Myeloperoxidase Genotypes and Enhanced Efficacy of Chemotherapy for Early-Stage Breast Cancer in SWOG-8897
Year: 2009
Type: article
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.
Source: Journal of Clinical Oncology
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
Awards: G1033243903, G117886320, G1202672505, G1216887118, G1235982543, SOUTHWEST ONCOLOGY GROUP, G1343089328, G1375689152, Columbus Community Clinical Oncology Program (Columbus CCOP), G1545560008, G1646027999, COOPERATIVE STUDY OF CANCER CHEMOTHERAPY, G1790576020, G1911575068, G1958973285, G1985252453, G2043432835, Scott & White Community Clinical Oncology Program, G2160369479, G2261465654, G2276667821, G2405064429, G2419449687, G2435896781, G2485941414, G2562936776, G2646278872, G268786457, G2750730928, Ozark Health Ventures, LLC dba Cancer Research for the Ozarks, GRAND RAPIDS CLINICAL ONCOLOGY PROGRAM, SOUTHWEST ONCOLOGY GROUP STATISTICAL CENTER, G3103693091, G3126600779, G313314762, G3239274266, G3242537740, G3295642875, G3334379738, G345775953, G3484997517, G3521018462, G36541222, G3737421695, G379387698, G4110529384, G413878341, G425646771, Southwest Oncology Group, G4292856267, G444114835, G4499432180, G4525186751, G4527800867, SOUTHWEST ONCOLOGY GROUP, CANCER AND LEUKEMIA GROUP B: RPMI/SUNYAB, G5264753430, G5566132837, G5660033547, G591690631, SOUTHWEST ONCOLOGY GROUP, SOUTHWEST ONCOLOGY GROUP, G6211207823, G6358381031, G6723594983, SOUTHWEST ONCOLOGY GROUP, G6782300252, G7222907299, G7520596819, G758084519, Virginia Mason Community Clinical Oncology Program, G7926913928, G8006406963, G8036334546, G8432681756, G860872252, SOUTHWEST ONCOLOGY GROUP, G8740717309, G8777682367, PARTICIPATE AS MEMBER OF SOUTHWEST ONCOLOGY GROUP, G8937348795, G933283670, G971274320
OpenAlex ID: W2154400632