The Position of Combination Chemotherapy with Mitomycin C and Methotrexate in the Treatment of Metastatic Breast Cancer - Especially Triple Negative Breast Cancer

Complete cure of metastatic breast cancer (MBC) remains difficult, despite the development of new drugs. Triple negative (TN) breast cancer, which is defined by lack of hormone receptor (estrogen and progesterone receptors) expressions and the absence of human epidermal growth factor receptor type 2 (HER2) overexpression, is especially associated with poor long-term outcomes as compared with other breast cancer subtypes. Therefore, many patients with TN-MBC eagerly await promising novel treatments for TN-MBC. While new drugs are being developed, several conventional drugs such as mitomycin C (MMC) and methotrexate (MTX) are being used less. We reviewed our previous reports on combination chemotherapy with MMC and MTX (MMC/MTX) after multiple treatments. For the MMC/MTX regimen, MMC 8 mg/m2 on day 1 and MTX 60mg/m2 on days 1 and 15 were administered intravenously every 4 weeks. MMC/MTX was effective for 24% of 48 MBC patients who had been treated with anthracycline and taxane, resulting in a median time to progression (TTP) of 4.8 months. In addition, MMC/MTX was effective for 9.7 - 19.4 % of 31 patients with HER2-negative MBC after multiple treatments with anthracycline, taxane, capecitabine and vinorelbine, resulting in a median TTP of 3.9 months. Among 10 patients with TN-MBC, a partial response was observed in two (20%) and stable disease in three (30%). Thus, MMC/MTX controlled TN-MBC relatively well. Among TN-MBC patients maintaining good performance status without myelosuppression, MMC/MTX might be an option for those in whom no other treatments are effective after multiple regimens suggested in the guidelines.