Abstract | BACKGROUND: In vitro studies suggest basal breast cancers are more sensitive to gemcitabine relative to other intrinsic subtypes. The main objective of this study was to use specimens from a randomized clinical trial to evaluate whether the basal-like subtype identifies patients with advanced breast cancer who benefit from gemcitabine plus docetaxel (GD) compared to single agent docetaxel (D). MATERIAL AND METHODS: From patients randomly assigned to GD or D, RNA was isolated from archival formalin-fixed, paraffin-embedded primary breast tumor tissue and used for PAM50 intrinsic subtyping by NanoString nCounter. Statistical analyses were prespecified as a formal prospective-retrospective clinical trial correlative study. Using time to progression ( TTP) as primary endpoint, overall survival (OS) and response rate as secondary endpoints, relationships between subtypes and outcome after chemotherapy were analyzed by the Kaplan-Meier method, and Cox proportional hazards regression models. Data analysis was performed independently by the Danish Breast Cancer Cooperative Group (DBCG) statistical core and all statistical tests were two-sided. RESULTS:
RNA from 270 patients was evaluable; 84 patients (31%) were classified as luminal A, 97 (36%) luminal B, 43 (16%) basal-like, and 46 (17%) as HER2-enriched. PAM50 intrinsic subtype was a significant independent prognostic factor for both TTP (p=0.014) and OS (p=0.0003). Response rate was not different by subtype, and PAM50 was not a predictor of TTP by treatment arm. PAM50 was however a highly significant predictor of OS following GD compared to D (pinteraction=0.0016). Patients with a basal-like subtype had a significant reduction in OS events [hazard ratio (HR)=0.29, 95% confidence interval (CI)=0.15-0.57; pinteraction=0.0006]. CONCLUSION: A significantly improved and clinically important prolongation of survival was seen from the addition of gemcitabine to docetaxel in advanced basal-like breast cancer patients.
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Authors | Charlotte L T Jørgensen, Torsten O Nielsen, Karsten D Bjerre, Shuzhen Liu, Brett Wallden, Eva Balslev, Dorte L Nielsen, Bent Ejlertsen |
Journal | Acta oncologica (Stockholm, Sweden)
(Acta Oncol)
Vol. 53
Issue 6
Pg. 776-87
(Jun 2014)
ISSN: 1651-226X [Electronic] England |
PMID | 24359601
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- RNA, Messenger
- Taxoids
- Deoxycytidine
- Docetaxel
- Gemcitabine
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Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Breast Neoplasms
(drug therapy, genetics, pathology)
- Carcinoma
(drug therapy, genetics, pathology)
- Deoxycytidine
(administration & dosage, analogs & derivatives)
- Docetaxel
- Female
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Humans
- Middle Aged
- Multivariate Analysis
- Proportional Hazards Models
- RNA, Messenger
(analysis)
- Taxoids
(administration & dosage)
- Gemcitabine
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