Letrozole

Letrozole (molecular formula: C17H11N5) is an active substance from the group of non-steroidal aromatase inhibitors. By blocking the aromatases, the remaining oestrogen production in and after menopause decreases significantly. In addition, letrozole directly inhibits the aromatase in the tumour cells, thus limiting the growth and spread of the tumour cells.

Letrozole has no gestagenic, androgenic or estrogenic effect. The effect and strength of the preparation is similar to that of anastrozole.

Aromatase inhibitors such as letrozole switch off the aromatase enzyme. This enzyme is an essential prerequisite for women to be able to produce a small amount of oestrogen even after the menopause. This oestrogen production occurs, for example, in the liver, adrenal glands or fatty tissue, as well as in hormone receptor-positive breast cancer cells. By stopping estrogen production, letrozole also limits the growth of estrogen-dependent tumors such as breast cancer carcinomas and reduces to some extent the likelihood that breast cancer can flare up again.

In the hormone treatment of women with an unfulfilled desire to have children, letrozole has so far been used experimentally without approval to stimulate the maturation of fertilizable eggs. According to the current state of research, letrozole has the advantage of significantly reducing the number of multiple births compared to the standard gonadotropin and clomiphene therapies.

Advanced or metastatic breast cancer in postmenopausal patients

Adults and elderly patients: The recommended dosage is 2.5 mg letrozole once daily.

Duration of therapy:

• advanced or metastatic breast cancer: until progression of the tumor disease
• adjuvant and extended adjuvant therapy: over 5 years or until tumor recurrence
• sequential treatment (2 years of letrozole followed by 3 years of tamoxifen) possible in adjuvant therapy
• neoadjuvant therapy: should be continued for 4 to 8 months to achieve optimal tumor reduction
• if not sufficiently effective, treatment should be discontinued and other treatment options discussed

Children and adolescents

• Letrozole is not recommended in children and adolescents, as the safety and efficacy of letrozole in children and adolescents up to 17 years of age has not been established.

The most common side effects of letrozole result from its anti-hormonal effect and are similar to those of oestrogen deficiency-related menopausal symptoms.
Hot flushes and flushing

Tiredness

headaches

nausea

depression

Sleep disorders

Deterioration of cholesterol levels

osteoporosis

Rarer skin changes: vasculitis, non-specific dermatitis, erythema nodosum, subacute cutaneous lupus erythematosus (see aromatase inhibitors below)

Letrozole has been described in association with radiation recall dermatitis (Sweren E et al. 2021).

The active ingredient was placed on the Prohibited List by the World Anti-Doping Agency (WADA) in 2008. Possession of more than 75 mg is classified as "not small quantity" under the German Medicines Act, in accordance with the Doping Drug Quantity Ordinance.

1. Mamounas EP et al. (2019) Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 20: 88-99.
2. Rugo HS et al. (2019) Palbociclib plus letrozole as first-line therapy in estrogen receptor- positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Breast Cancer Res Treat 174:719-729.

3. Sweren E et al. (2021) Radiation recall dermatitis following letrozole administration in patient with a remote history of radiation therapy. NPJ Breast Cancer 7:62.