimization of therapeutics for breast cancer. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology SN - 1527-7755 TI - Myeloperoxidase Genotypes and Enhanced Efficacy of Chemotherapy for Early-Stage Breast Cancer in SWOG-8897. KW - ambrosone KW - breast KW - cancer KW - mpo KW - pharmacogenetics AU - Ambrosone, Christine AU - Barlow, William AU - Reynolds, Wanda AU - Livingston, Robert AU - Yeh, I-Tien AU - Choi, Ji-Yeob AU - Davis, Warren AU - Rae, James AU - Tang, Li AU - Hutchins, Laura AU - Ravdin, Peter AU - Martino, Silvana AU - Osborne, Kent AU - Lyss, Alan AU - Hayes, Daniel AU - Albain, Kathy PY - 2009/09/14/ UR - http://dx.doi.org/10.1200/JCO.2009.21.8669 ER -