Correlation of MYC Gene and Protein Status With Breast Cancer Subtypes and Outcome of Patients Treated With Anthracycline-Based Adjuvant Chemotherapy. Pooled Analysis of 2 Hellenic Cooperative Group Phase III Trials

摘要

BackgroundThe prognostic/predictive value of aberrant MYC gene copies and protein expression is not clear in breast cancer. Patients and MethodsEarly breast cancer patients were treated with anthracycline-containing chemotherapy within 2 randomized adjuvant trials.MYCgene and centromere-8 status, as well as Myc protein expression were investigated on 1060 paraffin tumors with fluorescence in situ hybridization and immunohistochemistry, respectively. ResultsMYCamplification was present in 45% and polysomy-8 in 23% of the tumors. Cytoplasmic staining was observed in 60% and nuclear staining in 26% of the tumors, strongly correlating with each other but not withMYCgene status.MYCgene amplification in the absence of polysomy-8 was associated with adverse disease-free survival (DFS) and overall survival (OS), and remained as an independent unfavorable prognostic factor in multivariate analysis (WaldP?= .022 for DFS;P?= .032 for OS), whereas patients withMYCamplification and polysomy-8, with polysomy-8 only, and with normalMYCwithout polysomy-8 performed significantly better compared with those withMYCgene amplification only. Nuclear Myc protein expression benefitted patients treated with paclitaxel (interactionP?= .052 for DFS;P?= .049 for OS). This interaction remained independently significant in multivariate analysis for OS (overallP?= .028). ConclusionThe effect ofMYCgene status on breast cancer patient outcome seems to depend on the underlying chromosomal instability and appears unfavorable for tumors withMYCamplification without polysomy. Nuclear Myc protein expression seems predictive for benefit from adjuvant paclitaxel. These data might aid in the interpretation of relevant findings from large clinical trials.