Breast Cancer (Breast Cancer)

Breast cancer, or breast cancer, occurs in every tenth woman. Mortality among the sick is about 50%. The main cause of high mortality is the neglect of the disease. So, patients with I, II stages, when there are real chances for success of the operation and successful long-term results, on average in Ukraine make up only 56%.

[1], [2], [3], [4], [5], [6], [7]

Symptoms of the breast cancer

The signs of breast cancer are quite variable and may be similar to other diseases of the mammary glands. The main signs of this disease include erosive formations on the nipple and around it, discharge from the nipple with an admixture of blood, violation of the boundaries of the breast, the constantly present hardening in the gland. Puffy nipple and wrinkling of the skin, chest swelling and deformity can also be signs of development of the lesion. It should be remembered that you can only differentiate the symptoms and diagnose a qualified specialist, so for any symptoms that concern you, you should seek advice from a mammologist.

Characteristic clinical features:

• a tumor, as a rule, one-sided;
• the size of the tumor from a few millimeters to 10 cm or more;
• the boundaries of the tumor are indistinct, the surface is uneven, bumpy, consistency - depending on the histotype;
• characteristic localization - upper-outer quadrant;
• mammary gland asymmetry;
• changes in the skin in the form of a "pad", "lemon crust";
• with Paget's cancer - eczema, psoriasis-like changes in the areola and nipple;
• retraction of the nipple;
• spotting from the nipple;
• palpation of axillary, sub- and supraclavicular lymph nodes.

Depending on the form and type of the disease, the mammalian oncologist differentiates breast cancer and distinguishes the following forms:

• With the nodular form of the disease during palpation, it is possible to find a solid formation of a rounded shape that does not have clear boundaries and does not usually cause pain syndrome. In the future, the skin may be retracted and wrinkled, the formation of a lemon peel, lack of mobility or complete immobility of the neoplasm, a change in the appearance of the nipple, an increase in the size of the lymph nodes in the armpits.
• With edematous form, the pain syndrome is often not expressed, the densification is characterized by rapid growth, the skin and mammary gland tissues swell, turn red, become thicker, early metastases arise in the axillary lymph nodes.
• Rozhistopodobnaya form is characterized by a distinctly expressed hyperemia of the skin and the appearance on its surface of formations, in appearance resembling flames. At palpation the tumor is not probed, the redness of the skin can affect the area of the chest, the body temperature can increase to forty degrees, there is a rapid metastasis to the lymph nodes.
• With mastitis-like form, there is a high temperature, an increase in the size of the breast or its individual segments, swelling, hyperemia, rapid disease, the earlier appearance of metastases.
• Paget's cancer (lesion of the nipple and areola around it) is characterized by the disconnection of cells in the tissues and the formation of ulceration on the nipple. During the development of the disease, the nipple is destroyed and the appearance of ulcerative formation instead.
• When carcinoma of the breast, the breast decreases in size, its mobility is limited, the skin is compacted and uneven, like a shell, and both mammary glands can be affected.
• The latent form can be manifested in the form of an increase in lymph nodes in the axillary region, while the neoplasm itself, as a rule, is not probed.

[8], [9], [10], [11]

Stages

• The zero stage is characterized by the finding of a tumor in its area of appearance and its non-occurrence beyond its limits.
• The first stage is characterized by affection of nearby tissues, the size of the neoplasm usually does not exceed two centimeters, the lymph nodes are not affected.
• In the second stage, the size of the lesion can reach five centimeters, the lymph nodes in the axillary region are damaged from the side of the injured organ, at this stage the lymph nodes do not coalesce with each other and with surrounding tissues.
• The third stage is divided into two types - A and B. In type A, the tumor sizes exceed five centimeters, the lymph nodes are greatly enlarged and are intertwined with each other or with nearby tissues. In type B, the tumor affects the skin of the mammary glands, the thorax or the lymph nodes, and may be of different magnitude. There is also hyperemia, wrinkling and redness of the skin, the breast or some of its segments become dense and increase in size. Similar symptoms are also noted in the development of mastitis.
• At the fourth stage, the tumor affects the lymph nodes in the armpits and inside the chest and extends beyond the boundaries of the chest. It may also be noted that the neoplasm spreads to the lymph nodes located above the clavicle, as well as the damage to the liver, lungs, brain, etc.

[12], [13]

Forms

Currently, two clinical breast cancer classifications have been adopted.

[14], [15], [16], [17]

Classification by stages

• 1 - a small tumor up to 2 cm in diameter is located in the thickness of the affected organ, does not pass to the surrounding cellulose and integuments and without a histologically verified lesion of the regional lymph system
• 2a - The diameter of the tumor is not> 5 cm, passing on the fiber, there is a cohesion with the skin: a symptom of wrinkling, without metastases
• 2b - The diameter of the tumor is not> 5 cm, passing on the fiber, there is a cohesion with the skin: a symptom of wrinkles, with the defeat of single axillary lymph nodes
• 3a - Size> 5 cm in diameter. Adhesion is the germination and ulceration of the skin. Penetration of the neoplasm into the underlying fascial-muscular layers, but without regional metastases
• 3b - Tumors of any size with multiple axillary or subclavian and subscapular metastases
• 3c - Tumors of any size with metastases to supraclavicular lymph nodes or revealed parasternal metastases
• 4 - Common organ damage with dissemination through the skin or extensive ulceration. The size of the tumor node (s) is any, the nodes are tightly fixed to the chest, with metastases to the regional lymph nodes or without them. The presence of distant metastases.

[18], [19]

Classification of breast cancer by TNM

• T1 - Tumor less than 2 cm without skin lesion, nipple (except Paget's disease) and fixation to the chest wall
• T2 - Tumor 2-5 cm with limited retraction, wrinkling of the skin, retraction of the nipple at subarsolar location of the tumor, Paget's disease spreading beyond the nipple
• TK - Tumor 5-10 cm or skin lesions in one form or another or fixation to the pectoral muscle
• T4 - Tumor more than 10 cm or skin lesions and some form that exceeds the size of the tumor, but within the affected organ, or fixation of the breast to the chest wall

Regional lymph nodes

• N0 - Regional lymph nodes are not probed
• N1 - Dense, displaced lymph nodes are probed
• N2 - Axillary lymph nodes of large size, welded, organically movable

Remote metastases

• M0 - Unilateral supraclavicular or subclavian lymph nodes or swelling of the hands
• M1 - No distant metastases

The presence of distant metastases - damage to the skin outside the breast, metastases in the opposite armpit, metastases in another mammary gland, metastases in other organs

[20], [21], [22]

Classification of breast cancer by WHO (1981)

1. Preinvasive (intraprotective and lobular).
2. Invasive (protocol, lobular, mucous, medullary, tubular, adenoid-cystic, secreting, apocrine, meta-plastic).
3. Paget's disease (nipple cancer).

The histological structure is distinguished by:

• Intraflow and intralobular non-infiltrating carcinoma, the so-called cancer in situ;
• Infiltrating carcinoma;
• Special histological variants of carcinoma:
  • medullary;
  • papillary;
  • lattice;
  • mucous membranes;
  • squamous cell;
  • Paget's disease.

[23], [24], [25], [26], [27],

Clinical forms of breast cancer

Clinical forms of breast cancer are very diverse. It is not uncommon to confuse the symptoms of breast fibroadenoma that can mimic a heavier disease. There are nodular (most common), diffuse forms of malignant neoplasm and Paget's cancer. With a nodular form, the tumor can be spherical, star-shaped or mixed. A tumor of a dense consistency, usually painless, shifts only to the tissue of the breast. Often already in the early stages of it, a symptom of skin wrinkling, a symptom of the site or a symptom of retraction is determined. Significant local spread of the process is indicated by skin edema (a symptom of the "orange peel"), skin germination, ulceration, intradermal disseminata, and entrainment of the nipple. Nodular, limited-growing forms of cancer are characterized by slower flow and less metastasis than diffuse ones.

[28], [29], [30]

Complications and consequences

Metastases begin to develop virtually from the time of malignant formation. Its cells enter the lumen of blood or lymph vessels and move to other areas, after which they begin to grow and form metastases that are characterized by rapid or gradual progression. Metastases in breast cancer occur in the armpits, under the clavicles and above the clavicles (lymphogenous metastasis). Hematogenous metastases are often formed in the bones, lungs, in the liver, kidneys. Breast cancer can cause latent metastases that can manifest only after seven to ten years or more after the primary tumor has been removed.

Metastasis is primarily a lymphogenous way.

Regional lymph nodes are:

Axillary (on the side of the lesion) and interintegral (Rothger lymph nodes); are located along the axillary vein and its tributaries and are divided into the following levels:

• Level 1 (lower axillary) - lymph nodes located lateral to the lateral border of the small pectoral muscle;
• Level 2 (middle axillary) - lymph nodes located between the medial and lateral margins of the small pectoralis muscle, and the intervertebral (Rothger lymph nodes);
• Level 3 (apical axillary) - lymph nodes located medially in relation to the medial edge of the small pectoral muscle, including subclavian and apical.

The internal lymph nodes of the mammary gland (on the side of the lesion) are located in the endoracal fascia in the intercostal space along the edge of the sternum. Any other lymph nodes affected by metastases, including supraclavicular, cervical or contralateral internal lymph nodes of the breast, are referred to as distant metastases - Ml.

At the time of diagnosis, regional metastases are found in 50% of patients.

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

Diagnostics of the breast cancer

Breast cancer is diagnosed according to established worldwide standards: 

• Examination, palpation; 
• Biopsy is the study of gland cells, a biopsy can be partial or total (in the case of a resection of the pathological sector). It is carried out with a needle; 
• Ultrasound scanning of the gland and axillary cavities; 
• Mammography is the main part of diagnosis for determining fibroblasts, cysts, fibroadenoma, tumor localization. This X-ray study is absolutely painless and very informative; 
• Immunohistochemical analysis - the determination of receptors for estrogens, progesterone, that is, the resistance of the neoplasm to hormonal therapy. The material for the study is a tumor tissue taken with a biopsy; 
• Analysis for oncomarkers.

A visit to a mammologist, a gynecologist, must be mandatory even when self-examination does not reveal any alarming symptoms that characterize a malignant neoplasm. Such prophylactic acute it is necessary to pass at least once a year, a woman older than 50 years - once every six months. The consultation should be scheduled for the period between the 5th and 12th day of the menstrual cycle, starting from the first day. Inspection is done visually and with the help of palpation. The symmetry of the glands is revealed, the presence of possible changes in skin integuments, nipples, and axillary cavities where the lymph nodes are located are subject to examination. 

Radiography of the glands - mammography. The period between the 5th and 12th day of the cycle is also chosen, as a rule the mammogram is appointed on the day of the examination by the doctor. Mammography is mandatory for women over 40 years of age. 

Often appointed and doktografiya, that is, contrast mammography. So the ducts of the gland are examined for hidden pathologies, which can be asymptomatic. If breast cancer is hidden in the ducts, the X-ray shows it in the form of an area unfilled with contrast medium. 

The ultrasonic scanning method helps to specify the state and structure of the test compaction. So, cysts, adenomas, benign seals can be differentiated, similar in symptoms to malignant neoplasms. If using the above methods, the diagnosis is still not specified, a biopsy is administered. 

A biopsy can finally either confirm the diagnosis or exclude it. A biopsy involves taking a material with a thin needle, the tissue is then examined microscopically. There are cases when a material can not be taken with a needle, then the tissue is obtained with the help of an incision or as a result of excision (resection) of the pathological region of the gland. 

If a malignant tumor of the glandular tissue of the breast is diagnosed, a set of additional examinations can be assigned. Depending on the diagnosis of the oncology development stage, an ultrasound examination of the abdominal organs, pelvic organs, MRI or CT, ultrasound examination of the bone system is prescribed.

[35], [36], [37], [38],

Treatment of the breast cancer

The main therapeutic effects are divided into local-regonar (surgical intervention, radiation therapy) and systemic (chemotherapy, hormone therapy).

Treatment of breast cancer includes an integrated approach and involves surgical intervention, chemotherapy and radiation therapy, hormone treatment. The choice of method depends on many circumstances, in particular, the structure of the tumor, the rate of its development, the presence of metastases, the age of the patient, the functioning of the ovaries, etc. The treatment regimen is prescribed only by an experienced specialist after a complete examination. In the early stages, malignant neoplasm can be completely cured. The following methods are used in treatment:

• Lamectomy. The tumor is removed along with the adjacent unaffected tissues, while the breast is partially preserved. This procedure is performed exclusively at the zero stage of malignant neoplasm and is combined with radiation therapy methods in women at a young age.
• Sectoral resection of the affected organ involves partial removal of the mammary gland and complete removal of lymph nodes in the armpits, performed at the zero and first stages of the disease, combined with the conduct of radiotherapy sessions.
• When carrying out the mastectomy, the mammary gland and a part of the lymph nodes with the pectoral muscle retained. With an expanded mastectomy, along with the gland, lymph nodes in the subclavian and axillary regions are removed. When performing an extensive radical mastectomy with the mammary gland and lymph nodes, the ribs, sternum and pectoral muscle are partially removed. This procedure is carried out in cases when the tumor grows into surrounding tissues.
• Chemotherapy for breast cancer contributes to the elimination of atypical cells that could spread to other areas. Such treatment is usually given, usually from two weeks to two months after surgery for three months to six months.
• Hormonal therapy is necessary in order to stop the influence of sex hormones (mainly estrogens) on malignant cells, which contributes to their development. For these purposes, women are prescribed tamoxifen, in some cases the ovaries are removed.
• Radiation therapy has a local effect and the pathway of the lymph drainage. Before the operation, a radiotherapy session is prescribed in order for the tumor to shrink in size and disappear the most aggressive cells. In the postoperative period, radiation therapy contributes to the elimination of tumor cells, which could remain in the affected area and outside it. Side effects of radiation therapy are fraught with burns of the skin, the development of pneumonia, fracture of the ribs.

Treatment of breast cancer in stages

The choice of method of treatment depends mainly on the stage of the disease.

In stages I and IIa, surgical treatment is indicated without additional therapies.

The volume of surgical treatment:

• Radical mastectomy according to Holstel-Meier.
• Extended radical mastectomy.
• Operation Poethy is a radical mastectomy with the preservation of a large pectoral muscle.
• Mastectomy with removal of axillary lymph nodes.
• Mastectomy.
• Radical resection of the mammary gland in combination with parasternal lymphadenectomy (in the endoscopic version).

With malignant neoplasm in stages III, IIIa and IIIb, combined treatment is indicated - radical mastectomy with preoperative radiation or chemotherapy.

Radiation therapy irradiates the mammary gland and the zones of regional metastasis.

When carrying out chemotherapy, it is recommended to apply the following regimens:

• CMF (Cyclophosphamide, Methotrexate, 5-Fluorouracil);
• AS (Doxorubipine, Cyclophosphamide);
• RAS (5-Fluorouracil, Doxorubipine, Cyclophosphamide);
• ICE (Ifosfamide, Carboplatin, Etoposide);
• Paclitaxel.

With malignant neoplasm in stage IIIc complex treatment is used: preoperative radiotherapy, radical mastectomy and hormonal therapy.

The principle of hormonal action is to act on hormonal receptors, inhibit the development of tumor cells or cause their regression. Hormonal therapy can be carried out by the following methods:

• operative removal of the source of hormones (ovariectomy, adrenalectomy, hypophysectomy) or suppression of organ function through radiation exposure;
• the introduction of hormones to suppress the function of the endocrine gland (estrogens, androgens, corticosteroids);
• introduction of antagonists of hormones competing at the cellular level (antiestrogens - tamoxifen, bromocriptine).

In stage IV, especially in the presence of multiple distant metastases, treatment includes hormone and chemotherapy.

In recent years, worldwide trends in organ-preserving operations have begun to prevail in the treatment of breast cancer.

It is proved that patients with the stage of the T1-2, N0-1 process are suitable for carrying out the organ-preserving treatment.

The volume of surgery should correspond to the methods of ablastics, that is, sufficient to remove the entire tumor with adjacent tissues. Practice in regional lymph nodes remains controversial. Conducted in the postoperative period, adjuvant polychemotherapy can increase the chances of disease-free flow.

Prevention

In a complex of preventive measures aimed at early detection of breast cancer, a large role belongs to self-examination. Palpation of their mammary glands is advisable to conduct a woman once a month in the first phase of the menstrual cycle. When conducting a survey, it is necessary to pay attention to the presence of formations in the thickness of the gland and the detection of painful areas of it.

From the instrumental methods for the prophylactic examination of the mammary glands, X-ray mammography and sonomammography are used. Mammography should be performed on the 5th-12th day from the beginning of the menstrual cycle. The study is shown to women over 40 years - regularly every 2 years, after 50 years - every year.

Sonomammography should be performed:

• when examining mammary glands in women under 30;
• when detecting radiologically dense mammary gland formations and suspected malignant neoplasm;
• on indications for children and adolescents, pregnant and lactating women.

Breast cancer is today one of the most dangerous female diseases, a feature of this pathology is the ability to prevent this disease and stop it under the condition of early diagnosis. That is why it is necessary to regularly perform self-palpation of the glands, and even more expedient are scheduled preventive examinations by a specialist.

[39], [40], [41],