Triple-negative breast cancer

Abstract

Recent advances in biological characterization of breast cancer have eventually increased our understanding of underlying tumour biology. While for endocrine responsive and Her2-positive disease different molecular targeted therapies are available, up to now no specific targeted approach for triple-negative breast cancer has been developed. Patients with triple-negative disease are at high risk for tumour recurrence. Preclinical and limited clinical data suggest that platinum-based regimens may be the most active conventional chemotherapy, but prospective randomized trials are missing. Bevacizumab and other agents targeting tumour vessel growth have potential activity in all subtypes of breast cancer, and therefore are not considered a targeted approach for triple-negative tumours alone. Due to specific defects in DNA-damage repair, basal-like cancers depend on alternative, more error-prone repair pathways. Currently, scientific interest is focussing on drugs blocking those mechanisms. PARP-1 inhibitors, in conjunction with platinum derivatives, were found to exhibit significant survival benefit over chemotherapy alone even in a relatively small phase II study. For the first time, this approach offers the chance of highly active, specific therapy for triple-negative disease.

Poly(ADP-ribose) polymerase inhibition: a new direction for BRCAand triple-negative breast cancer?

“…Following encouraging results with iniparib in combination with chemotherapy with various solid tumours [39], clinical investigators have gone on to study this agent with chemotherapy in TNBC, a disease with a biological phenotype similar to BRCA1 -defective cancers [40]. It must be borne in mind that iniparib may act via a different mechanism to the PARP inhibitors discussed above, and does not appear to have the limitation of enhanced toxicity in normal tissue [39,41,42].…”

Optimized Protocol for Protein Extraction from the Breast Tissue that is Compatible with Two-Dimensional Gel Electrophoresis

“…They control many different and important functions related to the cell proliferation, differentiation and death. Changes in the protein expression and structure affect protein’s functions 1. A number of reports have shown that even small changes in protein functions may lead to a disease development 2.…”

DNA Repair, Cancer and Cancer Therapy - The Current State of Art

“…Thus, PARP1 inhibitors potentiate the effect of platinum compounds (Bartsch et al, 2010). PARP-1 inhibitors, in conjunction with platinum derivatives, were found to exhibit significant survival benefit over monotherapy in a relatively small phase II study.…”

“…In this study, data were reported from a randomized phase II study of combination chemotherapy with carboplatin and gemcitabine with or without PARP1 inhibitor (BSI-201) in patients with triple negative breast cancer (O'Shaughnessy et al, 2009). In combined chemotherapy, PARP-inhibition is highly attractive, as carboplatin will cause DNA strand-breaks while BSI-201 will block PARP1-dependent repair (Bartsch et al, 2010). BSI-201 is currently in phase III clinical trials for breast cancer and squamous cell lung cancer therapy in combination with gemcitabine/carboplatin.…”