Special Feature From improved survival to potential cure in patients with metastatic breast cancer

Breast Cancer

, Volume 19, Issue 3, pp 206-211

Eradication of breast cancer cells in patients with distant metastasis: the finishing touches?

  • Yoshinori ItoAffiliated withDepartment of Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer ResearchDepartment of Breast Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research Email author 
  • , Takuji IwaseAffiliated withDepartment of Breast Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research
  • , Kiyohiko HatakeAffiliated withDepartment of Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research

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Abstract

Cytotoxic agents are significantly active in breast cancer cells, but their usefulness has been limited in treating metastatic breast cancer (MBC). This has facilitated the development of an approach using molecular-targeted agents. Intrinsic subtypes including luminal A, luminal B, human epidermal growth factor receptor type 2 (HER2)-enriched, basal-like, and claudin-low tumors exhibit original drug responsiveness and clinical prognosis. Anti-HER2 treatments, trastuzumab or lapatinib, have demonstrated clinically significant efficacy. Poly ADP-ribose polymerase-1 inhibitors act against BRCA1-disabled breast cancer. Cancer stem cells could be the major obstacle to achieving a cure in systemic treatment. Extensive investigations are underway to develop novel agents that act on the genes or signaling of Hedgehog, Wnt, and Notch, which regulate cancer stem cells. Cancer cells undergo epithelial–mesenchymal transition (EMT) and acquire invasive properties. Breast cancer cells alter their phenotype in blood and bone marrow, e.g., circulating tumor cells or disseminated tumor cells. Cancer stem cells, like normal stem cells, may exist at niches in bone marrow. To achieve a cure for MBC, it is necessary to disrupt cancer stem cell–niche interactions or eradicate cancer stem cells. Traditional treatments with cytotoxic or endocrine agents require development in relation to intrinsic subtypes, stem cells, or EMT.

Keywords

Breast cancer CTC DTC Stem cell Epithelial–mesenchymal transition