Effect of oral cyclophosphamide use on pathologic complete response rate in the neoadjuvant treatment of breast cancer.

Abstract

276 Background: Continuous exposure to cyclophosphamide (C) can result in selective cytotoxicity for endothelial cells, followed by antiangiogenic effects on tumor cells. In this study we analyzed the pathological complete response (pCR) rate in a cohort of patients (p) diagnosed with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (CT) based on anthracyclines and taxanes, depending on the route of administration of C (intravenous (IV) and oral arms). Methods: We retrospectively studied a consecutive series of p. with LABC treated with neoadjuvant CT in 2 hospitals in Asturias. The regimens used were CE100F, AC (regimens with IV C) or oral CAF (C 100mg/m2/day orally x 14 days, doxorubicin 30 mg/m2 day 1 and 8 and 5-FU 500 mg/m2 days 1 and 8 every 28 days) x 4 cycles. The anthracycline regimen was followed by weekly paclitaxel or docetaxel every 3 weeks. If HER2 overexpression, trastuzumab was given in combination with the taxane. Results: We identified 105 p., 65 of them treated with oral C and 40 with IV C (CEF 3 patients and AC 37 patients). The median age was slightly higher in the p. treated with C IV (52.2 vs. 47.7, p = 0.022), which also received a higher number of cycles (7.1 vs. 6.7, p = 0.025), although there were no significant differences in the anthracycline dose intensity (93% vs 89%, p = 0.093). There were no significant differences in tumor size, lymph node involvement, grade, estrogen receptor (ER) or HER2. The rate of pCR was significantly higher in p. receiving oral C (33.8% vs 10%, p = 0.004). Grade 3, negative estrogen receptors and HER2 were also significantly associated with a higher rate of pCR. On multivariate analysis only oral C was an independent factor associated with pCR. With a median follow up of 27.3 months (95% CI 24 to 30.6), there have been 10 recurrences (15.4%) in the continuous arm and 9 (22.5%) in the standard arm, without significant differences in disease free survival. Conclusions: Our results suggest that the pCR rate can be higher using oral C in the neoadjuvant treatment of LABC based on anthracyclines and taxanes. This hypothesis should be confirmed in a randomized and prospective study.