Cardiac toxicity assessment in locally advanced breast cancer treated neoadjuvantly with doxorubicin/paclitaxel regimen

Abstract

Background: The psychological difficulty of accepting a mastectomy for locally advanced breast cancer (LABC) justifies the use of chemotherapy as neoadjuvant primary treatment. The aim of this prospective study was to assess the efficacy of the doxorubicin/paclitaxel (AT) schedule neoadjuvantly administered in terms of response rates and survival in patients with LABC, with a special focus on cardiac toxicity.

Patients and method: All patients were treated by doxorubicin (60 mg/m2 i.v.) bolus followed by paclitaxel (200 mg/m2) as a 3-h infusion. Treatment was repeated every 3 weeks for four or six courses and followed by surgery, radiotherapy, and hormonotherapy for patients with positive hormonal receptors. Patients with significant cardiovascular history or ECG abnormalities were not eligible for the study. Measurements of left ventricular ejection fraction (LVEF) were performed at baseline and at the end of chemotherapy.

Results: From 1998 to 2001, 34 consecutive patients followed up in our institution were entered into this study. Median age was 49 years (range, 32-68 years). Seventeen patients had stage IIB, 5 patients stage IIIA, and 12 patients stage IIIB disease. Twenty-one patients underwent conservative surgery, 7 radical surgery, and 6 patients no surgery due to metastatic disease occurring during treatment. An objective clinical response was noted in 22 (65%) of 34 patients (6 patients with histological complete response, 10 patients with rare malignant cells, and 6 patients with a partial response), 6 patients presented a progressive disease, and 8 patients a stable disease. Twenty-four patients have kept normal cardiac function, 7 patients had a cardiac toxicity as defined by the institution [4 (24%) of 17 patients received 360 mg/m2 of doxorubicin (A), 2 of 4 presented congestive heart failure (CHF), and 3 (21%) of 14 patients received 240 mg/m(2) of A without CHF]. Three patients did not receive four or six cycles as initially planned due to the progressive disease during the chemotherapy courses. These patients were excluded from the final analysis, particularly cardiac toxicity analysis. At time of median follow-up (42 months), 28 of 34 patients were alive (one death due to CHF, five others due to progressive disease).

Conclusion: The AT regimen in neoadjuvant treatment for LABC remains efficient, but cardiac toxicity reported in this study underlies the necessity to optimize the schedule of AT combination.