Cell killing and resistance in pre-operative breast cancer chemotherapy.
BACKGROUND
Despite the recent development of technologies giving detailed images of tumours in vivo, direct or indirect ways to measure how many cells are actually killed by a treatment or are resistant to it are still beyond our reach.


METHODS
We designed a simple model of tumour progression during treatment, based on descriptions of the key phenomena of proliferation, quiescence, cell killing and resistance, and giving as output the macroscopically measurable tumour volume and growth fraction. The model was applied to a database of the time course of volumes of breast cancer in patients undergoing pre-operative chemotherapy, for which the initial estimate of proliferating cells by the measure of the percentage of Ki67-positive cells was available.


RESULTS
The analysis recognises different patterns of response to treatment. In one subgroup of patients the fitting implied drug resistance. In another subgroup there was a shift to higher sensitivity during the therapy. In the subgroup of patients where killing of cycling cells had the highest score, the drugs showed variable efficacy against quiescent cells.


CONCLUSIONS
The approach was feasible, providing items of information not otherwise available. Additional data, particularly sequential Ki67 measures, could be added to the system, potentially reducing uncertainty in estimates of parameter values.
Ubezio
Paolo
P
Biophysics Unit, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, I-20156 Milan, Italy. ubezio@marionegri.it
Cameron
David
D
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004341:Drug Evaluation / Q000639:trends; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen; D008954:Models, Biological; D009365:Neoplasm Regression, Spontaneous; D016896:Treatment Outcome
D019394:Ki-67 Antigen; D004317:Doxorubicin; D003520:Cyclophosphamide