What is Exemestane?
Exemestane is an irreversible, steroidal aromatase inactivator (also called an aromatase inhibitor) used to treat hormone receptor-positive breast cancer in postmenopausal women by blocking the enzyme that converts androgens to estrogens, thereby significantly lowering circulating estrogen levels. 1
Mechanism of Action
- Exemestane works as a "suicide inhibitor" by acting as a false substrate for the aromatase enzyme, binding irreversibly to its active site and permanently inactivating it 1
- It suppresses plasma estrogen levels (estradiol, estrone, and estrone sulfate) by 85-95% at the standard 25 mg daily dose 1
- The drug reduces whole body aromatization by 98% in postmenopausal women with breast cancer 1
- Maximal estrogen suppression occurs 2-3 days after dosing and persists for 4-5 days 1
Clinical Uses
Treatment of Advanced Breast Cancer:
- FDA-approved for treating estrogen receptor-positive advanced breast cancer in postmenopausal women whose disease has progressed after tamoxifen therapy 2, 1
- Recommended by the American Society of Clinical Oncology as a first-line option for postmenopausal women with HR-positive metastatic breast cancer 2, 3
Adjuvant Treatment:
- FDA-approved for adjuvant treatment of ER-positive early breast cancer in postmenopausal women 2, 1
- Used sequentially after 2-3 years of tamoxifen to complete 5 years of hormonal therapy 2, 1
Breast Cancer Risk Reduction:
- The American Society of Clinical Oncology recommends exemestane (25 mg daily for 5 years) as an alternative to tamoxifen or raloxifene for reducing invasive breast cancer risk in postmenopausal women age ≥35 years with 5-year projected breast cancer risk ≥1.66% or with lobular carcinoma in situ (LCIS) 2
- Reduces overall invasive breast cancer risk by up to 73% and ER-positive breast cancer by 73% based on the MAP.3 trial 2
Standard Dosing
Side Effects of Exemestane
Common Side Effects
Most Frequent (Early Breast Cancer): 1
- Hot flashes
- Headache
- Fatigue
- Trouble sleeping (insomnia)
- Joint pain (arthralgias)
- Increased sweating
Most Frequent (Advanced Breast Cancer): 1
- Hot flashes
- Increased sweating
- Nausea
- Increased appetite
- Fatigue
Additional Common Side Effects: 2
- Muscle pain (myalgias)
- Diarrhea
- Constitutional and gastrointestinal symptoms
Serious Side Effects
Bone Loss (Most Important):
- Exemestane decreases bone mineral density (BMD) and increases fracture risk 2, 1
- Causes statistically significant reduction in BMD at the distal tibia, distal radius, lumbar spine, total hip, and femoral neck 2
- Worsens age-related bone loss despite calcium and vitamin D supplementation 2
- Bone monitoring is required during treatment, and adequate vitamin D and calcium supplementation must be provided 2
Quality of Life Effects: 2
- Statistically significant increase in vasomotor symptoms (hot flashes, sweating)
- Bodily pain
- Sexual problems
Fertility:
- May cause decreased fertility in males and females 1
Important Safety Considerations
No Significant Increase in Serious Events:
- The MAP.3 trial showed no statistically significant differences in cardiovascular events, skeletal fractures, other cancers, or treatment-related deaths compared to placebo 2
- Mortality rates were not different between exemestane and placebo groups 2
Contraindications and Precautions: 1
- Do not use in premenopausal women (only for postmenopausal women)
- Contraindicated in pregnancy (can harm unborn baby)
- Females of childbearing potential need pregnancy test within 7 days before starting and must use effective contraception during treatment and for 1 month after
- Do not breastfeed during treatment and for 1 month after last dose
- Should not be taken with estrogen-containing medications (hormone replacement therapy, birth control pills/patches)
Tolerability Profile: