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Prompted by complaints of dyspnea in breast cancer patients receiving adjuvant dose-dense chemotherapy (DDC), we sought to evaluate the possible association of DDC with pulmonary dysfunction.A total of 34 consecutive patients receiving adjuvant DDC were enrolled. The chemotherapy regimen consisted of i.v. doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (AC) every 14 days ×4 with growth factor support followed by weekly i.v. paclitaxel 80 mg/m2 ×12. The following parameters were prospectively measured before and after the AC protocol (P1, P2) and at completion of paclitaxel treatment (P3): presence of dyspnea, blood pressure, pulse rate, hemoglobin, erythrocyte sedimentation rate, C-reactive protein level, cardiac ejection fraction, and pulmonary function. Repeated measures analysis was used to evaluate differences among the time points, and paired t-test was used to evaluate differences between consecutive time points.Although only five patients (15%) complained of dyspnea, there was a significant decrease in mean carbon monoxide diffusing capacity (DLCO), in all patients from P1 (22.09 ml/min/mmHg) to P3 (15 ml/min/mmHg) and in 29 of 32 patients (90.6%) from P1 to P2 (15.96 ml/min/mmHg) (P < 0.001).DDC is associated with a statistical significant reduction in DLCO. Awareness of this potential toxicity may be important in women with preexisting lung disease.