Breast Cancer Research and Treatment

, Volume 139, Issue 2, pp 371–379 | Cite as

Prognostic significance of the tumor-stroma ratio: validation study in node-negative premenopausal breast cancer patients from the EORTC perioperative chemotherapy (POP) trial (10854)

  • T. J. A. Dekker
  • C. J. H. van de Velde
  • G. W. van Pelt
  • J. R. Kroep
  • J-P. Julien
  • V. T. H. B. M. Smit
  • R. A. E. M. Tollenaar
  • W. E. Mesker
Preclinical study


The tumor-stroma ratio has previously been shown to be prognostic for patients with invasive breast cancer. We present a validation study to assess the prognostic significance in lymph node-negative, premenopausal patients from the perioperative chemotherapy trial (POP trial, 10854) conducted by the European Organization for Research and Treatment of Cancer. The POP trial assessed the efficacy of one course of perioperative chemotherapy (consisting of fluorouracil, doxorubicin, and cyclophosphamide). Hematoxylin and eosin (H&E) stained sections were retrieved from a subset of premenopausal, node-negative patients from this trial and were scored for the percentage of intra-tumoral stroma. The tumor-stroma ratio was associated with disease-free survival in univariate and multivariate analysis. Tumors with a high tumor-stroma ratio had an increased hazard of 1.853 for disease relapse (95 %CI 1.327–2.585, P < 0.001) independent of other parameters. Combining other parameters with the tumor-stroma ratio improved risk stratification. For triple-negative tumors, the tumor-stroma ratio was associated with an increased hazard for disease relapse, independent of other parameters (HR 2.711, 95 %CI 1.111–6.614, P = 0.028). The tumor-stroma ratio was also independently associated with locoregional recurrence even in breast cancer patients ≤40 years of age (HR 2.201, 95 %CI 1.038–4.669, P = 0.040). This study validates the prognostic value of the tumor-stroma ratio. This parameter can be easily assessed on HE slides and can be implemented next to pathological staging reports to determine patient prognosis.


Breast cancer Tumor-stroma Prognosis Node-negative Pre-menopausal Validation study 



Hematoxylin and eosin


Estrogen receptor


Progesterone receptor


Human epidermal growth factor receptor 2


Microvessel density


Disease-free survival


Overall survival


Locoregional recurrence


European organization for research and treatment of cancer


Transforming growth factor-β


Cluster of differentiation


Matrix metalloproteinase


Extracellular matrix


Hazard ratio 95 %CI, 95 % confidence interval


Ductal carcinoma in situ


Lobular carcinoma in situ



The tumor material that was used for the analysis in this study was collected as part of a trial by the EORTC. We, therefore, gratefully acknowledge the EORTC, the enrolled patients, and investigators at local centers who collected the material.

Conflict of interests

The authors report no conflicts of interests.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • T. J. A. Dekker
    • 1
    • 2
  • C. J. H. van de Velde
    • 1
  • G. W. van Pelt
    • 1
  • J. R. Kroep
    • 2
  • J-P. Julien
    • 3
  • V. T. H. B. M. Smit
    • 4
  • R. A. E. M. Tollenaar
    • 1
  • W. E. Mesker
    • 1
  1. 1.Department of SurgeryLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Department of Clinical OncologyLeiden University Medical CenterLeidenThe Netherlands
  3. 3.Department of SurgeryCentre Henri BecquerelRouenFrance
  4. 4.Department of PathologyLeiden University Medical CenterLeidenThe Netherlands

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