Hormone therapy for breast cancer

Hormonal therapy has been used to treat breast cancer for over a century. The first results of treating breast cancer patients with oophorectomy (removal of the ovaries) were published in the late 19th century and showed good efficacy.

Afterwards, oncologists proposed various methods of hormone therapy: radiation castration, androgen administration, adrenal gland removal, surgical destruction of the pituitary gland, antiestrogens, antiprogestins, and aromatase inhibitors.

Over time, effective methods of hormone therapy were developed – radiation, surgical, and medicinal.

Today, hormone therapy is an integral part of complex therapy at any stage of breast cancer.

There are two directions of this type of breast cancer treatment: stopping (inhibiting) estrogen production and taking anti-estrogenic drugs.

The treatment is selected by a specialist, taking into account various factors - the patient's age and condition, the stage of the disease, concomitant diseases. Ovarian removal surgery is prescribed only to women with preserved menstrual function or at early menopause, in postmenopause, drugs that reduce estrogen levels are effective, in reproductive age, releasing hormones are used

Breast tumors are considered hormone-dependent, but only about 40% of patients experience a positive effect from hormone therapy.

It is worth noting that some drugs can replace surgical treatment, for example, taking aromatase inhibitors allows you to avoid removal of the adrenal glands, releasing hormones - removal of the ovaries.

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Consequences of hormone therapy for breast cancer

Like any other treatment, hormone therapy for breast cancer has consequences, which include weight gain, swelling, early menopause, increased sweating, and vaginal dryness.

In addition, some patients report mood depression and the development of depression during treatment.

Some drugs have severe side effects, for example, the widely used tamoxifen increases the risk of blood clots and can lead to uterine cancer and infertility.

Drugs that reduce estrogen production (aromatase inhibitors), which are prescribed during the postmenopausal period, provoke osteoporosis, increase the risk of blood clots, gastrointestinal diseases, and increase cholesterol levels.

The effectiveness of treatment for hormone-dependent tumors is quite high. If both progesterone and estrogen receptors are detected in cancer cells, then hormone therapy will be 70% effective, if only one type of receptor is detected - 33%.

For other types of tumors, the effectiveness of hormone therapy for breast cancer reaches only 10%.

Hormone therapy for breast cancer is a fairly effective method of treating hormone-dependent breast tumors. This method is also called anti-estrogen and the main goal of such treatment is to prevent the effect of the female hormone on cancer cells.

Indications for hormone therapy

Hormone therapy for breast cancer is indicated for women with non-invasive forms of cancer (to prevent recurrence of the disease or transition to an invasive cancerous process), after surgery, radiation or chemotherapy to reduce the likelihood of relapse, with large tumors (before surgery, therapy allows to reduce the tumor and helps the surgeon to identify pathological tissues), with metastases (hormone therapy allows to stop further metastasis), as well as with a genetic predisposition.

Hormonal therapy drugs

Hormone therapy for breast cancer today occurs in two directions: treatment taking into account the menstrual cycle and regardless of it.

Universal methods of hormone therapy that are independent of the menstrual cycle use antiestrogens and progestins.

The most common and researched, used for a long time by oncologists, is the anti-estrogen drug - tamoxifen. With prolonged use, the drug can increase the level of estrogen in the blood, increases the risk of developing hormone-dependent tumors in other organs, and the likelihood of developing thromboembolic complications and toxic effects on the liver have also been clinically proven.

Today, in most cases, tamoxifen is prescribed for no longer than 5 years.

No less popular drugs from this group are toremifene and raloxifene.

Fulvestrant deserves special mention, as it has a special place in modern hormone therapy for breast cancer. The drug destroys tumor estrogen receptors, which is why a number of specialists classify it as a “true antagonist.”

Typically, oncologists prescribe hormone therapy according to one of three main schemes, which differ in their principle of action - reducing the level of estrogen in the blood, blocking estrogen receptors, and reducing estrogen synthesis.

After examination, the following treatment may be prescribed:

1. selective estrogen receptor modulators - therapy aimed at disabling estrogen receptors (chemicals have a selective effect on cells, producing an effect similar to estrogens), the main drug in this direction is tamoxifen.
2. Aromatase inhibitors - used in postmenopausal periods, reduce estrogen production. Oncologists use letrozole, anastorozole, and exemestane.
3. blocking and destruction of estrogen receptors (Fulvestrant, Faslodex).

Estrogen receptors are located on cancer cells and attract estrogens, which promote further tumor growth. Depending on their level, the laboratory makes a conclusion about the hormone dependence of the tumor, after which the doctor determines the treatment regimen to choose.

The antitumor drug Tamoxifen has an antiestrogenic effect. After administration, tamoxifen binds to estrogen receptors in organs susceptible to the development of hormone-dependent tumors and inhibits the growth of cancer cells (if the tumor development is caused by ß-17-estrogens).

It is prescribed to men and women (mainly during menopause) with breast cancer, ovarian cancer, endometrial cancer, kidney cancer, prostate cancer, and after surgery to correct hormonal levels.

The dosage is determined individually, taking into account the patient’s condition.

For breast cancer, the usual dosage is 10 mg 1-2 times a day. If necessary, the specialist can increase the dosage to 30-40 mg per day.

Tamoxifen must be taken for a long time (from 2 months to 3 years) under the supervision of a doctor. The course of treatment is determined individually (usually the drug is stopped 1-2 months after regression).

A repeat course is carried out after a 2-month break.

After removal of the mammary gland, 20 mg per day is prescribed to correct hormone levels.

Taking the drug may cause nausea, vomiting, indigestion, loss of appetite, and in some cases leads to excessive accumulation of fat in the liver and hepatitis. Depression, headaches, swelling, allergic reactions, bone pain, and fever are possible. Long-term use may cause retinal damage, cataracts, and corneal pathologies.

In women it can cause endometrial proliferation, bleeding, suppression of menstruation, and in men – impotence.

Toremifene is similar in action to tamoxifen, the drug prevents the body from producing estrogen. It is prescribed during the postmenopausal period, from 60 to 240 mg every day for several years.

During treatment, negative reactions of the body may occur, in particular, dizziness, increased intraocular pressure and development of cataracts, myocardial infarction, acute vascular occlusion, decreased platelet levels, allergic reactions, enlargement of endometrial tissue, thrombosis, feeling of heat, increased sweating.

Toremifene is toxic to the liver.

Concomitant use with drugs that reduce urinary calcium excretion increases the risk of hypercalcemia.

Toremifene should not be taken concomitantly with drugs that prolong the QT interval.

During treatment with rifampicin, phenobarbital, dexamethasone, phenytoin and other CYP3A4 inducers, an increase in the dosage of Toremifene may be required.

Treatment should be carried out under the supervision of a physician.

Raloxifene is a selective estrogen receptor modulator. It is prescribed for breast cancer during menopause to prevent the development of osteoporosis (decreased density and disruption of bone structure).

The drug normalizes calcium levels, reducing its excretion from the body by the kidneys.

Raloxifene must be taken for a long time (60 mg per day), usually in old age the dosage is not adjusted.

During treatment, cramps in the calf muscles, thromboembolism, edema, and a feeling of heat in the body may occur. If uterine bleeding occurs, you should contact your doctor and undergo additional examination.

It is necessary to take calcium during treatment.

The anticancer drug Fulvestrant also inhibits estrogen receptors. The drug blocks the action of estrogens, but estrogen-like activity is not observed.

There is no data on the possible impact on the endometrium, endothelium in the postmenopausal period, or bone tissue.

In oncology it is used to treat breast cancer in the form of injections, the recommended dose is 250 mg once a month.

During treatment, nausea, bowel disorder, loss of appetite, thromboembolism, allergic reactions, swelling, back pain, nipple discharge may occur, and the risk of urinary tract infections and bleeding increases.

Faslodex contains the same active ingredient as Fulvestrant and has an anti-estrogen effect.

Prescribed for advanced breast cancer in the postmenopausal period.

The drug is used in the form of injections (intramuscularly) once a month at 250 mg.

In case of moderate liver dysfunction, no dosage adjustment is required.

The safety of the drug in patients with renal impairment has not been tested.

Letrozole suppresses estrogen synthesis, has an antiestrogenic effect, and selectively inhibits aromatase.

The standard dose is 2.5 mg per day for 5 years. The drug should be taken daily, regardless of food intake.

Letrozole should be discontinued if the first symptoms of disease progression appear.

In the later stages, with metastasis, the drug is indicated while tumor growth is observed.

In case of hepatic insufficiency and in elderly patients, no dosage adjustment is required.

There are no data on concomitant administration with other anticancer drugs.

Letrozole should be administered with caution with drugs that are metabolized by CYP2A6 and CYP2C19 isoenzymes.

Anastrozole is an estrogen antagonist that selectively inhibits aromatase.

It is indicated for the treatment of early stages of hormone-dependent breast tumors in postmenopause, as well as after treatment with tamoxifen.

The drug should be taken 1 hour before meals (or 2-3 hours after).

Usually, 1 mg per day is prescribed; the duration of treatment is determined individually, taking into account the severity and form of the disease.

Hormonal medications should not be taken simultaneously with Anastrozole.

During treatment, bone density decreases.

There is no data on the effectiveness of combination treatment (Anastrozole + chemotherapy).

Taking the drug may cause severe dizziness, persistent headaches, drowsiness, depression, loss of appetite, vomiting, dry mouth, allergies, bronchitis, rhinitis, pharyngitis, chest pain, back pain, increased sweating, decreased joint mobility, swelling, baldness, weight gain.

Concomitant administration of tomoxifen and anastrozole is contraindicated.

Exmestane is indicated for the treatment and prevention of cancer or malignant neoplasms in the mammary gland and is an estrogen antagonist.

Exmestane is taken after meals at 25 mg per day, the duration of administration is until the tumor progresses again.

It is not recommended to prescribe the drug to women with premenopausal endocrine status, since there is no data on the efficacy and safety of treatment in this group of patients. In case of liver dysfunction, dosage adjustment is not required.

Exmestane is prescribed after determining the patient's postmenopausal status.

During treatment, rapid fatigue, dizziness, headaches, sleep disturbances, depression, vomiting, loss of appetite, bowel disorders, allergies, increased sweating, baldness, and swelling may occur.

Preparations containing estrogens suppress the therapeutic effect of Exmestane.