John R Benson1, Vassilis Pitsinis. 1. Cambridge Breast Unit, Department of Surgery, Addenbrooke's Hospital, Cambridge, UK. john.benson@addenbrookes.nhs.uk
Abstract
PURPOSE OF REVIEW: Breast cancer is the most common malignancy amongst women in the United States and decreased mortality over the past decade has been attributed to a combination of screening and adjuvant therapies. There has been a resurgence of interest in hormonal therapies and this article discusses the clinical status of tamoxifen in the context of emerging alternative agents for treatment and prevention of breast cancer. RECENT FINDINGS: Tamoxifen has served as a prototype for the development of selective estrogen receptor modulators at the laboratory-clinical interface. Molecular technologies have permitted elucidation of mechanisms for tissue specific action and led to newer selective estrogen receptor modulators with potentially greater antitumour efficacy and attenuated uterotrophic profile. Publications over the past 12 months have emphasized the risks of thromboembolism and endometrial carcinoma associated with tamoxifen use which has accelerated application of other hormonal agents for treatment of advanced disease and as neoadjuvant therapy. This article reviews the current role of tamoxifen in the treatment of early and advanced breast cancer together with its potential for chemoprevention. Models for quantitative risk assessment are being developed to identify women for whom chemoprotection is justified. SUMMARY: Recent data showing a survival advantage for the aromatase inhibitor letrozole compared with tamoxifen in the advanced setting and improvement in disease-free survival for the aromatase inhibitor anastrozole versus tamoxifen as adjuvant treatment may herald a major shift in standard first-line endocrine therapies for both advanced and early disease and ultimately chemoprevention of breast cancer. Other agents including newer SERMs and pure antiestrogens are undergoing phase III clinical trials and future endocrine and biological therapies are likely to include more selective and targeted therapies, which may be efficacious in both hormone-sensitive and receptor-negative disease.
PURPOSE OF REVIEW: Breast cancer is the most common malignancy amongst women in the United States and decreased mortality over the past decade has been attributed to a combination of screening and adjuvant therapies. There has been a resurgence of interest in hormonal therapies and this article discusses the clinical status of tamoxifen in the context of emerging alternative agents for treatment and prevention of breast cancer. RECENT FINDINGS:Tamoxifen has served as a prototype for the development of selective estrogen receptor modulators at the laboratory-clinical interface. Molecular technologies have permitted elucidation of mechanisms for tissue specific action and led to newer selective estrogen receptor modulators with potentially greater antitumour efficacy and attenuated uterotrophic profile. Publications over the past 12 months have emphasized the risks of thromboembolism and endometrial carcinoma associated with tamoxifen use which has accelerated application of other hormonal agents for treatment of advanced disease and as neoadjuvant therapy. This article reviews the current role of tamoxifen in the treatment of early and advanced breast cancer together with its potential for chemoprevention. Models for quantitative risk assessment are being developed to identify women for whom chemoprotection is justified. SUMMARY: Recent data showing a survival advantage for the aromatase inhibitor letrozole compared with tamoxifen in the advanced setting and improvement in disease-free survival for the aromatase inhibitor anastrozole versus tamoxifen as adjuvant treatment may herald a major shift in standard first-line endocrine therapies for both advanced and early disease and ultimately chemoprevention of breast cancer. Other agents including newer SERMs and pure antiestrogens are undergoing phase III clinical trials and future endocrine and biological therapies are likely to include more selective and targeted therapies, which may be efficacious in both hormone-sensitive and receptor-negative disease.