Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2017

01-11-2017 | Preclinical study

The prognostic value of the tumour-stroma ratio in primary operable invasive cancer of the breast: a validation study

Authors: Toni Roeke, Marcelo Sobral-Leite, Tim J. A. Dekker, Jelle Wesseling, Vincent T. H. B. M. Smit, Rob A. E. M. Tollenaar, Marjanka K. Schmidt, Wilma E. Mesker

Published in: Breast Cancer Research and Treatment | Issue 2/2017

Login to get access

Abstract

Purpose

The primary aim of the current study is to validate the prognostic relevance of the relative amount of tumour-associated stroma, the tumour-stroma ratio, in a large cohort of primary operable breast cancer patients.

Methods

A retrospective cohort study was performed on women diagnosed and treated for primarily operable invasive breast cancer in the period from 1 January 1990 till 31 December 1999. Tumour-stroma ratio was estimated by microscopic evaluation of haematoxylin and eosin tumour slides. Two independent observers (k = 0.68) performed tumour-stroma ratio evaluation in a significant part of the cohort. The prognostic potential with respect to overall, recurrence-free and distant metastasis-free survival was evaluated.

Results

A total of n = 737 women were evaluated. Median follow-up time was 11.5 years. High stromal content was an independent prognosticator for worse overall (hazard ratio 1.56, p = 0.002, 95% confidence interval 1.18–2.05), distant metastasis-free (hazard ratio 1.52, p = 0.008, 95% confidence interval 1.12–2.06) and recurrence-free survival (hazard ratio 1.35, p = 0.046, 95% confidence interval 1.01–1.81). In subgroups of hormone receptor-positive and lymph node-negative cases, high stromal content was also an independent prognosticator for worse outcome.

Conclusion

Tumour-stroma ratio is an independent risk factor for worse overall, distant metastasis-free and recurrence-free survival in primarily operable breast cancer. However, detailed prospective studies with respect to tumour-stroma ratio are necessary to gain more insight in its prognostic potential in clinical practice.
Appendix
Available only for authorised users
Literature
1.
Ferlay J, Soerjomataram I, Ervik M et al. (2013) GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase no. 11. Lyon, France, International Agency for Research on Cancer
2.
Engstrom MJ, Opdahl S, Hagen AI et al (2013) Molecular subtypes, histopathological grade and survival in a historic cohort of breast cancer patients. Breast Cancer Res Treat 140(3):463–473CrossRefPubMedPubMedCentral
3.
Soerjomataram I, Louwman MW, Ribot JG, Roukema JA, Coebergh JW (2008) An overview of prognostic factors for long-term survivors of breast cancer. Breast Cancer Res Treat 107(3):309–330CrossRefPubMed
4.
Pietras K, Ostman A (2010) Hallmarks of cancer: interactions with the tumor stroma. Exp Cell Res 316(8):1324–1331CrossRefPubMed
5.
6.
de Kruijf EM, Sajet A, van Nes JG et al (2010) HLA-E and HLA-G expression in classical HLA class I-negative tumors is of prognostic value for clinical outcome of early breast cancer patients. J Immunol 185(12):7452–7459CrossRefPubMed
7.
Mesker WE, Liefers GJ, Junggeburt JM et al (2009) Presence of a high amount of stroma and downregulation of SMAD4 predict for worse survival for stage I-II colon cancer patients. Cell Oncol 31(3):169–178PubMedPubMedCentral
8.
Witkiewicz AK, Whitaker-Menezes D, Dasgupta A et al (2012) Using the “reverse Warburg effect” to identify high-risk breast cancer patients: stromal MCT4 predicts poor clinical outcome in triple-negative breast cancers. Cell Cycle 11(6):1108–1117CrossRefPubMedPubMedCentral
9.
Tchou J, Conejo-Garcia J (2012) Targeting the tumor stroma as a novel treatment strategy for breast cancer: shifting from the neoplastic cell-centric to a stroma-centric paradigm. Adv Pharmacol 65:45–61CrossRefPubMed
10.
Finak G, Bertos N, Pepin F et al (2008) Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 14(5):518–527CrossRefPubMed
11.
Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315(26):1650–1659CrossRefPubMed
12.
13.
Dekker TJ, Balluff BD, Jones EA et al (2014) Multicenter matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) identifies proteomic differences in breast-cancer-associated stroma. J Proteome Res 13:4730–4738CrossRefPubMed
14.
Mesker WE, Junggeburt JM, Szuhai K et al (2007) The carcinoma-stromal ratio of colon carcinoma is an independent factor for survival compared to lymph node status and tumor stage. Cell Oncol 29(5):387–398PubMedPubMedCentral
15.
de Kruijf EM, van Nes JG, van de Velde CJ et al (2011) Tumor-stroma ratio in the primary tumor is a prognostic factor in early breast cancer patients, especially in triple-negative carcinoma patients. Breast Cancer Res Treat 125(3):687–696CrossRefPubMed
16.
Dekker TJ, van de Velde CJ, van Pelt GW et al (2013) 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(2):371–379CrossRefPubMed
17.
Gujam FJ, Edwards J, Mohammed ZM, Going JJ, McMillan DC (2014) The relationship between the tumour stroma percentage, clinicopathological characteristics and outcome in patients with operable ductal breast cancer. Br J Cancer 111(1):157–165CrossRefPubMedPubMedCentral
18.
Moorman AM, Vink R, Heijmans HJ, van der Palen J, Kouwenhoven EA (2012) The prognostic value of tumour-stroma ratio in triple-negative breast cancer. Eur J Surg Oncol 38(4):307–313CrossRefPubMed
19.
Blamey RW, Hornmark-Stenstam B, Ball G et al (2010) ONCOPOOL—A European database for 16,944 cases of breast cancer. Eur J Cancer 46(1):56–71CrossRefPubMed
20.
Alkushi A (2009) Validation of tissue microarray biomarker expression of breast carcinomas in Saudi women. Hematol Oncol Stem Cell Ther 2(3):394–398CrossRefPubMed
21.
Bhargava R, Lal P, Chen B (2004) Feasibility of using tissue microarrays for the assessment of HER-2 gene amplification by fluorescence in situ hybridization in breast carcinoma. Diagn Mol Pathol 13(4):213–216CrossRefPubMed
22.
Glajcar A, Kaczmarczyk K, Szpor J, Okon K (2013) Application of tissue microarrays for receptor immunohistochemistry in breast carcinoma. Folia Histochem Cytobiol 51(4):326–332CrossRefPubMed
23.
Gulbahce HE, Gamez R, Dvorak L, Forster C, Varghese L (2012) Concordance between tissue microarray and whole-section estrogen receptor expression and intratumoral heterogeneity. Appl Immunohistochem Mol Morphol 20(4):340–343CrossRefPubMed
24.
Downey CL, Simpkins SA, White J et al (2014) The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer. Br J Cancer 110(7):1744–1747CrossRefPubMedPubMedCentral
25.
West NP, Dattani M, McShane P et al (2010) The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients. Br J Cancer 102(10):1519–1523CrossRefPubMedPubMedCentral
26.
Mesker WE, Dekker TJ, de Kruijf EM et al (2014) Comment on: the prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer. Br J Cancer 112(11):1833–1834
27.
28.
29.
Gabrielson M, Chiesa F, Paulsson J, Strell C et al (2016) Amount of stroma is associated with mammographic density and stromal expression of oestrogen receptor in normal breast tissues. Breast Cancer Res Treat 158:253–261CrossRefPubMed
30.
Lisanti M, Tsirigos A, Pavlides S et al (2014) JNK1 stress signaling is hyper-activated in high breast density and the tumor stroma: connecting fibrosis, inflammation, and stemness for cancer prevention. Cell Cycle 13(4):580–599CrossRefPubMed
Metadata
Title
The prognostic value of the tumour-stroma ratio in primary operable invasive cancer of the breast: a validation study
Authors
Toni Roeke
Marcelo Sobral-Leite
Tim J. A. Dekker
Jelle Wesseling
Vincent T. H. B. M. Smit
Rob A. E. M. Tollenaar
Marjanka K. Schmidt
Wilma E. Mesker
Publication date
01-11-2017
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4445-8

Other articles of this Issue 2/2017

Breast Cancer Research and Treatment 2/2017 Go to the issue

Rebuttal Letter

Rebuttal comments

Clinical trial

Impact of pathologic diagnosis of internal mammary lymph node metastasis in clinical N2b and N3b breast cancer patients

Epidemiology

Tamoxifen therapy benefit for patients with 70-gene signature high and low risk

Review

Meta-analysis of tumour burden in pre-operative axillary ultrasound positive and negative breast cancer patients

Epidemiology

Trends in adjuvant therapies after breast-conserving surgery for hormone receptor-positive ductal carcinoma in situ: findings from the National Cancer Database, 2004–2013

Epidemiology

FOXA1 hypermethylation: link between parity and ER-negative breast cancer in African American women?
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits