Mammary cancer

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Mammary cancer

The incidence of breast cancer has increased significantly over the past 10 years: the disease occurs in 1 out of 9 women. The most common localization is the upper outer quadrant.

Genetic Aspects

    • Only in 20% of cases there is an appropriate family history; inheritance pattern autosomal dominant (maternal)
    • Families with genes of predisposition to the development of breast cancer — BRCA1 (113705, 17q21, R) and BRCA2 — were identified. In these families, there are numerous cases of breast cancer in relatives of the 1st and 2nd degree of kinship and ovarian cancer. Approximately 1 in 400 women in the US has a BRCA1 gene mutation. In the presence of the BRCA1 gene, breast cancer develops in 85% of cases. Men who carry the BRCA2 mutant gene are at high risk of developing breast cancer
    • Cancer of the breast, ovary, and endometrium also develops with mutations in the E-cadherin gene (192090, 16q22.1, SOYA/, UVO, R), a protein of intercellular interactions
    • Breast cancer may be a component of the familial cancer syndrome
    • see also Tumors, genetic predisposition (nl), Lynch syndrome (nl), Appendix 2. Hereditary diseases; mapped phenotypes,

Risk factors

    • Family history of breast cancer (especially premenopausal cancer in direct relatives)
    • early menarche
    • Late onset of menopause
    • Late first births (after 30 years) and nulliparous women
    • Fibrocystosis and areas of atypical hyperplasia in the mammary gland
    • History of invasive or non-invasive breast cancer (intraductal or lobular carcinoma in situ)
    • Mutations in the BRCA-1, BRCA-2 and BRCA-3 genes
    • Cancer of the breast, ovary, and endometrium also develops with mutations in the E-cadherin gene, one of the group of intercellular interaction proteins (192090, 16q22.1, CDH1, UVO, R). Pathological anatomy. Breast cancers are predominantly adenocarcinomas; Distinguish between ductal and lobular cancers, represented by infiltrating and non-infiltrating forms. Forms of breast tumors
    • Papillary carcinoma (1% of all breast cancers) is a low-grade intraductal non-invasive neoplasm
    • Medullary carcinoma (5-10%) is often a large voluminous tumor with a weak ability for invasive growth, surrounded by a lymphocytic swell. The prognosis (compared to infiltrating ductal carcinoma) is more favorable
    • Inflammatory cancer (mastitis-like, 5-10%) spreads through the lymphatic vessels of the skin, which is accompanied by its redness, induration and erysipelas-like inflammation, an increase in body temperature
    • Infiltrating ductal scirrhous carcinoma (70%) characterizes the formation of nests and strands of tumor cells surrounded by a dense collagenous stroma.
    • Paget’s disease (cancer of the nipple and areola of the breast) is a type of breast cancer; characterized by an eczema-like lesion of the nipple. In the deep layers of the epidermis, large cells with a light cytoplasm originating from the epithelium of the apocrine glands are detected. Cytological examination of a smear taken from an ulcerated plane is essential.
    • Status of estrogen receptors (ERts). Breast cancers are classified by the presence or absence of ERts. The condition of the ER can completely change the course of the disease
    • ERc-positive tumors are more common in postmenopausal women. About 60-70% of primary breast cancers are characterized by the presence of ER
    • ERc-negative tumors are more common in premenopausal patients. One third of patients with ERc-negative primary breast cancers subsequently develop recurrent ERc-positive tumors.

Clinical staging is based on the TNM classification (see also Tumor, staging)

    • Stage I: the tumor is less than 2 cm in diameter, there is no involvement of the lymph nodes and distant metastases. 5-year survival – 85%
    • Stage II: tumor 2–5 cm in diameter; palpate mobile axillary lymph nodes; absence of distant metastases. 5-year survival – 66%
    • Stage III: tumor more than 5 cm in diameter; probably local germination; palpate lymph nodes outside the armpit; absence of distant metastases. 5-year survival – 41%
    • Stage IV is characterized by distant metastases. 5-year survival – 10%
    • The degree of cure is determined only after 10 years after the treatment.

Diagnostics

    • Symptoms
    • Palpable mass, single or multiple, dense, sometimes with skin retraction in the form of a lemon peel
    • Pain in the breast area
    • Enlarged, firm axillary lymph nodes
    • Among patients with an increase in axillary lymph nodes, 1/3-1/2 find breast cancer. Exclude Hjken’s disease, lung, ovarian, pancreatic, and squamous cell carcinoma of the skin
    • A blind mastectomy is indicated (removal of the mammary gland without prior cytological examination).
    • Early diagnosis. Routine breast self-examination and mammography provide early detection of cancerous tumors. Self-examination is recommended to be performed monthly after the end of menstruation.
    • Breast self-examination. All women should be proficient in breast self-examination techniques. The examination will need to be performed monthly after menstruation, when the swelling of the gland is less likely to interfere with the detection of the tumor.
    • Mammography. All women aged 35 to 40 are recommended to have a mammogram.
    • In the presence of risk factors, women 40-50 years old are recommended mammography annually or 1 time in 2 years, and over the age of 50 years – annually
    • For women at risk, an annual mammogram is recommended, starting as early as possible.
    • Ultrasound is performed to determine the solid or cystic nature of the formation (palpable or non-palpable).
    • Aspiration biopsy followed by cytological examination of the aspirate confirms the diagnosis.
    • Excisional biopsy is the method of choice in the diagnosis of breast diseases. Biopsy is not always possible in deep lesions
    • Estrogen and progesterone receptors are determined in the biopsy. Receptor-positive tumors are more amenable to hormone therapy and have a better prognosis
    • Cytometry in the duct is performed to determine the diploidy (DNA index is equal to 1.00) or aneuploidy (DNA index is not equal to 1.00) and the fraction of cells in the S-phase of mitosis. Aneuploid tumors with a high S-phase fraction have a worse prognosis.

Treatment: breast carcinoma – combined (surgical, chemo-, radiation and hormonal therapy). Preoperative preparation.

    • Criteria for inoperability according to Haagensen
    • Extensive swelling of the breast
    • Availability of satellite nodes
    • Inflammatory carcinoma of the lymphatic vessels and lymph nodes of the breast; ligaments that support the breast
    • Metastases to supraclavicular lymph nodes
    • Edema of the upper limb
    • Distant metastases.
    • Instrumental study of the presence of distant metastases
    • Bone scan
    • Liver Function Tests
    • Chest x-ray
    • Chest CT is performed to examine the supraclavicular region and mediastinum
    • Radioisotope or CT scan of the brain is indicated in the presence of neurological symptoms
    • Abdominal CT is performed to exclude damage to the adrenal glands, ovaries, liver.
    • Pregnancy at the time of diagnosis of carcinoma is not a contraindication to mastectomy. Chemotherapy is not indicated. In some cases, they resort to radiation therapy and breast preservation. The issue of maintaining pregnancy is decided together with the woman.

Surgery

    • The following factors determine the optimal surgical approach
    • disease stage
    • tumor size
    • localization of the tumor in the breast
    • size and shape of the breast
    • the number of tumor foci in the breast
    • available technical probabilities for radiotherapy and surgery
    • the desire of the patient to save the mammary gland.
    • In most cases, a modified radical mastectomy is used. Operations with preservation of the mammary gland (for example, tilectomy) allow you to correctly assess the prevalence of the tumor process and improve the cosmetic result; however, not all patients are likely to retain the gland.
    • Contraindications for organ-preserving breast surgery
    • Large tumor in a small breast (increased chance of negative cosmetic outcome)
    • Location of primary tumors near the nipple
    • More than one tumor in the breast
    • Contraindications for radiotherapy
    • Advanced disease (eg, stage II or more)
    • Large intraductal lesion or presence of microcalcifications.
    • Surgery can be radical or palliative
    • Removal of the entire affected mammary gland will be necessary due to the multifocal nature of the disease. Approximately 30-35% of patients find precancerous or cancerous lesions in areas adjacent to the affected primary tumor.
    • Removal of axillary lymph nodes will be necessary to determine the damage to the nodes and the stage of the disease.
    • Operation types
    • Lumpectomy (sectoral resection), lymphadenectomy of the axillary lymph nodes (1st and 2nd level) and postoperative radiation are used for small primary tumors (less than 4 cm) and for intraductal carcinomas
    • Simple mastectomy (Maden operation) involves removal of the mammary gland within the nipple space together with removal of the 1st level lymph nodes
    • Modified radical mastectomy (Patey operation). Remove the skin within the gland,

mammary gland, pectoralis minor muscle and adipose tissue with lymph nodes of the axillary, subclavian and subscapular regions

    • Survival and recurrence rates for this operation are comparable to those for radical mastectomy (Halstead operation)
    • The cosmetic defect is smaller than after a Hdlstead mastectomy. Reconstructive surgery – subpectoral prosthetics
    • Halsted’s radical mastectomy. Together with all the tissues mentioned above, the pectoralis major muscle is also removed.
    • The long thoracic nerve is preserved to avoid denervation of the serratus anterior and the development of a pterygoid scapula symptom.
    • The Halsted operation results in severe chest deformity. Effective in preventing recurrence of the disease
    • Major radical mastectomy involves the removal of mediastinal lymph nodes. The operation is indicated for large or medially located tumors with the presence of intrathoracic (parasternal) metastases. High risk of intraoperative mortality
    • Breast reconstruction operations are performed simultaneously with mastectomy or the second stage after complete healing of the primary surgical wound. Radiation therapy
    • Preoperative. Patients with breast cancer, after the diagnosis is established, receive a course of preoperative radiation therapy for the mammary gland and areas of regional metastasis.
    • Postoperative. Patients who underwent removal of the tumor and axillary lymph nodes and did not undergo a course of preoperative radiation therapy should receive final radiation therapy to the area of ​​the breast and lymph nodes (if metastases are detected in them).
    • Obligate later operational. Breast cancer patients should receive postoperative radiation if any of the following risk factors are present
    • The size of the primary tumor is more than 5 cm
    • Metastasis to more than 4 axillary lymph nodes
    • The tumor reaches the resection line, invades the thoracic fascia and/or muscle, or spreads from the lymph nodes into the axillary fat.
    • Patients at increased risk of distant metastasis may receive radiation therapy until completion of adjuvant chemotherapy, or it may be given in conjunction with radiation. Postoperative irradiation of the armpit increases the risk of swelling of the upper limb. Adjuvant chemotherapy slows down or prevents recurrence, improves survival in patients with axillary lymph node metastases, and in some patients without axillary metastases.
    • Combination chemotherapy is preferred over monotherapy, especially in metastatic breast cancer. Taking products in six courses or for 6 months is the optimal method of treatment in terms of effectiveness and duration.
    • Drugs of choice (in the absence of significant toxic reactions should be prescribed in maximum doses
    • Combination of cyclophosphamide (cyclophosphamide), methotrexate and fluorouracil
    • With a high risk of recurrence or metastasis, a combination of cyclophosphamide, doxorubicin hydrochloride and fluorouracil is likely to be prescribed.
    • Alternative products for metastatic cancer: Combination of doxorubicin, thiophosfamide, and vinblastine; taxol (paclitaxel).

adjuvant hormone therapy

    • Hormonal treatment A positive response to hormone therapy is likely under the following conditions: long period without metastasis (>5 years), advanced age, presence of bone metastases, regional metastases and minimal lung metastases, histologically confirmed grade I and II malignancy, long-term remission as a result prior hormone therapy.
    • Hormonal products used in metastatic breast cancer
    • Premenopausal patients – tamoxifen, luliberin antagonists (eg, leuprolide acetate), aminoglutethimide, and hydrocortisone
    • Postmenopausal patients – tamoxifen, megestrol acetate, aminoglutethimide, high dose estrogens (diethylstilbestrol), luliberin antagonists
    • The effectiveness of tamoxifen is more pronounced in patients with ERc-positive tumors and low in ERc-negative tumors.
    • Hormonal treatment of metastatic breast cancer
    • Indications: subcutaneous metastases, involvement of lymph nodes, presence of pleural effusion, bone metastases and non-lymphogenic pulmonary metastases. Chemotherapy is indicated for liver metastases, lymphogenous metastases to the lungs, pericardium, and other life-threatening metastases.
    • Patients with ERc-positive primary tumors respond positively to hormonal treatment in at least 30% of cases. The presence of both estrogen and progesterone receptors in the tumor increases the therapeutic effect up to 75%
    • Patients with unknown hormonal receptor status in tumors may respond to hormone treatment in well-differentiated tumors or if there is an interval of 1–2 years between the appearance of the primary breast tumor and the development of metastases.

Features of medical recommendations

    • The best prognosis is with intraductal breast cancer, because this tumor is non-invasive (located only in the ducts)
    • A total mastectomy or tilectomy followed by radiation is possible, although this approach is associated with an increased risk of developing secondary breast tumors.
    • The subject of discussion remains the expediency of removing axillary lymph nodes; most experts consider the procedure optional.
    • Lobular cancer from situ. Patients with this non-invasive cancer have a very high risk of developing invasive cancer in both breasts. Treatment: bilateral mastectomy or careful monitoring and control of the course of the disease.
    • I and II stages of cancer. Modified radical mastectomy or gland-sparing lumpectomy, axillary lymphadenectomy, and subsequent operative radiation therapy may be performed.
    • III stage of breast cancer. The choice of treatment determines the likelihood of tumor resection
    • Resectable tumors will require extended mastectomy and radiation therapy. Preoperative and postoperative adjuvant chemotherapy can also be performed
    • With inoperable stage III tumors, there is a high degree of probability of local recurrences and distant metastases; poor prognosis
    • Combination treatment required (surgery, radiation, chemotherapy)
    • In most cases, active combined chemotherapy is started immediately after biopsy to reduce the tumor mass, facilitate local treatment and destroy distant micrometastases.