Exemestane

• Breast Cancer (Hormone Receptor-Positive)
• Adjuvant Breast Cancer Treatment
• Aromatase Inhibitor Therapy
• Estrogen Receptor-Positive Cancer

Exemestane is a steroidal aromatase inhibitor used in the treatment of hormone receptor-positive breast cancer in postmenopausal women. This medication irreversibly inactivates aromatase, reducing estrogen production and thereby slowing the growth of estrogen-dependent tumors.

Mechanism of Action

Exemestane is a steroidal compound structurally related to the natural substrate androstenedione. It acts as a false substrate for the aromatase enzyme complex, binding irreversibly to the enzyme's active site and causing permanent inactivation (suicide inhibition). Unlike non-steroidal aromatase inhibitors (letrozole, anastrozole), which reversibly bind to the enzyme, exemestane's irreversible binding means new enzyme synthesis is required to restore aromatase activity. This results in significant suppression (85-95%) of circulating estrogen levels in postmenopausal women, where aromatization of adrenal androgens is the primary estrogen source. Reduced estrogen levels slow the growth of estrogen receptor-positive breast cancer cells.

Available Formulations

Exemestane is available as oral tablets containing 25 mg. The tablets should be taken once daily after a meal, as food increases absorption by approximately 40%. Generic formulations are available.

Medical Uses

Exemestane is FDA-approved for adjuvant treatment of postmenopausal women with estrogen receptor-positive early breast cancer who have received 2-3 years of tamoxifen and are switched to exemestane to complete a total of 5 consecutive years of adjuvant hormonal therapy, and for treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy. Clinical trials have demonstrated reduced recurrence rates and improved disease-free survival compared to continued tamoxifen.

Dosing Guidelines

The recommended dose is 25 mg once daily after a meal. Treatment should continue until tumor progression (in advanced disease) or for a total of 5 years of adjuvant hormonal therapy (in early breast cancer). For women also receiving strong CYP3A4 inducers, the dose may be increased to 50 mg once daily. No dose titration is required.

Important Safety Information

Exemestane can cause a decrease in bone mineral density; baseline and periodic bone mineral density assessments should be performed. Patients should receive vitamin D and calcium supplementation. The medication should not be used in premenopausal women—premenopausal status should be verified before starting therapy. Elevated liver enzymes, including hepatitis, have been reported. The medication may cause fetal harm; pregnancy should be ruled out before starting therapy.

Drug Interactions

Strong CYP3A4 inducers (rifampin, phenytoin, carbamazepine, St. John's Wort) reduce exemestane exposure; dose increase to 50 mg daily may be considered. Estrogen-containing products should not be used as they may interfere with exemestane's action. No significant interactions with CYP3A4 inhibitors have been observed. Exemestane does not significantly inhibit CYP enzymes at therapeutic concentrations.

Special Populations

Exemestane is contraindicated in premenopausal women and may cause fetal harm. Women of reproductive potential should use effective contraception during treatment and for 1 month after discontinuation. It is unknown whether exemestane is excreted in human breast milk; breastfeeding is not recommended. Safety and efficacy have not been established in pediatric patients. Elderly patients do not require dose adjustment. No dose adjustment is needed for renal impairment. Use with caution in patients with hepatic impairment, though no dose adjustment is recommended based on available data.