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Abstract Background Visfatin has been reported to be associated with breast cancer progression, but the interaction between the visfatin and clinicopathologic factors in breast cancer progression status requires further investigation. To address this problem, it is better to simultaneously consider multiple factors in sensitivity and specificity assays. Methods In this study, a dataset for 105 breast cancer patients (84 disease-free and 21 progressing) were chosen. Individual and cumulative receiver operating characteristics (ROC) were used to analyze the impact of each factor along with interaction effects. Results In individual ROC analysis, only 3 of 13 factors showed better performance for area under curve (AUC), i.e., AUC > 7 for hormone therapy (HT), tissue visfatin, and lymph node (LN) metastasis. Under our proposed scoring system, the cumulative ROC analysis provides higher AUC performance (0.746–0.886) than individual ROC analysis in predicting breast cancer progression. Considering the interaction between these factors, a minimum of six factors, including HT, tissue visfatin, LN metastasis, tumor stage, age, and tumor size, were identified as being highly interactive and associated with breast cancer progression, providing potential and optimal discriminators for predicting breast cancer progression. Conclusion Taken together, the cumulative ROC analysis provides better prediction for breast cancer progression than individual ROC analysis.