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


CONCLUSIONS
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.
Department of Clinical Oncology, Leiden University Medical Center, The Netherlands; Department of Surgery, Leiden University Medical Center, The Netherlands.
T J A
TJ
Dekker
Department of Clinical Oncology, Leiden University Medical Center, The Netherlands; Department of Surgery, Leiden University Medical Center, The Netherlands.
A
A
Charehbili
Department of Pathology, Leiden University Medical Center, The Netherlands.
V T H B M
VT
Smit
Department of Molecular Cell Biology and Cancer Genomics Centre Netherlands, Leiden University Medical Center, The Netherlands; Ludwig Institute for Cancer Research, Uppsala, Sweden.
P
P
ten Dijke
Department of Surgery, Leiden University Medical Center, The Netherlands.
E Meershoek-Klein
EM
Kranenbarg
Department of Surgery, Leiden University Medical Center, The Netherlands.
C J H
CJ
van de Velde
Department of Clinical Oncology, Leiden University Medical Center, The Netherlands.
J W R
JW
Nortier
Department of Surgery, Leiden University Medical Center, The Netherlands.
R A E M
RA
Tollenaar
Department of Surgery, Leiden University Medical Center, The Netherlands.
W E
WE
Mesker
Department of Clinical Oncology, Leiden University Medical Center, The Netherlands. Electronic address: j.r.kroep@lumc.nl.
J R
JR
Kroep
D001706:Biopsy; D001943:Breast Neoplasms / Q000473:pathology* / Q000628:therapy*; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy
Breast cancer; Neoadjuvant; Organisation; Stroma; TGF-B