期刊
ANNALS OF ONCOLOGY
卷 19, 期 5, 页码 861-870出版社
ELSEVIER
DOI: 10.1093/annonc/mdm551
关键词
basal-like; breast cancer; high dose chemotherapy; triple negative; breast cancer
类别
Background: This paper evaluates the prognostic and predictive impact of protein expression of various molecular markers in high- risk breast cancer ( HRBC) patients with > 9 involved lymph nodes, who received different chemotherapy dose- intensification strategies within a prospective randomized WSG AM- 01 trial. Materials and methods: Paraffin- embedded tumors from 236 patients, who were randomly assigned to dose-dense conventional chemotherapy with four cycles of E90C600 followed by three cycles of C600M40F600 every 2 weeks ( DD) or a rapidly cycled tandem high- dose regimen with two cycles of E90C600 every 2 weeks followed by two cycles of E90C3000 Thiotepa(400) every 3 weeks ( HD), were available for retrospective central pathological review ( 116 HD/ 120 DD). Expression of estrogen receptor ( ER), progesterone receptor ( PR), MIB- 1, epidermal growth factor receptor, and Her-2/ neu was evaluated immunohistochemically using tissue microarrays. Results were correlated with follow- up data and treatment effects by proportional hazard Cox regression models ( including interaction analysis). Results: After a median follow- up of 61.7 months, 5- year event- free survival ( EFS) as well as overall survival ( OS) rates for the 236 patients were significantly better in the HD arm: EFS: 62% versus 41% [ hazard ratio ( HR) = 0.60, 95% CI 0.43 - 0.85, P = 0.004]; OS: 76% versus 61% ( HR = 0.58, 95% CI 0.39 - 0.87, P = 0.007). In multivariate analysis, HD, tumor size < 3 cm, positive PR, negative MIB- 1 staining, and grade 1/ 2 were associated with favorable outcome. Interaction analysis showed that regarding predictive effects, triple negative ( ER/ PR/ Her- 2/ neu) and G3 tumors derived most benefit from HD. Conclusion: Tandem HD improves both EFS and OS in HRBC. This therapy effect may be partly attributable to superior efficacy in the subgroup of triple- negative tumors and/ or G3 with their poor prognostic marker profile.
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