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Breast cancer, as a heterogeneous disease, has different molecular subtypes. The most common molecular subtype is hormone receptor positive (HR +). Endocrine therapy is the predominant treatment for this subtype. The main treatment modality for HR +/human epidermal growth factor receptor 2-negative (HER2 -) metastatic breast cancer (MBC) is novel targeted agents combined with endocrine therapy. In this review, researches in endocrine clinical treatment of HR +/HER2 - MBC was reviewed to provide a new targeted therapy, including CDK4/6 inhibitors combined with endocrine therapy, the debate between CDK4/6 inhibitors combined with endocrine therapy and chemotherapy, new directions of CDK4/6 inhibitor combination, exploration of multiple treatment strategies after CDK4/6 inhibitor therapy progresses, histone deacetylase inhibitor combined with endocrine therapy, PI3K/Akt/mTOR pathway targeting drugs in combination with endocrine therapy, polyadenosine diphosphate ribose polymerase (PARP) inhibitors for gBRCA1/2 mutated breast cancer, novel targeted drugs, and multi-target/multi-combination therapy model.
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Cancer stem cells (CSCs) are a class of cells with self-renewal, differentiation, and tumorigenic potential in tumors. It is currently believed that the resistance of CSCs to chemotherapy and radiotherapy is an important cause of tumor recurrence and metastasis. Researchers have found that related factors in many signaling pathways endow CSCs with the ability to adapt to changes in the microenvironment, including inflammatory factors, hypoxia, low pH, and a lack of nutrients. In recent years, the mechanism of CSCs' resistance to therapy has been studied, mainly including the drug efflux mediated by the ATP-binding cassette transporter, the effect of aldehyde dehydrogenase 1 (ALDH1) activity on tumor stem cells, the enhancement of DNA damage repair and degradation of reactive oxygen species, autophagy, activation of development-related pathways, stimulation of the microenvironment, and EMT. The targeting strategies for CSCs include targeting signaling pathway inhibitors, targeting multidrug resistance, DNA damage repair, ALDH, targeting the tumor microenvironment, immunotherapy, etc. In this review, the research progress in CSCs treatment resistance and related treatment strategies was reviewed.
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Objective:To analyze the prognostic factors in patients with metastatic breast cancer (MBC). Methods:A total of 205 patients with pretreated MBC were included in this study. These patients were admitted to the Tianjin Medical University Cancer Insti-tute&Hospital and had undergone radical surgery of breast cancer between January 2008 and December 2010. The clinicopathologic information of the patients was collected in this retrospective analysis. Results: The median overall survival of the patients was 32 months (1 month to 132 months). Luminal A, Luminal B, HER-2 overexpression, and triple-negative patients had a median overall sur-vival of 36 months (4 months to 132 months), 32 months (7 months to 122 months), 29 months (1 month to 85 months), and 24 months (1 month to 98 months), respectively. Univariate analysis showed that lymph node metastases, clinical stage, molecular type, visceral disease, first multiple metastatic sites, and shorter metastasis-free interval were significantly associated with poor outcomes. In multivar-iate analysis, lymph node metastases, clinical stage, molecular type, visceral metastasis, and the number of first metastatic sites were significant predictors of patient survival. Conclusion:Lymph node metastasis, clinical stage, triple-negative breast cancer, and visceral metastasis were used as independent poor prognostic indicators for survival in patients. Results of this study may assist physicians in evaluating the survival potential and determining the appropriate therapeutic strategy for MBC patients.
RESUMO
10.3969/j.issn.1000-8179.2013.12.006