Triple-negative breast cancer

Triple-negative breast cancer is a pathology with an aggressive course and life-threatening complications. Let's consider the features of this type of oncology and the prognosis.

Immunohistochemistry is used to determine the main cancer receptors. The analysis provides information on estrogen receptors (ER), sensitivity to herceptin (her2neu), and progesterone receptors (PR). Most tumors have a positive response to all three receptors. If the cancer is not sensitive to herceptin (ER0, PR0, her2neu 0-1), this indicates TNBC.

This cancer belongs to a separate group of diseases, as it is characterized by an aggressive course in comparison with other malignant lesions of the mammary gland. It has a specific histological structure (basal-like form). Squamous cell and apocrine carcinomas may be found in this group. TNBC occurs in 10-20% of all cancer cases. Women taking oral contraceptives, patients with a hereditary predisposition and African Americans are susceptible to the pathology.

In most cases, tumors are diagnosed at advanced stages. Oncology manifests itself as a long-term inflammatory process. Many hereditary forms of the disease belong to this category. It has different subtypes and groups that allow you to study the mechanism of its development in more detail and make an effective treatment plan. Oncology is characterized by a negative prognosis. But with timely therapy and the absence of relapses for five years, the survival prognosis is the same as with other forms of malignant lesions of the mammary glands. But in 80% of cases, the disease recurs in the first 1-2 years after radical therapy.

ICD-10 code

According to medical statistics, triple-negative breast cancer is quite common in our country. The disease belongs to a heterogeneous group of tumors.

To diagnose the pathology, the ICD 10 code is used; the disease belongs to category II neoplasms.

C50 Malignant neoplasm of breast:

• C50.0 Nipple and areola.
• C50.1 Central part of mammary gland.
• C50.2 Upper inner quadrant of mammary gland.
• C50.3 Lower inner quadrant of mammary gland.
• C50.4 Upper outer quadrant of mammary gland.
• C50.5 Lower outer quadrant of mammary gland.
• C50.6 Axillary posterior part of mammary gland.
• C50.8 Overlapping lesion of breast.
• C50.9 Mammary gland, unspecified part.

Molecular genetic classification indicates four groups of cancer, each of which has individual epidophysiological properties, typical clinical picture and prognosis.

Causes of Triple Negative Breast Cancer

The etiology of oncological lesions of the mammary glands is associated with various changes in the body. The causes may be caused by hormonal changes - menopause (the production of estrogens and progesterone decreases, the ovaries go into passive mode of operation), early menstruation or menstrual cycle disorders. An excess of sex hormones creates a favorable background for the development of the disease. Pregnancy, lactation and abortion also create a hormonal surge, increasing the risk of developing pathology.

For a complete risk assessment, the most important factors are taken into account:

• Early menarche and late menopause
• Late first birth and nulliparous women
• Women over 50 years old
• History of cancer
• Hereditary predisposition
• Mutations in the BRCA-1, BRCA-2, and BRCA-3 genes
• Atypical hyperplasia of mammary gland tissue
• Long-term use of oral contraceptives
• Hormone replacement therapy
• Various injuries and damage to the mammary glands

The presence of the above factors is not a direct threat to cancer, but significantly increases the risk of its development. But the absence of these factors is not a guarantee of complete health. Do not forget that various benign breast lesions (fibrocystic mastopathy, intraductal papillomatosis, fibroadenosis) create a favorable background for tumor development. Constitutional obesity and irradiation of the chest with other diseases (lung cancer, damage to the lymphatic system) increase the risk of the disease.

Pathogenesis

The mechanism of development of triple-negative breast cancer largely depends on the cause that provoked it. Pathogenesis is associated with the accumulation of negative cells that cause tumor growth. Residual viral diseases are considered the main stimulator of tumor growth. A viral cell, that is, an antigen, contains information that is foreign to the gene structure of the human body. It causes a response from the immune system - the production of antibodies. If the body cannot produce antibodies and remove harmful cells from the body, then their accumulation leads to the formation of tumors.

During the diagnostic process, the tumor is classified depending on the presence of HER2 receptors, estrogen and progesterone. If the tumor is negative for all three receptors, then the cancer is triple negative. This form is considered very aggressive, with a high risk of metastasis and a negative survival prognosis.

Symptoms of Triple Negative Breast Cancer

Clinical manifestations of malignant disease depend on the factors that caused the disease and the individual characteristics of the patient's body. Symptoms of triple-negative breast cancer are associated with a specific histological structure.

The symptoms of the disease are no different from other forms of oncology. First of all, these are painful sensations in the chest, the appearance of a compaction of a dense consistency, which is painless at first. As the disease progresses, a characteristic retraction of the nipple, bloody or purulent discharge, and deformation of the gland appear.

Let's consider the main clinical characteristics of TNBC:

• Rare occurrence 10-20% of all malignant breast lesions.
• Patients' age: 40-60 years (premenopause, menopause).
• Hereditary predisposition.
• The appearance of a tumor-like node of dense consistency (painless).
• Inflammatory or inflammatory-infiltrative form, which leads to erroneous diagnosis with mastitis.
• According to the histological structure, the tumor is represented by basaloid cancer.
• Early metastasis, the appearance of distant and regional metastases.
• Rapid and aggressive progression.
• Difficult treatment due to low sensitivity to drugs.
• Frequent recurrence after radical therapy.

This symptomatic complex significantly facilitates the diagnostic process, which allows timely treatment of the pathology to begin.

First signs

At the initial stages of development, oncological lesions of the mammary gland do not manifest themselves in any way. The first signs are blurred, which significantly complicates the process of diagnosis and treatment. The neoplasm can be suspected when symptoms such as:

• A small compaction of dense consistency
• Deformation of the nipple shape
• Thickening of the gland skin due to impaired lymph drainage
• Swelling
• Nipple discharge
• The skin above the affected area takes on a reddish, inflamed hue.
• Enlarged axillary lymph nodes

At the initial stages, the lump is mobile and small in size. But it quickly increases in size and becomes painful when palpated. The presence of all these signs allows you to suspect cancer and undergo a medical examination. It is very important to respond to the symptoms in a timely manner and seek medical help.

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Consequences

Any form of oncology, regardless of its stage and location, causes irreparable harm to health. The consequences of the disease are very noticeable. The skin changes its appearance, hair falls out due to chemotherapy and radiation, the nervous system is shattered and exhausted. Surgical treatment of cancer also leaves a negative psychological effect. Radical therapy leaves its mark on the patient's body, requiring reconstructive plastic surgery.

The aftermath consists of a number of possible complications and side effects that arise during the process of tumor growth, diagnosis, and treatment. Common complications of triple-negative breast cancer include:

• Compression and destruction of healthy tissue of the gland and milk ducts due to tumor growth.
• A strong inflammatory process complicating the diagnostic process.
• Metastasis to nearby and distant organs and systems.
• Impaired lymph flow due to removal of axillary lymph nodes along with the breast.
• Hair loss, dry and flaky skin due to chemotherapy.

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Complications

Triple negative cancer has a detrimental effect on the patient's body. Complications depend on the type of treatment chosen and the severity of the oncology. These may include frequent bleeding from neoplasms and inflammation of surrounding tissues. Complications also arise when the tumor metastasizes. Thus, bone fractures, pleurisy with fluid accumulation, renal and hepatic failure occur in the metastasis zone.

Surgical treatment is also characterized by certain consequences. This is inflammation of the postoperative surface, prolonged lymphorrhea, swelling of the extremities, prolonged wound healing. Lack of treatment or late therapy promise the most serious complications that lead to death. But even with timely therapy, TNBC recurs within 1-2 years, causing irreversible consequences.

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Diagnosis of triple negative breast cancer

Detection of oncology is based on the clinical symptoms of the disease. Diagnostics consists of several methods, which allows for reliable recognition of the disease. The final diagnosis is made only after microscopic and immunohistochemical examination of the affected tissues. The reason for the examination are various seals and painful sensations in the chest.

• The woman undergoes a mammogram, i.e. an X-ray of the mammary glands and, if necessary, an ultrasound. This allows the slightest changes in the gland tissue to be detected.
• At the second stage, the patient undergoes a biopsy. The study identifies the benign or malignant nature of the neoplasm.
• Some patients are given ductography, which is an X-ray with a radiopaque substance injected into the ducts. This method can detect intraductal papillomas that can develop into cancer.

If the results of the above methods and symptoms indicate oncology, then additional studies are carried out. First of all, this is an ultrasound of the axillary lymph nodes to detect metastases, X-ray and ultrasound of the abdominal cavity and chest wall to exclude distant metastasis.

A blood test is performed for tumor markers (proteins produced by the tumor). For lesions of the mammary gland, this is Ca 15.3 with reduced diagnostic value. To identify a triple-negative form of cancer, an analysis of tumor tissues for hormone receptors is prescribed - progesterone, estrogen, Her2neu. For timely recognition of pathologies, it is recommended to undergo routine examinations and mammography.

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Tests

Diagnosis of any disease involves laboratory tests. Tests are necessary to determine tumor-associated markers in differential diagnostics and preoperative examination. CA15-3, CEA, Cyfra 21-1 are markers that confirm breast cancer.

Particular attention is paid to cytology, which is carried out in the presence of pathological discharge from the nipple. With the help of tests, it is possible to identify papillary structures in intraductal papillomas and malignant cancer cells. Taking a tissue sample for analysis can be done by several methods, let's consider them:

• Fine needle aspiration biopsy is a diagnostic and therapeutic measure at the same time. It is performed when a cyst is suspected and when pneumocystography is indicated.
• Trepan biopsy – tissue sampling is performed with a special needle, which allows obtaining complete histological information about the nature of the pathology and the degree of differentiation. To study non-palpable formations, the procedure is performed under ultrasound.
• Surgical biopsy is performed if the above procedures do not confirm (exclude) a malignant process.

For a comprehensive assessment of pathology, a triple test is used. This method is a combination of laboratory and instrumental methods. The conclusion is made based on the sum of points for each analysis.

Type of examination	Results	Points
Clinical examination	Benign	1
	Suspicious for cancer	2
	Malignant	3
Mammography	Benign	1
	Suspicious for cancer	2
	Malignant	3
Fine needle aspiration biopsy	Benign	1
	Suspicious for cancer	2
	Malignant	3

Test score:

• 3-4 points – benign neoplasm;
• 5 points – uncertain changes requiring additional diagnostics;
• 6-9 points – malignant lesion.

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Instrumental diagnostics

Detection of basal-like breast cancer involves the use of various methods. Instrumental diagnostics are performed with appropriate clinical indications. Let's consider the main instrumental methods:

• Mammography – used to differentiate cancer and tumor-like formations. It helps to identify non-palpable changes in breast tissue. In the absence of clinical symptoms of oncology, it is performed as a screening study.
• Ultrasound, CT, MRI are auxiliary methods for detecting primary tumors, metastases and assessing the condition of lymph nodes and internal organs.

In addition to the above methods, isotope scanning can be performed. This study is necessary to detect subclinical metastases in advanced stages of cancer.

Differential diagnostics

Since triple-negative breast cancer is similar in its symptoms to other malignant lesions, many different methods are used to detect it. Differential diagnostics are carried out with diseases such as:

• Dishormonal disorders – increased density, granularity or lobularity of glandular tissue. Symptoms are cyclical, intensify before menstruation.
• Fibroadenoma is a mobile neoplasm with clear contours. To differentiate it from cancer, ultrasound and fine-needle aspiration biopsy are performed.
• Subareolar abscess is a painful swelling under the areola with skin hyperemia. Biopsy and screening examination are performed to confirm the diagnosis.
• A cyst is a neoplasm that is painful when palpated. When performing an ultrasound, multiple cystic foci are detected.
• Intraductal papilloma – characterized by abundant discharge from the duct. For differentiation, ductography and cytological examination are performed.

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Treatment of triple negative breast cancer

To eliminate the basal-like form of malignant breast lesions, only modern methods and technologies are used. Treatment of triple-negative breast cancer is based on diagnostic results. This form of oncology is included in a separate group, as it is characterized by an aggressive course in comparison with other types of cancer. Such tumors differ in histological structure, therefore, they require specific treatment.

Very often, TNBC is detected at the last stages, which are accompanied by a severe inflammatory process. Often, the pathology is hereditary, can occur in patients of all ages, but most often in carriers of the BRCA-1 and BRCA-2 gene mutations.

Let's consider the features of therapy:

• There are no uniform standards for the treatment of negative cancer. The tumor is sensitive to chemotherapy, which is prescribed after radical removal of the gland.
• If surgical treatment is not possible, then chemotherapy or radiation is prescribed to reduce the size of the tumor.
• The better the tumor responds to chemotherapy, the better the prognosis for survival.

If triple-negative cancer is insensitive to chemotherapy, then new protocols are used that involve surgery, the use of taxanes and anthracyclines. The surgery involves partial removal of the breast, tumor irradiation, lymphatic drainage or complete removal of the gland. In case of relapses, a second course is carried out, with platinum drugs (Cisplatin, Carbaplatin), taxanes and xelodes. This type of treatment is effective for patients with the BRCA gene mutation.

Treatment regimens for triple negative breast cancer

When breast cancer is detected, the tumor is tested and classified based on the presence of progesterone, HER2, and estrogen receptors. If the tumor is negative for all three receptors, it is called triple-negative cancer. This form is considered the most aggressive, characterized by a high rate of metastasis and low survival compared to other forms of breast cancer.

Treatment regimens for triple-negative breast cancer are developed for each patient individually. That is, there is no single standard of treatment. But despite the poor prognosis, cancer is sensitive to many regimens. Therapy may consist of anthracycline- and taxane-containing drugs. Today, doctors are testing alternative chemotherapeutic agents: platinum compounds, antiangiogenics, topoisomerase inhibitors.

Medicines

One of the problems with treating triple-negative cancer is that it is considered the most aggressive form of oncology and is difficult to treat. Medicines are selected based on the results of laboratory and instrumental diagnostics. The peculiarity of the pathology is that it is not sensitive to the hormones progesterone and estrogen, does not have HER2 receptors. Targeted therapy, that is, drugs that act only on cancer cells and do not affect healthy tissue, is not used. It is for this reason that the tumor has a poor prognosis.

The international protocol for the treatment of TNBC indicates the effectiveness of using drugs from the taxane group. Such drugs reduce the risk of relapse and improve the prognosis. The best results were obtained when using drugs according to the Dose-dense protocol. It involves the use of cytostatic drugs every two weeks with the gradual addition of drugs from the taxon group according to the scheme 4 AC (Adriamycin and Cytoxan) + 4 Taxol (taxanes) with a break of 2 weeks. The duration of such therapy is about 4 months.

If cancer has affected the lymph nodes, then Carboplatin or Cisplatin are prescribed to the main scheme. Such treatment is effective in the presence of the BRCA1 gene mutation. If the disease recurs, then drugs that prevent or slow down cell development are added to the treatment scheme, that is, inhibitors - Ixempra, Xeloda, platinum drugs and antimetabolites.

The new generation of drugs is represented by the following preparations:

• Bevacizumab - blocks the growth of the neoplasm's blood vessel network. Since malignant cells actively multiply, they need constant nutrition. The drug reduces the number of blood vessels, reducing the energy supply of tumor tissue, which leads to its destruction. This drug has proven itself in combination with Taxol.
• Nexavar – used in cases of Her1 growth factor receptor positive. Used only in combination with Cisplatin.
• Iniparib – this drug is still in clinical trials. But according to studies, it significantly increases survival.
• Eribulin is a non-taxane microtubule inhibitor. It has proven itself in the treatment of late stages of TNBC. It is used only with special medical permission, as it is still in the research stage.

In addition to the above-described drugs, such an innovation as vaccination is used to combat triple-negative cancer. This method is based on the fact that it is easier to prevent the disease than to treat it. Since this form of pathology is very often diagnosed at the last stages. Vaccination can help women who are at risk. Vaxon Biotech is developing and testing the Vx-001 vaccine, which plans to introduce the drug by 2020.

Folk remedies

Treatment of malignant diseases requires a comprehensive approach. Traditional treatment is used along with classical methods of therapy. Let's consider the main methods of alternative therapy:

• If there are contraindications to surgical treatment, then you can use birch mushroom. The plant should be grated and infused in warm water 1:5 for 2-3 days. The finished tincture is taken 2-3 times a day 30 minutes before meals. The product can be stored in the refrigerator, but not longer than 4 days.
• To destroy malignant cells, it is recommended to use propolis. Ointments and tinctures are prepared from the plant, which slow down the growth of neoplasms and alleviate the symptoms of cancer. When using this product, you should know that if it is heated above 50 degrees, it will lose its medicinal properties.
• At the initial stages, you can use a decoction of oats. To prepare it, mix a glass of the plant with a liter of water and boil for 50-60 minutes. This decoction effectively removes toxins from the body that are formed during the disease. The medicine supplies the weakened body with vitamins B, A, E, PP and amino acids.
• You can make healing poultices from garlic and onions. Apply a cloth bag with chopped garlic and onions to the affected tissues. It is better to apply the poultice at night, the course of treatment is 6-7 procedures.
• To relieve painful symptoms, apply oak bark compresses to the sore chest. To prepare the remedy, mix a spoonful of crushed oak bark and pour cold water over it overnight. Boil the infusion in the morning, cool it and boil it again. The infusion should stand for 3-4 hours, after which you can make compresses from it for 20-30 minutes.

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Herbal treatment

Many methods are used to destroy cancer cells, but herbal therapy deserves special attention. Herbal treatment has a minimum of contraindications and side effects, but at the same time it has a beneficial effect on the body. To choose the right herb and its application scheme, it is necessary to consider such factors as:

• Localization and stage of cancer, treatment performed.
• The presence or absence of metastases, their localization.
• Undergoing chemotherapy or radiation.
• General condition of the patient before and after primary therapy.

The correct selection of herbs and the results of such therapy depend on the factors described above.

Poisonous herbs can be used to destroy cancer cells. But their improper use causes significant harm not only to malignant cells, but also to the entire body. That is why herbalists recommend using such tinctures only under medical supervision.

Poisonous herbs:

• Hemlock - a tincture is prepared from the plant, which has pronounced pain-relieving properties. To prepare it, use a three-liter bottle. The container should be 1/3 filled with the plant and poured with vodka on top. The remedy is infused for 2-3 weeks, shaking the jar periodically. On the first day, drink a glass of water with a drop of tincture, on the second two drops, and so on up to 40 drops. After this, the dosage must be reduced, returning to one drop. As a rule, 2-3 full circles are needed to achieve lasting results.
• Aconitum dzungarianum – take 20g of the plant root and pour 500 ml of vodka. The mixture should be infused for 14 days, then strain well. The medicine is taken 30 minutes before meals, diluted in a glass of water. The application scheme is similar to the one described above, only the concentration should be brought to 10 drops and in reverse order. After a break of 2-3 weeks, the course is repeated.
• Siberian agaric (dry) - the plant is crushed and placed in a dark glass bottle, filling it to the top with vodka. The mixture is infused for 15 days in a dark, cool place. The finished tincture is taken 30-40 drops 3 times a day, the course of therapy is 3 months.

In addition to poisonous plants, safer plants are also used for treatment:

• Grind 500 g of burdock roots, squeeze the juice out of the resulting mass. The remedy must be settled and the sediment must be drained, add 250 g of honey (buckwheat) and the juice of 3 lemons. All ingredients are mixed well and poured into a dark glass vessel. The remedy is taken at night, 1 tablespoon for 12 days.
• Pour two liters of goat milk over a couple of handfuls of young cherry branches. Simmer the remedy over low heat for 6 hours. Take the medicine ½ cup 2-3 times a day, between meals, the course of therapy is 70 days.
• Collect potato flowers and dry them. Prepare an infusion from the plant: pour 1 spoon of flowers with 500 ml of boiling water and leave for 3-4 hours. Take the infusion ½ cup 3 times a day before meals. Duration of therapy is 3 weeks.

Homeopathy

Treatment of one of the most aggressive forms of breast cancer is quite long and complicated. Homeopathy is used as an additional therapy for triple-negative cancer. The danger of the disease is that cancer cells do not respond to standard hormonal and HER2 treatment regimens. Homeopathic remedies are made from plant components that have a destructive effect on the tumor. The following are used from traditional homeopathic preparations:

• Alumen is a long-acting antipsoric agent.
• Argentum metallicum – helps in restoring normal functioning of the body.
• Arsenicum album is a palliative remedy that reduces painful symptoms.
• Arsenicum Iodatum – stops the growth of malignant cells.
• Arsenicum Sulfuratum Flavum – eliminates painful symptoms, restores the normal appearance of the gland.

The Chinese herbal remedy curcumin affects the growth of malignant cells. The plant inhibits the expression of EGFR, epidermal growth factor, and slows tumor growth. Medicines from medicinal mushrooms Ganoderma lucidum, Trametes versicolor, and Phellinus linteus have effective properties. They reduce cell growth and reproduction and promote their death.

Surgical treatment

Surgical removal of a breast cancer tumor is a radical therapy. Surgical treatment can be performed using several methods. Modern medicine allows organ-preserving operations to be performed with high results.

Let's consider the main types of operations:

• Lumpectomy is an organ-preserving operation, during which both the tumor and the adjacent tissues are removed. It is performed in the early stages of the disease, after which the patient undergoes radiation therapy.
• Quadrantectomy – during the operation, a quarter of the breast with the tumor is removed and irradiation is performed.
• Modified radical mastectomy – is performed when the tumor has metastasized to the lymph nodes. During the operation, the tumor and lymph nodes are removed.
• Segmentectomy is the excision of the tumor and part of the healthy tissue around it, followed by radiation and chemotherapy.
• Radical mastectomy – not only the tumor and lymph nodes are removed, but also the chest muscles located under the breast.

Surgical treatment may cause side effects and complications. Most often, this is numbness of the skin in the incision area, but with gradual restoration of the nerves, sensitivity returns to normal. In some cases, there is a risk of infection of the incision site. The infection is characterized by signs of skin inflammation, that is, its redness, swelling and soreness. An increase in skin temperature is observed at the site of the lesion. If there is suppuration, then fever, chills, increased sweating appear. To eliminate it, the wound is opened, washed with an antiseptic and drained. The patient is prescribed a course of antibiotics.

Prevention

There are many methods used to prevent triple-negative breast cancer. Prevention is based on early detection of the tumor. About 1 million cases of this disease are registered worldwide every year. According to medical statistics, 30% of women with oncology are over 45 years old.

Self-examination as a preventive measure:

• Carefully examine your breasts every day, paying attention to their shape and symmetry.
• To detect various seals, carefully palpate the glands. Alternately holding the breast with one hand, palpate with the other clockwise.
• If there are any lumps or swellings that do not go away after menstruation, then this is a reason to see a doctor.
• Pay attention to the nipples, if there is any discharge that is not related to lactation, urgently contact a mammologist. The skin also requires attention, if there is swelling, peeling or wet areas of erosion, then this also requires medical attention.

In addition to regular check-ups, it is necessary to choose underwear correctly. A bra that is not the right size irritates the mammary glands and disrupts their anatomical position. Another important method of cancer prevention is proper nutrition. This is due to the fact that the main cause of oncology is free radicals.

A healthy diet should include plenty of fruits, vegetables, greens, cereals and dairy products. Don't forget about physical activity. Regular exercise helps keep your body in good shape. Physical exercise is prescribed as a mandatory rehabilitation method after chemotherapy or surgery. Women with a family history should pay special attention to cancer prevention.

Forecast

Cancer that is not sensitive to hormonal and other classical therapy is characterized not only by an aggressive course, but also by a negative outcome. The prognosis depends on the stage at which the pathology was detected, the presence of concomitant diseases and other individual characteristics of the patient's body.

With timely diagnosis and treatment, the prognosis is favorable, but it worsens significantly if the cancer is detected in the last stages and has metastasized not only to regional lymph nodes, but also to distant organs and systems.

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Survival

Triple negative cancer is the most severe and complex form of oncology. Survival depends on many factors. Patients with this diagnosis have a 5 times higher risk of metastasis to other systems and organs within 5 years, unlike other forms of oncology. Most often, malignant cells spread to such vital organs as the lungs and brain.

Triple-negative breast cancer has a risk of metastasis and recurrence within 2-5 years, even after initial radical treatment. To prevent recurrence and metastasis, the patient undergoes radiation, radiotherapy, or chemotherapy. This increases the chances of no recurrence for five years from the time the disease is detected. But most women with TNBC get repeated cases of pathology and cancerous tumors in other organs.