Anticancer chemosensitivity profiles of human breast cancer cells assessed by in vitro DNA synthesis inhibition assay.

The present study was designed to assess the profile of the chemosensitivity of breast cancer cells and to screen effective agents for combination regimens. Chemosensitivity to anticancer agents was assessed by the 3H-thymidine incorporation assay, as the rate of inhibition of DNA synthesis in 145 samples (88 primary and 57 metastatic or recurrent lesions) from 136 patients with breast cancer. The correlations of the anticancer agents with various clinicopathological factors were analysed. The effectiveness of the agents was classified as a rate of inhibition on log scale as follows: highly sensitive (> or = 30%), moderately sensitive (25-30%), slightly sensitive (20-25%), resistant (< 20%). The chemosensitivity of breast cancer showed variations according to tumor location: primary lesions seemed to be slightly sensitive to carboquone (CQ), adriamycin (ADR), and cytosine arabinoside (Ara-C); nodal involvement was moderately sensitive to CQ and slightly sensitive to Ara-C, 5-FU, ADR, mitomycin-C (MMC), and cisplatin (CDDP); malignant effusions were highly sensitive to ADR, moderately sensitive to CQ, and slightly sensitive to Ara-C and CDDP; local recurrences were slightly sensitive to Ara-C, CQ and 5-FU; vincristine (VCR) and nimustine chloride (ACNU), however, seemed to be ineffective against breast cancer. There were significant correlations in chemosensitivity between most agents, but no correlation was found between 5-FU and CDDP, 5-FU and ACNU, MMC and VCR, ADR and CDDP, ADR and VCR, and ADR and ACNU. There were no differences in chemosensitivity between stages of primary lesions or between estrogen receptor-positive and -negative tumors. In 10 patients, simultaneous nodal involvement was more sensitive to the agents than were primary lesions, and the correlation of chemosensitivity to ADR and CQ between such lesions was significant. On the other hand, there was no significant difference or correlation of chemosensitivity between the original lesions and recurrent ones after chemotherapy. The heterogeneity and homogeneity in the chemosensitivity of breast cancer suggested not only the necessity of patient-specific chemotherapy based on a sensitivity assay, but also the usefulness of choosing agents for widely-applicable combination regimens against breast cancer.