The Johns Hopkins Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
Address for correspondence: Antonio C. Wolff, M.D., Division of Medical Oncology, The Johns Hopkins Oncology Center, Cancer Research Building, 1650 Orleans Street, Room 189, Baltimore, MD 21231-1000. Voice: 410-614-4192; fax: 410-955-0125.
awolff{at}jhmi.edu
Tamoxifen was the first in a class of drugs now commonly referred
to as selective estrogen receptor modulators or SERMs. SERMs
exhibit tissue-specific estrogenic agonist/antagonist activity
through their ability to bind to the estrogen receptor
(ER)
protein and interact with coregulatory proteins, thereby modulating
transcription of estrogen target genes. Since its first approval
by the United States Food and Drug Administration (FDA) in 1977,
tamoxifen has been found to (a) lower the risk of recurrence
and death for women with early-stage hormone receptor-positive
breast cancer, irrespective of menopausal and node status or
use of adjuvant chemotherapy; (b) reduce the risk of invasive
breast cancer following breast conservation in women with ductal
carcinoma
in situ (DCIS); and (c) reduce the risk of breast
cancer in high-risk women. Toremifene is the only other SERM
approved by the FDA for breast cancer treatment. However, it
offers no clear clinical advantage over tamoxifen in the adjuvant
or metastatic settings. Several other SERMs are in various phases
of clinical development. In addition, strategies to combine
SERMs with other endocrine therapy like ovarian suppression
or aromatase inhibitors are active areas of investigations.
At present, SERMs are recognized as the first targeted and relatively
nontoxic medical therapy for women with high-risk or steroid
hormone receptor-positive breast cancer.
