Use of endocrine therapy to study the biology of breast cancer.
Drug resistance is the main reason for therapeutic failure and death in breast cancer. In vitro investigations have identified some mechanisms that may be responsible for resistance to chemotherapeutic agents in breast cancer, but we know little about the mechanisms responsible for resistance to endocrine treatment in receptor-positive tumors. Accordingly, a major task for future studies is to explore the mechanisms of both primary and acquired resistance to endocrine treatment as well as to chemotherapy in breast cancer. Drug resistance may be related to alterations in endocrine as well as paracrine delivery of certain growth factors or hormones, but it may also be caused by alterations in drug disposition. Primary resistance may be evaluated by comparing the response to drug treatment with the expression of different biochemical parameters in the tumor before treatment. To explore the mechanisms of acquired drug resistance requires study of the changes in biological parameters developing over time during drug therapy. Also, it may be of interest to use certain drugs (like a 'classical' anti-estrogen and a steroidal anti-estrogen) in a particular sequence to explore the possibility of cross-resistance (or lack of it) between particular treatment modalities. Possible implications for the design of future trials in breast cancer treatment are discussed.
Lønning
E
E
Department of Oncology, University of Bergen, Haukeland Hospital, Norway.
D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000503:physiopathology* / Q000628:therapy*; D004351:Drug Resistance; D005260:Female; D006133:Growth Substances / Q000627:therapeutic use; D006801:Humans; D011372:Progestins / Q000008:administration & dosage / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000502:physiology; D013629:Tamoxifen / Q000627:therapeutic use
D047072:Aromatase Inhibitors; D006133:Growth Substances; D011372:Progestins; D011960:Receptors, Estrogen; D013629:Tamoxifen