Publication: Novel biomarkers in primary breast core biopsies to predict poor response to neoadjuvant chemotherapy and appearance of metastases
Authors
Novell, Anna ; Morales, Serafin ; Valls, Joan ; Panadés, Maria José ; Salud, Antonieta ; Iglesias, Edelmiro ; Vilardell, Felip ; Matias Guiu, Xavier ; Llombart Cussac, Antonio
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Publisher
Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
DOI: 10.14670/HH-11-849
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info:eu-repo/semantics/article
Description
Abstract
Drug resistance has been one of the major
obstacles limiting the success of cancer chemotherapy.
In two thirds of breast cancer patients, large (>1cm)
residual tumors are present after neoadjuvant
chemotherapy (NCT). The residual tumor and involved
nodes have been indicators of relapse and survival very
important in breast cancer.
The goal of this preliminary study was to assess the
predictive significance of a panel of molecular
biomarkers, related with the response to treatment or
drug resistance to NCT, as determined on the diagnostic
tumor. The expression of 22 proteins was examined
using immunohistochemistry in tissue microarrays
(TMA) from 115 patients of stage II-III breast cancer,
treated with NCT. Among studied proteins, there are
some that are anti-apoptotic, pro-proliferative, cancer
stem cell markers and the Vitamin D Receptor. Other
proteins are involved in the identification of molecular
subtype, cell cycle regulation or DNA repair. Next, a
predictive signature of poor response was generated
from independent markers of predictive value. Tumors
that expressed four or five conditions (biomarkers of
chemoresistance with a determinated cutoff) were
associated with a 9-fold increase in the chances of these
patients of having a poor response to NCT. Additionally,
we also found a worse prognostic signature, generated
from independent markers of prognostic value. Tumors
which expressed two or three conditions of worst
prognostic, were associated with a 6-fold reduction in
Distant Disease Free Survival. In conclusion, finding
biomarkers of chemoresitance (ypTNM II-III) and
metastases can become a stepping stone for future
studies that will need to be assessed in a bigger scale.
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