Estrogen induced expansion of the growth fraction in receptor negative human breast cancer.
The feasibility of a cytokinetic chemotherapy based on estrogenic recruitment has been evaluated in 5 patients, affected by locally advanced breast cancer with low or absent receptor content. Tumor proliferative activity was evaluated by the thymidine labeling index (TLI) and the primer-dependent alpha DNA polymerase assay (PDP-LI) which gives an in vitro estimation of tumor growth fraction. The patients have been treated with diethylstilbestrol (DES) 1 mg/die. for 3 days, followed by FAC (5-Fluorouracil 600 mg/m2, Adriamycin 50 mg/m2, Cytoxan 600 mg/m2) i.v. on day 4 q. 21 days. Radical surgery was performed after 3 DES-FAC regimens. Tumor biopsies for evaluation of tumor proliferative activity were performed immediately before and after DES and 24 h after chemotherapy. Our results demonstrate that DES was able to induce an increase in TLI in 3/5 of the patients while the PDP-LI was significantly increased in 5/5 of the patients; subsequent chemotherapy induced a sharp decrease in tumor proliferation. These results provide the rationale for the design of cytokinetic regimens where chemotherapy is administered at the time of estrogen induced tumor cell recruitment.
D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003520:Cyclophosphamide / Q000627:therapeutic use; D004257:DNA Polymerase II / Q000032:analysis; D004261:DNA Replication / Q000187:drug effects; D004054:Diethylstilbestrol / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D011960:Receptors, Estrogen / Q000032:analysis; D013936:Thymidine / Q000378:metabolism
D004967:Estrogens; D011960:Receptors, Estrogen; D004054:Diethylstilbestrol; D004317:Doxorubicin; D003520:Cyclophosphamide; D004257:DNA Polymerase II; D005472:Fluorouracil; D013936:Thymidine