Secretory clusterin (sCLU) overexpression is associated with resistance to preoperative neoadjuvant chemotherapy in primary breast cancer

Objectives: Preoperative chemotherapy is often used in patients with locally advanced breast cancer. However, commonly used clinical and pathological parameters are poor predictors of response to this type of therapy. The secreted form of the CLU protein (sCLU) is a glycosylated protein of 76-80 kDa. It has become increasingly clear that in most cells sCLU is a stress-associated cytoprotective protein that is upregulated by various apoptotic triggers. Furthermore, sCLU confers resistance by some unknown mechanism when overexpressed. The purpose of the present study was to examine the sCLU proteins as predictors of clinical outcome and response to chemotherapy in locally advanced breast cancer.

Patients and methods: The expression levels of sCLU was determined by immunohistochemistry before preoperative chemotherapy in 72 patients with locally advanced breast cancer. All patients were treated with cyclophosphamide/doxorubicin/5-FU(CAF) and some patients received additional treatment with docetaxel. Expression data were compared with patients' clinical and pathological features, clinical outcome, and response to chemotherapy.

Results: The results showed sCLU expression before preoperative chemotherapy was inversely related to the tumor size, expression of estrogen and progesterone receptors. High preoperative expression of sCLU was associated with resistance to CAF therapy, but not with resistance to docetaxel.

Conclusions: We, therefore, suggested sCLU expression may be a useful marker for predicting response to preoperative chemotherapy and clinical outcome in patients with locally advanced breast cancer.