What is the recommended treatment and management for breast cancer using Letrozole (Femara)?

From the Guidelines

Letrozole (Femara) is recommended as a first-line treatment for postmenopausal women with hormone receptor-positive breast cancer, at a standard dose of 2.5 mg taken orally once daily, due to its efficacy in reducing recurrence risk and improving disease-free survival, as demonstrated in recent studies such as the BIG 1-98 trial 1.

Key Considerations

• Letrozole is used as adjuvant therapy for 5-10 years after surgery to reduce recurrence risk in early-stage breast cancer, and treatment continues until disease progression or unacceptable toxicity occurs in metastatic breast cancer.
• Common side effects include hot flashes, joint pain, fatigue, and bone density loss, so regular bone density scans and calcium/vitamin D supplementation are recommended.
• Patients should have periodic liver function tests and cholesterol monitoring, as letrozole can affect liver function and lipid profiles.
• Letrozole works by inhibiting aromatase, an enzyme that converts androgens to estrogens, thereby dramatically reducing estrogen levels and depriving hormone-sensitive breast cancer cells of the estrogen they need to grow.

Efficacy and Safety

• The BIG 1-98 trial demonstrated that letrozole is superior to tamoxifen in terms of disease-free survival, with a hazard ratio of 0.81 (95% CI, 0.70-0.93; P = .003) 1.
• The NCIC-CTG MA-17 trial showed a survival advantage with extended therapy with letrozole compared with placebo in patients with ALN-positive (but not lymph node-negative), ER-positive breast cancer 1.
• Letrozole may also be used neoadjuvantly before surgery to shrink tumors, and its efficacy and safety have been established in several clinical trials, including the ATAC trial and the IES trial 1.

Quality of Life

• Letrozole has been shown to have a similar quality of life profile to tamoxifen, with most patients reporting that overall quality of life was not significantly impaired 1.
• However, letrozole may cause more bone fractures and musculoskeletal symptoms than tamoxifen, so regular monitoring and management of these side effects are necessary.
• The SOLE trial demonstrated that continuous letrozole therapy may have a better quality of life profile than intermittent therapy, with fewer vaginal problems and musculoskeletal pain 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE 1.1 Adjuvant Treatment of Early Breast Cancer Letrozole Tablets, USP are indicated for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer. 1.2 Extended Adjuvant Treatment of Early Breast Cancer Letrozole Tablets, USP are indicated for the extended adjuvant treatment of early breast cancer in postmenopausal women, who have received 5 years of adjuvant tamoxifen therapy 1.3 First and Second-Line Treatment of Advanced Breast Cancer Letrozole Tablets, USP are indicated for first-line treatment of postmenopausal women with hormone receptor positive or unknown, locally advanced or metastatic breast cancer. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dose The recommended dose of Letrozole tablets is one 2.5 mg tablet administered once a day, without regard to meals.

The recommended treatment and management for breast cancer using Letrozole (Femara) is as follows:

• Adjuvant treatment: Letrozole is indicated for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer.
• Extended adjuvant treatment: Letrozole is indicated for the extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy.
• First and second-line treatment of advanced breast cancer: Letrozole is indicated for first-line treatment of postmenopausal women with hormone receptor positive or unknown, locally advanced or metastatic breast cancer.
• Recommended dose: The recommended dose of Letrozole is 2.5 mg administered once a day, without regard to meals 2.

From the Research

Treatment and Management of Breast Cancer using Letrozole

• Letrozole is an oral reversible nonsteroidal aromatase inhibitor that inhibits peripheral aromatase by over 98% and suppresses blood and urinary estrogen levels by over 95% after 2 weeks of treatment in postmenopausal women 3.
• The recommended dose of letrozole is 2.5 mg/day, which has been shown to achieve objective response rates of 19.5 and 23.6% in phase IIb/III trials 3.
• Letrozole has a good short-term tolerability profile, with common adverse events including headache, nausea, fatigue, hot flushes, and peripheral oedema 3.

Adjuvant and Extended Adjuvant Therapy

• Letrozole is more effective than tamoxifen in postmenopausal women with hormone-responsive early breast cancer, and extended adjuvant therapy with letrozole after the completion of adjuvant tamoxifen therapy is more effective than placebo 4.
• Letrozole should be considered a valuable option in the treatment of postmenopausal women with hormone-responsive early breast cancer, both as adjuvant and extended adjuvant therapy 4.

Bone Loss and Osteoporosis

• Aromatase inhibitors, including letrozole, are associated with significantly more osteoporotic fractures and greater bone mineral loss 5.
• Bisphosphonate therapy, such as zoledronic acid, should be prescribed for patients with osteoporosis (T score < -2.5) and considered on an individual basis for those with osteopenia (T score < -1) 5.
• Zoledronic acid has been shown to prevent bone loss in postmenopausal women with osteoporosis/osteopenia starting letrozole and is associated with improvements in bone mineral density 6.

Combination Therapy

• The combination of letrozole and other agents, such as lapatinib and everolimus, has been shown to improve overall disease outcome in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer 7.
• The coadministration of letrozole and trastuzumab can overcome resistance to both drugs administered as single agents in patients with advanced breast cancer 7.