In vitro clonogenic growth and metastatic potential of human operable breast cancer

In 254 patients with operable [International Union against Cancer (1972) Stages I, II, and III] breast cancer, the relations between in vitro clonogenic growth in soft agar of primary breast cancer tumors and their metastatic potential expressed by the relapse-free survivals (RFS) as well as overall survivals were studied. Sixty-four % (163 of 254) of cancers formed distinct colonies (30 or more colonies in a single dish, or 10 or more colonies in plural dishes). Other breast cancers (36%, 91 of 254) were designated to be negative for the clonogenicity. There was no correlation between the positive or negative clonogenicity and clinicopathological characteristics in breast cancer patients, including the age of patients, menopausal status, tumor size, T classification, International Union against Cancer stage, histological type (Japanese Breast Cancer Society), histologically proved axillary lymph node metastasis, and estrogen receptor (ER). At the time of median follow-up of 43 mo (range, 25 to 61 mo) after mastectomy, a recurrence of malignancy occurred in 19.0% (31 of 163) of the patients with positive clonogenic tumors, and in 8.8% (8 of 91) of those with negative clonogenic tumors (P = 0.03). There also was a significant difference (P less than 0.03 by log rank test, P less than 0.05 by generalized Wilcoxon test) in RFS curves between positive and negative clonogenicity groups. These differences in RFS were also noted in Stage II patients in favor of the negative colony formation group. In ER-negative cancer patients, the RFS of patients with positive clonogenic cancers was shown to be worse (P less than 0.03 by log rank test, P less than 0.05 by generalized Wilcoxon test) than patients with negative clonogenic cancers. There was no difference in RFS in ER-positive cancer patients. There was a trend (P = 0.09 by log rank test) of worse overall survival rate in patients with positive clonogenic growth. In a multivariate comparison using the principal component analysis composed of factors including positive node, T classification, histological type, age, ER, and colony formation, the clonogenicity showed a significant effect on the recurrence of malignancy and also on the survival of the patients after mastectomy. In conclusion, in vitro clonogenic growth of the primary tumor of breast cancer was shown to be one of the independent factors of metastatic potential in operable breast cancer patients after mastectomy.