Effects of alpha-difluoromethylornithine on markers of proliferation, invasion, and apoptosis in breast cancer.
OBJECTIVE
To examine changes in biomarkers expressed in breast tumors in response to patient treatment with the polyamine synthesis inhibitor alpha-difluoromethylornithine (DFMO).


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.


CONCLUSIONS
Unexpected correlation of proapoptotic DFMO activity in postmenopausal women with breast cancer warrants further study.
Izbicka
Elzbieta
E
BTNS LLC, Box 810, Marion, TX 78124, USA. btns.llc@gmail.com
Streeper
Robert T
RT
Yeh
I-Tien
IT
Pressley
Oredius
O
Grant
Michael
M
Andrews
J Valerie R
JV
Kuhn
Joseph
J
O'Shaughnessy
Joyce
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D000518:Eflornithine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D009361:Neoplasm Invasiveness
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000518:Eflornithine