Drugs for the treatment of breast cancer

There are many known ways to combat malignant tumors, but the most popular are drugs for the treatment of breast cancer. Medicines are used both at the initial stages of the disease and in cases where surgery is no longer possible. In most cases, drugs can alleviate the patient's condition and slow down the growth of the tumor. Based on this, the action of such medications should be aimed at slowing down the processes of reproduction of cancer cells, or at strengthening the body and stimulating its own defenses to fight the disease.

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Characteristics of drugs for the treatment of breast cancer

There are more than fifty known drugs used to treat breast cancer. According to their mode of action, such medications are grouped into certain groups that can be combined or replaced depending on the characteristics of the disease and at the doctor's discretion. These groups of drugs are:

• alkylating agents;
• antimetabolites;
• alkaloids;
• anticancer antibiotics (cytotoxic agents);
• hormonal agents;
• immunostimulants;
• herbal preparations;
• platinum preparations.

In this topic, we will look at the main characteristics of the most common representatives of each group of drugs for the treatment of breast cancer.

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Indications for use

Alkylating agents can be used in cancer treatment regimens, mainly in combination with other medications. As a rule, in most cases the active substance of such agents is cyclophosphamide, an active antitumor component. In addition to malignant processes in the mammary gland, cyclophosphamide is prescribed for lymphocytic leukemia, ovarian cancer, retinoblastoma, lymphomas, and to prevent implant rejection.

• Antimetabolites are used in the treatment of acute and other forms of leukemia, reticulosis, cancer in the mammary gland, ovaries and cervix, as well as chorioepithelioma.
• Plant alkaloids can be prescribed not only for breast cancer, but also for other malignant tumors, including testicular tumors, chronic leukemia or lymphomas.
• Cytotoxic drugs (for example, the most well-known of them is Doxorubicin) can be used to treat various types of neoplastic pathologies. Often, such drugs are prescribed for acute leukemia, lymphomas, breast or lung carcinoma.
• Hormonal agents are used in the treatment of hormone-dependent tumors, i.e. those that cannot continue to develop without the presence of a certain hormone, such as estrogen or progesterone. According to statistics, such hormone-dependent tumors account for 75% of all breast tumors.
• Immunostimulants help to support the body's own defense, which is especially important in case of malignant tumors of any etiology. Immunostimulants are prescribed to prevent infectious complications, after surgical interventions, radiation therapy, during treatment with hormonal and cytostatic drugs.
• Herbal preparations are indicated as biogenic stimulants to support the body of patients with malignant neoplasms and chronic diseases. These agents cannot eliminate the malignant lesion, but can significantly improve the well-being of patients. A typical representative of herbal preparations used for breast cancer is Befungin.
• Platinum-based drugs (including Carboplatin) are recommended for use in independent or complex therapy of ovarian and breast cancer.

Release form

The most common drugs used to treat breast cancer may come in the following dosage forms:

• Cyclophosphamide (alkylating agent) – in powder form for the preparation of a solution for subsequent intravenous or intramuscular administration;
• Methotrexate (anti-metabolic agent) – in tablets or solution for injection (in ampoules or vials);
• Vinblastine (alkaloid preparations) – in the form of a lyophilisate (powder substance) for dissolution followed by injection;
• Doxorubicin (anthracycline, cytotoxic drug) - in the form of a lyophilisate (porous mass of orange-red color) for the preparation of an injection solution;
• hormonal anti-estrogenic agent Tamoxifen - in the form of tablets of 10 mg, 20 mg, 40 mg;
• Polyoxidonium (immunostimulating agent) - in the form of a porous lyophilisate in vials or ampoules for subsequent injection, as well as in suppositories of 10 pieces;
• Befungin (herbal remedy) – in the form of a semi-liquid extract of brown color, packaged in bottles;
• Carboplatin (platinum drug) – in the form of a concentrate for the preparation of a solution for subsequent intravenous infusion.

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Pharmacodynamics of drugs for the treatment of breast cancer

• Cyclophosphamide, which is a group of alkylating agents and cytostatics, is close in chemical composition to nitrogen compounds like mustard gas. Experts believe that the effect of cyclophosphamide is explained by the formation of cross-links with DNA and RNA strands. In addition, the production of proteins in atypical cells is inhibited.
• Methotrexate is an antimetabolite that is also an immunosuppressant. Methotrexate is an inhibitor of a substance involved in the transformation of dihydrofolic acid into tetrahydrofolic acid, which is considered an important link in the production of nucleotides. In addition, the antimetabolite blocks DNA formation and cell mitosis. Highly proliferative tissues, in particular, tumor tissue layers, are particularly sensitive to the drug.
• The alkaloid Vinblastine is obtained from the periwinkle plant. This agent makes cellular mitosis impossible by binding to microtubular elements and slowing the formation of mitotic spindle-shaped inclusions. In malignant tumor cells, the drug inhibits the processes of DNA and RNA synthesis.
• Doxorubicin (anthracycline) causes the death of cancer cells, presumably by affecting the production of nucleic acids. There is currently no precise information on the pharmacodynamics of the drug. It is assumed that the active component of the drug inhibits the synthesis of DNA, RNA and proteins.
• Tamoxifen (a hormonal anti-estrogenic agent) interferes with the formation and function of estrogens by binding to estrogen receptors. As a result, the formation of the reacting complex is disrupted.
• Polyoxidonium has immunomodulatory properties, increasing the body's ability to resist infections. Under the influence of the drug, the activity of killer cells and phagocytes is stimulated, and antibody production increases. Polyoxidonium stabilizes the immune system even in severe cases, with severe immune deficiency. At the same time, the toxic effect of drugs is reduced, and the resistance of cells to intoxication is increased.
• Befungin is a herbal remedy produced from a birch fungus. The pharmacodynamic properties of this drug have not been studied.
• Carboplatin is an inorganic combined platinum compound. The action of this drug is aimed at destroying various types of tumors, regardless of their location. The process of action consists in inhibiting the production of nucleic acids, which provokes cell death. Carboplatin, in addition, affects the body's immunity, which can accelerate the regressive processes of primary neoplasms and metastatic elements.

Pharmacokinetics

Cyclophosphamide-based alkylating agents form metabolites in the liver: some of them undergo further conversion into inactive metabolites, and the rest into products with cytotoxic activity. The maximum amount of such active products is observed 2-3 hours after intravenous infusion. Binding to plasma proteins is small and amounts to approximately 13%. However, individual metabolites can bind by 65% or more. Penetration through the blood-brain barrier is insignificant.

The active ingredient leaves the body via the filtering system of the kidneys, and in small quantities with bile. The half-life can be from 3 to 12 hours.

• The antimetabolite Methotrexate is absorbed in the digestive tract mainly well, which depends on the dose taken and the presence of food in the stomach. The maximum concentration of the substance with oral administration is reached in about 1.5 hours, and with intramuscular injection - in 0.5-1 hour. Binding to plasma proteins is about 50%. Metabolism occurs mainly in the liver. The half-life is from 2 to 15 hours depending on the dose taken. Excretion occurs with urine, and only 10% with bile. Methotrexate tends to accumulate as metabolites.
• The alkaloid Vinblastine penetrates tissues and organs perfectly when injected intravenously, while only a small portion of the drug can penetrate the blood-brain barrier. The active ingredient is capable of binding to plasma proteins. Biological transformation occurs in the liver, where active metabolic products are formed. The half-life can be 24-25 hours. Excretion from the body occurs through the intestines, with feces.
• When administered intravenously, Doxorubicin is eliminated from the body in three stages – after 12 minutes, after three hours and after 30 hours. This occurs due to the prolonged distribution of the drug in tissues. Inactive decay products leave the body through the urinary system.
• The hormonal antiestrogen Tamoxifen is well absorbed, reaching maximum plasma concentrations within 5-7 hours. A stable amount of the drug is observed after a month-long course of therapy at a standard dosage. The connection with whey protein is more than 99%. Pharmacologically active metabolites are excreted mainly with feces. The half-life of the drug itself is usually one week, and the active metabolic product is about two weeks.
• The immunomodulator Polyoxidonium in tablet form is well absorbed in the digestive system and becomes biologically available approximately half. The maximum content in the blood serum is observed 60 minutes after oral administration.
• Polyoxidonium is distributed mostly between cells. The half-life is about 18 hours. The drug is excreted mainly by the kidneys, without accumulating in the body.
• Befungin is a herbal preparation whose pharmacokinetic properties have not been thoroughly studied.
• Platinum preparations in the form of Carboplatin have a half-life of 1-2 hours. With prolonged use, accumulation of the active substance does not occur. About 80% of platinum binds to plasma proteins within 24 hours after infusion.

The drug is excreted from the body through the kidneys, unchanged.

Use during pregnancy

• Cyclophosphamide is not used by pregnant or breastfeeding women.
• Methotrexate is contraindicated during pregnancy and lactation. Moreover, before prescribing the drug and during the course of treatment, it is necessary to make sure that there is no pregnancy.
• Vinblastine is not recommended for use by pregnant women, but sometimes it is prescribed. This is possible in cases where the benefit of the drug outweighs the risk to the unborn child. When used by nursing women, it is necessary to temporarily stop breastfeeding.
• Doxorubicin is also prohibited for use during pregnancy and breastfeeding.
• Tamoxifen is strictly contraindicated for pregnant and lactating women.
• Polyoxidonium is not prescribed to pregnant women due to the lack of clinical experience with the drug. The extent to which the drug enters breast milk has not been studied.
• Befungin is approved for use by pregnant and lactating women, but treatment should be carried out with caution and under constant supervision of a doctor. Experiments have shown the safety of the drug for the child and mother.
• Carboplatin is considered toxic to the developing fetus and breastfed infant, so its use during these periods is contraindicated.

Contraindications for use

Alkylating drugs, in particular Cyclophosphamide, like the vast majority of drugs, have their own contraindications for use:

• allergic reaction of the body to the ingredients of the drug;
• bone marrow dysfunction;
• inflammation of the bladder;
• difficulty urinating;
• acute infectious diseases, or chronic diseases in the acute stage.

Methotrexate has the following contraindications:

• significant anemia, decreased levels of leukocytes, neutrophils and platelets in the blood;
• renal or hepatic failure;
• tendency to allergic reactions to the components of the drug.

Contraindications to the use of Vinblastine are:

• hypersensitivity of the body;
• acute viral and bacterial infections;
• current myelosuppressive therapy;
• severe liver disease;
• old age.

Doxorubicin also has its contraindications:

• allergy to the drug;
• myelosuppressive conditions;
• severe liver dysfunction;
• severe heart disease;
• infectious diseases of the urinary system.

Tamoxifen is not prescribed:

• before menopause;
• if you are prone to allergic reactions;
• for kidney diseases, diabetes, and pathologies of the visual organs.

Contraindications to the use of Polyoxidonium:

• excessive hypersensitivity of the body;
• children under 12 years of age.

Befungin should not be taken:

• in case of allergic tendency;
• for dyspeptic disorders such as diarrhea, vomiting, etc.

Contraindications to the use of Carboplatin may include:

• allergy to the drug and its components;
• severe myelosuppression;
• significant volumes of bleeding;
• renal dysfunction;
• auditory disorders.

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Side effects of breast cancer drugs

Antitumor drugs are known for their numerous side effects, due to the high toxicity of active substances and damage to healthy cells and tissues. What are the most common side effects of typical representatives of antitumor drug groups?

Hematopoietic organs.

• Cyclophosphamide: signs of anemia, decreased levels of leukocytes, platelets;
• Methotrexate: anemia, leukopenia, lymphopenia, thrombocytopenia;
• Vinblastine: leukopenia;
• Doxorubicin: bone marrow depression, anemia, myeloid leukemia;
• Tamoxifen: thrombocytopenia;
• Polyoxidonium: hematopoiesis parameters are normal;
• Befungin: indicators are normal;
• Carboplatin: bone marrow dysfunction, myelosuppression.

Digestive system.

• Cyclophosphamide: dyspepsia, eating disorders, colitis, less commonly – liver dysfunction;
• Methotrexate: inflammatory diseases of the gums and oral cavity, erosions and ulcers of the stomach, cirrhosis and necrotic changes in the liver, gastrointestinal bleeding;
• Vinblastine: hemorrhagic colitis, gastrointestinal bleeding, attacks of vomiting and nausea;
• Doxorubicin: dyspepsia, lesions of the oral mucosa, esophagitis, stomach pain, gastric erosion, enterocolitis;
• Tamoxifen: fatty liver infiltration, hepatitis, cholestasis;
• Polyoxidonium: has no side effects;
• Befungin: disorders of the digestive organs with prolonged use of the drug;
• Carboplatin: nausea (usually without vomiting), bowel disorders, epigastric pain.

Skin.

• Cyclophosphamide: baldness, skin hyperpigmentation, rashes, changes in the condition of the nail plate;
• Methotrexate: skin itching, erythema, petechial hemorrhages, furuncles, dermatitis, acne;
• Vinblastine: hair loss, skin numbness;
• Doxorubicin: alopecia, itching and rashes, photosensitivity and hypersensitivity of the skin, redness of the palms and feet;
• Tamoxifen: skin rash;
• Polyoxidonium: no side effects;
• Befungin: no cutaneous side effects;
• Carboplatin: alopecia.

Cardiovascular system and central nervous system.

• Cyclophosphamide: cardiac congestion, hemorrhagic myocarditis;
• Methotrexate: dizziness, convulsions, headaches, paralysis, tremors;
• Vinblastine: double vision, depression, headaches;
• Doxorubicin: tachycardia, arrhythmia, heart failure, changes in the electrocardiogram;
• Tamoxifen: thrombosis;
• Polyoxidonium: no side effects;
• Befungin: no side effects;
• Carboplatin: hemorrhages, decreased blood pressure.

In addition, the reproductive system may also suffer, which may manifest itself in the form of impaired spermatogenesis and difficulties with conception. After discontinuing the medication, such problems usually gradually disappear.

Method of administration and dosage of drugs for the treatment of breast cancer

Any antitumor drugs are prescribed according to an individually selected treatment regimen, when all the features of the disease and the patient's body are taken into account. However, there are also standard drug regimens, on which further doctor's prescriptions are based. Here you can see such sample regimens.

• Cyclophosphamide is administered intravenously by drip or by intramuscular injection, 50-100 mg/m² every day for 14-20 days.
• Methotrexate is administered orally or intramuscularly from 15 to 30 mg every day for five days, after which a break of 1 week should be taken. This scheme can be changed at the discretion of the attending physician.
• Vinblastine is administered intravenously once a week at 0.1 mg/kg. Children are given a lower dosage of 2.5 mg/m².
• Doxorubicin is administered intravenously or into an artery. The dosage is calculated based on the patient's weight. The most common dose is 1.2 to 2.4 mg/kg once every three weeks.
• Tamoxifen is used from 20 to 40 mg up to 2 times a day. The duration of therapy is determined by the doctor.
• Polyoxidonium is prescribed in the form of intramuscular or intravenous drip administrations, in quantities from 6 to 12 g, once a day, every other day, or according to an individual regimen.
• Befungin is taken 2 teaspoons in 150 ml of warm water (1 tablespoon three times a day before meals). The course of therapy is usually long, with breaks of one week.
• There is a specially developed list of schemes for treatment with Carboplatin. Treatment is selected depending on the patient's risk group and the characteristics of the disease. The drug is prescribed starting with a dose of 400 mg/m². Duration of treatment is 1 month.

Overdose

In case of overdose of antitumor drugs, there is an increase in the severity of side effects. As a rule, there are no special drugs with the opposite effect, therefore, in case of obvious signs of overdose, symptomatic and detoxifying treatment is carried out with monitoring of blood parameters. The only drug that has its own antidote is Methotrexate. Its antidote is Calcium Folinate, which is administered in the same dose as the drug (or higher, but not lower).

In severe cases, transfusion may be necessary.

A drug such as Doxorubicin deserves special mention. Its high dosages above 250 mg are lethal: degenerative processes of the myocardium and severe damage to the bone marrow occur. For this reason, medical professionals are advised to carefully monitor the dosages used by patients, and in case of symptoms of cardiac insufficiency, take appropriate emergency measures.

Interactions with other drugs

• The simultaneous use of Cyclophosphamide and Allopurinol is not recommended, as this increases bone marrow intoxication.
• Cyclophosphamide may affect blood clotting processes, which should be taken into account when prescribing anticoagulants.
• Cyclophosphamide increases the cardiotoxic activity of Doxorubicin.
• The combination of treatment with cyclophosphamide and other myelosuppressive agents, as well as the simultaneous use of radiation therapy, can lead to a violation of hematopoiesis.
• Vinblastine and Mitamycin, when taken simultaneously, may cause bronchospasm.
• Vinblastine and Phenytoin in combination increase the likelihood of developing convulsive syndrome.
• Vinblastine and neurotoxic agents are incompatible under any circumstances.
• Doxorubicin is not recommended to be mixed with other drugs due to the risk of sediment formation in the solution.
• Carboplatin should not be used simultaneously with drugs containing aluminum salts.
• The toxic effect of Methotrexate increases significantly in combination with non-steroidal anti-inflammatory drugs (acetylsalicylic acid, diclofenac, etc.). For the same reason, simultaneous administration with sulfonamides is avoided.
• Methotrexate and Acyclovir may cause nervous system disorders.
• The effect of Methotrexate is reduced by taking folic acid.
• Tamoxifen and Allopurinol together have a negative effect on liver function.

Storage conditions for drugs for the treatment of mammary glands

Anti-tumor drugs are usually only available on prescription because they are quite specific and toxic drugs. Therefore, they should never be stored in places where children can reach them - this can have unpredictably dangerous consequences.

• Cyclophosphamide is stored at temperatures no higher than +10°C. The shelf life is up to 3 years, after which the drug should be disposed of.
• Methotrexate is stored at room temperature, away from direct sunlight. Shelf life is up to 3 years.
• Vinblastine is stored in the refrigerator, without freezing. Shelf life is up to 2 years. The prepared solution can be stored for up to 1 month.
• Doxorubicin is stored at t° +8°C for up to 2 years.
• Tamoxifen can be stored at room temperature.
• Polyoxidonium is stored at temperatures from +4 to +25°C. Shelf life is up to 2 years.
• Befungin can be stored at normal room temperature conditions for up to 2 years.
• Carboplatin should be stored in a refrigerator at a temperature of up to +8°C. The prepared solution is stored for one day at the same temperature.

Medicines for the treatment of mammary glands are prescribed only by a qualified oncologist. Self-treatment with such drugs is not allowed.

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Chemotherapy drugs for breast cancer

Chemotherapy for the treatment of breast cancer is carried out using specially developed schemes, with different combinations of drugs. Cancer is sensitive to such drugs as:

• Herceptin is an antineoplastic agent that blocks tumor growth, with the active ingredient trastuzumab. It is usually used in combination with Doxorubicin and Cyclophosphamide, or Docetaxel and Carboplatin;
• Avastin is a Bevacizumab drug containing antitumor monoclonal antibodies. It is very effective in inhibiting tumor development and preventing metastases.
• Methotrexate is a structural analogue of folic acid. It can be used both orally and by injection.
• Adriblastin is a Doxorubicin-based drug. It is an anthracycline antibiotic and inhibits the production of nucleic acids. It suppresses the immune system.
• 5-fluorouracil is one of the most well-known antitumor drugs, which is represented by the antimetabolite Fluorouracil. It suppresses the process of cancer cell division.
• Cyclophosphamide is an alkylating and cytostatic drug that disrupts stable processes in cancer cells and blocks the growth of atypical cellular structures.
• Docetaxel – refers to alkaloids of plant origin. Represents a series of taxanes. Often prescribed in combination with Trastuzumab or Capecitabine.
• Paclitaxel is used for lesions of the lymph nodes, in combination with anthracyclines and cyclophosphamides.
• Xeloda is a cytostatic agent with the active ingredient Capecitabine, which is transformed into active 5-fluorouracil in tumor tissue.

The names of chemotherapy drugs for breast cancer are provided for informational purposes only, self-treatment is strictly prohibited. Chemotherapy regimens are selected individually, which allows to alleviate the condition and improve the quality of life of the most hopeless patients. If you combine treatment with chemotherapy drugs with surgery and radiation therapy, then it is quite possible to forget about the disease for a long time.

Antitumor drugs for breast cancer

In our country, more than two hundred drugs with antitumor activity have been registered. A large number of medications can be divided into categories based on the principle of action.

1. Alkylating agents are drugs capable of functional alkylation of DNA strands, which leads to prolonged inhibition of the bioproduction of nucleic acids and cell death (Cyclophosphamide, Thiotepa, Melphalan).
2. Antimetabolites are cytostatics or antitumor drugs whose action is aimed at inhibiting certain biological processes in cancer cells, which makes their further development impossible (Methotrexate, Gemcitabine, Tegafur, Fluorouracil).
3. Naturally occurring alkaloids are heterocyclic bases containing nitrogen. Such drugs are characterized by powerful biological activity (Vinblastine, Vincristine, Vinorelbine, Vindesine, Docetaxel).
4. Cytotoxic and similar drugs are medicines that trigger the process of necrosis of the cancer cell structure. The difference between cytotoxic drugs and cytostatics is that the latter cause apoptosis, not necrosis, of the atypical cell (Doxorubicin, Mitoxantrone, Epirubicin).
5. Other antitumor drugs – these include, for example, platinum compounds – Carboplatin. The action of Carboplatin is based on the inhibition of nucleic acid synthesis, which contributes to cell death.
6. Androgens are substances with the biological activity of male sex hormones. They are prescribed to suppress the action of estrogens (testosterone preparations: Adriol, Tetrasterone, etc.).
7. Phytomedicines are preparations that stimulate the body's internal defenses. Phytomedicines include chaga, Befungin, Immunal, grape seed extract, etc.

In addition to the listed agents, depending on the hormonal status of the tumor, hormonal drugs may be prescribed.

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Hormonal drugs for breast cancer

Hormonal medications are prescribed only after taking tests for hormonal levels and the degree of receptor sensitivity to progesterone and estrogens. As a rule, medications are used according to a specific scheme. There are three options for such standard schemes:

• Reducing estrogen levels in the bloodstream is achieved by prescribing specific modulator drugs (for example, Tamoxifen);
• inhibition of estrogen receptor sensitivity occurs due to aromatase inhibitors (Letrozole, Anastrozole, Exemestane);
• suppression of estrogen production (Faslodex).

The most commonly used drug in hormone therapy is Tamoxifen. In most cases, it is prescribed to women in the premenopausal period in the early stages of breast cancer. The duration of treatment can be 3-5 years.

Drugs that reduce the sensitivity of receptors to estrogens act more effectively, even in contrast to Tamoxifen. They are usually used as a drug treatment at any stage of the development of hormone-dependent invasive breast cancer. Often, such treatment is used in patients who have reached postmenopause, complementing the main type of therapy, be it surgery or other procedures.

Targeted drugs for breast cancer

Targeted agents are substances that block the growth and reproduction of atypical cells by influencing the components that determine tumor development. Such drugs are used quite successfully in oncology, especially since their impact on surrounding healthy tissues is minimal.

The effect of targeted therapy is expected to be as follows:

• stopping the cancer process and inhibiting its activity;
• relapse prevention;
• relatively low degree of intoxication.

The most well-known targeted agents are:

• Avastin is a drug that blocks the growth of the vascular network in the tumor. Thus, this drug transfers the process from a state of increased activity to a stable chronic state.
• Panitumumab is a drug that inhibits the growth and survival of selective cancer cell lines.
• Olaparib - blocks the action of an enzyme that restores cells.
• Herceptin is a drug that blocks proliferative processes in cancer cells.

Targeted drugs can significantly increase the life expectancy of breast cancer patients. In addition, such medications are used to prevent tumor recurrence and the spread of metastases.

Drugs for the prevention of breast cancer

The hormone therapy drug Tamoxifen may sometimes be prescribed as a preventive measure against breast cancer. Many doctors believe that the use of Tamoxifen can significantly reduce the risk of developing breast cancer.

However, it is necessary to take into account that this drug has such a side effect as a decrease in the effect of estrogens on the function of the mammary gland. In the future, this threatens the emergence and development of a malignant process in the uterus. Because of this, most medical specialists agree that there are currently no specific drugs for the prevention of breast cancer.

Medicines for the treatment of breast cancer are prescribed only by a doctor, depending on the characteristics of the tumor and the age category of the patient. In some cases (for example, in the absence of the expected effect), one drug can be replaced by another. Such treatment often allows you to successfully fight the disease. One of the few disadvantages of these drugs are considered to be side effects - anemia, baldness, dyspeptic syndrome, etc.