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Clinical Trial
. 2015 Jun;9(6):1120-8.
doi: 10.1016/j.molonc.2015.02.001. Epub 2015 Feb 14.

Disorganised stroma determined on pre-treatment breast cancer biopsies is associated with poor response to neoadjuvant chemotherapy: Results from the NEOZOTAC trial

T J A Dekker  1 , A Charehbili  1 , V T H B M Smit  2 , P ten Dijke  3 , E Meershoek-Klein Kranenbarg  4 , C J H van de Velde  4 , J W R Nortier  5 , R A E M Tollenaar  4 , W E Mesker  4 , J R Kroep  6
Affiliations
Clinical Trial

Disorganised stroma determined on pre-treatment breast cancer biopsies is associated with poor response to neoadjuvant chemotherapy: Results from the NEOZOTAC trial

T J A Dekker et al. Mol Oncol. 2015 Jun.

Abstract

Introduction: The tumor-associated stroma is of importance for tumor progression and is generally accepted to have a significant influence on patient prognosis. However, little is known regarding specific features of tumor-associated stromal tissues and response to (neoadjuvant) chemotherapy. This study investigated the predictive value of extracellular matrix organization on response to chemotherapy in patients treated in the NEOZOTAC trial.

Methods: Stromal organisation was analyzed via a simple method using image analysis software on hematoxylin and eosin (H&E)-stained slides from primary tumor biopsies collected as part of the NEOZOTAC trial. Heidenhain's AZAN trichrome-stained slides were also analyzed for comparison of collagen evaluation. Sections were stained for phospho-Smad2 (pS2) in order to determine the relationship of TGF-β signaling with stromal organization.

Results: A statistically significant relationship was observed between stroma consisting of organised collagen and pathological response to neoadjuvant chemotherapy (Odds Ratio 0.276, 95%CI 0.124-0.614, P = 0.002). This parameter was also related to ER-status (P = 0.003), clinical tumor -status (P = 0.041), nodal status (P = 0.029) and pS2 status (P = 0.025). Correlation between stromal organisation determined on H&E-stained and AZAN-stained tissue sections was high (Pearson's correlation coefficient = 0.806).

Conclusion: Intratumoral stromal organisation determined using pre-treatment breast cancer biopsies was related to pathological response to chemotherapy. This parameter might play a role in the management of breast cancer for identifying those patients that are likely to benefit from neoadjuvant chemotherapy.

Keywords: Breast cancer; Neoadjuvant; Organisation; Stroma; TGF-B.

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Figures

Figure 1
Figure 1
A: example of breast tumor biospy with linearly aligned stroma. B: example of breast tumor biospy with disorganised stroma.
Figure 2
Figure 2
Example of the trichrome AZAN‐staining for collagen fibers.
Figure 3
Figure 3
Correlation between pS2 immunostaining and stromal alignment.
See this image and copyright information in PMC

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