Abstract PD07-05: A randomized controlled trial comparing zoledronic acid plus chemotherapy with chemotherapy alone as a neoadjuvant treatment in patients with HER2-negative primary breast cancer

Abstract

Abstract 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 bone, an inhibitory effect on invasion of the extracellular matrix, and activation of a gdT cells. In addition, it has been found to have a synergistic anti-proliferative effect when used in combination with antitumor drugs. In this study we investigated the pathological complete response (pCR) rate when ZOL is added to anthracycline followed by taxane to treat T2 and T3 breast cancer patients as a neoadjuvant chemotherapy. Methods: Women with resectable invasive StageIIA-IIIB (T ≥3 cm or T ≥2 cm and lymph node positive) breast cancer who are HER-2-negative, between 20 and 70 years of age, and ECOG PS 0–1 were 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 were excluded. A total of 4 courses of FEC100 were administered every 3 weeks followed by weekly paclitaxel for 12 courses. ZOL 4mg was administered every 3–4 weeks a total of 7 times. Patients were 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 was the rate of pCR defined as absence of invasive disease in the breast at surgery. Secondary endpoints were tumor response rate (RECIST ver1.0), 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 5% significance level based on the one-sided chi-square test with the statistical power of 80%, and as a result we targeted a patient sample size of 180 patients. Results: 188 patients were recruited between March 2010 and April 2012. Results of the primary analysis of efficacy and safety will be presented. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD07-05.