Management of advanced HR-positive breast cancer using metabolically supported chemotherapy and repurposed drugs: a...

Metastatic hormone receptor-positive (HR+) breast cancer is largely incurable once resistance to conventional treatments occurs. Emerging evidence suggests that progression free and overall survival can improve by targeting the distinct metabolic phenotype of cancer cells (Warburg effect). We report a durable response in a patient with advanced metastatic breast cancer treated with a multimodal "press-pulse" metabolic strategy.

A 49-year-old female from Torino, Italy presented with Stage IV (cT4N1M1) invasive ductal carcinoma (HR+/HER2-, grade 3) with extensive osseous and lymph node metastases, poor performance status (ECOG 3) and severe, debilitating pain. She underwent a combinatorial protocol at ChemoThermia Oncology Center (Istanbul, Turkey) comprising of Metabolically Supported Chemotherapy (MSCT) consisting of docetaxel, doxorubicin, and cyclophosphamide administered following a 14-hour fast and low dose insulin-induced mild hypoglycemia, alongside a strict ketogenic diet (GKI < 2.0). Adjunctive therapies included local and whole-body hyperthermia, hyperbaric oxygen therapy (HBOT), and a combination of repurposed drugs (metformin, aspirin, doxycycline, mebendazole, ivermectin, and famotidine) designed to target metabolic, inflammatory, and survival pathways.

This multimodal treatment protocol was well tolerated, and grade 3/4 adverse events were not observed. The patient noticed symptomatic improvement and functional recovery shortly following the onset of therapy. Follow-up PET-CT scan conducted at 3 months revealed reduced tumor burden. At 6 months, the patient was reported to have a near complete response with the resolution of active bone metastases. On a maintenance schedule, the patient remains in sustained remission as of January 2026, over three years following diagnosis, with a full return to normal daily activities (ECOG 0).

This case highlights the potential of a comprehensive metabolic approach to cancer treatment that combines therapeutic ketosis, metabolically supported chemotherapy, physical modalities (hyperthermia/HBOT), and repurposed drugs. A durable response in a patient with otherwise poor prognosis was achieved after systematically targeting cancer cell bioenergetics and the tumor microenvironment. These findings support further clinical investigation into multimodal metabolic therapies for advanced HR+ breast cancer.