Chemosensitivities of human clonogenic breast tumor cells

We developed an in vitro system for the testing of the inherent chemosensitivity of clonogenic tumor cells, and we applied the system to the evaluation of 104 human breast tumors. We observed the following: clonogenic breast tumor cells were more sensitive to 4-hydroperoxycyclophosphamide (a metabolite of cyclophosphamide with in vitro activity) than to 5-fluorouracil and to doxorubicin (the other two agents used in the frontline treatment of breast carcinoma). The sensitivity of these clonogenic breast tumor cells for mitoxantrone, bisantrene, 4′-epi-doxorubicin, and VP-16 was similar to that for doxorubicin and 5-fluorouracil, but it was less for cis-platinum. In vivo exposure to a combination of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) did not change the sensitivity of cells towards 5-fluorouracil and doxorubicin, but lessened the sensitivity of some cells towards 4-hydroperoxycyclophosphamide. Furthermore, in vivo exposure to doxorubicin did not influence the sensitivity of cells towards the anthraquinone derivatives, 4′-epi-doxorubicin, mitoxantrone, and bisantrene. A comparison of the in vitro and in vivo chemosensitivity revealed that the assayed cell populations were biologically relevant: the concordance of sensitivity on 41 tumors was 68%, or 95%, if the in vitro sensitivity score was adjusted to the tumor bulk. We conclude that our system provides a valid tool to determine the inherent chemosensitivity pattern of the individual tumor types, and to compare the tumor cytotoxic potential of drugs.