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Eribulinmesilate is shown to suppress epithelial–mesenchymal
transition in tumours of patients withmetastatic breast cancer
E
ribulin mesilate has been shown to
suppress epithelial–mesenchymal
transition in tumours of patients with
metastatic breast cancer.
This was the finding of the first prospec-
tive investigation of the effect of eribulin on
expression of epithelial–mesenchymal transi-
tion markers in tumours from patients with
metastatic breast cancer.
Toshiaki Utsumi, MD, of Fujita Health
University, Toyoake, Japan, explained that
recent evidence suggests that epithelial–mesenchymal transition contributes to
metastasis in patients with breast cancer and
leads to poor prognosis. Pivotal phase III tri-
als have shown that eribulin improved overall
survival in patients with triple-negative met-
astatic breast cancer.
“Preclinical studies have demonstrated that
eribulin suppressed epithelial–mesenchymal
transition,” Dr Utsumi said. “This phenome-
non could be one of the underlying reasons
for the improved prognosis of patients with
metastatic breast cancer treated with eribu-
lin. No direct clinical data, however, exists on
the effect of eribulin treatment on epithelial–
mesenchymal transition in tumours of
patients with metastatic breast cancer.”
He added, “So we designed a prospective
study to clarify whether eribulin suppresses
epithelial–mesenchymal transition in tumours
of patients with metastatic breast cancer.”
Patients with recurrent or metastatic breast
cancer were treated with eribulin 1.4 mg/m
2
intravenously on days 1 and 8 of a 21-day
cycle. Treatment continued until disease
progression, unacceptable toxic effects, or
discontinuation request from patients or
physicians.
Breast cancer tissue samples were obtained
from patients before and on day 15 of the
first cycle of eribulin treatment. Epithelial–
mesenchymal markers (E-cadherin, claudin,
N-cadherin, vimentin) were analysed by
western blot. Change in protein expression
from baseline to day 15 ± 4 in epithelia–mesenchymal transition-related markers in
tumour tissue was assessed.
Eleven patients were enrolled. Median
patient age was 63 (44–72) years. Of the
11 tumours, six were luminal B and five tri-
ple-negative. Zero (0–3) prior chemotherapy
regimens had been administered for recurrent
or metastatic disease.
After treatment, E-cadherin protein levels
were increased in seven tumours (63.6%),
unchanged in one tumour (9.1%), and
decreased in three (27.3%).
Claudin protein levels were increased in
eight tumours (72.7%) and decreased in three
tumours (27.3%).
Vimentin protein levels were increased in two
tumours (18.2%), unchanged in one tumour
(9.1%), and decreased in eight (72.7%).
N-cadherin protein levels were increased
in one tumour (9.1%), unchanged in four
tumours (36.4%), and decreased in six
tumours (54.5%).
Dr Utsumi concluded that the study demon-
strated that eribulin treatment suppressed the
epithelial–mesenchymal transition in tumours
from patients with metastatic breast cancer.
The results suggested that eribulin showed
antitumour activity by improving the tumour
microenvironment. The finding may provide
a scientific basis of underlying mechanisms
for improvement of overall survival of patients
with metastatic breast cancer treated with
eribulin.
Dr Utsumi added, “We cannot completely
confirm that eribulin suppress the epithelial–
mesenchymal transition in tumours, because
the study was small and is still ongoing. But,
I think our preliminary results have shown
that eribulin can potentially suppress the
epithelial–mesenchymal transition. I base
this conclusion on the observation that
after eribulin treatment, epithelial makers
were increased and mesenchymal markers
decreased in two thirds of tumours.”
“We hope to further study eribulin in an effort
to understand its mechanism of anticancer
effect.”
PracticeUpdate Editorial Team
laboratory tests and ultrasonography, con-
trast-enhanced CT scanning, and MRI
scanning was 42 months (3.5 years). No
deterioration in renal function was observed
postoperatively.
Dr Cuni concluded that appropriate patient
selection criteria and surgical techniques are
important for satisfactory functional long-
term outcome of nephron-sparing surgery.
Open nephron-sparing surgery and laparo-
scopic radical nephrectomy are relatively
recent, significant developments for treat-
ing renal tumours and represent acceptable
standards of care in cases of small renal mass
and normal contralateral kidney.
Nephron-sparing surgery has become a
modality of choice in Dr Cuni’s centre for
patients with renal tumour size <4 cm. The
present data suggest that nephron-sparing
surgery can be performed safely and with
maximum preservation of renal function.
PracticeUpdate Editorial Team
© ECCO2017 European Cancer Congress
ECCO2017
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VOL. 2 • NO. 2 • 2017