What is the recommended treatment with aromatase inhibitors (AIs) for hormone receptor-positive breast cancer in postmenopausal women?

From the Guidelines

Aromatase inhibitors (AIs) are recommended as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer, either as initial therapy or following 2-3 years of tamoxifen, with treatment duration typically being 5 years, though extended therapy for up to 10 years may be considered for high-risk patients, as supported by the most recent guidelines from 2019 1.

Key Considerations

• The standard AI options include anastrozole (1 mg daily), letrozole (2.5 mg daily), or exemestane (25 mg daily) 1.
• AIs can be used in three main approaches: upfront for 5 years, as part of a sequential strategy after 2-3 years of tamoxifen (for a total of 5 years of endocrine therapy), or as extended therapy after completing 5 years of tamoxifen 1.
• These medications work by blocking the aromatase enzyme, which converts androgens to estrogens in postmenopausal women, thereby reducing estrogen levels and inhibiting hormone-dependent tumor growth.

Side Effects and Monitoring

• Common side effects include joint pain, bone loss, and increased fracture risk, so bone density monitoring and supplementation with calcium (1200 mg daily) and vitamin D (800-1000 IU daily) are recommended 1.
• Regular follow-up appointments are essential to monitor treatment adherence, manage side effects, and assess treatment response.

Guidelines and Recommendations

• The 2019 ASCO guidelines recommend that postmenopausal women with hormone receptor-positive breast cancer be offered adjuvant endocrine therapy with an AI, either as initial therapy or after 2-3 years of tamoxifen, for a total duration of up to 10 years 1.
• The guidelines also recommend that women with node-positive breast cancer be offered extended AI therapy for up to a total of 10 years of adjuvant endocrine treatment.

From the FDA Drug Label

EXEMESTANE is an aromatase inhibitor indicated for: • adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to EXEMESTANE for completion of a total of five consecutive years of adjuvant hormonal therapy (14.1). • treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy (14.2). Recommended Dose: One 25 mg tablet once daily after a meal (2.1).

The recommended treatment with aromatase inhibitors (AIs) for hormone receptor-positive breast cancer in postmenopausal women is:

• Adjuvant treatment: EXEMESTANE is indicated for postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to EXEMESTANE for completion of a total of five consecutive years of adjuvant hormonal therapy.
• Treatment of advanced breast cancer: EXEMESTANE is indicated for postmenopausal women whose disease has progressed following tamoxifen therapy. The recommended dose is 25 mg once daily after a meal 2.

From the Research

Aromatase Inhibitors for Hormone Receptor-Positive Breast Cancer

• Aromatase inhibitors (AIs) are the gold standard for treatment of early and advanced breast cancer in postmenopausal women suffering from an estrogen receptor-positive disease 3.
• The currently established group of anti-aromatase compounds comprises two reversible aromatase inhibitors (anastrozole and letrozole) and the irreversible aromatase inactivator exemestane 3.

Recommended Treatment

• Letrozole seems to be the best choice for the majority of breast cancer patients whenever a non-steroidal aromatase inhibitor has to be chosen in a clinical setting 3.
• Aromatase inhibitors provide an alternative to tamoxifen as adjuvant therapy for post-menopausal, hormone-receptor-positive breast cancer patients 4.
• The options include anastrozole and letrozole for five years, as well as anastrozole and exemestane following two to three years of tamoxifen, for a total five years of hormonal therapy 4.
• Five years of letrozole should be considered following five years of tamoxifen 4.

Adverse Effects and Monitoring

• AIs have adverse effects on bone turnover with a reduction of bone mineral density and an increase in the rate of fragility fractures 5.
• AIs present lower thrombotic risk and a less favorable impact on lipid profile, whereas the true effects on cardiovascular risk still remain to be clarified 5.
• An adequate monitoring of bone mineral density (BMD) and lipid profile could be recommended for post-menopausal women candidate to AIs 5.
• Patients receiving aromatase inhibitors should be monitored for changes in bone mineral density and for cardiovascular disease risk factors and outcomes 4.