280P - Copy number of centromere of chromosome 17 (CEP17) as predictor of benefit for adjuvant anthracycline for breast cancer: Systematic review with met...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Breast Cancer, Early Stage
Pathology/Molecular Biology
Presenter João Paulo Lima
Citation Annals of Oncology (2014) 25 (suppl_4): iv85-iv109. 10.1093/annonc/mdu327
Authors J.P. Lima1, D.N. Rodrigues2, R. Canario3, L.V. Dos Santos4
  • 1Medical Oncology, The Royal Marsden Hospital, sm2 5pt - London/GB
  • 2Prostate Cancer Targeted Therapy Group And Drug Development Unit, Institute of Cancer Research, sm2 5pt - Surrey/GB
  • 3Medical Oncology, Portuguese Oncology Institute of Coimbra, 3000-075 - Coimbra/PT
  • 4Medical Oncology Department, Hemomed Institute, Sao Paulo/BR



The high efficacy of anthracyclines made them the backbone of adjuvant therapy for early breast cancer (EBC), in spite their relevant toxicity. Considering anthracyclines challenge chromosome stability, tumours harbouring chromosomal instability (CIN) may be more sensitive to them. Changes CEP17, which also harbours relevant cancer genes (BRCA1, P53, ERBB2), have been suggested as a surrogate of CIN. We sought to evaluate the role of CEP17 copy number as a biomarker.


We searched electronic databases and meeting proceeding for randomised controlled trials (RCTs) comparing anthracycline-based versus anthracycline-free adjuvant therapy for EBC. RCTs presenting outcomes of tumours with normal CEP17 and duplication CEP17 were included. We calculated hazard ratios for disease-free survival (DFS) and overall survival (OS), and pertinent confidence intervals (95% CI) using random-effects model. Results across CEP17 groups were compared using interaction test. Heterogeneity was expressed by I2 test.


Three trials enrolled a total of 4117 patients (pts), comparing CMF versus anthracycline plus CMF met inclusion criteria. Each of these three trials had positive results in terms of OS or DFS for their entire population. A total of 2390 patients had CEP17 tumour assessed and their clinical features were similar to general population. CEP17 number was not a prognostic marker; however it had a strong effect on outcomes (table).

Pts HR (95%CI) P-value P for interaction
Normal CEP17 1731 0.99 [0.78-1.24] 0.91 0.02
Duplicated CEP17 659 0.58 [0.40-0.85] 0.005
Normal CEP17 1731 0.94 [0.76-1.16] 0.57 0.0009
Duplicated CEP17 659 0.54 [0.38-0.77] 0.0007


CEP17 seemed to identify patient who derive benefit from anthracycline therapy. These findings merit further assessment and validation in other scenarios as in taxane combination and anti-her2 therapy. Mechanisms underlying this relationship must be better understood and explored.


All authors have declared no conflicts of interest.