Effects of alpha-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 alpha-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 >or=50 years who received DFMO for >or=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.