Breast cancer: current and future endocrine therapies.
Endocrine therapy forms a central modality in the treatment of estrogen receptor positive breast cancer. The routine use of 5 years of adjuvant tamoxifen has improved survival rates for early breast cancer, and more recently has evolved in the postmenopausal setting to include aromatase inhibitors. The optimal duration of adjuvant endocrine therapy remains an active area of clinical study with recent data supporting 10 years rather than 5 years of adjuvant tamoxifen. However, endocrine therapy is limited by the development of resistance, this can occur by a number of possible mechanisms and numerous studies have been performed which combine endocrine therapy with agents that modulate these mechanisms with the aim of preventing or delaying the emergence of resistance. Recent trial data regarding the combination of the mammalian target of rapamycin (mTOR) inhibitor, everolimus with endocrine therapy have resulted in a redefinition of the clinical treatment pathway in the metastatic setting. This review details the current endocrine therapy utilized in both early and advanced disease, as well as exploring potential new targets which modulate pathways of resistance, as well as agents which aim to modulate adrenal derived steroidogenic hormones.
The University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, Liverpool L69 3GA, UK; Liverpool & Merseyside Breast Academic Unit, The Linda McCartney Centre, Royal Liverpool University Hospital, Liverpool L7 8XP, UK; Academic Department of Medical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Wiral CH63 4JY, UK. Electronic address: c.palmieri@liverpool.ac.uk.
Carlo
C
Palmieri
Department of Surgery, Imperial College Healthcare NHS Trust, Fulham Palace Road, London W6 8RF, UK.
Darren K
DK
Patten
Department of Medical Oncology, Imperial College Healthcare NHS Trust, Fulham Palace Road, London W6 8RF, UK.
Adam
A
Januszewski
The University of Manchester, Institute of Cancer Studies, Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK.
Giorgia
G
Zucchini
The University of Manchester, Institute of Cancer Studies, Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK.
Sacha J
SJ
Howell
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D011960:Receptors, Estrogen / Q000378:metabolism
D004967:Estrogens; D011960:Receptors, Estrogen
Breast cancer; Endocrine therapy; Targeted therapy