What is anastrozole?

Anastrozole: A Potent Aromatase Inhibitor for Breast Cancer Risk Reduction and Treatment

Anastrozole is a non-steroidal aromatase inhibitor that works by suppressing estrogen production in postmenopausal women and is primarily used for breast cancer risk reduction and treatment. 1

Mechanism of Action

• Anastrozole selectively inhibits the aromatase enzyme, which converts androgens (primarily androstenedione and testosterone) to estrogens in peripheral tissues, significantly lowering serum estradiol concentrations by approximately 80% after 14 days of daily dosing 1
• Unlike some other medications, anastrozole does not affect adrenal corticosteroid or aldosterone formation, making it a highly selective aromatase inhibitor 1
• The medication has no direct progestogenic, androgenic, or estrogenic activity in animals, but does alter circulating levels of progesterone, androgens, and estrogens 1

Indications

• Anastrozole (1 mg/day orally for 5 years) is recommended as an alternative to tamoxifen, raloxifene, or exemestane to reduce the risk of invasive breast cancer in postmenopausal women at increased risk 2
• It is FDA approved for:
  • Adjuvant treatment of hormone receptor-positive early breast cancer in postmenopausal women
  • First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer
  • Treatment of advanced breast cancer in postmenopausal women with disease progression after tamoxifen therapy 2

Patient Selection

• Women most likely to benefit from anastrozole for breast cancer risk reduction include those with:
  • A diagnosis of atypical (ductal or lobular) hyperplasia or lobular carcinoma in situ
  • An estimated 5-year risk of at least 3% using the National Cancer Institute Breast Cancer Risk Assessment Tool
  • A 10-year risk of at least 5% using the IBIS/Tyrer-Cuzick Risk Calculator
  • A relative risk of at least four times the population risk for women aged 40-44 years or two times the population risk for women aged 45-69 years 2

Contraindications and Precautions

• Anastrozole should not be prescribed for breast cancer risk reduction in premenopausal women 2
• The medication should not be used in pregnant women or those who could become pregnant as it may harm the unborn baby 1
• Prior to initiating anastrozole, clinicians should:
  • Evaluate patients for baseline fracture risk
  • Measure bone mineral density
  • Use caution in postmenopausal women with moderate bone mineral density loss 2
• A history of osteoporosis and/or severe bone loss is a relative contraindication for anastrozole use 2
• Women with severe osteoporosis (T score < -4 or more than two vertebral fractures) were excluded from clinical trials 2

Side Effects and Management

• Common side effects include:
  • Joint stiffness and arthralgias
  • Vasomotor symptoms (hot flashes)
  • Hypertension
  • Dry eyes
  • Vaginal dryness 2
• Gastrointestinal disturbances occur in approximately 29-33% of patients but are generally mild to moderate and transient 3
• Bone health considerations:
  • Anastrozole increases the risk of bone fractures during the treatment period 4
  • All patients receiving anastrozole should be encouraged to exercise regularly and take adequate calcium and vitamin D supplements 2
  • Consider bone-protective agents such as bisphosphonates and RANKL inhibitors for patients at risk of bone loss 2
• Cardiovascular considerations:
  • Women with early breast cancer who have a history of ischemic heart disease may experience increased symptoms of decreased blood flow to the heart 1
  • Patients should seek immediate medical help for new or worsening chest pain or shortness of breath 1

Pharmacokinetics

• Absorption is rapid with maximum plasma concentrations typically occurring within 2 hours under fasted conditions 1
• Food reduces the rate but not the overall extent of absorption 1
• Anastrozole is 40% bound to plasma proteins 1
• Metabolism occurs through N-dealkylation, hydroxylation, and glucuronidation 1
• The pharmacokinetics are linear over the dose range of 1-20 mg and do not change with repeated dosing 1

Clinical Evidence

• The International Breast Intervention Study-II (IBIS-II) randomized, placebo-controlled trial demonstrated that anastrozole (1 mg/day orally for 5 years) reduced the incidence of breast cancer in postmenopausal women at increased risk 2
• Anastrozole has shown superior efficacy to tamoxifen for the first-line treatment of postmenopausal women with hormone-sensitive advanced breast cancer 5
• In clinical trials, anastrozole showed similar clinical efficacy to oral megestrol acetate but with a significant survival advantage in follow-up analyses (median time to death 26.7 vs 22.5 months) 3

By understanding anastrozole's mechanism of action, indications, and side effect profile, healthcare providers can appropriately select patients who will benefit most from this medication while minimizing potential risks.