How Does Letrozole Work for Breast Cancer?
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Letrozole - Indications, Contraindications, and Pharmacology

Published on Feb 13, 2024   -  10 min read


Letrozole is a highly potent and efficacious medicine that can deal with breast cancer.


Letrozole is a widely employed medication that is primarily advised for tackling breast cancer. The drug regulatory authority of the United States, the Food and Drug Administration (FDA), authorized and endorsed the usage of Letrozole in patients detected with breast cancer. Letrozole attained FDA authorization in the year 1998, and since then, it has been widely prescribed for those who are diagnosed with breast cancer in the advanced stage. In 2004, the FDA also granted authorization for using Letrozole as an adjuvant therapy when breast cancer is in its initial stage. However, its application is restricted to women who have attained menopause. It is now marketed and circulated under various brand names and is available from pharmacies upon production of a doctor’s prescription.

Drug Group:

Letrozole falls under the nonsteroidal aromatase inhibitor drug class, where the drug molecules potentially depreciate the level of female hormone estrogen by a series of steps. Once the estrogen level collapses considerably, the breast cancer cells, which are largely dependent on this hormone, fail to thrive and advance.

Available Doses and Dosage Forms:

Letrozole is manufactured in a single dosage strength of 2.5 milligrams (mg). The medicine is intended to be taken by mouth and is available in tablet form. The FDA approves no other drug form of Letrozole for dealing with breast cancer.

For Patients:

What Is Breast Cancer?

Breast cancer is a typical form of cancer, where abnormal cell growth and multiplication are elicited in the breast.As the human breast is an amalgamation of different cell types, breast cancer also differs based on the cell type that elicits cancerous properties. Lump or thickening in the breast is the most common frequently encountered manifestation associated with breast cancer. Some patients may notice alterations in the breast shape, abnormal discharge, tenderness, and skin changes, particularly in the nipple region.

Breast cancers are mostly encountered in over 50 age groups. The presence of certain genetic alterations is capable of enhancing the likelihood of developing breast cancer. Similarly, familial association of breast cancer also enhances the breast cancer risk. Individuals having susceptible risk factors are advised to undergo periodic screening to expose breast cancers in the early stage. Mammograms are employed for the purpose of breast cancer detection. In the initial stages, the abnormal growth will be confined within the breast, and as the cancer advances, it extends into nearby structures. Prompt therapeutic interventions at the initial stage can potentially curb cancer progression.

How Does Letrozole Work?

Being a nonsteroidal aromatase inhibitor, Letrozole mitigates the bodily estrogen level. Letrozole is found to be fruitful for those breast cancers that are responsive to estrogen. The drug molecule interacts with an enzyme that is concerned with estrogen synthesis. The interaction blocks the enzyme activity, thereby checking estrogen production. In this way, Letrozole makes the cancer cells starve for estrogen and checks further proliferation.

What Is the Dosage of Letrozole?

The generally prescribed daily dosage of Letrozole is 2.5 mg, often advised to be taken as a single dose. However, the dosage may be altered in the presence of other underlying health conditions. The patients are strictly instructed to stick to the dosage regimen advised by the concerned doctor. Altering the dosage without medical consultation can make the drug ineffective or can bring in adverse complications.

How Effective Is Letrozole?

Letrozole is proven to be efficacious against estrogen-responsive breast cancer. It also demonstrated a considerable decline in the cancer spreading rate. Letrozole therapy also depreciates the possibility of reoccurrence of breast cancer following eradication of the primary breast cancer. Recurrence prevention by Letrozole overrides the recurrence prevention exhibited by other standard therapies like Tamoxifen.

What Are the Things to Inform the Doctor Before Taking the Drug?

Before initiating any treatment, it is necessary to have a proper discussion with the doctor. It enables the doctor to establish a rapport with the patients and facilitates the treatment.

  • Previous hypersensitivity encounters with Letrozole or any of the components listed among the Letrozole pill ingredients need to be informed before Letrozole therapy initiation. Subsequent exposure to the allergic component can trigger severe adverse reactions in the body.

  • It is imperative to provide a comprehensive medical history of the patient. Understanding the health status of the patient aids the concerned doctors in determining the right medicine choice that is apt for the person’s health condition. The medical history should underscore the underlying health conditions, past surgeries, and all other health-related events. Liver diseases, osteoporosis (impaired bone density), and enhanced cholesterol levels must be drawn to the doctor’s attention before commencing the therapy using Letrozole.

  • Detailed drug history encompassing all the medications, be it herbal, non-prescription, hormonal, or dietary supplements, needs to be provided so that unpleasant drug-to-drug associations can be tackled beforehand. Hormonal contraceptives and other hormonal therapies require special emphasis, and the doctor should be informed about it.

  • Letrozole is indicated for reproductively inactive women who have attained menopause and not for reproductively active females. Letrozole is not safe during pregnancy, and if the patient is still capable of conception, the doctor should be made aware of it.

How Is Letrozole Administered?

Being manufactured in tablet form, Letrozole is advised to be taken orally, preferably with a tumbler of water. The pill should always be intact and chewed. Instead, the Letrozole pill should be consumed as a whole. It is better to stick to a specific time for the pill administration as it aids in keeping the drug concentration consistent throughout the treatment regimen.

What Are the Side Effects of Letrozole?

Letrozole can bring in a spectrum of adverse effects. Some effects are minor, while some are alarming and necessitate medical attention. Some of the frequently encountered side effects include the following:

  • Digestive issues like constipation, diarrhea, loss of appetite, vomiting, and acid reflux (heartburn).

  • Hormonal issues like hair loss, night sweats, hot flashes (experiences sudden intense heat), and altered body weight.

  • Other side effects like body pain, stomach pain, headache, impaired vision, breast pain, tiredness, puffy arms and legs, tiredness, troubled sleeping, and vaginal bleeding.

In addition, Letrozole may also bring about certain alarming adverse reactions in the form of extensive skin rashes, troubled breathing, abnormal skin bruising, yellowish skin, slurred speech, severe tiredness, and collapse. In such reactions, immediate medical care needs to be sought.

Dietary Considerations:

There are no specific dietary instructions that need to be adhered to. The presence of food does not seem to alter the working mechanism of Letrozole significantly. However, considering other underlying medical conditions, doctors may advise certain dietary restrictions for certain patients, which should be followed without fail.

Missed Dose:

Proper adherence to the treatment regimen is essential to ensure the effectiveness of Letrozole. However, the patient may sometimes need to remember the dose administration. The overlooked dose can be taken once the patient becomes aware of the missed pill. However, if the patient recalls the missed dose at the time of the next dose, it is advised to forgo it. No attempt should be made to alter the drug dosage to cover up for the overlooked dose.


Consuming more than the intended dosage of Letrozole can bring in potential overdose issues. There is not much information available concerning overdose. Emesis (induced vomiting) aids in throwing out the gut content, which could bring down the severity of overdose. Following this, the patient should be kept under surveillance to keep track of the vital parameters and ensure normal organ functioning.


Letrozole is available in both blister packaging and medicine bottles. Keeping the medicine in the same packaging is advised until it is time for take medicine. 25 degrees Celsius (77 degrees Fahrenheit) is the ideal temperature that is advised for Letrozole storage. However, storage temperature within the range of 15 to 30 degrees Celsius (59 to 86 degrees Fahrenheit) is also reported to be safe for Letrozole’s storage. Ensure that the medicine is within its usage period. Medicines that are out of date can be disposed of through drug take-back programs.

For Doctors:


  • Early Breast Cancer: Letrozole is employed as adjuvant therapy for dealing with early-stage breast cancers which are tested positive for hormone receptors. It is also indicated for extended adjuvant therapy, following adjuvant therapy using Tamoxifen for a period of five years.

  • Advanced Breast Cancer: Metastatic breast cancers and locally advanced breast cancers, which are hormonally responsive, are indicated with Letrozole therapy as both the first and second line of therapy.


A daily dose of 2.5 milligrams of Letrozole is the preferred dosage schedule for breast cancer patients. The dosage remains more or less the same for all the patients. However, the duration of the therapy is determined by taking into consideration the stage of the breast cancer.

Dosing Considerations:

The dosing frequency is modified considering the functional status of the other vital organs like the kidney and liver. Patients with moderately compromised liver function well tolerate a daily dose of 2.5 milligrams of Letrozole. However, the presence of severe liver dysfunction and liver cirrhosis mandates dose depreciation, and hence, the frequency of intake is extended to alternate days instead of daily basis. Similarly, dosage depreciation is advised for kidney patients with creatinine clearance rates below 10 milliliters per minute.

What Are the Pharmacological Aspects of Letrozole?

  • Mechanism of Action: A specific category of breast cancers is hormonally responsive. In hormonally responsive breast cancers, the cancer cells are fed by hormones like estrogen and progesterone. Therefore, by checking the hormonal availability, the cancer growth and progression can be hampered and impeded significantly. This principle is being employed by using Letrozole for breast cancer. Adrenal androgens are the primary source of estrogen in women who have attained menopause. Adrenal androgens are acted upon by the aromatase enzyme, which facilitates estrogen synthesis. Letrozole works by modifying the activity of the aromatase enzyme and hinders estrogen production by establishing a bond with the enzyme molecules. Structurally and functionally modified aromatase enzymes fail to process the adrenal androgens and thereby curb estrogen production. Once the estrogen level is depleted, the cancer cell growth will be directly hindered. Thus, Letrozole efficiently tackles the progression.

  • Pharmacodynamics: Aromatase inhibition elicited by Letrozole is highly precise, so the adrenal steroidogenesis process is left unhindered. Other bodily hormones like thyroid hormone, luteinizing hormone, aldosterone, and follicle-stimulating hormone levels remain the same without any change. The depreciation in the estrogen level is directly influenced by the dosage of Letrozole that is administered.

  • Pharmacokinetics: Following oral intake, Letrozole reaches the intestine, which is uptaken instantly into the bloodstream. 1.9 liters per kilogram is reported to be the Letrozole’s mean volume of distribution. Liver microsomal enzymes, particularly CYP3A4 (cytochrome P3A4) and CYP2A6 are concerned with the breakdown of the Letrozole drug molecules. A major proportion of the breakdown product is carbinol metabolite, while ketone analog and other metabolic products are also identified in a smaller proportion. Urine is the primary elimination pathway for Letrozole.


Instances of clinical toxicity are fewer, and no grave toxicity issues reported to date. There is only limited information available concerning the mutagenic and carcinogenic properties of Letrozole. However, nonclinical study reports revealed Letrozole’s potential for inducing hepatocellular and ovarian cancers when tested at a higher dosage level.

Clinical Studies:

Various clinical studies and trials have been conducted to expose the efficacy of Letrozole in dealing with hormone-sensitive breast cancers. Randomized comparative clinical trials were conducted for Tamoxifen and Letrozole, and the therapeutic benefits elicited by Letrozole therapy were on par with that of Tamoxifen. Certain studies demonstrated Letrozole’s upper hand in checking and delaying the recurrence of breast cancer lesions following long-term therapy. The studies conducted on advanced breast cancer patients diagnosed with either metastatic breast cancer or locally advanced cancer flagged an appreciable rise in the survival rate when compared with subjects who were trialed with Tamoxifen therapy for the same duration. Numerous clinical studies have unequivocally proved the safety and effectiveness of Letrozole.

What Are the Contraindications of Letrozole?

Letrozole possesses certain potential contraindications and is not advised for all categories of breast cancer patients. Some of the contraindications for Letrozole include the following:

  • Letrozole Allergy: Patients with prior allergic encounters with Letrozole are not supposed to undergo Letrozole therapy. Previous hyperreactivity to any of the components of the Letrozole pill is also a potential threat to allergic response upon Letrozole therapy initiation.

  • Pregnancy: Letrozole is designed and advised for post-menopausal women and not for premenopausal women who are particularly in the reproductive age group. Letrozole can bring deleterious effects on the baby in the womb when taken during pregnancy. Therefore, expectant women are not supposed to undergo Letrozole therapy. In addition, if the patient is planning for conception in the near future, they are also contraindicated for Letrozole therapy.

Warnings and Precautions:

  • Bone Density Depletion: Prolonged exposure to Letrozole can result in deterioration of bone density. Therefore, keeping track of the bone mineral density at specific intervals is advised throughout the treatment course. When Letrozole is advised for patients with compromised bone density, there is a possibility for enhanced bone density deterioration. In addition, it also enhances the likelihood of developing fractures. Hence, Letrozole therapy in osteoporotic patients warrants caution.

  • Compromised Liver Functions: The severely impaired functional status of the liver potentiates the Letrozole exposure, which necessitates depreciation in the Letrozole dose so that the plasma drug concentration remains within the desired therapeutic level.

  • Hypercholesterolemia: Reports suggested an enhanced incidence of hypercholesterolemia in patients who underwent Letrozole therapy. Therefore, periodic assessment of the patient’s lipid profile is imperative. In case of appreciated cholesterol levels, appropriate medication must be advised to control it.

  • Disparities in Blood Profile: Collapses in the blood cell count, typically lymphocytes, were demonstrated in certain patients undergoing Letrozole therapy. However, these disparities often return to normal upon cessation of the Letrozole therapy and do not warrant medical intervention.

  • Dizziness: Letrozole can induce sleepiness, compromising the patient’s ability to do activities that demand fine motor skills and concentration. The patient should be warned beforehand as it can bring unexpected consequences.

What Are the Drug Interactions of Letrozole?

Letrozole, when administered simultaneously with other medicines, can precipitate unwanted effects and may alter the efficacy of both or either of the medicines. Letrozole and Tamoxifen, when administered concurrently, result in collapsed Letrozole concentration, which impairs Letrozole’s efficacy, and the desired results cannot be attained. No reliable sources of information concerning the interaction of Letrozole with other anticancer medicines are available and need to be explored more.

Specific Considerations:

  • Letrozole During Pregnancy: Letrozole can potentially harm and endanger the baby in the womb and, hence, is strictly warned not to be taken by expectant women. The therapeutic intake of Letrozole by women within the reproductive age group needs to be evaluated and is still vague and unclear. For women with suspected menopause, Letrozole therapy should be accompanied by appropriate contraceptive measures to check all the possibilities for accidental conception.

  • Letrozole During Lactation: Letrozole therapy is generally not advisable for lactating women. However, there is no clear information concerning Letrozole discharge through breast milk following maternal Letrozole therapy.

  • Letrozole in Geriatric Patients: No appreciable disparities were reported concerning Letrozole’s efficacy and safety aspects in geriatric patients over 75 years of age compared to patients within the 50 to 75 years of age range. The treatment outcomes were on par with that of the younger patients. However, in geriatric patients, there is an enhanced possibility for underlying disease conditions like liver and kidney dysfunction, which necessitates dose modification.

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Last reviewed at:
13 Feb 2024  -  10 min read




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