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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

Abstract

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.

Keywords

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

Abbreviations

H&E

Hematoxylin and eosin

ER

Estrogen receptor

PgR

Progesterone receptor

HER2

Human epidermal growth factor receptor 2

MVD

Microvessel density

DFS

Disease-free survival

OS

Overall survival

LRR

Locoregional recurrence

EORTC

European organization for research and treatment of cancer

TGF-β

Transforming growth factor-β

CD

Cluster of differentiation

MMP

Matrix metalloproteinase

ECM

Extracellular matrix

HR

Hazard ratio 95 %CI, 95 % confidence interval

DCIS

Ductal carcinoma in situ

LCIS

Lobular carcinoma in situ

Notes

Acknowledgments

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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