Over-expression of Skp2 is associated with resistance to preoperative doxorubicin-based chemotherapy in primary breast cancer

The expression levels of Skp2 and p27Kip1 were determined by immunohistochemistry both before and after preoperative chemotherapy in 40 patients with locally advanced breast cancer. All patients were treated with cyclophosphamide/doxorubicin (adriamycin)/5-fluorouracil (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.Skp2 expression before preoperative chemotherapy was inversely related to p27Kip1 levels, tumor grade, and expression of estrogen and progesterone receptors. Both Skp2 and p27Kip1 were found to be accurate prognostic markers for disease-free and overall survival. High preoperative expression of Skp2 was associated with resistance to CAF therapy in 94% of patients (P < 0.0001) but not with resistance to docetaxel.Skp2 expression may be a useful marker for predicting response to doxorubicin-based preoperative chemotherapy and clinical outcome in patients with locally advanced breast cancer.Preoperative chemotherapy is widely used in the management of primary breast cancer, and particularly in patients who present with locally advanced disease [1-3]. Studies have clearly shown that initiating treatment with chemotherapy can lead to tumor regression in a substantial number of patients, thereby improving local control and allowing breast-conserving surgery in many patients without compromising clinical outcomes [3]. In addition, this practice permits direct assessment of tumor responsiveness to a given drug regimen and may allow one to determine the need to add or switch to a different regimen. However, not all tumors respond equally to a given chemotherapy combination. Some tumors may be responsive only to specific drugs, which may not be in the initial preoperative protocol used, whereas other tumors may not respond to a large variety of chemotherapies. This may lead to unnecessary exposure to drug side effect