Breast Tumors

It is one of the most common tumors ever. They form two basic groups:
 * 1) Benigntumor;
 * 2) Malignanttumor.

Malignant tumors of the breast
They represent the most common malignant tumors in women in the Czech Republic, their incidence is still rising.

Epidemiology

 * Although the incidence is increasing, the mortality is not, because they are diagnosed at earlier stages;
 * Maximum incidence is around 57 years;
 * In men it occurs in a ratio of 1:140.

Etiology

 * The most serious risk is age (from the age of 30 the incidence rises, over 45 years represent 85% of tumors);
 * sporadic carcinomas – dysplastic changes of epithelial cells occur ( carcinoma in situ ) up to the development of cancer;
 * The activity of stromal cells is also applied, which produce proteolytic enzymes and angiogenic factors - they facilitate growth and metastasis ;
 * Hormonal influences – long-term effect of estrogens ;
 * Genetically determined cancers – occurrence in direct relatives (mother, sister, daughter) or cumulation of tumors within syndromes ( Li-Fraumeni syndrome – mutation of one p53 allele, Cowden syndrome – rare, associated with hamartomas);
 * BRCA 1 and 2 genes are of greatest importance for the detection of genetic conditions ;
 * a woman with a BRCA 1 mutation has a lifetime risk of cancer of 55-85% (for ovarian cancer 15-45%);
 * common in Jewish population;
 * male BRCA carriers are in turn at risk of prostate and colorectal cancer ;
 * hereditary carcinoma is often bilateral;
 * BRCA 2 positive cancer is usually very poorly differentiated, aggressive.

Risk factors:

 * 1) Length of exposure to estrogens – early menarche, late menopause , nulliparity;
 * 2) Other breast diseases – cystic adenomas, ductal papillomas (risk of overlooking cancer);
 * 3) Effects of ionizing radiation – including mammography ;
 * 4) Obesity, increased fat intake and lack of exercise;
 * 5) The influence of smoking, chemical substances, hormonal contraception has not been clearly documented.

Clinical manifestations

 * Most often it is a palpable painless lump in the breast (in 75% it is the first manifestation of the disease);
 * However, it would be optimal to find a non-palpable lesion on mammography;
 * Other symptoms (less often) – breast pain (5%), breast enlargement (1%), indentation of the skin or nipple (5%), discharge (2%), surface changes on the nipple (1%);
 * Enlargement of axillary nodes - regional spread;
 * At an advanced stage – bone pain, weight loss,...
 * Paraneoplasia – dermatomyositis, neuromuscular syndrome, acanthosis nigrans , hypercalcemia in bone metastases.

Clinical examination:

 * Careful personal, family and gynecological anamnesis ;
 * Look - symmetry of the breasts, movements with breathing, regularity of the nipple, color of the skin, expansion of the veins can indicate the activity of the tumor;
 * Palpation – systematically all quadrants, magnitude of resistance, mobility, boundaries, consistency;
 * Frequency of cancer findings in individual quadrants – most often HZK (47%), nipple (22%) and HVK (14%), lower quadrants only a few;
 * Palpation of nodes axillary, above the clavicle.

Display methods:

 * Mammography has a dominant position – the yield is up to 90%;
 * Finding – microcalcifications are often visible, a solid deposit with jagged edges;
 * USG – usually complementary to mammography, has high sensitivity (95%) but limited specificity, is preferred in women under 40;
 * CT, MRI , less – ductography , PET.

Biochemical examination:

 * standard - liver tests, urea , creatinine , electrolytes, ...
 * tumor markers – CEA, CA 15-3, TPA;
 * Determination of hormonal receptors is of particular importance - immunohistochemically in a tissue section; the effect of estrogen and progesterone on tumor growth is assumed
 * Molecular biology – mainly determination of HER-2/neu – causes increased proliferative activity (prognostic and predictive significance);
 * Biopsy - fine needle aspiration (FNA) - more important for distinguishing between cystic and solid formation;
 * Histology is only possible with a self-cutting needle (core biopsy) under anesthesia (local or general).

Screening:

 * early diagnosis is the basis of successful treatment;
 * mammographic screening for women aged 45 and over (once every two years)).

Histopathology

 * Cancer most often arises from the terminal lobules of the gland or from the ducts (TDLU - terminal ductal lobular unit);
 * It is usually preceded by a non-invasive form – carcinoma in situ.

Carcinoma in situ

 * Lobular carcinoma in situ - from the cells of the mammary lobules, proliferation of cells in the lobules that dilate;
 * Not detectable mammographically (unlike the previous one);
 * It often arises multicentrically, even in the contralateral breast;
 * More common in premenopausal women.
 * Ductal carcinoma in situ – proliferation of ductal epithelium without crossing the basement membrane, can create microcalcifications (detected mammographically), can turn into invasive ductal carcinoma;
 * A special form is Paget's carcinoma of the nipple - when tumor cells from the ducts invade the nipple, more often in postmenopausal women.

Invasive forms of carcinomas

 * There are different forms, infiltrating is divided into 2 forms - lobular and ductal.
 * Lobular:
 * About 10%, often in the HZK (upper outer quadrant);
 * It often metastasizes to the serous membranes, meninges, to the ovary, retroperitoneally.
 * Ductal:
 * The most common (75%), it often has a tubular arrangement, it is accompanied by reactive fibrosis – the tumor has a so-called scirrhotic form, when it is hard as a rock;
 * Metastasizes to bones, liver and lungs;
 * Inflammatory (erysipeloid) carcinoma:
 * Rarely (1–3%), the most aggressive form;
 * Infiltration of the entire breast, diffuse erythema, induration of the skin (typical orange peel appearance);
 * 50-70% of tumors have nodal metastases at the time of diagnosis.

Therapy
The definitive treatment procedure is the result of a joint decision of the multidisciplinary team.

Surgical treatment

 * Since 1882, radical mastectomy with exenteration of the axilla has been performed (pectoral muscles, nerves, etc. were removed);
 * Today, a modified radical mastectomy is performed more often - the breast is separated from the pectoral muscle fascia, the nodes are removed from the superficial layers, the nodes below the pectoralis minor muscle are usually not removed;
 * Another option – sentinel node ;
 * conservative procedures – quadrantectomy, tumorectomy ;
 * It is necessary to supplement with radiotherapy, reconstructive surgery is performed;
 * Also as a modality of hormonal treatment – ​​ovariectomy ;
 * In BRCA, surgery can also be used as prophylaxis.

Radiotherapy

 * Carcinoma has limited radiosensitivity;
 * It is indicated after conservative operations, the result is then the same as ablation;
 * It is therefore given adjuvantly;
 * Brachyradiotherapy – application of iridium wires;
 * Palliative treatment – ​​for bone metastases.

Chemotherapy

 * Breast cancer is relatively sensitive to a number of cytostatics, mainly a combination is used;
 * The basic combination is CFM – cyclophosphamide, methotrexate, 5-FU, or a combination with anthracyclines;
 * Monotherapy – in elderly women with limited marrow reserve;
 * Adjuvantly - before menopause, always when the nodes are affected, it is not given for carcinoma in situ or for tumors smaller than 1 cm;
 * Neoadjuvant – for extensive tumors;
 * Palliation – the main treatment method for disseminated disease, can greatly extend survival time.

Hormonal treatment

 * Adjuvantly, neoadj. also palliatively;
 * In premenopausal – castration – surgical or pharmacological.
 * SERM - Tamoxifen
 * Aromatase inhibitors - reduction of the synthesis of female sex hormones

Biological treatment

 * Inhibition of membrane receptors – Ig against HER-2/neu receptors– Herceptin.

related articles

 * Breast
 * Hereditary tumor syndromes
 * Benign breast disease
 * Classification of breast tumors according to Tabár
 * classification of breast tumors
 * Diagnostic imaging methods in senology
 * Infiltrating mammary carcinoma (preparation)