BACKGROUND AND PURPOSE: We analyzed the clinical outcome of breast cancer patients carrying sequence variants in the ATM gene who received postoperative radiotherapy after breast conservative surgery to test whether an increased cellular radiosensitivity may translate into enhanced tumor cell killing and thereby result in an improvement of the therapeutic ratio. PATIENTS AND METHODS: We investigated a cohort of 138 breast cancer patients who received adjuvant radiotherapy following breast conservative surgery for T1 and T2 tumors. Genomic DNA samples of these patients had previously been scanned for mutations in the ATM gene. Follow-up data were available in 135 patients, with a median follow-up of 87 months. Local relapse-free, metastasis-free and overall survival were compared between carriers and non-carriers of a sequence variant in the ATM gene. RESULTS: Twenty patients were found to carry a sequence variant in the ATM gene (truncating, 7; missense, 13). The actuarial 7-year local relapse-free survival of carriers vs. non-carriers were 88 vs. 94% (P=0.34). Actuarial metastasis-free and overall survival after 7 years were 63 vs. 85% (P=0.01) and 73 vs. 89% (P=0.055), respectively. However, the presence of a variant in the ATM gene did not remain a significant discriminator for metastasis-free survival in a multivariate Cox regression analysis (P=0.068). CONCLUSIONS: Our results do not support the hypothesis that breast cancer patients carrying a sequence variant in the ATM gene differentially benefit from postoperative radiotherapy. These findings have to be verified using larger number of cases to clarify the clinical consequences of sequence variants in the ATM gene.
BACKGROUND AND PURPOSE: We analyzed the clinical outcome of breast cancerpatients carrying sequence variants in the ATM gene who received postoperative radiotherapy after breast conservative surgery to test whether an increased cellular radiosensitivity may translate into enhanced tumor cell killing and thereby result in an improvement of the therapeutic ratio. PATIENTS AND METHODS: We investigated a cohort of 138 breast cancerpatients who received adjuvant radiotherapy following breast conservative surgery for T1 and T2 tumors. Genomic DNA samples of these patients had previously been scanned for mutations in the ATM gene. Follow-up data were available in 135 patients, with a median follow-up of 87 months. Local relapse-free, metastasis-free and overall survival were compared between carriers and non-carriers of a sequence variant in the ATM gene. RESULTS: Twenty patients were found to carry a sequence variant in the ATM gene (truncating, 7; missense, 13). The actuarial 7-year local relapse-free survival of carriers vs. non-carriers were 88 vs. 94% (P=0.34). Actuarial metastasis-free and overall survival after 7 years were 63 vs. 85% (P=0.01) and 73 vs. 89% (P=0.055), respectively. However, the presence of a variant in the ATM gene did not remain a significant discriminator for metastasis-free survival in a multivariate Cox regression analysis (P=0.068). CONCLUSIONS: Our results do not support the hypothesis that breast cancerpatients carrying a sequence variant in the ATM gene differentially benefit from postoperative radiotherapy. These findings have to be verified using larger number of cases to clarify the clinical consequences of sequence variants in the ATM gene.
Authors: Kathleen Claes; Julie Depuydt; A Malcolm R Taylor; James I Last; Annelot Baert; Peter Schietecatte; Veerle Vandersickel; Bruce Poppe; Kim De Leeneer; Marc D'Hooghe; Anne Vral Journal: Neuromolecular Med Date: 2013-04-30 Impact factor: 3.843