The Prognostic Significance of Hsp70/Hsp90 Expression in Breast Cancer: A Systematic Review and Meta-analysis

Abstract

Studies have focused on heat shock protein (Hsp) inhibitors as potential treatment agents in breast cancer, with controversial results. Adopting a pathophysiological perspective, this systematic review aims to synthesize the evidence examining the association between Hsp70/Hsp90 expression and breast cancer prognosis, as well as prognosis-related clinicopathological indices. Secondarily, changes in Hsp70/Hsp90 expression in the continuum of breast neoplasia were assessed. Hsp70/Hsp90 expression was approached globally, quantified by means of immunohistochemistry, western blot or PCR. This study was performed in accordance with the PRISMA guidelines. Relevant studies were sought in PubMed, up to December 31, 2015. A total of 23 eligible studies were identified (7,288 breast cancer cases). High Hsp90 expre s sion was associated with worse overall survival (pooled RR=1.48, 95%CI=1.21-1.82) and marginally with worse disease-free survival. High Hsp70 expression also correlated with worse disease-free survival (pooled RR=1.77, 95%CI=1.71-2.82). Hsp70 intense expression correlated with ER positivity (pooled OR=3.51, 95%CI=1.31-9.40) and PR positivity (pooled OR=2.48, 95%CI=1.39-4.44). No significant associations were noted between Hsp70/Hsp90 expression and clinicopathological variables including histological grade, tumor size, nodal metastasis or patient age at diagnosis. No clear pattern emerged for Hsp70/Hsp90 expression along the breast neoplasia continuum. This systematic review and meta-analysis highlights the prognostic role of Hsp90 and Hsp70 expression in breast cancer. Further high-quality studies, with detailed reporting are needed to provide epidemiological evidence complementing the findings of ongoing clinical trials on Hsp inhibitors.