Letrozole (Femara)

Raw research findings for this medication. Mostly single studies, not curated or confirmed robust.

About Letrozole

What it is

Letrozole is an aromatase inhibitor: it blocks aromatase, the enzyme that makes oestrogen in fat and other tissues, the main source of oestrogen after the menopause. It is used for hormone receptor-positive breast cancer in postmenopausal women, and off label to bring on ovulation in fertility treatment. It is sold as Femara, among other names.

How genes come into it

Letrozole is broken down mainly by CYP2A6 and CYP3A4. Studies have linked low-activity CYP2A6 versions to higher letrozole levels, and variants in CYP19A1, the aromatase gene itself, and in the oestrogen receptor gene ESR1 to oestrogen levels, response and side effects such as joint pain and bone loss. The findings come from single or a few studies, and there is no CPIC or DPWG guideline.

What research found

Every published finding on gene variants and Letrozole. Upload your DNA file to see which of these rows apply to you.

Rated evidence (19 rated variants)

PharmGKB weighs all studies of a variant and rates how strong the evidence is, from 1A (strongest) to 4.

CYP2A6 CYP2A6*1, CYP2A6*2, CYP2A6*4, CYP2A6*7, CYP2A6*9, CYP2A6*12, CYP2A6*17, CYP2A6*20, CYP2A6*23, CYP2A6*35, CYP2A6*46: Level 3. Metabolism/PK: Breast Neoplasms. 3.

CYP19A1 rs10046: Level 3. Other: Breast Neoplasms, Menopause. 1.

ESR1 rs2234693: Level 3. Toxicity: Neoplasms. 1.

ESR1 rs9340799: Level 3. Toxicity: Neoplasms. 1.

Metabolism (4 findings)

Studies of how quickly the body processes this medication.

CYP2A6 CYP2A6*1, CYP2A6*2, CYP2A6*4, CYP2A6*9, CYP2A6*12: CYP2A6 *1/*1 (assigned as normal metabolizer phenotype) is associated with decreased concentrations of letrozole in women with Breast Neoplasms as compared to CYP2A6 *1/*2 + *1/*4 + *1/*9 + *1/*12 + *9/*9 (assigned as poor metabolizers and intermediate metabolizers phenotype) .

CYP2A6 CYP2A6*1, CYP2A6*2, CYP2A6*4, CYP2A6*9, CYP2A6*12, CYP2A6*17, CYP2A6*20, CYP2A6*23, CYP2A6*35: CYP2A6 *1/*17 + *20/*23 + *9/*9 + *1/*4 + *1/*2 + *17/*17 + *17/*35 + *2/*9 + *9/*12 + *1/*9 + *1/*12 are associated with decreased clearance of letrozole in women with Breast Neoplasms as compared to CYP2A6 *1/*1.

CYP2A6 CYP2A6*1, CYP2A6*26: CYP2A6 *1/*26 is associated with metabolism of letrozole in women with Breast Neoplasms.

CYP2A6 CYP2A6*1, CYP2A6*4, CYP2A6*7, CYP2A6*9, CYP2A6*46: CYP2A6 *1/*46 + *1/*46 + *46/*46 are associated with increased clearance of letrozole in women as compared to CYP2A6 *1/*4 + *1/*9 + *46/*4 + *46/*7 + *46/*9 + *4/*7 + *4/*9 + *7/*9 + *9/*9.

Response (4 findings)

Studies of how well it worked in people carrying a variant.

CYP19A1 rs4646: Genotype AA is associated with decreased response to anastrozole, letrozole or tamoxifen in women with Breast Neoplasms and Menopause as compared to genotypes AC + CC.

CYP19A1 rs4646: Genotype AA is associated with increased response to anastrozole, letrozole or tamoxifen in women with Breast Neoplasms as compared to genotypes AC + CC.

CYP2A6 CYP2A6*1, CYP2A6*4, CYP2A6*9: CYP2A6 *1/*9 + *1/*4 + *4/*4 + *4/*9 (assigned as intermediate metabolizer and poor metabolizer phenotype) is associated with increased clinical benefit to letrozole in women with Breast Neoplasms as compared to CYP2A6 *1/*1 (assigned as normal metabolizer phenotype) .

CYP19A1 rs4646: Allele A is associated with increased clinical benefit to letrozole in people with Breast Neoplasms as compared to allele C.

Other findings (3 findings)

Studies that do not fall into the groups above.

rs7937: Allele C is associated with increased concentrations of letrozole in women with Breast Neoplasms as compared to allele T.

CYP2A6 CYP2A6*1, CYP2A6*35: CYP2A6 *1/*35 is associated with metabolism of letrozole in women with Breast Neoplasms.

CYP2A6 rs56113850: Allele T is associated with increased concentrations of letrozole in women with Breast Neoplasms as compared to allele C.

Study findings and evidence levels: PharmGKB (CC BY-SA 4.0). Guidelines: CPIC and DPWG, as bundled in PharmCAT. Most studies were done mainly in people of European ancestry.

Related Drugs

More drugs from the same category

Arimidex (Aromatase Inhibitors)

Aromasin (Aromatase Inhibitors)

5-FU (Antimetabolites)

Not a prescribing recommendation. This page is educational information about pharmacogenomic research and clinical guidelines - it is not medical or dosing advice, and not a prediction of how any medication will work for you. Never start, stop, or change a medication or dose based on it; talk to your doctor or pharmacist, who can order clinical-grade testing if appropriate.

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Content updated September 2026.

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