Randomized controlled trial comparing zoledronic acid plus chemotherapy with chemotherapy alone as a neoadjuvant treatment in patients with HER2-negative primary breast cancer.

Abstract

TPS1141 Background: Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate, and it induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. ZOL has also been found to have antitumor effects that include an angiogenesis inhibiting action, an inhibitory effect on tumor cell adhesion to and invasion of the extracellular matrix, and activation of a gdT cells. In addition, it has been found to have a synergistic apoptosis-inducing effect when used in combination with antitumor drugs. In this study we will investigate the pCR rate when ZOL is added to anthracycline followed by taxane to treat T2 and T3 breast cancer patients. Methods: Women with resectable invasive StageIIA-IIIB (T ≥ a3 cm or T ≥ a2 cm and lymph node positive) breast cancer who are HER-2-negative, between 20 and 70 years of age, and ECOG PS 0-1 are eligible. Patients with distant metastasis, patients who have had received chemotherapy, hormone therapy, or radiotherapy for breast cancer, patients with serious complications, such as heart disease or an infection, patients with a complicating dental or jaw infection or traumatic condition of the teeth, and patients with a history of treatment with a bisphosphonate within the previous 12 months are excluded. A total of 4 courses of FEC100 are administered every 3 weeks followed by weekly paclitaxel for 12 courses. ZOL 4mg is administered every 3-4 weeks a total of 7 times. Patients are randomized 1:1 to chemotherapy + ZOL group or chemotherapy alone group, according to the presence or absence of lymph node metastasis, estrogen receptor (ER) status, and their menopausal status. The primary endpoint is pCR. Secondary endpoints are tumor response rate, the breast-conserving surgery ratio, and disease-free survival (DFS). We calculated the sample size on the basis of a pCR rate of 18% in the chemotherapy alone group and 35% in the chemotherapy + ZOL group, at a one-sided significance rate of 5%, and test power of 80%, and as a result we will target a patient sample size of 180 patients. 162 of planned 180 patients have been enrolled as of January 24, 2012.