Selective oestrogen receptor modulators/new antioestrogens: a clinical perspective

Area of Science:

• Oncology
• Pharmacology
• Endocrinology

Background:

• Tamoxifen, the first selective oestrogen receptor modulator (SERM), paved the way for new antioestrogen therapies.
• First-generation SERMs showed cross-resistance and uterine agonist effects, limiting their utility.
• Second-generation SERMs and high-dose oestrogens have shown mixed results in advanced breast cancer treatment.

Purpose of the Study:

• To review the development and efficacy of antioestrogens, including SERMs and pure oestrogen receptor antagonists.
• To evaluate the clinical potential of fulvestrant as a novel treatment for advanced breast cancer.
• To explore therapeutic sequencing strategies involving fulvestrant, tamoxifen, and aromatase inhibitors.

Main Methods:

• Review of clinical trial data and pharmacological studies on various antioestrogens.
• Comparison of response rates and adverse effects between different drug classes.
• Analysis of cross-resistance patterns and potential for sequential therapy.

Main Results:

• Fulvestrant, a pure oestrogen receptor antagonist, demonstrates high response rates in postmenopausal women with advanced breast cancer.
• Fulvestrant exhibits no cross-resistance with SERMs or aromatase inhibitors (AIs).
• Fulvestrant shows comparable efficacy to anastrozole in patients progressing after prior antioestrogen therapy.

Conclusions:

• Fulvestrant represents a significant advancement in breast cancer treatment, offering a new mechanism of action.
• Pure antioestrogens like fulvestrant provide valuable options for therapeutic sequencing.
• Fulvestrant holds promise for improving outcomes in advanced breast cancer management.