Indication of metronomic chemotherapy for metastatic breast cancer: clinical outcomes and responsive subtypes

The survival of patients with metastatic breast cancer (MBC) has not improved, despite recent advances in therapeutic strategies. This is mainly due to the fact that cytotoxic agents cannot be administered over a long period, even if they exhibit favorable activity, due to treatment-related side effects or acquisition of tumor resistance to the administered agents. Thus, the development of therapeutic strategies that may be used over a long time period is required to improve survival. We assessed the availability and clinical outcomes of metronomic chemotherapy, which is defined as continuous or frequent treatment with low doses of cytotoxic drugs. A total of 80 patients with MBC received chemotherapy in the metastatic setting, and the clinicopathological factors and clinical outcomes were retrospectively compared between 52 patients who received metronomic regimens and 28 patients who received other cytotoxic regimens. As regards clinical outcomes, the median time-to-treatment failure (TTF) and overall survival (OS) were significantly longer in the metronomic group compared with those in the non-metronomic group (TTF, 15 vs. 4 months, P=0.0001; and OS, 53 vs. 28 months P=0.0012, respectively). In the metronomic group, none of the 18 patients who responded to the regimen had triple-negative (TN) cancer (17 had luminal-type tumors and 1 had a human epidermal factor receptor 2-type tumor). Furthermore, TTF and OS were significantly longer in patients with non-TN cancer compared with those in patients with TN cancer in the metronomic group (TTF, 16 vs. 7 months, P=0.0014; and OS, 108 vs. 20 months, P=0.000007, respectively). The proportion of patients who experienced treatment-related adverse events was significantly lower in the metronomic group compared with that in the non-metronomic group (36.5 vs. 61.5%, respectively; P=0.038). In conclusion, metronomic chemotherapy is a viable option for luminal-type MBC in terms of effectiveness and minimal toxicity, regardless of metastatic sites or prior treatment. However, an alternative treatment is required for TN cancer.