PAM50 breast cancer intrinsic subtypes and effect of gemcitabine in advanced breast cancer patients

Authors

  • Charlotte L. T. Jørgensen Department of Pathology, Herlev University Hospital, Herlev, Denmark; Danish Breast Cancer Cooperative Group, Copenhagen Ø, Denmark
  • Torsten O. Nielsen Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada
  • Karsten D. Bjerre Danish Breast Cancer Cooperative Group, Copenhagen Ø, Denmark
  • Shuzhen Liu Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada
  • Brett Wallden NanoString Technologies, Seattle, Washington, USA
  • Eva Balslev Department of Pathology, Herlev University Hospital, Herlev, Denmark
  • Dorte L. Nielsen Department of Oncology, Herlev University Hospital, Herlev, Denmark
  • Bent Ejlertsen Danish Breast Cancer Cooperative Group, Copenhagen Ø, Denmark

DOI:

https://doi.org/10.3109/0284186X.2013.865076

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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Published

2014-06-01

How to Cite

Jørgensen, C. L. T., Nielsen, T. O., Bjerre, K. D., Liu, S., Wallden, B., Balslev, E., … Ejlertsen, B. (2014). PAM50 breast cancer intrinsic subtypes and effect of gemcitabine in advanced breast cancer patients. Acta Oncologica, 53(6), 776–787. https://doi.org/10.3109/0284186X.2013.865076

Issue

Vol. 53 No. 6 (2014): Acta Oncologica

Section

Articles