From the Guidelines
Letrozole is recommended as a first-line treatment for hormone receptor-positive breast cancer in postmenopausal women, due to its efficacy in reducing estrogen levels and improving disease-free survival, as shown in the most recent study from 2024 1. The standard dose of letrozole is 2.5 mg taken orally once daily, typically continued for 5-10 years in early-stage hormone receptor-positive breast cancer.
- It works by blocking the enzyme aromatase, which converts androgens to estrogens, thereby reducing estrogen levels in the body.
- This is particularly effective for treating estrogen receptor-positive breast cancers that depend on estrogen for growth.
- Letrozole is also used off-label for ovulation induction in infertility treatment at doses of 2.5-5 mg daily for 5 days early in the menstrual cycle. Common side effects of letrozole include:
- Hot flashes
- Joint pain
- Muscle aches
- Fatigue
- Bone loss with long-term use Patients should take calcium and vitamin D supplements and have regular bone density tests while on letrozole, as shown in the study from 2019 1. The medication should be taken at the same time each day with or without food, and patients should not stop taking it without consulting their healthcare provider, even if they feel well. It is essential to note that letrozole has different side effect profiles compared to tamoxifen, with a higher incidence of musculoskeletal symptoms, osteoporosis, and increased rate of bone fracture, as reported in the study from 2009 1. However, the most recent study from 2024 1 provides the strongest evidence for the use of letrozole as a first-line treatment, and its findings should be prioritized in clinical practice.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Letrozole Overview
- Letrozole is a highly selective, nonsteroidal, third-generation aromatase inhibitor approved for first-line and extended adjuvant therapy in postmenopausal women with hormone-responsive, early-stage breast cancer 2.
- It works by binding to the haeme component of the cytochrome P450 subunit of aromatase, inhibiting estrogen biosynthesis throughout the body 2.
Efficacy and Safety
- Letrozole has been shown to significantly prolong disease-free survival (DFS) and reduce the risk of relapse at distant sites relative to tamoxifen in postmenopausal women with hormone-responsive, early-stage breast cancer 2, 3.
- Extended adjuvant therapy with letrozole has also been shown to significantly prolong DFS relative to placebo treatment in postmenopausal women who were disease-free after 4.5-6 years of tamoxifen therapy 2.
- Letrozole treatment is generally well tolerated, with common adverse effects including hot flushes, arthritis, arthralgia, and myalgia, as well as a trend towards increased risk of fracture 4.
Comparison to Other Aromatase Inhibitors
- Letrozole has been compared to other aromatase inhibitors, such as anastrozole and exemestane, in terms of efficacy and pharmacokinetics 5, 6.
- While all three aromatase inhibitors have shown clinical efficacy, there are differences in terms of pharmacokinetics and effects on lipid levels and adrenosteroidogenesis 6.
- 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, based on available evidence 5.