Metabolic reprograming confers tamoxifen resistance in breast cancer

Chem Biol Interact. 2021 Sep 25;347:109602. doi: 10.1016/j.cbi.2021.109602. Epub 2021 Jul 28.


Breast cancer is the most common cancer among females and the leading cause of cancer-related deaths. Approximately 70 % of breast cancers are estrogen receptor (ER) positive. An ER antagonist such as tamoxifen is used as adjuvant therapy in ER-positive patients. The major problem with endocrine therapy is the emergence of acquired resistance in approximately 40 % of patients receiving tamoxifen. Metabolic alteration is one of the hallmarks of cancer cells. Rapidly proliferating cancer cells require increased nutritional support to fuel various functions such as proliferation, cell migration, and metastasis. Recent studies have established that the metabolic state of cancer cells influences their susceptibility to chemotherapeutic drugs and that cancer cells reprogram their metabolism to develop into resistant phenotypes. In this review, we discuss the major findings on metabolic pathway alterations in tamoxifen-resistant (TAMR) breast cancer and the molecular mechanisms known to regulate the expression and function of metabolic enzymes and the respective metabolite levels upon tamoxifen treatment. It is anticipated that this in-depth analysis of specific metabolic pathways in TAMR cancer might be exploited therapeutically.

Keywords: Breast cancer; Estrogen receptor; Metabolism; Tamoxifen; Tamoxifen resistance.

Publication types

  • Review

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / physiology*
  • Energy Metabolism / physiology
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Lipid Metabolism / physiology
  • Nucleic Acids / metabolism
  • Tamoxifen / therapeutic use*


  • Amino Acids
  • Nucleic Acids
  • Tamoxifen