What does diagnosis d 50.9 mean? D50 Iron deficiency anemia

The main cause of skin disorders in allergic urticaria is massive degranulation of tissue basophils (mast cells). The granules of these cells contain histamine, heparin, leukotrienes and a number of other biologically active compounds that can significantly change metabolic processes in tissues. Basically, they lead to dilation of blood vessels, increase the permeability of their walls, cause the accumulation of tissue fluid, stimulate pain receptors in the skin, which leads to itching. In most cases, such reactions in allergic urticaria are local in nature and affect only a certain area of ​​the skin or, less commonly, the entire surface of the body. However, sometimes such a massive release of active compounds can lead to general reactions such as anaphylactic shock and Quincke's edema.
  The causes that cause mast cell degranulation differ among different forms of allergic urticaria. Usually this is a reagin type of hypersensitivity (type 1 allergy), mediated by type E immunoglobulins. Allergens for this type of allergic urticaria are food components, pollen, household dust, some medications and other factors. In this case, skin manifestations are just one of the symptoms of a food or other allergy. In some cases, type 2 allergies can also cause such skin disorders - this mainly happens with blood transfusions. Intravenous administration of certain drugs with the development of an immune complex intolerance reaction can also cause allergic urticaria.
  It has been noted that some infectious diseases, endocrine disorders, and psycho-emotional disorders increase the likelihood of developing allergic urticaria. This is especially true in relation to idiopathic or chronic forms of pathology. The pathogenesis of the development of skin disorders in this case has been poorly studied; both immune and non-immune mechanisms of activation of tissue basophils of the skin are assumed. Therefore, in the presence of allergic urticaria of unspecified etiology, a complete examination of the patient’s body is performed in order to identify hidden and chronic diseases and disorders.
  In pseudoallergic urticaria, the pathogenesis is largely similar - massive activation of skin tissue basophils occurs with the release of biologically active compounds. However, the reasons and mechanisms of this process are somewhat different - it may be congenital or acquired instability of mast cell membranes, their abnormal response to various physical or humoral factors. In addition, in some cases of pseudoallergic urticaria, the patient exhibits increased sensitivity of skin tissue to histamine and other components of basophil granules. Therefore, even a slight release of these substances can lead to the clinical picture of urticaria.

Definition. A disease, the leading sign of which is a decrease in the number of erythrocytes less than 4.0x1012/l and hemoglobin less than 120 g/l with a color index below 0.8 and a serum iron level less than 13 µmol/l.

Statistics. One of the most common human diseases. Up to 25% of the total population is affected, 40% of women of childbearing age, 33% of people of both sexes over 60 years of age.

Etiology.

Chronic blood loss exceeding the body's regenerative capabilities:

Menorrhagia (menstruation lasting 6-7 days, heavy; or with clots - of any duration);

Hemorrhoidal bleeding;

Gastrointestinal bleeding with erosive and ulcerative lesions.

Chronic diseases of the gastrointestinal tract, especially with reduced secretory function of the stomach, leading to impaired absorption of dietary iron.

Poor nutrition (starvation, anorexia, etc.)

Hyper- and hypothyroid conditions.

Pregnancy, lactation, early childhood.

Long-term uncontrolled use of certain medications, especially non-steroidal anti-inflammatory drugs (ibuprofen, diclofenac, etc.), analgin, biseptol.

Clinic, diagnostics. In women, the disease often occurs with chlorosis syndrome. Complaints of fainting, low-grade fever, pain in the tongue, perversion of taste and smell; irresistible

The desire to eat chalk, lime, clay, earth, whitewash from the walls, I like heavy spicy aromas. Brittle nails and hair. The nails are flattened in appearance, soft and layered to the touch. Hair is dry, split ends, dull. In men, the disease always occurs without chlorosis syndrome. Pale skin, sometimes with a greenish tint. Heart sounds are muffled, gentle systolic murmur at all points. Tachycardia, hypotension. Nervous system - signs of asthenodepressive, asthenoneurotic, asthenohypochondriacal syndromes. Laboratory indicators: decrease in the number of erythrocytes, hemoglobin, color index, serum iron, increase in ESR, anisocytosis, poikilocytosis of erythrocytes.

Classification. The degree of severity, etiological factor, and phase of the disease (exacerbation, remission) are specified.

Anemia severity:

Light (erythrocytes 3.0-3.5x10|2/l, Hb 100 g/l and above);

Moderate severity (erythrocytes 2.0-3.0x10|2/l, Hb 80-100 g/l);

Severe (erythrocytes 1.0-2.0x10"7l, Hb 55-80 g/l);

Extremely severe, threatening the development of anemic coma (red blood cells
Criteria for exacerbation: a decrease in the numbers of erythrocytes and Hb in women below 4.0x10"2/l and 120 g/l, in men below 4.5x1012/l and 130 g/l, respectively.

Remission criterion: return of red blood cell and Hb numbers to normal values. Any increase in red blood numbers that does not reach the norm should be considered not a remission, but an improvement.

Formulation of the diagnosis.

Chronic iron deficiency anemia due to menorrhagia, moderate severity, exacerbation.

Chronic iron deficiency anemia of mixed origin due to menorrhagia and gastrogenic, severe, exacerbation.

Psychological and social status are formulated according to general principles.

Differential diagnosis

To exclude hemoblastosis, one should verify the absence of hemorrhagic and ulcerative-necrotic syndromes, and laboratory tests should ensure that there are no changes in the patient’s leukogram characteristic of leukemia.

To exclude oncological pathology, first-level screening is carried out: large-frame fluorography (CCF), fluoroscopy of the gastrointestinal tract or fibrogastroduodenoscopy (FGDS); for women, an examination by a gynecologist is required. If the source is not identified when collecting anamnesis, there is no indication of diseases of the gastrointestinal tract, the patient If you are elderly, then in addition to exclude a malignant neoplasm, chest X-ray, irrigoscopy, sigmoidoscopy, and ultrasound examination of the abdominal organs are performed.

Vitamin B12 and folate deficiency anemia is hyperchromic, the number of reticulopitis is reduced, serum iron is normal, liver enlargement is common, megaloblastic hematopoiesis is found in the sternal punctate.

With hemolytic anemia: icterus of the skin, enlargement of the spleen and liver, laboratory tests - normochromic anemia, a sharp increase in the number of reticulocytes, serum iron is normal or increased, hyperbilirubinemia due to indirect bilirubin, hemosiderin in the urine, pronounced hyperplasia of the erythroid lineage in bone marrow punctate.

With hypoplastic anemia, hemorrhagic and (or) purulent-necrotic syndrome, a sharp decrease in all blood parameters (erythrocytes, leukocytes, platelets), in the punctate, inhibition of all hematopoietic germs.

Sideroachrestic anemia, according to the clinical picture and data from a general blood test, is no different from iron deficiency, but the iron content in the blood serum of such patients is high (50-90 µmol/l). Treatment with iron preparations leads to hemosiderosis of organs without relieving the symptoms of the disease.

Anemia is a clinical and hematological syndrome characterized by a decrease in the number of red blood cells and hemoglobin in the blood. A wide variety of pathological processes can serve as the basis for the development of anemic conditions, and therefore anemia should be considered as one of the symptoms of the underlying disease. The prevalence of anemia varies significantly, ranging from 0.7 to 6.9%. The cause of anemia can be one of three factors or a combination of them: blood loss, insufficient production of red blood cells, or increased destruction of red blood cells (hemolysis).

Among various anemic conditions iron deficiency anemia are the most common and account for about 80% of all anemias.

Iron deficiency anemia- hypochromic microcytic anemia, which develops as a result of an absolute decrease in iron reserves in the body. Iron deficiency anemia occurs, as a rule, with chronic blood loss or insufficient intake of iron into the body.

According to the World Health Organization, every 3rd woman and every 6th man in the world (200 million people) suffer from iron deficiency anemia.

Iron metabolism
Iron is an essential biometal that plays an important role in the functioning of cells in many body systems. The biological significance of iron is determined by its ability to reversibly oxidize and reduce. This property ensures the participation of iron in the processes of tissue respiration. Iron makes up only 0.0065% of body weight. The body of a man weighing 70 kg contains approximately 3.5 g (50 mg/kg body weight) of iron. The iron content in the body of a woman weighing 60 kg is approximately 2.1 g (35 mg/kg body weight). Iron compounds have different structures, have unique functional activity and play an important biological role. The most important iron-containing compounds include: hemoproteins, the structural component of which is heme (hemoglobin, myoglobin, cytochromes, catalase, peroxidase), enzymes of the non-heme group (succinate dehydrogenase, acetyl-CoA dehydrogenase, xanthine oxidase), ferritin, hemosiderin, transferrin. Iron is part of complex compounds and is distributed in the body as follows:
- heme iron - 70%;
- iron depot - 18% (intracellular accumulation in the form of ferritin and hemosiderin);
- functioning iron - 12% (myoglobin and iron-containing enzymes);
- transported iron - 0.1% (iron bound to transferrin).

There are two types of iron: heme and non-heme. Heme iron is part of hemoglobin. It is contained only in a small part of the diet (meat products), is well absorbed (20-30%), its absorption is practically not affected by other food components. Non-heme iron is in free ionic form - ferrous (Fe II) or ferric iron (Fe III). Most dietary iron is non-heme (found primarily in vegetables). The degree of its absorption is lower than that of heme and depends on a number of factors. Only divalent non-heme iron is absorbed from food. To “convert” ferric iron into divalent iron, a reducing agent is needed, the role of which in most cases is played by ascorbic acid (vitamin C). During absorption in the cells of the intestinal mucosa, ferrous iron Fe2+ is converted into oxide Fe3+ and binds to a special carrier protein - transferrin, which transports iron to hematopoietic tissues and sites of iron deposition.

Iron accumulation is carried out by the proteins ferritin and hemosiderin. If necessary, iron can be actively released from ferritin and used for erythropoiesis. Hemosiderin is a ferritin derivative with a higher iron content. Iron is released slowly from hemosiderin. Incipient (prelatent) iron deficiency can be determined by a reduced concentration of ferritin even before the depletion of iron stores, while still maintaining normal concentrations of iron and transferrin in the blood serum.

What causes iron deficiency anemia:

The main etiopathogenetic factor in the development of iron deficiency anemia is iron deficiency. The most common causes of iron deficiency conditions are:
1. iron loss due to chronic bleeding (the most common cause, reaching 80%):
- bleeding from the gastrointestinal tract: peptic ulcer, erosive gastritis, esophageal varicose veins, colon diverticula, hookworm infestations, tumors, ulcerative colitis, hemorrhoids;
- long and heavy menstruation, endometriosis, fibroids;
-- macro- and microhematuria: chronic glomerulo- and pyelonephritis, urolithiasis, polycystic kidney disease, kidney and bladder tumors;
- nosebleeds, pulmonary bleeding;
-- blood loss during hemodialysis;
-- uncontrolled donation;
2. insufficient absorption of iron:
-- resection of the small intestine;
- chronic enteritis;
- malabsorption syndrome;
- intestinal amyloidosis;
3. increased need for iron:
-- intensive growth;
-- pregnancy;
- period of breastfeeding;
- playing sports;
4. insufficient intake of iron from food:
-- newborns;
-- small children;
-- vegetarianism.

Pathogenesis (what happens?) during Iron deficiency anemia:

Pathogenetically, the development of iron deficiency can be divided into several stages:
1. prelatent iron deficiency (insufficient accumulation) - there is a decrease in ferritin levels and a decrease in iron content in the bone marrow, increased iron absorption;
2. latent iron deficiency (iron deficiency erythropoiesis) - serum iron is further reduced, transferrin concentration increases, and the content of sideroblasts in the bone marrow decreases;
3. severe iron deficiency = iron deficiency anemia - the concentration of hemoglobin, red blood cells and hematocrit further decreases.

Symptoms of Iron Deficiency Anemia:

During the period of latent iron deficiency, many subjective complaints and clinical signs characteristic of iron deficiency anemia appear. Patients note general weakness, malaise, and decreased performance. Already during this period, distortion of taste, dryness and tingling of the tongue, difficulty swallowing with the sensation of a foreign body in the throat, palpitations, and shortness of breath may be observed.
An objective examination of patients reveals “minor symptoms of iron deficiency”: atrophy of the tongue papillae, cheilitis, dry skin and hair, brittle nails, burning and itching of the vulva. All these signs of impaired trophism of epithelial tissues are associated with tissue sideropenia and hypoxia.

Patients with iron deficiency anemia report general weakness, fatigue, difficulty concentrating, and sometimes drowsiness. Headache and dizziness appear. Severe anemia may cause fainting. These complaints, as a rule, do not depend on the degree of decrease in hemoglobin, but on the duration of the disease and the age of the patients.

Iron deficiency anemia is also characterized by changes in the skin, nails and hair. The skin is usually pale, sometimes with a slight greenish tint (chlorosis) and with an easy blush on the cheeks, it becomes dry, flabby, peels, and cracks easily form. Hair loses its shine, turns grey, thins, breaks easily, thins and turns gray early. Changes in nails are specific: they become thin, matte, flattened, easily peel and break, and striations appear. With pronounced changes, the nails acquire a concave, spoon-shaped shape (koilonychia). Patients with iron deficiency anemia experience muscle weakness, which is not observed in other types of anemia. It is classified as a manifestation of tissue sideropenia. Atrophic changes occur in the mucous membranes of the digestive canal, respiratory organs, and genital organs. Damage to the mucous membrane of the digestive canal is a typical sign of iron deficiency.
There is a decrease in appetite. There is a need for sour, spicy, salty foods. In more severe cases, distortions of smell and taste (pica chlorotica) are observed: eating chalk, lime, raw cereals, pogophagia (craving for eating ice). Signs of tissue sideropenia quickly disappear after taking iron supplements.

Diagnosis of Iron Deficiency Anemia:

Basic guidelines in laboratory diagnosis of iron deficiency anemia the following:
1. The average hemoglobin content in an erythrocyte in picograms (normal 27-35 pg) is reduced. To calculate it, the color index is multiplied by 33.3. For example, with a color index of 0.7 x 33.3, the hemoglobin content is 23.3 pg.
2. The average concentration of hemoglobin in the erythrocyte is reduced; Normally it is 31-36 g/dl.
3. Hypochromia of erythrocytes is determined by microscopy of a peripheral blood smear and is characterized by an increase in the zone of central clearing in the erythrocyte; Normally, the ratio of central clearing to peripheral darkening is 1:1; for iron deficiency anemia - 2+3:1.
4. Microcytosis of erythrocytes - reduction in their size.
5. Coloring of erythrocytes of different intensity - anisochromia; the presence of both hypo- and normochromic red blood cells.
6. Different shapes of red blood cells - poikilocytosis.
7. The number of reticulocytes (in the absence of blood loss and a period of ferrotherapy) in iron deficiency anemia remains normal.
8. The leukocyte count is also within normal limits (except in cases of blood loss or oncopathology).
9. The platelet count often remains within normal limits; moderate thrombocytosis is possible with blood loss at the time of examination, and the platelet count decreases when the basis of iron deficiency anemia is blood loss due to thrombocytopenia (for example, with DIC syndrome, Werlhof's disease).
10. Reducing the number of siderocytes until they disappear (a siderocyte is an erythrocyte containing iron granules). In order to standardize the production of peripheral blood smears, it is recommended to use special automatic devices; the resulting monolayer of cells increases the quality of their identification.

Biochemical blood test:
1. Decrease in iron content in blood serum (normally in men 13-30 µmol/l, in women 12-25 µmol/l).
2. The life-saving ratio is increased (reflects the amount of iron that can be bound due to free transferrin; the normal life-value percentage is 30-86 µmol/l).
3. Study of transferrin receptors using the enzyme immunoassay method; their level is increased in patients with iron deficiency anemia (in patients with anemia of chronic diseases - normal or reduced, despite similar indicators of iron metabolism.
4. The latent iron-binding capacity of blood serum is increased (determined by subtracting the serum iron content from the TLC indicators).
5. The percentage of transferrin saturation with iron (the ratio of the serum iron indicator to the total life-saving value; normally 16-50%) is reduced.
6. The level of serum ferritin is also reduced (normally 15-150 mcg/l).

At the same time, in patients with iron deficiency anemia, the number of transferrin receptors is increased and the level of erythropoietin in the blood serum is increased (compensatory reactions of hematopoiesis). The volume of erythropoietin secretion is inversely proportional to the oxygen transport capacity of the blood and directly proportional to the oxygen demand of the blood. It should be taken into account that serum iron levels are higher in the morning; before and during menstruation it is higher than after menstruation. The iron content in blood serum in the first weeks of pregnancy is higher than in its last trimester. Serum iron levels increase on days 2-4 after treatment with iron-containing drugs and then decrease. Significant consumption of meat products on the eve of the study is accompanied by hypersideremia. These data must be taken into account when assessing the results of serum iron studies. It is equally important to follow laboratory testing techniques and blood sampling rules. Thus, the tubes in which blood is collected must first be washed with hydrochloric acid and double-distilled water.

Myelogram study reveals a moderate normoblastic reaction and a sharp decrease in the content of sideroblasts (erythrokaryocytes containing iron granules).

Iron reserves in the body are judged by the results of the desferal test. In a healthy person, after intravenous administration of 500 mg of desferal, 0.8 to 1.2 mg of iron is excreted in the urine, while in a patient with iron deficiency anemia, iron excretion decreases to 0.2 mg. The new domestic drug defericolixam is identical to desferal, but circulates in the blood longer and therefore more accurately reflects the level of iron reserves in the body.

Taking into account the level of hemoglobin, iron deficiency anemia, like other forms of anemia, is divided into severe, moderate and mild anemia. With mild iron deficiency anemia, the hemoglobin concentration is below normal, but more than 90 g/l; with moderate iron deficiency anemia, the hemoglobin content is less than 90 g/l, but more than 70 g/l; with severe iron deficiency anemia, the hemoglobin concentration is less than 70 g/l. However, clinical signs of the severity of anemia (symptoms of a hypoxic nature) do not always correspond to the severity of anemia according to laboratory criteria. Therefore, a classification of anemia according to the severity of clinical symptoms has been proposed.

Based on clinical manifestations, there are 5 degrees of severity of anemia:
1. anemia without clinical manifestations;
2. moderate anemic syndrome;
3. severe anemic syndrome;
4. anemic precoma;
5. anemic coma.

Moderate severity of anemia is characterized by general weakness, specific signs (for example, sideropenic or signs of vitamin B12 deficiency); with a pronounced degree of severity of anemia, palpitations, shortness of breath, dizziness, etc. appear. Precomatose and comatose states can develop in a matter of hours, which is especially typical for megaloblastic anemia.

Modern clinical studies show that laboratory and clinical heterogeneity is observed among patients with iron deficiency anemia. Thus, in some patients with signs of iron deficiency anemia and concomitant inflammatory and infectious diseases, the level of serum and erythrocyte ferritin does not decrease, but after the exacerbation of the underlying disease is eliminated, their content drops, which indicates the activation of macrophages in the processes of iron consumption. In some patients, the level of erythrocyte ferritin even increases, especially in patients with long-term iron deficiency anemia, which leads to ineffective erythropoiesis. Sometimes there is an increase in the level of serum iron and erythrocyte ferritin, a decrease in serum transferrin. It is assumed that in these cases the process of iron transfer to heme-synthesizing cells is disrupted. In some cases, a deficiency of iron, vitamin B12 and folic acid is determined simultaneously.

Thus, even the level of serum iron does not always reflect the degree of iron deficiency in the body in the presence of other signs of iron deficiency anemia. Only the level of THC in iron deficiency anemia is always elevated. Therefore, not a single biochemical indicator, incl. OZHSS cannot be considered as an absolute diagnostic criterion for iron deficiency anemia. At the same time, the morphological characteristics of peripheral blood erythrocytes and computer analysis of the main parameters of erythrocytes are decisive in the screening diagnosis of iron deficiency anemia.

Diagnosis of iron deficiency conditions is difficult in cases where the hemoglobin level remains normal. Iron deficiency anemia develops in the presence of the same risk factors as for iron deficiency anemia, as well as in individuals with an increased physiological need for iron, especially in premature infants at an early age, in adolescents with a rapid increase in height and body weight, in blood donors, with nutritional dystrophy. At the first stage of iron deficiency, there are no clinical manifestations, and iron deficiency is determined by the content of hemosiderin in bone marrow macrophages and by the absorption of radioactive iron in the gastrointestinal tract. At the second stage (latent iron deficiency), an increase in the concentration of protoporphyrin in erythrocytes is observed, the number of sideroblasts decreases, morphological signs appear (microcytosis, hypochromia of erythrocytes), the average content and concentration of hemoglobin in erythrocytes decreases, the level of serum and erythrocyte ferritin, and transferrin saturation with iron decrease. The hemoglobin level at this stage remains quite high, and clinical signs are characterized by a decrease in exercise tolerance. The third stage is manifested by obvious clinical and laboratory signs of anemia.

Examination of patients with iron deficiency anemia
To exclude anemia that has common features with iron deficiency anemia and to identify the cause of iron deficiency, a complete clinical examination of the patient is necessary:

General blood test with the obligatory determination of the number of platelets, reticulocytes, and the study of erythrocyte morphology.

Biochemical blood test: determination of the level of iron, TLC, ferritin, bilirubin (bound and free), hemoglobin.

In all cases it is necessary examine bone marrow aspirate before prescribing vitamin B12 (primarily for differential diagnosis with megaloblastic anemia).

To identify the cause of iron deficiency anemia in women, a preliminary consultation with a gynecologist is required to exclude diseases of the uterus and its appendages, and in men, an examination by a proctologist to exclude bleeding hemorrhoids and a urologist to exclude prostate pathology.

There are known cases of extragenital endometriosis, for example in the respiratory tract. In these cases, hemoptysis is observed; fiberoptic bronchoscopy with histological examination of a biopsy of the bronchial mucosa makes it possible to establish a diagnosis.

The examination plan also includes x-ray and endoscopic examination of the stomach and intestines to exclude ulcers, tumors, incl. glomic, as well as polyps, diverticulum, Crohn's disease, ulcerative colitis, etc. If pulmonary siderosis is suspected, X-ray and tomography of the lungs and sputum examination for alveolar macrophages containing hemosiderin are performed; in rare cases, histological examination of a lung biopsy is necessary. If kidney pathology is suspected, a general urine test, blood serum testing for urea and creatinine are required, and, if indicated, an ultrasound and x-ray examination of the kidneys. In some cases, it is necessary to exclude endocrine pathology: myxedema, in which iron deficiency can develop secondary to damage to the small intestine; polymyalgia rheumatica is a rare connective tissue disease in older women (less often in men), characterized by pain in the muscles of the shoulder or pelvic girdle without any objective changes in them, and in a blood test - anemia and an increase in ESR.

Differential diagnosis of iron deficiency anemia
When diagnosing iron deficiency anemia, it is necessary to carry out a differential diagnosis with other hypochromic anemias.

Iron redistribution anemia is a fairly common pathology and in terms of frequency of development it ranks second among all anemias (after iron deficiency anemia). It develops in acute and chronic infectious and inflammatory diseases, sepsis, tuberculosis, rheumatoid arthritis, liver diseases, cancer, ischemic heart disease, etc. The mechanism of development of hypochromic anemia in these conditions is associated with the redistribution of iron in the body (it is located mainly in the depot) and a violation mechanism for recycling iron from the depot. In the above diseases, activation of the macrophage system occurs, when macrophages, under activation conditions, firmly retain iron, thereby disrupting the process of its reutilization. A general blood test shows a moderate decrease in hemoglobin (<80 г/л).

The main differences from iron deficiency anemia are:
- increased level of serum ferritin, which indicates an increased iron content in the depot;
- serum iron levels may remain within normal limits or be moderately reduced;
- TIHR remains within normal values ​​or decreases, which indicates the absence of serum Fe starvation.

Iron-saturated anemia develops as a result of a violation of heme synthesis, which is caused by heredity or can be acquired. Heme is formed from protoporphyrin and iron in erythrokaryocytes. In iron-saturated anemia, the activity of enzymes involved in the synthesis of protoporphyrin occurs. The consequence of this is a violation of heme synthesis. Iron, which was not used for heme synthesis, is deposited in the form of ferritin in bone marrow macrophages, as well as in the form of hemosiderin in the skin, liver, pancreas, and myocardium, resulting in the development of secondary hemosiderosis. A general blood test will record anemia, erythropenia, and a decrease in color index.

Indicators of iron metabolism in the body are characterized by an increase in the concentration of ferritin and serum iron levels, normal indicators of life-saving blood pressure, and an increase in transferrin saturation with iron (in some cases reaching 100%). Thus, the main biochemical indicators that make it possible to assess the state of iron metabolism in the body are ferritin, serum iron, TLC and % transferrin saturation with iron.

Using indicators of iron metabolism in the body allows the clinician to:
- identify the presence and nature of iron metabolism disorders in the body;
- identify the presence of iron deficiency in the body at the preclinical stage;
- carry out differential diagnosis of hypochromic anemia;
- evaluate the effectiveness of the therapy.

Treatment of Iron Deficiency Anemia:

In all cases of iron deficiency anemia, it is necessary to establish the immediate cause of this condition and, if possible, eliminate it (most often, eliminate the source of blood loss or treat the underlying disease, complicated by sideropenia).

Treatment of iron deficiency anemia should be pathogenetically substantiated, comprehensive and aimed not only at eliminating anemia as a symptom, but also at eliminating iron deficiency and replenishing its reserves in the body.

Iron deficiency anemia treatment program:
- eliminating the cause of iron deficiency anemia;
- therapeutic nutrition;
- ferrotherapy;
- prevention of relapses.

Patients with iron deficiency anemia are recommended to have a varied diet, including meat products (veal, liver) and products of plant origin (beans, soy, parsley, peas, spinach, dried apricots, prunes, pomegranates, raisins, rice, buckwheat, bread). However, it is impossible to achieve an antianemic effect with diet alone. Even if the patient eats high-calorie foods containing animal protein, iron salts, vitamins, and microelements, iron absorption of no more than 3-5 mg per day can be achieved. The use of iron supplements is necessary. Currently, the doctor has at his disposal a large arsenal of iron medications, characterized by different compositions and properties, the amount of iron they contain, the presence of additional components that affect the pharmacokinetics of the drug, and various dosage forms.

According to the recommendations developed by WHO, when prescribing iron supplements, preference is given to drugs containing divalent iron. The daily dose should reach 2 mg/kg of elemental iron in adults. The total duration of treatment is at least three months (sometimes up to 4-6 months). An ideal iron-containing drug should have a minimum number of side effects, have a simple regimen of use, the best efficiency/price ratio, optimal iron content, and preferably the presence of factors that enhance absorption and stimulate hematopoiesis.

Indications for parenteral administration of iron preparations arise in case of intolerance to all oral drugs, malabsorption (ulcerative colitis, enteritis), gastric and duodenal ulcers during an exacerbation, with severe anemia and the vital need to quickly replenish iron deficiency. The effectiveness of iron supplements is judged by changes in laboratory parameters over time. By the 5-7th day of treatment, the number of reticulocytes increases by 1.5-2 times compared to the initial data. Starting from the 10th day of therapy, the hemoglobin content increases.

Considering the pro-oxidant and lysosomotropic effect of iron preparations, their parental administration can be combined with intravenous drip administration of rheopolyglucin (400 ml - once a week), which helps protect the cell and avoid overload of macrophages with iron. Considering significant changes in the functional state of the erythrocyte membrane, activation of lipid peroxidation and a decrease in the antioxidant protection of erythrocytes in iron deficiency anemia, it is necessary to introduce antioxidants, membrane stabilizers, cytoprotectors, antihypoxants into the treatment regimen, such as a-tocopherol up to 100-150 mg per day (or ascorutin, vitamin A, vitamin C, lipostabil, methionine, mildronate, etc.), and also combined with vitamins B1, B2, B6, B15, lipoic acid. In some cases, it is advisable to use ceruloplasmin.

List of drugs used in the treatment of iron deficiency anemia:

Definition. A disease, the leading sign of which is a decrease in the number of erythrocytes less than 4.0x10 12 / l and hemoglobin less than 120 g/l with a color index below 0.8 and a serum iron level less than 13 µmol/l.

Statistics. One of the most common human diseases. Up to 25% of the total population is affected, 40% of women of childbearing age, 33% of people of both sexes over 60 years of age.

Etiology.

Chronic blood loss exceeding re
Generative capabilities of the body:

Menorrhagia (menstruation lasting
6-7 days, abundant; or with clots -
any duration);

Hemorrhoidal bleeding;

Gastrointestinal bleeding with
erosive and ulcerative lesions.

Chronic gastrointestinal diseases
tract, especially at reduced sec
retort function of the stomach, leading to
disruption of the absorption of dietary iron.

Poor nutrition (starvation, anorexia
etc.)

Hyper- and hypothyroid conditions.

Pregnancy, lactation, early childhood
rast.

Long-term uncontrolled use of some
ry medications, especially non-steroidal ones
anti-inflammatory drugs (ibupro-
hair dryer, diclofenac, etc.), analgin, biseptol.

Clinic, diagnostics. In women, the disease often occurs with chlorosis syndrome. Complaints of fainting, low-grade fever, pain in the tongue, perversion of taste and smell; irresistible

the desire to eat chalk, lime, clay, earth, whitewash from the walls, I like heavy spicy aromas. Brittle nails and hair. The nails are flattened in appearance, soft and layered to the touch. Hair is dry, split ends, dull. In men, the disease always occurs without chlorosis syndrome. Pale skin, sometimes with a greenish tint. Heart sounds are muffled, gentle systolic murmur at all points. Tachycardia, hypotension. Nervous system - signs of asthenodepressive, asthenoneurotic, asthenohypochondriacal syndromes. Laboratory indicators: decrease in the number of erythrocytes, hemoglobin, color index, serum iron, increase in ESR, anisocytosis, poikilocytosis of erythrocytes.

Classification. The degree of severity, etiological factor, and phase of the disease (exacerbation, remission) are specified.

Anemia severity:

Light (erythrocytes 3.0-3.5x10 |2 /l, Hb 100 g/l
and above);

Moderate (erythrocytes 2.0-3.0x10 |2 /l,
Hb 80-100 g/l);

Severe (erythrocytes 1.0-2.0x10"7l, Hb 55-
80 g/l);

Extremely severe, threatening development
anemic coma (red blood cells<1,0х10 12 /л, НЬ
<55 г/л).

Exacerbation criteria: a decrease in the numbers of erythrocytes and Hb in women below 4.0x10" 2 /l and 120 g/l, in men below 4.5x10 12 /l and 130 g/l, respectively.

Remission criterion: return of erythrocyte and Hb numbers to normal values. Any increase in red blood numbers that does not reach the norm should be considered not a remission, but an improvement.

Outpatient hematology

Formulation of the diagnosis.

due to menorrhagia, moderate severity,
friction.

Chronic iron deficiency anemia
Shanky genesis due to menorrhagia and gas
trogenic, severe, exacerbation.

Psychological, social status form
are regulated according to general principles.

Differential diagnosis

To exclude hemoblastosis should ube
to be treated in the absence of hemorrhagic and ulcerative
crotic syndromes, laboratory - in the absence
in the patient's leukogram changes characteristic of
leukemia.

To exclude oncological pathology
first level screening is carried out: close-up
fluorography (FCF), fluoroscopy of the stomach
no-intestinal tract or fibrogastroduodenoscopy
(FGDS), examination by a gynecologist is mandatory for women.
If the history does not reveal the source, no
indications of gastrointestinal diseases
that the patient is elderly, then additionally for
exclusion of malignant neoplasm
X-ray of the chest organs is performed, ir-
rigoscopy, sigmoidoscopy, ultrasound
follow-up (ultrasound) of the abdominal organs.

Vitamin B 12 and folate deficiency anemia
hyperchromic, the number of reticulopitis is reduced,
Serum iron is normal, high levels are common
identification of the liver, in sternal punctate megalo-
blast hematopoiesis.

At hemolytic anemia: icterus
skin, enlarged spleen and liver,
laboratory - normochromic anemia, sudden increase
decrease in the number of reticulocytes, serum
Lez is normal or increased, I also eat hyperbilirubin
due to indirect bilirubin, hemosiderin in the urine,
in the bone marrow punctate there is pronounced hyperplasia
erythroid germ.

At hypoplastic anemia hemorrhages
chelic and (or) purulent-necrotic syndrome, res
some decrease in all blood parameters (erythrocytes,
leukocytes, platelets), in punctate inhibition of all
germs of hematopoiesis.

Sideroachrestic anemias by clinic
and the data of a general blood test are no different
are from iron deficiency, but the jelly content
for V the blood serum of such patients is high (50-
90 µmol/l). Treatment with iron supplements for
leads to hemosiderosis of organs without relieving symptoms
volumes of disease.

Patient management

Goal of treatment: recovery (complete clinical and hematological remission for 5 years). Tasks:

Restoring normal values
red blood and serum iron;

Maintaining normal levels
at the proper level.

Organization of treatment. Most patients are treated on an outpatient basis, except in cases of severe or etiologically unclear iron deficiency anemia. In such cases, patients are hospitalized, based on the principle of the most likely nature of anemia, in gynecological, gastroenterological or other departments.

Treatment monitoring. During the period of first detection or exacerbation of the disease, blood is monitored once every 10-14 days, and the frequency of medical examinations should be the same. You should not count on an increase in the numbers of red blood cells and hemoglobin after 3-5 days.

During the period of partial remission, when the patient is able to work, but the hematological norm has not been achieved, blood monitoring and medical examination are carried out monthly. During the period of complete remission with normal red blood composition, monitoring is carried out quarterly during the first year, then once every 6 months. Recovery is considered to be the absence of exacerbations for 5 years. Consultation with a hematologist during an exacerbation - once every 2 months, then once every 4-6 months.

Planned therapy

Information for the patient and his family:

The reason for the development of anemia in this patient.

Fundamental curability of the disease.

Duration of drug therapy (initial
iron therapy course - 2-3 months, full course - up to
1 year).

Possibility of self-control (red norms)
blood and serum iron).

Explanation of harm for this category of pas
unqualified treatment patients, vegetarians
ancestry, fasting, “recipes” for self-medication.

Advice for the patient and his family:

Start treatment with iron supplements with
moment of detection of the disease, with the exception of
We eat the very initial stages, when red blood cells
>3.5x10 |2 /l, and Hb >P0 g/l. In these cases you can
use diet and herbal medicine as a stand-alone
telny method, but in its case it is ineffective
sti within 1 month. it is necessary to convince the patient of the need
the need for drug therapy.

Chronic iron deficiency anemia

If possible, eliminate etiological
factors: use hemostatic herbal medicine
in case of menorrhagia; treat chronic
diseases of the gastrointestinal tract, kidneys;
convince the patient (tku) of the need for surgery
who treats hemorrhoids or uterine fibroids with
persistent bleeding.

Organize therapeutic nutrition with predominantly
consumption of meat products and natural sources
of vitamins (black currants, lemons,
piha). For women with heavy periods - grana
you and nuts.

Eliminate chronic household and occupational
onal and, if possible, medicinal
toxicity during the treatment period (gasoline, dyes,
non-steroidal anti-inflammatory drugs,
biseptol).

Drug therapy

Iron supplements should be prescribed in sufficient doses and for a long period of time. Due to low efficiency and severe side effects Not should be prescribed: reduced iron, aloe syrup with iron, hemostimulin, ferramide. Food additives, containing iron, for therapeutic purposes are unsuitable because the iron content in them is not higher than 18 mg, with a requirement of at least 250 mg/day. Their use is possible only during the period of complete remission to prevent relapses.

Tardiferon(hypotardiferon for pregnant women). Prescribed 1-2 tablets. per day, strictly after meals. Contains mucoprotease, which protects the gastric mucosa and has high bioavailability. Hypotardiferon contains folic acid necessary for pregnant women.

Sorbifer. Prescribed 1 tablet. 2 times a day, after meals. Well tolerated, contains ascorbic acid, which facilitates absorption of the drug.

Actiferrin. Depending on the severity of anemia, it is prescribed from 1 to 3 caps per day. There are forms for children: syrup and drops. The drug is highly effective, but individual intolerance is possible.

Ferroplex. Prescribed 2 tablets. 4 times a day. Compared to the retard forms described above, it is ineffective, but is well tolerated and has almost no side effects. Possible use for anemia in pregnant women.

NB! Warn the patient about the change in the color of the stool to black and that all iron supplements, without exception, are taken strictly after meals, regardless of the manufacturer's instructions.

Parenteral use of iron (the drug Ferrumlek) is limited to two situations:

Complete intolerance to oral medications
rats;

The need to quickly and briefly stabilize
zirate the numbers of red blood, for example, with
preparation for emergency surgery. Maybe challenges
cause anaphylactic reactions, hypercoagus
lation. Prescribes on an outpatient basis
only intramuscularly, injections (containing
pressing one ampoule) are carried out every other day,
course of 10-15 injections.

Auxiliary drugs

To improve iron absorption and stimulate erythropoiesis - multivitamin preparations with the addition of microelements: complivit 1 tablet. per day, during meals.

To correct protein metabolism - potassium orotate, 1 table. (0.5 g) 3 times a day for 20 days. Prescribing B vitamins in injection form is not justified.

Phytotherapy.Rose hip decoction. Chop the berries and pour boiling water at the rate of 1 cup of boiling water per 1 tbsp. l. berries, leave for 20-30 minutes. Drink during the day.

Antianemic collection. Mix nettles, string, currant leaves, strawberry leaves equally, add cold water (1 glass of water per 1 tablespoon of mixture) for 2-3 hours, then put on fire, boil for 5-7 minutes, cool, strain. Drink during the day.

An approximate treatment regimen for iron deficiency anemia in pregnant women:

Hypotardiferon 1 tablet. morning and evening
after eating; will take 1 caps. 2 times a day, orotate
potassium 1 table. (0.5 g) 3 times a day for
20 days; phytotherapy; diet therapy.

An approximate treatment regimen for iron deficiency anemia in the elderly:

Sorbifer 1 tablet. morning and evening after
food; undevit 1 tablet 2 times a day, potassium orotate
1 table each (0.5 g) 3 times a day for 20 days;
herbal medicine, diet therapy.

Rehabilitation therapy

During the period of partial remission, when the patient is able to work, until hemoglobin numbers normalize, daily medication should be continued. When the amount of hemoglobin reaches 120 g/l, one of the iron preparations is prescribed for 7 days after menstruation or 7 days of each month, up to a year.

During the period of complete remission, when hemoglobin numbers are normal without treatment, one-month anti-relapse courses of ferroplex or tardiferon in the spring and autumn.

Outpatient hematology

Criteria for the effectiveness of rehabilitation therapy: maintaining normal numbers of red blood and serum iron for three years during one-month anti-relapse courses of treatment in spring and autumn.

Medical examination

Examination of temporary disability
you. The terms of labor losses are determined by medical
(clinic, numbers of red blood cells and hemoglobin) and with
cial factor - the nature of the patient’s work.
During heavy physical labor and hazardous work
in industries, men’s ability to work was restored
occurs at hemoglobin levels of 130 g/l, in women -
120 g/l. For light physical work are allowed
hemoglobin numbers per 10 g/l, in mental workers
yes - 20 g/l lower than given.

Medical and social expertise. At MSEC
patients with severe, difficult correction are referred
controlled by anemia. In diagnostic formulation
anemia takes the place of a symptom or complication
underlying disease.

Military medical examination. For anemia
(according to Article 11), quickly or slowly progressing

with significant changes in blood composition and periodic exacerbations, conscripts are considered unfit for military service; with anemia, accompanied by moderate dysfunction of the hematopoietic system and rare exacerbations, they are considered to be of limited fitness.

Preliminary and periodic medical examinations. According to medical contraindications (in addition to general medical contraindications), persons suffering from anemia should not be allowed to work in contact with lead (1.25.1), aromatic hydrocarbons (1.33), naphthalene, naphthols (1.34), organochlorine pesticides (2.2.1 ), organofluorine pesticides (2.2.2), carbamic acid derivatives (2.2.4), chlorobenzoic acid derivatives (2.2.6), chlorophenoxyacetic acid derivatives (2.2.7), chlorophenoxybutyric acid derivatives (2.2.8), halogenated carboxylic acid anilides (2.2.9), urea and guanidine derivatives (2.2.10), polystyrenes (2.4.7), antitumor drugs (2.7.2), ionizing radiation (5.1).

Vitamin B 12 - and folate deficiency anemia (code D 51.9)

Definition. Anemia associated with impaired DNA and RNA synthesis caused by deficiency of vitamin B]2 or folic acid and manifested by megaloblastic hematopoiesis, hyperchromia and macrocytosis of erythrocytes. Combined deficiency of vitamin B 12 and folic acid is rare, but forms with isolated deficiency of both factors are clinically and laboratory indistinguishable, and therefore are considered together.

Statistics. In Russia, the incidence of the disease (20-60 cases per 100,000 population) varies significantly depending on the region: northerners are more likely to get sick, residents of the middle zone are less likely to get sick, and residents of the Far East are very rarely affected. Starting from the age of 45-55 years, in older age groups the incidence increases progressively. No significant differences in pathological involvement due to gender differences were identified.

Etiology and pathogenesis. Megaloblastic anemias are considered to be the result of a genetic defect that causes an immunological disorder manifested by the production of autoantibodies against gastric epithelial cells. This leads to degenerative lesions of the mucous membranes of the digestive tract due to insufficient absorption of vitamin B 12 and (or) folic acid. Vitamin B2 deficiency is the cause of severe damage to the spinal cord (funicular myelosis).

Clinic. As a rule, older people are affected. General weakness, change in skin color (pallor with a jaundiced tint), pain in the tongue and increased taste sensitivity to the point of discomfort, numbness of the feet and palms. History indicates chronic gastritis, colitis and other diseases of the gastrointestinal tract. On examination, patients are “more jaundiced than pale,” with bright red areas on the tongue. Palpation of the abdomen may reveal pain in the epigastric region, in the hypochondrium, along the intestine in the presence of chronic diseases of the gastrointestinal tract. Blood test: hyperchromic macrocytic anemia, usually significant. The color index can increase to 1.3. The number of reticulocytes is reduced, the number of leukocytes is also reduced, due to neutrophils. Sometimes I observe

24. Denisov

significant thrombocytosis without bleeding is observed. Moderate hyperbilirubinemia (up to 28-47 µmol/l) due to indirect bilirubin. The iron content in the blood serum is normal or slightly increased. Sterial punctate - megaloblastic hematopoiesis.

Formulation of the diagnosis. Vitamin B2 - deficiency anemia of moderate severity.

Differential diagnosis

First of all, it is necessary to exclude it
ecological disease. For this purpose they carry out
first level screening: CCF, fluoroscopy
stomach or FGDS, for women - examination by a gynecologist,
for persons over 50 years old - irrigoscopy and ultrasound examination
new abdominal cavity.

How does hyperchromic anemia syndrome occur?
yes in acute erythromyelosis. To exclude
of this disease it is necessary to make sure that there is no hepatitis
morrhagic and purulent-necrotic syndrome
mov, and also, since with this hemoblastosis the
stench cells appear in the peripheral blood
not immediately, the patient should undergo sternal
puncture.

At iron deficiency anemia unlike
vitamin B 12 - deficiency - pale skin with gray
greenish tint, the presence of chlorosis syndrome (in
women). Laboratory: color index 0.8 and
lower, the number of reticulocytes is increased, aniso-
cytosis and poikilocytosis of erythrocytes, in the sternal
punctate - moderate hyperplasia of the erythroid
sprout.

At hemolytic anemia unlike
vitamin B 12 - deficiency - severe jaundice
skin, significant hepato- and splenomegaly. Labo
Ratory: normochromic anemia, sharply increased blood
the number of reticulocytes, the number of leukocytes is higher
but, hyperbilirubinemia more than 50 µmol/l due to
indirect bilirubin, in urine - hemosiderin, in sterile
onal punctate - pronounced hyperplasia of erythritis
roid sprout.

Hypoplastic anemia from vitamin B 12 -
deficient is characterized by the severity of the general condition
niya, the presence of hemorrhagic or purulent-non-

Outpatient hematology

Crotic syndrome, absence of liver enlargement. Laboratory examination: normochromic anemia, all blood parameters are sharply reduced, there is no hyperbilirubinemia, in the sternal puncture there is inhibition of all hematopoietic germs.

Patient management

Goal of treatment: achieving and maintaining stable clinical and hematological remission. Tasks:

Translation of hematopoiesis from megaloblastic-
go to normoblastic;

Lifelong maintenance of normoblastic
what type of hematopoiesis is permanent injection
vitamin B 12 and (or) folic acid deficiency
lots.

Organization of treatment. Megaloblastic anemia is treated on an outpatient basis. However, in cases requiring transfusion therapy for life-saving reasons, hospitalization in a therapeutic or hematology department is necessary. Consultation with a hematologist is advisable when the disease is first detected, when remission occurs, and then once a year.

Planned therapy

Informationfor the patient And his families:

Brief information about the essence of the disease.

It is fundamentally possible to create a sustainable
howl clinical and hematological remission with adek
cotton maintenance therapy.

It is necessary to control the blood test once every
3 months, administration of vitamin B 12 monthly even in
period of stable remission.

. Advice for the patient and to his family:

Nutrition complete in protein and vitamins
mu composition.

If necessary, you must complete the coursework
treatment of chronic gastric diseases
but-intestinal tract.

Drug therapy

During the period of first detection and exacerbation of the disease, a home regime is necessary. The diet is the same as for iron deficiency anemia. Vitamin B 12 500 mcg intramuscularly daily for 7-10 days, then another 7-10 injections every other day. Improvement occurs after the first or second injection. On days 3-7 - reticulocyte crisis. Remission is induced quickly and is stable. Folic acid is prescribed at 5-15 mg/day. During the period of partial remission, when the patient is able to work, but the hematological norm has not yet been achieved, it is necessary to introduce

vitamin B 12 500 mcg intramuscularly once a week, 3 months. During the period of complete remission - lifelong administration of 500 mcg of vitamin B 12 once a month.

Approximate treatment plan for pregnant women:

200 mcg once every 10 days;

Folic acid 15 mg/day from 1st to 30th day
from the start of treatment with vitamin B 12;

Hypotardiferon 1 tablet. per day from the 30th day
within 1-2 months.

Iron supplements are necessary because In pregnant women, anemia is usually of mixed origin.

Approximate treatment plan for the elderly:

Vitamin B 12,500 mcg intramuscularly daily
gently for 10 days, then every other day 10 injections, then
500 mcg once a week, 2-3 months, then once every 2 weeks.
- 2 months, then 1 time per month. for life;

Folic acid 10 mg/day;

Multivitamin preparation (undevit) 1 tablet.
2 times a day from the 30th day from the start of vitamin treatment
At 12, for 1-2 months, with breaks for 2-3 months.

Phytotherapy- see section “Iron deficiency anemia”.

Rehabilitation therapy

During the period of complete remission, 500 mcg of vitamin B12 is administered once a month. If necessary (if there are signs of megal regional hematopoiesis), vitamin B 12 is administered in the spring and autumn, 200 mcg, once every 10 days. In 12 - and folate deficiency anemia during the period of clinical and hematological remission is not a contraindication to sanatorium treatment and does not entail restrictions in taking physical procedures.

Criteriaefficiency rehabilitation no therapy:

Preservation of normoblastic hematopoiesis
(normal red blood cell numbers, Hb, color
howl indicator is not higher than 1.1; lack of poppy
rocytosis) if present, I only support
cabbage soup therapy.

Absence of neurological disorders: from
rotation of taste, numbness of the feet and palms,
paresthesia, etc.

Medical examination

The patient is temporarily disabled until signs of megaloblastic hematopoiesis completely disappear and red blood counts are restored to normal.

Medical and social examination, military medical examination, preliminary and periodic medical examinations - see the section “Chronic iron deficiency anemia”.

Hemolytic anemia (codes D 58.9, D 59)

Definition. A group of anemic conditions in which the process of destruction of red blood cells prevails over the process of their reproduction. In hemolytic anemia, red blood cells live less than 100 days.

Statistics. Pathological incidence is low, amounting to 0.6-2.8 cases per 100,000 population. Congenital hemolytic anemia is more common in Dagestan, acquired - in large centers with a developed chemical industry.

Etiology, pathogenesis. Among causal factors highlighted:

Intraerythrocytic (erythrocytopathies,
fermentopathy, hemoglobinopathies).

Extra-erythrocyte:

Infectious;

Chemical (medicinal, professional
nal and household intoxications);

Physical (burns, presence of dental prostheses)
bowel valves);

Immunological (auto- and heteroimmune-
new forms);

Unknown (hemolysis in pathology,
liver and kidney pathologies).

In the pathogenesis, the leading role is played by the peripheral destruction of erythrocytes, the appearance of decay products in the circulatory system and, as a consequence, according to the analysis of peripheral blood, the bone marrow regenerative reaction and its markers.

Clinic, diagnostics. Hemolytic syndrome consists of three symptoms: anemia, jaundice and splenomegaly. Diagnosis is often difficult; many patients are diagnosed with chronic hepatitis or cirrhosis for many years, and anemia is taken as a consequence of these diseases. In

In all cases of jaundice with an enlarged spleen, a thorough examination of patients is required, regardless of hemoglobin numbers, since anemia can be mild. Laboratory indicators: anemia, often normochromic, multiple increase in the number of reticulocytes, severe hyperbilirubinemia due to indirect bilirubin, hemosiderin in the urine, severe hyperplasia of the erythroid lineage in the sternal punctate.

Classification. There are two large groups of hemolytic anemias: congenital and acquired. Congenital forms are often familial and hereditary, inherited in an autosomal dominant and autosomal recessive manner.

RCHR (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Archive - Clinical protocols of the Ministry of Health of the Republic of Kazakhstan - 2007 (Order No. 764)

Mammary gland, unspecified part (C50.9)

General information

Brief description

The most common tumor in women, classified as a classic hormone-related cancer; develops in an organ that is part of the body's reproductive system. These tumors originate from the epithelial tissue of the ducts or lobules of the mammary gland - the “target” for hormones produced by the ovaries (estrogens and progestins).

On average, about 3,000 patients with breast cancer are diagnosed annually in the Republic of Kazakhstan, of which more than 1,380 women die. In particular, in 2005, 2954 cases of breast cancer were registered, which amounted to 19.5 (32.3 in Almaty) per 100,000 population. The 1-year mortality rate is 10.8%, and the 5-year survival rate is 49.3%.

Protocol code: H-S-008 "Malignant neoplasms of the breast. Breast cancer"

Profile: surgical

Stage: hospital
ICD-10 code(s):C50 Malignant neoplasm of the breast

Classification

Histological classification of breast tumors

Currently, it is customary to use the histological classification of the International Union Against Cancer (2002, 6th edition).

A	Non-invasive cancer (in situ):
	Intraductal (intracanalicular) carcinoma in situ
	Lobular (lobular) carcinoma in situ
IN	Invasive cancer (infiltrating carcinoma):
	Ductal
	Lobular
	Mucous (mucinous)
	Medullary (medullary)
	Tubular
	Apocrine
	Other forms (papillary, squamous, juvenile, spindle cell, pseudosarcomatous, etc.)
WITH	Special (anatomical and clinical) forms:
	Paget's cancer
	Inflammatory cancer

Most often, patients experience invasive ductal cancer (50-70%), followed by lobular cancer (20%). Ductal cancer is characterized by more frequent spread along the milk ducts, and lobular cancer is characterized by primary multiplicity and bilaterality.

INTERNATIONAL TNM CLASSIFICATION

Currently, the classification of tumors according to the TNM system of the International Union Against Cancer (2002) is used. The stage of cancer is established during the initial examination of the patient, and then clarified after surgery (pTNM).

The classification applies only to carcinomas and applies to both the male breast and the female breast.

In the case of the presence of primary multiple synchronous tumors in one mammary gland, the tumor with the highest

category T. Synchronous bilateral breast tumors should be classified independently to allow cases to be separated according to histological type.

The following methods should be used to assess categories T, N and M:

Anatomical areas:

1. Nipple (C 50.0).

2. Central part (C 50.1).

3. Upper inner quadrant (C 50.2).

4. Lower inner quadrant (C 50.3).

5. Upper outer quadrant (C 50.4).

6. Lower outer quadrant (C 50.5).

7. Axillary tail (C 50.6).

Regional lymph nodes:

1. Axillary (ipsilateral), interthoracic nodes (Rotter) and lymph nodes along the axillary vein and its branches which can be divided into the following levels:

Level I (lower part of the axillary fossa): lymph nodes located lateral to the lateral border of the pectoralis minor muscle;

Level II (middle part of the axillary fossa): lymph nodes located between the medial and lateral borders of the pectoralis minor muscle and interthoracic lymph nodes (Rotter);

Level III (apical part of the axillary fossa): apical lymph nodes and nodes located medial to the medial border of the pectoralis minor muscle, with the exception of those defined as subclavian.

Note. Intramammary lymph nodes are coded as axillary lymph nodes.

2. Subclavian (ipsilateral) lymph nodes.

3. Intramammary (ipsilateral) lymph nodes: lymph nodes in the intercostal areas along the edge of the sternum in the endothoracic fascia.

4. Supraclavicular (ipsilateral) lymph nodes.

Metastasis to any other lymph nodes is defined as distant metastases (M1), including cervical or contralateral intramammary lymph nodes.

TNM symbols mean: T - primary tumor.

Tx	There is insufficient data to evaluate the primary tumor.
T0	The tumor in the mammary gland is not detected.
Тis	Preinvasive carcinoma (carcinoma in situ) Tis (DCIS) - ductal carcinoma in situ Tis (LCIS) - lobular carcinoma in situ Тis (Paget) - Paget's disease (nipple) without tumor Note: Paget's disease with the presence of a tumor is classified into according to the size of the tumor.
T1	Tumor no more than 2 cm in greatest dimension
Т1mic	Microinvasion up to 0.1 cm in greatest dimension Note: microinvasion is the spread of cancer cells beyond limits of basement membrane with lesions less than 0.1 cm If there are multiple foci of microinvasion, the largest one is classified according tosize of the lesion (it is impossible to summarize the sizes of microfoci) Availability multiple foci of microinvasion should be noted additionally
T1a	Tumor more than 0.1 cm, but not more than 0.5 cm in greatest dimension
Т1b	Tumor more than 0.5 cm but not more than 1 cm in greatest dimension
T1s	Tumor more than 1 cm but not more than 2 cm in greatest dimension
T2	Tumor more than 2 cm but not more than 5 cm in greatest dimension
T3	Tumor more than 5 cm in greatest dimension
T4	Tumor of any size with direct extension to the chest wall or skin Note: The chest wall includes the ribs, intercostal muscles and anteriorserratus muscle, but not pectoralis muscle
T4a	Spread to chest wall
Т4b	Swelling (including “lemon peel”) or ulceration of the skin of the breast,or satellites in the skin of the breast
Т4c	Signs listed in 4a and 4b together
Т4d	Inflammatory form of breast cancer

Note: Inflammatory breast carcinoma is characterized by diffuse brown induration of the skin with an erysipeloid margin, usually without an underlying mass. If skin biopsy indicates no involvement and there is no localized, detectable primary cancer, category T is pTx for pathohistological staging of inflammatory carcinoma (T4d).
Dimpled skin, nipple retraction, or other skin changes other than those found in T4b and T4d may be scored as T1, T2, or T3 without affecting the classification.

N - regional lymph nodes.

NX	There is insufficient data to assess the condition of regional lymph nodes
N0	There are no signs of metastatic lesions of regional lymph nodes
N1	Metastases in displaced axillary lymph nodes (e) on the side defeats
N2 N2a N2b	Metastasis to a fixed ipsilateral axillary lymph node (s) or in clinically obvious ipsilateral intramammary lymph node(s) In the absence of clinically obvious metastases in the axillary lymph nodes metastasis in axillary lymph node(s) linked to each other or to other structures Metastasis only in clinically obvious intramammary lymph node(s), with absence of clinically obvious metastasis in the axillary lymph node
N3	Metastasis to the ipsilateral subclavian lymph node(s) withdamage to the axillary lymph nodes or without them; or in clinically obvious ipsilateral intramammary lymph node(s) if clinically present obvious metastases in the axillary lymph nodes; or metastasis in the ipsilateralsupraclavicular lymph node(s) with or without involvement of axillary or intramammary lymph nodes
N3a N3b N3с	Metastasis in the subclavian lymph node(s) Metastases in intramammary and axillary lymph nodes
	Note. “Clinically obvious” means those identified as a result of clinical trial or imaging (for except for lymphoscintigraphy)

M - distant metastases.

rTNM pathohistological classification.

pT - primary tumor.

Pathohistological classification requires examination of the primary carcinoma, in the absence of macroscopic tumor at the resection margins. A case can be classified as pT if there is only microscopic tumor at the margin.

Note. When classifying pT, tumor size is the size of the invasive component. If there is a large in situ component (eg 4 cm) and a small invasive component (eg 0.5 cm), the tumor is classified as pT1a.

рN - regional lymph nodes.

Examination of one or more sentinel lymph nodes may be undertaken for histopathological classification. If the classification is based only on sentinel node biopsy without subsequent axillary node dissection, it should be designated (sn) (sentinel node), for example: pN1 (sn).

рN1mi	Micrometastasis (more than 0.2 mm, but not more than 2 mm in greatest dimension)
РN1	Metastases in 1-3 ipsilateral axillary lymph nodes (e) and/or ipsilateral intramammary nodes with microscopic metastasesidentified as a result of sentinel lymph node dissection, but not clinically obvious
рN1а	Metastases in 1-3 axillary lymph nodes (e), among them at leastone more than 2 mm in greatest dimension
рN1b рN1с	Intramammary lymph nodes with microscopic metastases, identified as a result of sentinel lymph node dissection, but clinically not explicit Metastases in 1-3 axillary lymph nodes and intramammary lymph nodes with microscopic metastases identified as a result of dissectionsentinel lymph node, but not clinically obvious
рN2	Metastases in 4-9 ipsilateral axillary lymph nodes or in clinically obvious ipsilateral intramammary lymph nodes, with
Note. “Clinically silent” means not detected by clinical examination or imaging (exceptlymphoscintigraphy); “clinically apparent” means those identified by clinical examination or imaging (except lymphoscintigraphy), or macroscopically visual.
рN2а	Metastases in 4-9 axillary lymph nodes, including at least one larger than 2 mm
рN2b	Metastasis to a clinically obvious intramammary lymph node(s) with absence of metastases in the axillary lymph nodes
рN3	Metastases in 10 or more ipsilateral axillary lymph nodes; or in ipsilateral subclavian lymph nodes; or in clinically obvious ipsilateral intramammary lymph nodes, if there is one or more affected axillary lymph nodes; or in more than 3 axillary lymph nodes with no clinically obvious microscopic metastases in intramammary lymph nodes; or in the ipsilateral supraclavicular lymph nodes
рN3а	Metastasis to 10 or more axillary lymph nodes (at least one of which more than 2 mm) or metastases in the subclavian lymph nodes
рN3b	Metastasis to clinically obvious intramammary lymph node(s) if presentaffected axillary lymph node(s); or metastases in more than 3 axillary lymph nodes and in intramammary lymph nodes with microscopic metastasis identified during sentinel dissection lymph node, but clinically not obvious
рN3с	Metastasis to the supraclavicular lymph node(s)

rM - distant metastases. The PM categories correspond to the M categories.

G histopathological classification

G1 - high degree of differentiation.

G2 - average degree of differentiation.

G3 - low degree of differentiation.

R classification

The absence or presence of residual tumor after treatment is described by the symbol R. R classification definitions:

RX - the presence of residual tumor cannot be determined.

R0 - no residual tumor.

R1 - microscopic residual tumor.

R2 - macroscopic residual tumor.

Grouping by stages

Stage 0	TiS	N0	M0
Stage I	T1*	N0	M0
Stage IIA	T0	N1	M0
	T1*	N1	M0
	T2	N0	M0
Stage IIB	T2	N1	M0
	T3	N0	M0
Stage IIIA	T0	N2	M0
	T1*	N2	M0
	T2	N2	M0
	T3	N1, N2	M0
Stage IIIB	T4	N0, N1, N2	M0
Stage IIIC	any T	N3	M0
Stage IV	any T	any N	M1

Note. *T1 includes T1mic (microinvasion 0.1 cm or less in greatest dimension).

Tis T1mic T1a T1b T1c T4a T4b T4d

in situ £ 2cm £ 0.1 cm > 0.1 to 0.5 cm >0.5 to 1 cm > 1 to 2 cm > 2 to 5 cm > 5 cm Chest wall/skin Chest wall Skin swelling/ulceration, satellite nodules on the skin Signs characteristic of T4a and T4b Inflammatory carcinoma

N1	Movable axillary	pN1mi pN1a pN1b pN1c	Micrometastases, > 0.2 mm £ 2 mm 1-3 Axillary nodes Intramammary nodes with micrometastasis, identified by sentinel node biopsy, but clinically undetectable 1-3 Axillary nodes and intramammary nodes with micrometastasis detected by sentinel node biopsy, but clinically undetectable
N2a	Fixed axillary	pN2a	4-9 Axillary nodes
N2b	Intramammary- clinically defined	pN2b	determined without axillary nodes
N3a	Subclavian	рN3a	³ 10 Axillary nodes or subclavian node(s)
N3b	Intramammary- nye and axillary new	рN3b	Intramammary nodes, clinically identified with axillary node(s) or> 3 axillary nodes and intramammary nodes with micrometastases that are detected with a biopsy of the sentinel node (sentinel node), but clinically undetectable
N3c	Supraclavicular	рN3c	Supraclavicular

Risk factors and groups

Classification of risk factors

1. Factors characterizing the functioning of the body’s reproductive system:

Menstrual function;

Sexual function;

Childbearing function;

Lactation function;

2. Hyperplastic and inflammatory diseases of the ovaries and uterus.

Endocrine-metabolic factors caused by concomitant and previous diseases:

1. Obesity.

2. Hypertension.

3. Diabetes mellitus.

4. Liver disease.

5. Atherosclerosis.

6. Diseases of the thyroid gland.

7. Dishormonal hyperplasia of the mammary glands.

Genetic factors(carriers of BRCA-1 or BRCA-2 genes):

1. Breast cancer in blood relatives (hereditary and “family” breast cancer).

2. Milk-ovarian syndrome (breast cancer and ovarian cancer in the family).

Exogenous factors:

1. Ionizing radiation.

2. Chemical carcinogens, including smoking.

3. Excessive consumption of animal fats, high-calorie diet.

4. Viruses.

5. Taking hormones.

Diagnostics

Diagnostic criteria

Complaints(no pathognomonic symptoms characteristic of breast cancer).

There may be complaints about the presence of a formation in the mammary glands, hyperemia, swelling, wrinkling, retractions or protrusions on it, narrowing of the areolar field, etc.

Anamnesis: the presence of cancer in close relatives, the onset of menstruation, the age of the first pregnancy and first birth, taking OCs or HRT, gynecological diseases.

Physical examination

1. Examination of the mammary glands.
Upon examination, determine:

Symmetrical location and shape of the mammary glands;

Level of position of the nipples and their appearance (retraction, deviation to the side);

Condition of the skin (hyperemia, swelling, wrinkling, retractions or protrusions on it, narrowing of the areolar field, etc.);

Pathological discharge from the nipple (quantity, color, duration);

The presence of swelling of the arm on the affected side.

2. Palpation of the mammary glands (in vertical and horizontal positions).

3. Palpation of regional and cervical-supraclavicular lymph nodes (usually performed in a vertical position).

Laboratory research

Laboratory tests that must be performed upon the patient’s initial visit before treatment: complete blood count, blood group, Rh factor, general urine test, biochemical blood test (urea, bilirubin, glucose), RW (Wassermann reaction), coagulogram, ECG ( electrocardiography).

Instrumental studies

X-ray diagnostics is one of the leading methods for detecting breast cancer, especially if the tumor is small and not palpable. Mammography is indicated for all patients with breast cancer.

Examination methods that must be performed by the patient before starting treatment:

1. Puncture biopsy of the tumor with cytological examination or trephine biopsy with determination of the level of expression of ER, PR, Her-2/neu and other genetic factors.

2. Ultrasound examination of the abdominal organs.

3. X-ray examination of the lungs.

4. Osteoscintigraphy (in institutions equipped with a radioisotope laboratory).

5. Ultrasound examination of the mammary glands, regional lymph nodes.

Mammography and ultrasound complement each other, because Mammography may reveal tumors that are not detected by ultrasound, and vice versa.

Morphological diagnosis:

1. Cytological (puncture) biopsy (fine needle biopsy).

2. Trephine biopsy or sectoral resection of the mammary gland.

Indications for consultation with specialists.

Mandatory: consultation with a gynecologist.

If necessary, consultation with an endocrinologist, neurologist, urologist, radiologist, chemotherapist, and other related specialists according to indications.

List of main diagnostic measures:

1. Determination of hemoglobin.

2. Counting leukocytes in the Goryaev chamber.

3. Counting red blood cells for CPK.

4. Determination of ESR.

5. Hematocrit.

6. Calculation of the leukocyte formula.

7. General urine analysis.

8. Determination of total protein.

9. Cytological examination and histological examination of tissue.

10. Determination of capillary blood clotting time.

11. Platelet count.

12. Blood test for HIV.

13. Microreaction.

14. HbsAg, Anti-HCV.

15. Determination of protein fractions.

16. Determination of bilirubin.

17. Coagulogram 1 (prothrombin time, fibrinogen, thrombin time, aPTT, plasma fibrinolytic activity, hematocrit.

18. Determination of residual nitrogen.

19. Determination of glucose.

20. Definition of ALT.

21. Definition of AST.

22. Thymol test.

23. Determination of blood group and Rh factor.

24. Ultrasound of the abdominal organs.

25. Electrocardiography.

26. Chest X-ray in two projections.

27. Ultrasound of the mammary glands.

28. Mammography.

29. Ductography.

30. Ultrasound of the pelvic organs.

31. Magnetic resonance imaging (MRI) of the breast.

32. Computed tomography (CT) of the breast.

List of additional diagnostic measures:

1. Consultation with a cardiologist.

Differential diagnosis

	Complaints	Physical data	Ultrasound, mammography	Morphologicallye signs
RMJ	Availability of education in mammary gland, hyperemia, edema, rugosity, retractions or bulges on it, narrowing of the areolar field	Upon inspection, presence pathognomic signs, breast asymmetry On palpation the presence of a tumor in the breast, increased regional lymph nodes	Availability education in dairy gland, calcifications, increase regional lymph nodes	Presence of cells tumors in smears. Conclusion pathologist about availability malignant tumors
Inflammatory breast diseases	Hyperemia, hyperthermia, breast pain gland, purulent discharge from the nipple	On examination there is hyperemia Andbreast skin hyperthermia On palpation presence of painful seals in the breast, possible reactively sometimes enlarged painful lymph nodes	The presence of a cavity with liquid content without clear boundaries	Availability elements purulent inflammation, inflammation leukocytes, neutrophils macrophages, fibroblasts in strokes. Histologically - abscess picture, purulent infiltration
Fibroadenoma, cystadenoma MJ, localized fibroadenoma toz	Availability of education in mammary gland, pain	Upon inspection it is possible breast deformation. On palpation presence of seal in MJ	Availability education with clear contours, with mammography - the presence of a "rim" security"	The presence of peri-, intracanal- cular and mixed fibroadenomas
Cyst mammary gland	Availability of soft-elastic education in mammary gland, pain, nipple discharge	Upon examination possible deformation MJ. On palpation availability of education soft-elastic consistency in the breast	Availability cavities with liquid content with clear contours	Presence of a wall cysts, liquid contents

Treatment abroad

Get treatment in Korea, Israel, Germany, USA

Get advice on medical tourism

Treatment

Treatment tactics

Treatment goals: achieving radical treatment.

Non-drug treatment

Breast cancer is one of the few oncological diseases for which treatment of all stages is multivariate.

Despite significant progress in the development of new methods for treating breast cancer, surgery still remains the main, and in some cases, the only method of treating this disease (Ca in situ).

The choice of one or another type of radical surgery is determined not only by the degree of spread of the tumor process, but also by the clinical form, location of the tumor, the age of the patients and some other factors characterizing their general condition.

Recently, increasing importance has been attached to improving the quality of life, which is achieved by performing organ-preserving operations on the mammary gland, as well as reconstructive operations using local tissues.

Organ-conserving operations for breast cancer provide, along with high survival rates, good cosmetic and functional results. Social and labor rehabilitation of patients after segmental resection of the mammary gland occurs faster than after mastectomy.

Indications for performing organ-preserving operations on the mammary gland:

The presence of a nodular form of cancer up to 2.5 cm in size;

Absence of multicentricity and multifocality of tumor growth (on mammograms, ultrasound, clinically);

Slow and moderate growth rates, doubling the size of the tumor no faster than in 3 months (according to medical history);

Favorable ratio of the size of the breast and tumor to obtain a good cosmetic result of the operation;

No distant metastases;

The presence of single metastases in the axillary region is acceptable;

Reconstructive operations can be performed for stages I-III of breast cancer at the request of the patient at any tumor location.

A woman should be familiar with all types of surgical interventions.

Radiotherapy technique

Radiation therapy of the breast and areas of regional metastasis (supraclavicular, axillary) is carried out with bremsstrahlung radiation from an accelerator (6 MeV) or on gamma therapeutic devices (1.25 MeV), and for the parasternal zone - by alternating photon and electron beams or only with electron radiation up to 20 MeV depending on the depth of the chain of parasternal lymph nodes.

Irradiation of the parasternal zone with 60C o or only with a photon beam with an energy above 4 MeV is fraught with the development of post-radiation pulmonitis, mediastinitis, and pericarditis. Preoperative radiation therapy is not performed in many scientific centers around the world, with the exception of locally advanced breast cancer that is resistant to neoadjuvant chemotherapy and endocrine therapy.

Postoperative irradiation of the anterior chest wall after mastectomy or irradiation of the remaining mammary gland after radical resection is carried out with a 1.25 MeV or 6 MeV photon beam from tangential fields directed so that no more than 2 cm of lung tissue falls into the 100% isodose zone.

Tangential fields. Borders:

1. Upper - level of the sternoclavicular joint (Louis angle); if necessary, the upper border can be positioned higher to include the entire breast.

2. Medial - along the middle of the sternum.

3. Lower - 2 cm below the submammary (transitional) fold.

4. Lateral - 2 cm lateral to the palpable breast tissue, usually along the mid-axillary line.

In the postoperative period after mastectomy, the boundaries of the tangential fields are as follows:

1. Upper - corner of Louis.

2. Medial - midline of the body.

3. Lower - at the level of the submammary fold of the opposite gland.

4. Lateral - middle axillary line.

If the localization of the postoperative scar is atypical and it is located outside the designated boundaries of the irradiation fields, additional irradiation of the scar zone is recommended with tissue coverage at least 2 cm beyond its boundaries. Such irradiation should be carried out with an electron beam or using contact radiation therapy.

Suprasubclavian field.

Irradiation of the supraclavicular and axillary lymph nodes occurs from the anterior field and the beam is tilted 10-150 to the side of the same name to avoid irradiation of the esophagus and trachea.

The upper edge of the field is at the level of the upper edge of the cricothyroid recess.

The medial border is the middle of the sternum.

Lateral border - medial edge of the humeral head; if it is necessary to irradiate the entire axilla, the lateral border should be expanded to the lateral edge of the humeral head, which should be covered with a protective block.

The lower border is in contact with the upper border of the tangential field at the level of attachment of the second rib to the sternum (Louis angle).

The larynx, esophagus, and trachea are always protected with a lead block.

The posterior axillary field is used when it is necessary to irradiate the entire axillary zone.

The medial border of the field is located 1 cm inward from the edge of the chest.

The superior border is the upper edge of the clavicle.

Lateral border - the lateral edge of the head of the humerus.

The inferior border is the same level as the inferior border of the supraclavicular field.

Parasternal field. Borders:

The medial edge is the midline of the sternum.

The lateral edge is 4-5 cm lateral to the midline.

The superior edge is the lower edge of the supraclavicular field.

The lower edge is the base of the xiphoid process of the sternum.

When irradiating several adjacent fields, the distance between the boundaries of these fields should be determined depending on the selected type of radiation energy.

The dimensions of the irradiation field are selected individually during pre-radiation preparation using ultrasound, computed tomography, and an x-ray simulator.

Standard postoperative irradiation is carried out in the usual dose fractionation mode (ROD 2 Gy, SOD 40 Gy) to the mammary gland, chest wall and areas of regional metastasis. If the institution has an electron beam, in patients undergoing segmental resection, the area of ​​the postoperative scar (i.e., the tumor bed) can be additionally irradiated at a dose of 12 Gy.

Adjuvant therapy for breast cancer

Different subtypes of breast cancer have become clearly recognized based on genetic profile and immunohistochemical demonstration of selected targets (Sorlie, 2001; Regan, 2006). The overall treatment strategy emphasizes the primary importance of targeted therapy whenever possible, although additional less “target-specific” chemotherapy may be required.

The absolute importance of timely, accurate and reliable histopathological assessment, including target identification, has become apparent. Therefore, a close collaboration between clinicians and pathologists will provide significant improvements in long-term treatment outcomes.

Further clarification of terminology also concerned the definition of endocrine sensitivity. The three sensitivity categories described in 2005 remained essentially unchanged, but were set out more clearly in the 2007 guidance:

1. Tumors are highly sensitive to endocrine therapy (high expression of estrogen receptors (ER) and progesterone receptors (PR) in most tumor cells).

2. Tumors that are incompletely (insufficiently) sensitive to endocrine therapy (lower expression of ER and/or PR).

3. Tumors insensitive to endocrine therapy (complete absence of both ER and PR).

The degree of endocrine sensitivity varies quantitatively and is correlated with an assessment of the risk of relapse to decide whether endocrine therapy alone will be sufficient. Although it is not possible to define an absolute threshold for high endocrine sensitivity, patients at low risk (Table 1) may be considered suitable for endocrine therapy alone, while additional chemotherapy may be required in patients also with highly endocrine-sensitive tumors in the presence of intermediate or high risk factors for relapse, as well as patients with insufficient endocrine sensitivity of the tumor.

Peritumoral vascular invasion must be extensive (ie, tumor emboli observed in 2 or more tumor blocks) to be considered at increased risk;

Some small tumors and histologic subtypes may be considered low risk despite lacking steroid hormone receptor expression (eg, medullary carcinoma, apocrine carcinoma, etc.);

The level of expression or amplification of HER2 are both risk factors and, at the same time, therapeutic targets.

The proposed algorithm (Table 2) should help in choosing the optimal therapy in the near future.

Three sensitivity categories are defined:

1. Tumors that are highly sensitive to endocrine therapy. These are tumors with high expression of both steroid hormone receptors (determined by acceptable immunohistochemical methods).

2. Insufficient sensitivity to endocrine therapy (in the 2005 classification, designated as unclear endocrine sensitivity). In these tumors, there is some expression of steroid hormone receptors, but at low levels, or lack of expression of one of the receptors: ER or PR.

3. Tumors insensitive to endocrine therapy. There is no expression of steroid hormone receptors. Although this group is clearly defined as endocrine-resistant, it includes tumors of varying phenotypes (Sorlie, 2003).

HER2 positivity

There are two technologies for determining HER2 positivity.

Immunohistochemical technique - staining (up to 3+) of more than 30% of tumor cells.

An alternative method is to determine gene amplification by the FISH method (fluorescent in situ hybridization: the ratio of HER2 gene copies to the centromeres of chromosome 17 is more than 2.2) or the CISH method (chromogenic in situ hybridization) (Wolff, 2007).
It has already been clearly shown in a number of clinical trials that the presence of overt immunohistochemical staining (HER2+++) is associated with sensitivity to trastuzumab. Theoretically, weaker staining (1+ or 2+), even in the presence of amplification, should be associated with less activity of trastuzumab. Study 9831 (Perez, 2007) evaluates this hypothesis, but more large trials of the correlation between specific biological markers and anti-HER therapy are needed.

In 2007, the Panel made minor changes to the risk classification (Table 1).

Peritumoral vascular invasion increases the risk category only if it is extensive (Colleoni, 2007). Complete absence of steroid hormone receptors and amplification or increased expression of HER2 are each considered sufficient to rule out low risk, with the exception of rare forms of tumors such as medullary or apocrine carcinoma, which usually do not contain these receptors.
As in 2005, the Panel did not accept the so-called “Qncotype Dx™ molecular approach”, “Mamma Print™ gene expression profile” as sufficiently accurate tests for determining risk category. Both methods are currently being tested in prospective clinical studies (Sparano, 2006; Bogaerts, 2006).

SPECIFIC APPROACHES TO THE CHOICE OF TREATMENT

Local and regional treatment

Surgical treatments presented at the San Gallen conference mainly focused on breast-conserving surgery, technology for detecting and removing sentinel lymph nodes in order to avoid unnecessary axillary dissection. The rationale for breast surgery in the presence of distant metastases was also presented. However, these aspects of surgical treatment were not specifically addressed by the panel.

Some issues of radiation therapy were discussed. It is agreed that the ASCO and EUSOMA guidelines can be used as practice guidelines for planning postoperative radiotherapy (Recht, 2001; Kurtz, 2002).

Modern standards of radiation therapy involve the use of a CT scanning simulator when planning radiation therapy (especially on the left half of the chest) and the use of the technique of “minimal radiation exposure” to the heart (Korreman, 2006).

There was complete agreement among experts in refusing radiation therapy after mastectomy in patients with breast cancer without regional metastases (pNO) with tumors of category T1-T2. At the same time, slightly more than half of the experts consider it advisable to carry out radiation treatment in the presence of 4 or more affected lymph nodes. Data from the Oxford EBCTCG group presented in San Antonio in December 2006 indicate the appropriateness of radiation treatment after mastectomy and in women with 1-3 lymph nodes involved.

In patients with involved lymph nodes, it is recommended to include the chest wall and supraclavicular region in the irradiation volume. Experts agreed that irradiation of the axillary region. should be avoided if complete axillary dissection is performed. Most experts prefer to avoid radiation

Therapy (even after organ-sparing surgery) in elderly patients who are planning endocrine therapy. Only a few Panel members believe that older patients should also follow the standards of radiotherapy if it is indicated.

Many other “innovations” of radiation therapy were not supported by experts: simultaneous (combined) chemo-radiation therapy, “partial” radiation therapy of only the tumor bed, shortening the duration of radiation therapy with hypofractionation. The proposal to defer endocrine therapy until the end of radiation therapy is not supported.

SYSTEMIC ADJUVANT THERAPY PROGRAM

As in 2005, the main decision was to determine acceptable targeted therapy. For highly sensitive and insufficiently sensitive tumors to endocrine therapy, the choice of hormonal treatment will depend on the patient's menopausal status. It may be difficult to determine in patients who have just received cytotoxic chemotherapy when deciding whether to prescribe aromatase inhibitors. Experts have insisted on mandatory confirmation of postmenopausal status before and during the use of aromatase inhibitors.

Other factors characterizing the body and concomitant diseases are also important when choosing treatment. For example, a history of thromboembolism precludes the use of tamoxifen. The presence of concomitant cardiac pathology may influence the choice of certain chemotherapeutic agents (anthracyclines) or the possibility of treatment with trastuzumab. The patient's age and concomitant pathology may limit the use of more intensive chemotherapy regimens. Different types of expected side effects may influence patients' preferences from one treatment strategy to another.

Endocrine therapy for postmenopausal patients

The well-proven high efficacy of third-generation aromatase inhibitors (AIs) has greatly facilitated the choice of appropriate treatment after a quarter century of fairly successful use of tamoxifen (Winer, 2005; Coates, 2007; Coombes, 2007; Goss, 2005; Howell, 2005; Jakesz, 2005). However, the majority of Panel members believe that 5 years of tamoxifen alone remains a reliable adjuvant treatment for some patients. Among the strategies for using AIs, the panel of experts expressed a clear preference for “sequential” endocrine therapy - switching to AIs after 2-3 years of tamoxifen therapy.

A significant minority of the Panel also supported the initial use of IA. And very few Panel members were in favor of a “prospective” policy: 5 years of tamoxifen followed by an AI. For patients who have already completed 5 years of tamoxifen treatment, the Panel supports subsequent additional use of AIs, but only in patients with regional metastases. Initial (up front) use of AIs is more appropriate in patients with a high risk of relapse or with HER 2-positive breast cancer. Initial use of AIs in patients receiving SSRI antidepressants is also advisable.

The panel clearly preferred sequential rather than simultaneous administration of cytotoxic chemotherapy and endocrine therapy. The total duration of optimal adjuvant endocrine therapy can range from 5 to 10 years.

Most experts believe it is necessary to screen for ovarian suppression in younger postmenopausal women, although the timing and age for such testing remains unclear.

The panel supports the need to assess bone mineral density before prescribing AIs and the use of calcium and vitamin D and, especially, exercise to reduce the risk of bone loss and symptoms associated with AI use.

Endocrine therapy in premenopausal patients

The panel of experts unanimously accepted as the standard of adjuvant endocrine therapy for premenopausal patients with breast cancer or -
- administration of tamoxifen in combination with suppression of ovarian function or
- treatment with tamoxifen alone.

One suppression of ovarian function is considered possible if the patient plans a future pregnancy, although refusal of simultaneous treatment with tamoxifen cannot be completely justified.

The panel supports the use of a gonadotropin-releasing hormone (GHR) analogue as a means of suppressing ovarian function. A large majority of experts consider surgical oophorectomy to be an acceptable method. The method of “switching off” the ovaries depends on the type of disease and other circumstances. Most experts rejected irradiation of the ovaries to suppress them. It is important to be aware that in some patients, a single GnH analogue may not completely suppress ovarian function (Jimenz-Gordo, 2006).

Although the optimal duration of ovarian function suppression with GnRH analogues remains unclear, most experts believe that such treatment should be continued for 5 years, especially in patients with ER+ breast cancer at high risk of recurrence and/or with HER2 (+) disease (Mauriac , 2007).

Again, without sufficient evidence, most experts suggest delaying the use of GnRH analogues until chemotherapy is completed.

The use of aromatase inhibitors (AIs) as the only endocrine therapy for premenopausal breast cancer patients is considered unacceptable.

The use of AIs in the setting of ovarian function suppression is currently being tested in clinical trials.

And outside of clinical trials, such a combination (AI + GnRH analogue) is allowed if there are contraindications to the use of tamoxifen. Patients who were premenopausal at the time of diagnosis but became postmenopausal after chemotherapy or during adjuvant endocrine therapy can also receive AIs, but cessation of ovarian function should be clarified before and while receiving AIs, since such treatment usually stimulates endocrine-ovarian function

(Barroso, 2006).

CHEMOTHERAPY

Perhaps the most difficult issue when planning modern adjuvant therapy is the selection of patients with tumors that are highly or insufficiently endocrine sensitive, to whom, in addition to endocrine therapy, additional chemotherapy should be prescribed. Signs suggestive of questionable adequacy of endocrine therapy alone include relatively low expression of steroid hormone receptors, metastatic involvement of regional lymph nodes, high grade or high levels of “proliferative” markers, large tumor size, and extensive peritumoral vascular invasion. Proposed molecular genetic technologies (Oncotype DXTM, Mamma printTM) to facilitate treatment selection have not been supported by experts due to the lack of convincing evidence of their contribution to planning therapeutic approaches.

A wide range of chemotherapeutic regimens is considered acceptable, but there is little agreement on a specific “favorite.” Most experts support the use of anthracyclines in all patients, including those with HER-positive tumors.

The panel of experts considers it appropriate to include DNA-damaging drugs in patients with triple-negative tumors (ER-, PR-, HER2-) (James, 2007). Combinations of cyclophosphamide, 5-fluorouracil and anthracyclines (CAF, CEF, FEC, FAC) have broad support from the Panel, as does a combination of anthracyclines and cyclophosphamide followed by paclitaxel or docetaxel. Few Panel members supported dose-dense chemotherapy, and strongly rejected high-dose chemotherapy, which requires the maintenance of peripheral blood stem cells.

In general, the Panel allows the use of “less intensive” chemotherapy (4 courses of the AC regimen or 6 courses of the CMF regimen) in patients with highly endocrine-sensitive tumors but at high risk of relapse or in patients with insufficiently endocrine-sensitive tumors and HER 2-negative disease. Other regimens are also considered suitable for this group of patients, including the CAF regimen and the combination of docetaxel with AC (TAC regimen).

Most Panel members consider shorter durations of chemotherapy (12 to 16 weeks) to be appropriate for older patients, and early initiation of such therapy is particularly important for patients with receptor-negative tumors (ER-/PR-). However, elderly patients with sufficient life expectancy should be offered standard chemotherapy. Although Panel members appreciate the value of hematopoietic factors in patients with febrile neutropenia, few support their routine use. An increased risk of acute leukemia has been reported in older patients treated with hematopoietic factors (Hershman, 2007).

However, this information does not come from randomized trials, and no such complications were noted in prospective studies.

Table 3 summarizes the treatment approaches and concepts discussed above.

In 2007, oncologists had two therapeutic targets for targeted therapy: steroid hormone receptors (ER/PR) and HER 2. In treatment planning, the risk of disease relapse plays a secondary role, although the magnitude of the risk should be taken into account in patients with endocrine-sensitive tumors when determining indications for additional chemotherapy (before endocrine therapy).

Patients with tumors that are highly sensitive to endocrine therapy, especially in the absence of other unfavorable prognostic features (low and intermediate risk of relapse, HER2-), may successfully receive endocrine therapy alone, while those at high risk of relapse may require additional chemotherapy.

Decisions about additional chemotherapy should be based on an assessment of the degree of endocrine sensitivity of the tumor, risk factors, and patient preferences. Experts emphasize that there are no absolute rules when justifying treatment decisions, which remain the subject of discussion between the patient and the attending physician.

Preoperative systemic therapy

Clinically, one often encounters a difficult choice of treatment for patients with locally advanced breast cancer. The proportion of such tumors ranges from 5% to 40%. The rationale for prescribing neoadjuvant systemic therapy for MIBC is:

1. High probability of latent (micrometastatic) spread.

2. The ability to reduce the volume of surgical intervention within the “clean” surgical margins.

3. The ability to evaluate the clinical response to therapy in vivo.

4. Availability of accurate pathomorphological assessment of the degree of tumor regression.

5. Possibility of special studies of biopsy tumor material before, during and after completion of primary systemic treatment.

The goals of this type of systemic treatment are:
1. Achieve tumor regression and carry out radical local-regional treatment.
2. Taking into account the extremely unfavorable prognosis in this group of patients, using systemic therapy to improve long-term treatment results.

Scheme of neoadjuvant systemic treatment:

Mammography, ultrasound, trephine biopsy with determination of the level of ER, PR, Her 2/neu. 4 courses of neoadjuvant chemotherapy - surgery - 4 courses of adjuvant chemotherapy. If there is no effect after 4 courses of neoadjuvant chemotherapy, it is necessary to change the chemotherapy regimen.

Based on the already routine use of such treatment for large tumors, the majority of Panel members supported the use of preoperative systemic therapy (including chemotherapy and/or endocrine therapy for ER+ tumors) to improve surgical treatment, including breast-conserving treatment of breast cancer (Kaufmann, 2006; Semiglazov, 2007 ) Evaluation of the magnitude of response to neoadjuvant treatment may serve (in the opinion of some Panel members) as a basis for prescribing the same treatment in adjuvant regimens. The majority of Panel members also supported the inclusion of trastuzumab in preoperative treatment programs for patients with HER 2-positive breast cancer.

Table 1. Determination of risk categories in patients with operable forms of breast cancer. San Gallen, 2007.

Risk category
Low risk	Absence of affected lymph nodes (p NO) and all the following signs: p T ≤2 cm and degree of malignancy (G 1) and Absence of extensive peritumoral vascular invasion and Expression of ER and PR and No increased expression or amplification of HER 2/neu Age≥35 years
Intermediate risk	Absence of affected lymph nodes (p NO) and at least at least one of the following: p T> 2 cm or Grade of malignancy (G 2-3) or Presence of extensive peritumoral vascular invasion or Lack of expression of steroid hormone receptors (ER-/PR). Increased expression or amplification of HER 2/neu Age< 35 лет
	Presence of single regional metastases (1-3 involved l/u) Expression of ER+ /PR+, No increased expression or amplification of HER2/neu
High risk	The presence of single regional metastases (1-3 involved lymph nodes and lack of expression of steroid hormone receptors (ER-PR-) or Increased expression or amplification of HER 2/neu
	Presence of 4 or more affected lymph nodes

Table 2. Planning for adjuvant treatment of breast cancer. San Gallen, 2007.

	Highly sensitive to endocrine therapy	Not enough endocrine sensitive	Insensitive to endocrine therapy
HER (-)	Endocrine therapy, additionally chemotherapy for high risk groups relapse	Endocrine therapy, additionally chemotherapy for intermediate and high risk of relapse	Chemotherapy
HER (+++)	Endocrine therapy + trastuzumab+* Chemotherapy**	Endocrine therapy + Trastuzumab + Chemotherapy	Trastuzumab + Chemotherapy

*Trastuzumab (Herceptin®) is not considered a standard of care in women with tumors smaller than 1 cm and without metastatic lymph nodes (pNO), especially in women with highly endocrine-sensitive tumors.

**Available clinical trial data do not support the recommendation of trastuzumab without prior or concomitant chemotherapy.

Table 3. Adjuvant treatment depending on therapeutic targets and risk categories. San Gallen, 2007.

HER 2 (-)

HER 2 (+++)

High endocrine feels.

Incomplete feelings. To endocrine

Insensible To endocrine therapy

High endocrine feels

Incomplete feelings. To endocrine

Insensible To endocrine therapy

Low risk

uh

uh

uh

uh

Prome- creepy ny risk

x→

x→

x→ uh

x→ uh

x

x

x→ e+t

x→ e+t

x→ e+t

x→ e+t

x+t

x+t

x→

x→

X→

X→ EE

X→ EE

x

x→ e+t

x→ e+t

x→ e+t

x→ e+t

x+t

x+t

High risk

heh

heh

heh

heh

x+t

x+t

x→e

x→e

x→e

x→e

X

X

x→ e+t

x→ e+t

x→ e+t

x→ e+t

x+t x+t

x+t x+t

X-chemotherapy

E- Endocrine therapy

T-trastuzumab (Herceptin)

Adjuvant treatment of patients with breast cancer in accordance with sensitivity to endocrine therapy

AI - aromatase inhibitors

CT - chemotherapy

There - Tamoxifen

SOF - suppression of ovarian function (surgery, radiation therapy,

Conservative)

AC - anthracycline + cyclophosphamide

CEF, FEC - cyclophosphamide + epirubicin + 5-fluorouracil

CAF - anthracycline + cyclophosphamide + 5-fluorouracil

Tah - taxanes

Let - letrazole

EXE - exemestane

Ana - anastrazole

TREATMENT FOR DIFFERENT STAGES OF BC

0, stage I

1. Organ-preserving treatment.

After organ-conserving surgery, taking into account the level of expression of ER, PR, Her-2/neu, one of the types of systemic treatment is prescribed. If there is no need for systemic treatment, radiation therapy may be prescribed. Irradiation of the mammary gland is carried out using photon radiation (6 MeV) from a linear accelerator or gamma radiation from a 60Co installation (1.25 MeV) from two tangentially located fields, aimed at ensuring the most homogeneous irradiation of the gland. ROD 2 Gy, SOD 60 Gy. The postoperative area is additionally irradiated at a dose of 12 Gy (2 Gy each). Electron trigger irradiation is preferred.

2. Radical mastectomy.

For all of the above localizations of stage I of the disease, it is possible to perform a radical mastectomy with restoration of the shape of the gland or without restoration (at the patient’s request).

Systemic treatment includes: chemotherapy in patients under 50 years of age with invasive forms, hormone therapy with tamoxifen in postmenopausal patients with receptor-positive tumors for 5 years. Patients under 50 years of age with preserved menstrual function: bilateral oophorectomy or LHRH analogues monthly for 2 years while taking tamoxifen.

Patients with negative ER, PR - PCT (CMF or CAF) do not undergo hormone therapy.

Chemotherapy regimens for stages 0 and I:

CMF Bonadonna regimen

Methotrexate 40 mg/m*2 IV 1 day.

5FU 600 mg/m*2 IV 1 day.

Repeat every 3 weeks for 6 cycles

Cyclophosphamide 100 mg/m*2 orally for 1-14 days.

5FU 600 mg/m*2 IV 1 and 8 days.

Prednisolone 40 mg/m*2 orally 1 and 14 days.

Repeat every 4 weeks for 6 cycles.

Doxorubicin 60 mg/m*2 IV 1 day.

Cyclophosphamide 600 mg/m*2 IV 1 day.

Stage II

Treatment is identical to that for stage I, however, in patients with N0, but with the presence of unfavorable prognostic signs (age under 35 years, negative hormonal receptors, positive Her 2-neu status) in the postoperative period, except for the entire breast, when the tumor is localized in internal quadrants or central zone, as well as in all patients with N+ (with metastatic lesions of three or less axillary lymph nodes), the parasternal and supraclavicular zones from the side of the main lesion are additionally irradiated.

Postoperative RT is carried out in the classical dose fractionation mode (ROD 2 Gy, SOD 30 Gy) after performing organ-sparing surgery and systemic therapy. The postoperative area is additionally irradiated at a dose of 12 Gy (2 Gy each).

In patients with N+, when four or more axillary lymph nodes are affected and/or when the tumor invades the capsule of the lymph node, in addition to the remaining mammary gland, the parasternal, suprasubclavian-axillary zone on the affected side is irradiated.

ALL stage II patients should receive adjuvant systemic chemotherapy (CMF, AC, TAC, AC+T, FAC, CAF, FEC, A+ CMF).

With +ER tamoxifen for 5 years.

For -ER - chemotherapy.

For patients with positive Her 2-neu - trastuzumab 8 mg/kg on 1 day, every 21 days 4 mg/kg

Chemotherapy regimens:

cyclophosphamide 100 mg/m*2 orally for 1-14 days.

5FU 600 mg/m*2 IV 1 and 8 days.

repeat every 28 days.

methotrexate 40 mg/m*2 intravenously on days 1 and 8.

5FU 600 mg/m*2 IV 1 and 8 days.

repeat every 28 days.

repeat every 21-28 days.

5FU 500 mg/m*2 IV 1 and 8 days.

doxorubicin 50 mg/m*2 IV continuous infusion 72 hours 1-3 days.

cyclophosphamide 500 mg/m*2 IV 1 day.

repeat 21 if hematological parameters are restored.

Taxotere 75 mg/m*2 IV 1 day.

Doxorubicin 50 mg/m*2 IV 1 day.

Cyclophosphamide 500 mg/m*2 IV 1 day.

repeat every 21 days.

Cyclophosphamide 600 mg/m*2 IV 1 day.

5FU 600 mg/m*2 IV 1 day.

Repeat every 21-28 days.

Doxorubicin 60 mg/m*2 IV 1 day.

Cyclophosphamide 600 mg/m*2 IV 1 day.

Repeat every 3-4 weeks depending on the recovery of hematological parameters.

doxorubicin 60 mg/m*2 IV 1 day.

cyclophosphamide 600 mg/m*2 IV 1 day. X 4 cycles.

continue paclitaxel 175 mg/m*2 IV for a 3-hour infusion once every 3 weeks for 4 cycles.

Doxorubicin 60 mg/m*2 IV 1 day.

Cyclophosphamide 600 mg/m*2 IV 1 day x 4 cycles.

Continue docetaxel 75 mg/m*2 IV once every 3 weeks for 4 cycles.

Cyclophosphamide 75 mg/m*2 orally for 1-14 days.

Epirubicin 60 mg/m*2 IV 1 day.

5FU 500 mg/m*2 IV 1 and 8 days. every month 6 cycles.

Doxorubicin 75 mg/m*2 IV 1 day every 3 weeks for 4 cycles.

Cyclophosphamide 600 mg/m*2 IV 1 day.

Methotrexate 40 mg/m*2 IV 1 and 8 days.

5FU 600 mg/m*2 IV 1 and 8 days.

Repeat 8 cycles every 3 weeks.

In stage IIA, general effects are prescribed in accordance with table. 4.

Table 4. Absence of metastases in axillary lymph nodes

Menstrual status	Low risk	Intermediate and high risk
Hormone-sensitive tumors
Menstruating	Tamoxifen zoladex or diferelin	Chemotherapy chemotherapy + tamoxifen (if turning off ovarian function)
Postmenopause	Tamoxifen IA	Tamoxifen or chemotherapy + Tamoxifen or AI
Hormone-resistant tumors
Menstruating		Chemotherapy
Postmenopause		Chemotherapy

Patients with positive Her 2-neu - trastuzumab 8 mg/kg on 1 day, every 21 days 4 mg/kg for 1 year. In patients of reproductive age with ER (-) and PR (-) status in combination with PCT (taxanes or SMF, excluding anthracyclines). In postmenopausal patients with ER(+) and PR(+) status in combination with IA, with ER(-) and PR(-) status it is necessary to carry out therapy in combination with PCT (taxanes or SMF, excluding anthracyclines).

In premenopausal women with 8 or more metastatic lymph nodes after completion of 6 courses of chemotherapy and ongoing menstrual function, bilateral oophorectomy or switching off ovarian function by prescribing LHH releasing hormone agonists (giserelin - 3.6 mg subcutaneously in the abdominal wall every 28 days) is indicated for 2 years, triptorelin 3.75 mg every 28 days for 2 years) while taking tamoxifen 20 mg per day for 5 years. If menstrual function ceases after 6 courses of PCT, tamoxifen 20 mg per day is prescribed for 5 years.

Patients with positive Her 2-neu - trastuzumab 8 mg/kg on 1 day, every 21 days 4 mg/kg, for 1 year. In patients of reproductive age with ER (-) and PR (-) status in combination with PCT (taxanes or SMF, excluding anthracyclines). In postmenopausal patients with ER(+) and PR(+) status in combination with IA, with ER(-) and PR(-) status it is necessary to carry out therapy in combination with PCT (taxanes or SMF, excluding anthracyclines).

Surgery 3 weeks after the end of treatment in the scope of RME according to Maden, radical resection of the mammary gland, organ-preserving or reconstructive plastic surgery.

Surgical treatment. The surgical procedure is performed according to the generally accepted method in the scope of radical mastectomy (according to Madden, Patey). The extent of surgical intervention (mastectomy option) is determined by the extent of the tumor process. In all cases, removal of regional lymph nodes of three levels is indicated: axillary, subclavian, subscapular with their subsequent marking. The tumor must be marked according to size and location in the quadrants of the mammary gland.

It is possible to perform immediate or delayed reconstructive surgery (at the patient’s request).

Postoperative radiotherapy. Postoperative RT is carried out in a classical dose fractionation mode (ROD 2 Gy, SOD up to an equivalent dose of 60 Gy). Irradiation fields: supraclavicular, axillary, parasternal, chest wall (at рТ3, 4). 61. Red blood cell cytological or histological verification of diagnosis, general blood test (6 indicators), general urinalysis, blood for chemistry (9 indicators), blood for coagulogram, electrocardiography, fluorography or R-graphy of the lungs, ultrasound mammary glands, regional zones, liver, pelvic organs, mammography. Ductography, magnetic resonance imaging, computed tomography of the mammary glands, determination of hormone levels (ER -, ER +, Her-2-neu), apoptosis, CA15-3 if possible and according to indications.

Information

Sources and literature

1. Protocols for diagnosis and treatment of diseases of the Ministry of Health of the Republic of Kazakhstan (Order No. 764 of December 28, 2007)
   1. 1. V.F. Semiglazov, V.V. Semiglazov, K.Sh. Nurgaziev. Justification of standards for the treatment of breast cancer., 362 pp., Almaty, 2007. 1. Barroso G, Menqcal g. Felix H. Roias-Ruis J.C. et al. Comparison of the efficacy of the aromatase inhibitor letrozole and clomiphene citrate as adjuvants to recombinant folliclestimulating hormone in controlled ovarian hyperstimulation: a prospective, randomized, blinded clinical trial. //Fertil Steril .- 2006.- Vol 86p.1428-1431 2. Bogaerts J, Cardoso F, Buyse M, et al. Gene signature evaluation as a prognostic tool: challenges in the design of the MINDACT trial.//Nat Clin Pract Oncol .-2006.- Vol .3: p.540-551 3. Clarke CA, Glaser SL. Recent declines in hormone therapy utilization and breast cancer incidence: clinical and population-based evidence. // J Clin Oncol.-2006.-Vol.24.p 49 4. Coates AS, Keshaviah A, fthurlimann B, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98 // J Clin Oncol .-2007 -Vol. 25 p.486-492 5. Colleoni M, Rotrnensz N, Peruzzotti G, et al. Prognostic role of the extent of peritumoral vascular invasion in-operable breast cancer. Ann Oncol .-2007 (accepted for publication) 6. Coombes RC, Kilburn LS, Snowdon CF, et al. Survival and safety of exemestane versus tamoxifen after 2-3 years" tamoxifen treatment (Intergroup Exemestane Study): a randomized controlled trial. // Lancet.- 2007.- Vol.349.p.1110-1117 7. Goldhirsch A, Glick JH , Gelber RD et al. Meeting highlights: international expert consensus on the primary therapy of early breast cancer.//Ann Oncol.-2005.-Vol.16.p.1569-1583 8. Goldhirsch A; RD et al. First-select the target: better choice of adjuvant treatments for breast cancer patients. // Ann Oncol.-2006.-Vol. 17 p.1772-1776 9. Goss PE, Ingle JNJ Martino S, et al. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17 // JNCI Cancer Spectrum.-2005.- Vol.97.p.1262-1271 10. Howell A, Cuzick J, Baum M, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years" adjuvant treatment for breast cancer. // Lancet.- 2005.- Vol 365.p.60-62 11. Jakesz R, Jonat W, Gnant M, et al. Switching of postmenopausal women with endocrine responsive early breast cancer to anastrozole after 2 years" adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. // Lancet.- 2005.- Vol 366.p.455-462 12. James CR, Ouinn JE, Mullan PB et al. BRCA1, a Potential predictive biomarker in the treatment of breast cancer //Oncologist.-2007.-Vol. 2.p. 142-150 13. Jimenez-Gordo AM. De Las Heras B. Zamora P. et al.: Failure of Goserelin ovarian* ablation in premenopausal women with breast cancer: two case reports. //Gynecol Oncol .- 2000. - Vol 76 p.126-127 14. Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. // N Engl J Med .- 2006.- Vol 354. p.809-820 15. Kaufmann M, Hortobigyi GN, Goldhirsch A, : et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update // J Clin Oncol .- 2006.-Vol 24p.1940-1949 16. Korreman SS. Pedefsen AN. Aarup LR et"al. Reduction of cardiac and pulmonary complication probabilities after breathingadapted radiotehrapv for breast cancer. Int J Radiot //Oncol Biol Phvs.-2006.- Vol 65.p.1375-1380 17. Kurtz J. EUSOMA Working Party. The curative role of radiotherapy in the treatment of operable breast cancer. //Eur J Cancer.-2002.- Vol 38.p.1961-1974 18. Mauriac L, Keshaviah A. Debled M Mouridsen H et al. in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial//Ann Oncol.- 2007.- Vol. 14 p.320-327 19. Perez EA. Combining adjuvant chemotherapy with biological therapy. .- //Breast.-2007.- Vol.16 (Suppl): p105-111 20. Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al. Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast Cancer. N Engl J Medi -2005.-Vol.353p.1659-1672, 21. Recht A. Edge SB. Robinson PSet al. Postmastectomy radiotherapy: "clinical practice guidelines of the American Society of Clinical Oncology." J Clin Oncology. - 2001 - Vol 19.p.1539-69 22. Regan MM, Viale G, Mastropasqua MG, et al. Re-evaluating adjuvant breast cancer trials: assessing hormone receptor status by immunohistochemical versus extraction assays. //JNCI Cancer Spectrum.-2006-Vol. 98 p.1571-1581 23. Romond EH, Perez EA, Bryant J et al. Trastuzumab plus Adjuvant Chemotherapy for Operable HER2-Positive Breast Cancer. // N Engl J Med.-2005.-Vol. 353 p.1673-1684 24. Semiglazov V.F., Semiglazov V.V. Dashyan G.A. et.al. Phase 2 Randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer// Cancer. -2007-Vol 110.-p. 244-254 25. Slamon D, BCIRG 006 II interim analysis. San Antonio Breast Cancer Symposium, 2006. http://www.bcirg.org/Internet/BCIRG+at+SABCS+2006/default.htm 26. Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. // Proc Natl Acad Sci U S A .- 2003.- Vol.100p.8418-8423 27. Sorlie T., Perou CM, Tibshirani R et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. // Proc Natl Acad Sci U S A .-2001.- Vol. 98 p. 10869-10874 28. Sparano JA. TAILOR: trial assigning individualized options for treatment. // Clin Breast Cancer.- 2006.- Vol.7: p347-350 29. Winer EP, Hudis C, Burstein HJ, et al. American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. //J Clin Oncol.- 2005.- Vol 23: p.619-629. 30. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer // Arch Pathol Lab Med.-2007.- Vol.131p.18.

Information

Mukhambetov S.M., Oncology Research Center

Attached files

Attention!

• By self-medicating, you can cause irreparable harm to your health.
• The information posted on the MedElement website and in the mobile applications "MedElement", "Lekar Pro", "Dariger Pro", "Diseases: Therapist's Guide" cannot and should not replace a face-to-face consultation with a doctor. Be sure to contact a medical facility if you have any illnesses or symptoms that concern you.
• The choice of medications and their dosage must be discussed with a specialist. Only a doctor can prescribe the right medicine and its dosage, taking into account the disease and condition of the patient’s body.
• The MedElement website and mobile applications "MedElement", "Lekar Pro", "Dariger Pro", "Diseases: Therapist's Directory" are exclusively information and reference resources. The information posted on this site should not be used to unauthorizedly change doctor's orders.
• The editors of MedElement are not responsible for any personal injury or property damage resulting from the use of this site.