OBJECTIVES: Outcome and survival in anthracycline-based and cyclophosphamide/methotrexate/5-fluorouracil-based chemotherapy of invasive breast cancer are unpredictable. Insights into treatment prediction are expected from studies searching for an association between genetic polymorphisms and treatment outcome effects. A common feature of treatment with chemoreagents is therapeutically induced DNA damage. Therefore, we tested the hypothesis of a relationship between event-free survival and genotype distributions of seven polymorphic DNA repair enzymes and four cell cycle regulators. BASIC METHODS: This case-case comparison included 180 patients with primary invasive breast cancer diagnosed between 1986 and 2000 and subjected to adjuvant chemotherapy (anthracycline/cyclophosphamide or cyclophosphamide/methotrexate/5-fluorouracil). Ninety-two patients were reported without recurrence and 88 were reported with recurrences or dead. Median clinical follow-up was 61.7 months. Constitutional DNA isolated from archived tissues was genotyped at 19 loci by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Statistical analyses included adjusted risk estimates, Kaplan-Meier analyses, Cox proportional hazard model, and permutation testing. MAIN RESULTS: Carriers of the XRCC1_1196_AA genotype had a reduced risk for recurrence/death (odds ratio adjusted 0.19; 95% confidence interval: 0.06-0.61), which was observed in survival analyses of all patients (P=0.003) and patients treated with chemotherapy but not radiotherapy (P=0.006). Multivariate analysis confirmed XRCC1 as a potential treatment predictor (hazard ratio 0.62; 95% confidence interval: 0.43-0.89). The result was stable upon permutation testing. No other significant associations were observed. CONCLUSION: The DNA repair enzyme XRCC1 is a potential treatment predictor for the outcome and survival of anthracycline and cyclophosphamide/methotrexate/5-fluorouracil-based chemotherapy of invasive breast cancer.
OBJECTIVES: Outcome and survival in anthracycline-based and cyclophosphamide/methotrexate/5-fluorouracil-based chemotherapy of invasive breast cancer are unpredictable. Insights into treatment prediction are expected from studies searching for an association between genetic polymorphisms and treatment outcome effects. A common feature of treatment with chemoreagents is therapeutically induced DNA damage. Therefore, we tested the hypothesis of a relationship between event-free survival and genotype distributions of seven polymorphic DNA repair enzymes and four cell cycle regulators. BASIC METHODS: This case-case comparison included 180 patients with primary invasive breast cancer diagnosed between 1986 and 2000 and subjected to adjuvant chemotherapy (anthracycline/cyclophosphamide or cyclophosphamide/methotrexate/5-fluorouracil). Ninety-two patients were reported without recurrence and 88 were reported with recurrences or dead. Median clinical follow-up was 61.7 months. Constitutional DNA isolated from archived tissues was genotyped at 19 loci by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Statistical analyses included adjusted risk estimates, Kaplan-Meier analyses, Cox proportional hazard model, and permutation testing. MAIN RESULTS: Carriers of the XRCC1_1196_AA genotype had a reduced risk for recurrence/death (odds ratio adjusted 0.19; 95% confidence interval: 0.06-0.61), which was observed in survival analyses of all patients (P=0.003) and patients treated with chemotherapy but not radiotherapy (P=0.006). Multivariate analysis confirmed XRCC1 as a potential treatment predictor (hazard ratio 0.62; 95% confidence interval: 0.43-0.89). The result was stable upon permutation testing. No other significant associations were observed. CONCLUSION: The DNA repair enzyme XRCC1 is a potential treatment predictor for the outcome and survival of anthracycline and cyclophosphamide/methotrexate/5-fluorouracil-based chemotherapy of invasive breast cancer.
Authors: Tasha R Smith; Wen Liu-Mares; Beth O Van Emburgh; Edward A Levine; Glenn O Allen; Jeff W Hill; Isildinha M Reis; Laura A Kresty; Mark D Pegram; Mark S Miller; Jennifer J Hu Journal: Carcinogenesis Date: 2011-06-23 Impact factor: 4.944
Authors: Jasgit C Sachdev; Saira Ahmed; Muhammad M Mirza; Aamer Farooq; Lori Kronish; Mohammad Jahanzeb Journal: Breast Cancer (Auckl) Date: 2010-05-07
Authors: Petra Seibold; Peter Schmezer; Sabine Behrens; Kyriaki Michailidou; Manjeet K Bolla; Qin Wang; Dieter Flesch-Janys; Heli Nevanlinna; Rainer Fagerholm; Kristiina Aittomäki; Carl Blomqvist; Sara Margolin; Arto Mannermaa; Vesa Kataja; Veli-Matti Kosma; Jaana M Hartikainen; Diether Lambrechts; Hans Wildiers; Vessela Kristensen; Grethe Grenaker Alnæs; Silje Nord; Anne-Lise Borresen-Dale; Maartje J Hooning; Antoinette Hollestelle; Agnes Jager; Caroline Seynaeve; Jingmei Li; Jianjun Liu; Keith Humphreys; Alison M Dunning; Valerie Rhenius; Mitul Shah; Maria Kabisch; Diana Torres; Hans-Ulrich Ulmer; Ute Hamann; Joellen M Schildkraut; Kristen S Purrington; Fergus J Couch; Per Hall; Paul Pharoah; Doug F Easton; Marjanka K Schmidt; Jenny Chang-Claude; Odilia Popanda Journal: BMC Cancer Date: 2015-12-16 Impact factor: 4.430