Disclosed are methods for treating one or more mammalian cancers, particularly, human breast cancers, including triple-negative breast cancer (TNBC), that employ therapeutically-effective amounts of one or more iNOS pathway-inhibitory compounds, such as L-NMMA, in combination with one or more selected calcium channel antagonists, one or more chemotherapeutic agents, one or more anti-PD-1 antibodies, and one or more doses of ionizing radiation. Also disclosed are pharmaceutical formulations that comprise these compositions, as well as methods for their use in treating refractory, metastatic, and/or relapsed cancers, or, for use in the management or reversal of treatment resistance in one or more types of human breast cancer.