Three times negative breast cancer

Three times negative breast cancer is pathology, with aggressive course and life-threatening complications. Let's consider features of the given kind of an oncology and the forecast.

With the help of immunohistochemical research, the main cancer receptors are determined. The analysis provides information on the receptors of estrogens (ER), sensitivity to herceptin (her2neu) and receptors of progesterone (PR). Most tumors have a positive response to all three receptors. If the cancer is not sensitive to herceptin (ER0, PR0, her2neu 0-1), then this indicates TNF.

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 breast. It has a specific histological structure (basal-like form). Squamous and apocrine carcinomas may occur in this group. TNPR occurs in 10-20% of all cancers. Pathology affects women taking oral contraceptives, patients with hereditary predisposition and blacks.

In most cases, tumors are diagnosed at advanced stages. Oncology manifests itself in the form of a long inflammatory process. Many hereditary forms of ailment belong to this category. It has different subtypes and groups that allow for a more detailed study of the mechanism of its development and an effective treatment plan. Oncology is characterized by a negative prognosis. But with timely therapy and no relapse within five years, the prognosis of survival 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, three times negative breast cancer is quite common in our country. The disease belongs to a heterogeneous group of tumors.

For the diagnosis of pathology, the code is used for μb 10, the ailment belongs to the category II neoplasms.

C50 Malignant neoplasm of breast:

• C50.0 Nipple and areola.
• C50.1 The central part of the mammary gland.
• C50.2 The upper quadrant of the mammary gland.
• C50.3 The Inside Quadrant of the Breast.
• C50.4 The uppermost quadrant of the mammary gland.
• C50.5 Lower breast quadrant.
• C50.6 Axillary back of the breast.
• C50.8 Breast cancer that extends beyond one or more of the above locations.
• C50.9 Mammary gland, unspecified part.

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

The causes of the triple negative breast cancer

The etiology of breast cancer is associated with various changes in the body. The causes can be caused by hormonal adjustment - climax (the production of estrogen and progesterone decreases, the ovaries pass into the passive mode of work), early menstruation or menstrual irregularities. A favorable background for the development of the disease creates an excess of sex hormones. Pregnancy, lactation and abortion, also create a hormonal surge, increasing the risk of pathology.

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

• Earlier menarche and late menopause
• Late first births and nulliparous women
• Women over 50 years old
• Cancer in history
• Hereditary predisposition
• Mutations of the BRCA-1, BRCA-2 and BRCA-3 genes
• Atypical hyperplasia of breast tissue
• Long-term use of oral contraceptives
• Hormone replacement therapy
• Various injuries and lesions of 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 full health. Do not forget that various benign lesions of the breast (fibrocystic mastopathy, intraluminal papillomatosis, fibroadenosis) create a favorable background for tumor development. Constitutional obesity and chest irradiation in other diseases (lung cancer, lymphatic system damage), increase the risk of ailment.

Pathogenesis

The mechanism of development of thrice negative breast cancer largely depends on the cause that provoked it. Pathogenesis is associated with the accumulation of negative cells that cause tumor growth. The main stimulator of neoplasm growth is residual viral diseases. The viral cell, that is, the antigen contains information that is alien to the gene structure of the human body. It causes a response of the immune system - the production of antibodies. If the body can not develop antibodies and remove harmful cells from the body, then their accumulation leads to the formation of tumors.

During the diagnosis the neoplasm is classified according to the presence of HER2 receptors, estrogen and progesterone. If the tumor is negative to all three receptors, then the cancer is three times negative. This form is considered very aggressive, with a high risk of metastasis and a negative prognosis of survival.

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.

Symptoms of the disease do not differ from other forms of oncology. First of all, it is a pain in the chest, the appearance of densification of dense consistency, which at first is painless. With progression, there is a characteristic retraction of the nipple, a bloody or purulent discharge, a deformity of the gland.

Let's consider the basic clinical characteristics of TNDMZH:

• A rare occurrence of 10-20% of the total number of malignant lesions of the breast.
• The age of patients is 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 basal cancer.
• Early metastasis, the appearance of distant and regional metastases.
• Rapid and aggressive progression.
• Complex treatment due to low sensitivity to drugs.
• Frequent recurrence after radical therapy.

This symptomatic complex greatly facilitates the process of diagnosis, which allows us to begin timely treatment of pathology.

First signs

At the initial stages of development, the oncological lesion of the mammary gland does not manifest itself in any way. The first signs are smeared, which significantly complicates the process of diagnosis and treatment. Neoplasm can be suspected when symptoms such as:

• Small dense consistency seal
• Deformity of the nipple shape
• Sealing of the gland skin due to worsening of lymph drainage
• Puffiness
• Discharge from the nipple
• Above the lesion the skin acquires a reddish, inflamed hue
• Axillary lymph node enlargement

At the initial stages, the compaction is mobile and has small dimensions. But it grows rapidly and becomes painful on palpation. The presence of all these signs allows you to suspect cancer and undergo a medical examination. It is very important to timely respond to symptoms and seek medical help.

[1], [2]

Effects

Any form of oncology, regardless of the stage and location of localization, causes irreparable harm to health. The consequences of the disease are very noticeable. Skin changes change their appearance, because of chemotherapy and irradiation hair falls out, the nervous system is shattered and exhausted. Negative psychological consequence leaves and operative treatment of a cancer. Radical therapy imposes an imprint on the patient's body, requiring restorative plastic.

The consequences consist of a number of possible complications and side effects that arise during tumor growth, diagnosis and therapy. Common complications of thrice-negative breast cancer:

• Squeezing and destruction of healthy tissue of the gland and milk ducts due to tumor overgrowth.
• A strong inflammatory process that complicates the process of diagnosis.
• Metastasis in nearby and remote organs and systems.
• Disturbance of lymph drainage due to removal of axillary lymph nodes together with the breast.
• Hair loss, dryness and peeling of the skin due to chemotherapy.

[3], [4], [5], [6]

Complications

Three times the negative cancer has a disastrous effect on the patient's body. The complications depend on the type of treatment chosen and the severity of oncology. This can be frequent bleeding from neoplasms and inflammation of surrounding tissues. Complications also occur with tumor metastasis. So in the metastasis zone there are fractures of bones, pleurisy with accumulation of fluid, renal and hepatic insufficiency.

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

[7]

Diagnosis of triple negative breast cancer

The detection of oncology is based on the clinical symptoms of the disease. Diagnosis consists of several methods, which allows you to reliably recognize the disease. The final diagnosis is made only after a microscopic and immunohistochemical study of the affected tissue. The cause for the study are various seals and pain in the chest.

• A woman is given a mammogram, that is, an x-ray of the mammary glands and, if necessary, an ultrasound. This allows to reveal the slightest changes in the gland tissues.
• At the second stage, the patient undergoes a biopsy. The study recognizes the benign or malignant nature of the neoplasm.
• Some patients are prescribed doktografiyu, which is an x-ray with the introduction of radiopaque substances into the ducts. This method allows to identify intra-flow papillomas, which can degenerate into cancer.

If the results of the above methods and symptoms indicate an oncology, then further studies are carried out. First of all, it is ultrasound of the axillary lymph nodes for the detection of metastases, X-rays 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 breast, this is Ca 15.3 with a reduced diagnostic value. To identify the threefold negative form of cancer, an analysis of the neoplasm tissue for receptors for hormones is prescribed-progesterone, estrogen, Her2neu. For timely recognition of pathologies, it is recommended to undergo scheduled examinations and mammograms.

[8], [9]

Analyzes

Diagnosis of any disease involves laboratory research. Analyzes are needed to determine tumor-associated markers in differential diagnosis and preoperative studies. 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 analyzes, it is possible to identify papillary structures with intracapsular papillomas and malignant cancer cells. Sampling a tissue sample for analysis can be done in several ways, consider them:

• Fine needle aspiration biopsy is a diagnostic and therapeutic measure simultaneously. It is carried out with suspicions of the cyst and with pneumocystography.
• Trepan-biopsy - tissue extraction is performed with a special needle, which allows obtaining complete histological information about the nature of the pathology and degree of differentiation. For examination of non-palpable formations, the procedure is performed under ultrasound.
• Surgical biopsy - is carried out in the event that the above procedures have not confirmed (excluded) the 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 on the basis of the sum of balls according to the results of each analysis.

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

Evaluation of the test:

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

[10], [11], [12], [13], [14], [15], [16], [17], [18], [19]

Instrumental diagnostics

The detection of basal-like breast cancer involves the use of various methods. Instrumental diagnosis is performed with appropriate clinical indications. Let's consider the basic tool methods:

• Mammography - used to differentiate cancer and tumor formations. With its help, it is possible to detect non-palpable changes in the tissues of the breast. In the absence of clinical symptoms of oncology, it is carried out 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 carried out. This study is necessary to identify subclinical metastases in advanced stages of cancer.

Differential diagnostics

Because of its symptoms, three times negative breast cancer is similar to other malignant lesions, then many different methods are used to detect it. Differential diagnosis is carried out with such diseases as:

• Dyshormonal disorders - increased density, granularity or lobariness of the gland tissues. Symptoms are cyclical, intensified before menstruation.
• Fibroadenoma is a mobile neoplasm with clear contours. For differentiation with cancer, ultrasound is performed, a fine needle aspiration biopsy.
• Subareolar abscess is a painful tumor under the areola with skin hyperemia. To confirm the diagnosis, a biopsy and a screening test are performed.
• The cyst is a neoplasm, painful when trying to palpate. When performing ultrasound, multiple cystic foci are identified.
• Intra-flow papilloma - characterized by abundant discharge from the duct. For differentiation, doktografiya and cytological examination are carried out.

[20], [21], [22], [23], [24], [25]

Treatment of triple negative breast cancer

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

Very often TNF is diagnosed 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 more often in carriers of the gene mutation BRCA-1 and BRCA-2.

Let's consider features of therapy:

• There are no uniform standards for the treatment of negative cancers. The tumor is sensitive to chemotherapy, which is prescribed after radical removal of the gland.
• If surgical treatment can not be carried out, then chemotherapy or radiation is prescribed to reduce the size of the lesion.
• The better the tumor responds to chemotherapy, the more favorable is 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 operation involves partial removal of the breast, irradiation of the tumor, lymph drainage or complete removal of the gland. When relapses, conducting a second course, with platinum (Cisplatin, carbaplatin), taxanes and xeloda. This type of treatment is effective for patients with a 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 to all three receptors, then this indicates a triple negative oncology. This form is considered the most aggressive, characterized by a high level of metastasis and low survival in comparison with other forms of breast cancer.

Diagrams for treating triple negative breast cancer are made for each patient individually. That is, there is no single standard of treatment. But, despite the poor prognosis, cancer is sensitive to many schemes. Therapy may consist of anthracycline- and taksane-containing drugs. To date, doctors are testing alternative chemotherapeutic agents: platinum compounds, anti-angiogenic, topoisomerase inhibitors.

Medications

One of the problems of treating triply negative cancer is that it is considered to be the most aggressive form of oncology and does not respond well to therapy. 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 of progesterone and estrogen, it does not have HER2 receptors. Target therapy, that is, drugs that only act 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 TNFR suggests the effectiveness of the use of drugs from the taxane group. Such drugs reduce the risk of relapse and improve the prognosis. The best results were obtained with the use of drugs using the Dose-dense protocol. It involves the use of cytostatic drugs every two weeks with the gradual addition of medicaments from the group of taxa according to the scheme 4 AC (Adriamycin and Citoxane) + 4 Taxol (taxanes) with a break in 2 weeks. The duration of such therapy is about 4 months.

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

A new generation of drugs is represented by such drugs:

• Bevacizumab - blocks the proliferation of the neoplasm of the neoplasm. Since malignant cells actively multiply, they need constant nutrition. The medicine reduces the number of blood vessels, reducing the energy supply of tumor tissues, which leads to its destruction. This drug has proven itself in combination with Taxol.
• Nexavar - is used with a positive response to the Her1 growth factor receptors. Used only in combination with Cisplatinum.
• Iniparib - this remedy is still at the stage of clinical trials. But according to the studies significantly increases the survival rate.
• Erybulin - refers to the inhibitors of microtubules of the non-axonal series. He recommended himself in the treatment of the last stages of TNF. It is used only if there is a special medical authorization, because it is still at the research stage.

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

Alternative treatment

Treatment of malignant diseases requires an integrated approach. Alternative treatment is used on a par with classical methods of therapy. Let's consider the basic methods of non-traditional therapy:

• If there are contraindications to surgical treatment, then you can use a birch mushroom. The plant should be grated and insulted in warm water 1: 5 for 2-3 days. Ready tincture is taken 2-3 times a day for 30 minutes before meals. The product can be stored in the refrigerator, but no longer than 4 days.
• Propolis is recommended for the destruction of malignant cells. From the plant, ointments and tinctures are prepared that slow the growth of the tumor and alleviate the symptoms of cancer. When using this tool, you should know that if it is heated above 50 degrees, it will lose its healing properties.
• In the initial stages you can use oat broth. For its preparation, the glass of the plant must be mixed with a liter of water and boiled for 50-60 minutes. Such a decoction effectively removes toxins from the body, which are formed during illness. The medicine supplies the weakened organism with vitamins of group B, A, E, PP and amino acids.
• From garlic and onions it is possible to prepare medicinal lotions. To the affected tissues, a tissue sac with chopped garlic and onions is applied. It is better to put the lotion on overnight, the course of treatment is 6-7 procedures.
• For relief of painful symptoms, compresses from the oak bark are applied to the affected chest. To prepare the product, mix a spoon of the crushed oak bark and pour it overnight with cold water. In the morning, boil the infusion, cool and boil again. Infusion should stand for 3-4 hours, after which you can make compresses for 20-30 minutes.

[26], [27], [28], [29], [30]

Herbal Treatment

Many methods are used to kill cancer cells, but herbal therapy deserves special attention. Herbal treatment has a minimum of contraindications and side effects, but it has a beneficial effect on the body. For proper selection of herbs and the scheme of its application, it is necessary to take into account such factors as:

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

From the above described factors depends on the correct selection of herbs and the result of such therapy.

To destroy cancer cells can be used poisonous herbs. But their incorrect application causes significant harm not only to malignant cells, but to the whole organism. That is why phytotherapeutists recommend using such tinctures only under medical supervision.

Toxic herbs:

• Hemlock - from the plant prepare tincture, which has pronounced analgesic properties. For its preparation use a three-liter bottle. The container should be filled with a third of the plant and filled with vodka. It persists for 2-3 weeks, periodically shaking the jar. On the first day, drink a glass of water with a drop of tincture, on the second two drops and so on to 40 drops. After this, the dosage should be reduced by returning to one drop. As a rule, 2-3 full circles are needed to achieve lasting results.
• Aconite Dzhungar - take 20 g of the root of the plant and fill with 500 ml of vodka. The mixture should be infused for 14 days, after which it is well to strain. The medicine is taken 30 minutes before meals, diluting in a glass with water. The scheme of application is similar to the above, only the concentration should be brought to 10 drops and in the reverse order. After a break of 2-3 weeks, the course is repeated.
• Knyazhik Siberian (dry) - the plant is ground and placed in a bottle of dark glass, pouring up to the top with vodka. The mixture is infused for 15 days in a dark, cool place. Ready tincture is taken by 30-40 drops 3 times a day, the course of therapy is 3 months.

In addition to poisonous, more safe plants are used for treatment:

• Grind 500 g of burdock roots, then squeeze the juice out of the resulting mass. The product must be protected and drained, add 250 g of honey (buckwheat) and juice of 3 lemons. All ingredients are well mixed and poured into a vessel of dark glass. Take 1 tablespoon overnight for 12 days.
• Pour a couple of handfuls of young cherry twigs with two liters of goat's milk. Within 6 hours, the remedy should be simmered over low heat. The medicine is taken by ½ cup 2-3 times a day, between meals, the course of therapy is 70 days.
• Collect the potato flowers and dry them. From the plant prepare the infusion: 1 spoon of flowers poured 500 ml of boiling water and infused for 3-4 hours. Infusion take ½ cup 3 times daily before meals. Duration of therapy is 3 weeks.

Homeopathy

Treatment of one of the most aggressive forms of breast oncology 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. From traditional homeopathic remedies the following are used:

• Alumen is a long-acting antipsoric.
• Argentum metallicum - helps in the restoration of the normal functioning of the body.
• Arsenicum album is a palliative 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.

Chinese herbal remedy curcumin, affects the growth of malignant cells. The plant inhibits the expression of EGFR, the epidermal growth factor of cells and slows the growth of the tumor. Effective properties have medicines from therapeutic fungi Ganoderma lucidum, Trametes versicolor and Phellinus linteus. They reduce the growth and multiplication of cells and contribute to their death.

Operative treatment

Surgical removal of a breast cancer refers to radical therapy. Operative treatment can be carried out by several methods. Modern medicine allows you to perform organ-saving operations with high results.

Consider the main types of operation:

• Lamectomy is an organ-preserving operation, during which both the neoplasm and adjacent tissues are removed. It is carried out at the first stages of the disease, after which the patient is given radiation therapy.
• Quadrantectomy - during the operation, remove a quarter of the breast with a tumor and perform irradiation.
• Modified radical mastectomy - is performed when the tumor is metastasized into the lymph nodes. During the operation, the tumor and lymph nodes are removed.
• Segmentectomy - excision of the tumor and parts of healthy tissues around it with subsequent irradiation and chemotherapy.
• Radical mastectomy - remove not only the tumor and lymph nodes, but also the muscles of the chest that are under the breast.

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

Prevention

To prevent triple negative breast cancer, many methods are used. Prevention is based on early detection of a tumor. Annually around 1 million cases of this disease are registered in the world. According to medical statistics, 30% of women with oncology have an age of 45 years.

Self-examination as prevention:

• Every day, carefully examine your breasts, paying attention to the shape and their symmetry.
• To identify various seals, gently palpate the glands. Alternately holding the chest with one hand, the second in a clockwise direction is probed.
• If there are any seals or swelling that do not disappear after menstruation, then this is an occasion to consult a doctor.
• Pay attention to the nipples, if there are any secretions that are not associated with lactation, urgently consult a mammologist. Attention requires skin, if there is swelling, scaling or wetting areas of erosion, it also requires medical attention.

In addition to regular inspection, you must choose the right underwear. The bra is not the size of irritating the mammary glands, violates their anatomical position. Another important method of preventing cancer is proper nutrition. This is due to the fact that the main cause of oncology is free radicals.

In a healthy diet should be a lot of fruits, vegetables, greens, cereals and dairy products. Do not forget about physical activity. Regular exercise allows you to maintain the body in good shape. Physical education is prescribed as an obligatory method of rehabilitation after chemotherapy or surgery. Women with a family history should pay special attention to cancer prevention.

Forecast

Not sensitive to hormonal and other classical therapy of cancer, 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 significantly worsens if the cancer is detected in the last stages and has metastasized not only to the regional lymph nodes, but also to distant organs and systems.

[31], [32], [33], [34]

Survival

Triple negative cancer is the most difficult and complex form of oncology. Survival depends on many factors. Patients with this diagnosis are 5 times more likely to metastasize to other systems and organs for 5 years, unlike other forms of oncology. Most often, malignant cells spread to such vital organs as the lungs and the brain.

Three times negative breast cancer has a risk of metastatic injury and recurrence within 2-5 years, even after the initial radical treatment. To prevent recurrences and metastases, the patient is exposed to radiation, radiotherapy or chemotherapy. This increases the chances of no relapse within five years of the discovery of the disease. But the majority of women with TNFR receive repeated cases of pathology and cancerous tumors in other organs.