Effects of α-difluoromethylornithine on markers of proliferation, invasion, and apoptosis in breast cancer

Aim: To examine changes in biomarkers expressed in breast tumors in response to patient treatment with the polyamine synthesis inhibitor α-difluoromethylornithine (DFMO). Patients and Methods: The expression of Ki-67 (MIB-1), matrix metalloproteinases (MMP) 2 and 9, urokinase-type plasminogen activator (uPA) were examined by immunohistochemistry in breast tissue specimens (controls: n=15, 13 evaluable, and DFMO group; n=27, 21 evaluable). Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Results: Significant increases in apoptosis, MMP-9 and uPA (tumor) were observed in 7 patients ≥50 years who received DFMO for ≥14 days relative to patients <50 years and/or who received <14 days of treatment (n=11). No other measured characteristics, including tumor estrogen and progesterone receptor status, hormone replacement therapy history, histopathological characteristics or tumor grade were correlated with these biomarker changes. Conclusion: Unexpected correlation of proapoptotic DFMO activity in postmenopausal women with breast cancer warrants further study.