Introduction
tumor, breast cancers, toxicity, /HER2− metastatic breast cancer, tumors
TUMOR, CARCINOGENESIS, BREAST CANCER, NEOPLASTIC PROGRESSION, DISEASE, METASTATIC CANCER, TUMORS, METASTATIC BREAST CANCER
Through their mitogenic effects via the estrogen-receptor alpha (ERα), estrogens play a fundamental role in the carcinogenesis process. Blocking estrogenic signaling is therefore the basic principle of hormone therapy for the treatment of hormone receptor-positive (HR +) breast cancer. Despite the undeniable efficacy of molecules used in endocrine therapy, many tumors have intrinsic or acquired resistance, despite their positive tumor status for ERα. It is nevertheless interesting to note that some clinical studies have shown that 43% and 30% of patients who have relapsed, respectively, on tamoxifen or aromatase inhibitor will respond to fulvestrant treatment, indicating the interest of continuing endocrine therapy beyond neoplastic progression [Systemic chemotherapy with cytotoxic agents remains a standard treatment for metastatic cancer. "Metronomic" chemotherapy is a repeated reduced-dose chemotherapy treatment administered daily for antineoplastic purposes. These effects involve anti-angiogenic impact, interference with immune response and conventional cytotoxic activity [Metronomic chemotherapy was initially evaluated in 64 metastatic breast cancer patients by an Italian Phase II study. The treatment included methotrexate and cyclophosphamide and interesting results were reported, with 20% response rate, a 30% clinical benefit rate and no significant toxicity [The combination of endocrine therapy and metronomic chemotherapy with vinorelbine could therefore be of interest for HR + /HER2− (Hormone receptor positive, human epidermal growth factor receptor 2 negative) breast cancers in a metastatic hormone-resistance setting.We hypothesized that maintaining HR-targeted therapy after progression in combination with chemotherapy may improve disease control. The CHEOPS study aims to confirm the clinical benefit of a combination of an anti-aromatase and metronomic chemotherapy treatment, oral vinorelbine (OV), 50 mg, three times per week for AI pre-treated, HR + /HER2− metastatic breast cancer patients. It would have the theoretical advantage of being well tolerated and more effective than chemotherapy alone even after an anti-aromatase therapy.