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

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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.

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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

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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.

Author information

Authors and Affiliations

  1. Department of Surgery, Leiden University Medical Center, P.O. Box 9600 Albinusdreef, 2, 2300 RC, Leiden, The Netherlands

    T. J. A. Dekker, C. J. H. van de Velde, G. W. van Pelt, R. A. E. M. Tollenaar & W. E. Mesker

  2. Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands

    T. J. A. Dekker & J. R. Kroep

  3. Department of Surgery, Centre Henri Becquerel, Rouen, France

    J-P. Julien

  4. Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands

    V. T. H. B. M. Smit

Authors
  1. T. J. A. Dekker
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  2. C. J. H. van de Velde
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  3. G. W. van Pelt
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  4. J. R. Kroep
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  5. J-P. Julien
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  6. V. T. H. B. M. Smit
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  7. R. A. E. M. Tollenaar
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  8. W. E. Mesker
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Corresponding author

Correspondence to T. J. A. Dekker.

Additional information

C. J. H. van de Velde, Principal investigator EORTC trial 10854 (POP trial).

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Dekker, T.J.A., van de Velde, C.J.H., van Pelt, G.W. et al. Prognostic significance of the tumor-stroma ratio: validation study in node-negative premenopausal breast cancer patients from the EORTC perioperative chemotherapy (POP) trial (10854). Breast Cancer Res Treat 139, 371–379 (2013). https://doi.org/10.1007/s10549-013-2571-5

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  • DOI: https://doi.org/10.1007/s10549-013-2571-5

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