Using a Panel of Heat Shock Proteins for Diagnosis and Prognosis of Breast Cancer

Abstract

Purpose: The current work aimed to evaluate the diagnostic and prognostic role of a panel of heat shock proteins; HSP27, HSP60, HSP70 and HSP90, in sera of breast cancer patients, in comparison with CA 15.3 as the standard marker in breast cancer management. Methodology: The study included 248 females diagnosed with primary breast cancer and 232 normal healthy females. Patients were managed by modified radical mastectomy or breast conservative surgery then received adjuvant therapy and clinically followed up for 5 years. In sera of all patients and controls; HSP27, HSP60, HSP70 and HSP90 were measured by ELISA while CA 15.3 was measured by IRMA. Findings: Pre-treatment serum levels of HSP27, HSP60, HSP70 and HSP90 were significantly elevated in breast cancer patients than in controls, furthermore, they were significant as diagnostic markers, especially when using a panel of HSP70≥9.2 ng/ml and HSP60≥7.5 ng/ml with AUC, sensitivity and specificity of 0.995, 98% and 95%; respectively. As prognostic markers, patients with elevated serum HSP27, HSP60 or HSP70 had significantly lower DFS than patients having lower serum levels. In addition, in patients with at least two HSPs of the three above their cutoffs, the HR increased to 4.65, and it jumped to 17.88 for patients having all three HSPs elevated above their respective cutoff values. CA 15.3 was not significant as diagnostic or prognostic marker. Conclusion: A panel of pre-treatment serum HSP70≥9.2 ng/ml and HSP60≥7.5 ng/ml may be useful for screening of populations at high risk of developing breast cancer. For prediction of treatment response, patients who have elevated pre-treatment serum HSP27, HSP60 or HSP70 had significantly lower DFS. In addition, the risk of relapse in patients having at least two HSPs and patients having all three HSPs elevated above their respective cutoffs were 4.65-times and 17.88-times that of patients with HSPs below their respective cutoffs.