Breast tumours

It is one of the most common tumours in general. They form two basic groups:
 * 1) tumours benign';
 * 2) tumours malignant'.

Malignant breast tumours
They are the most common malignant tumours of women in the Czech Republic, their incidence is still increasing.

Epidemiology

 * Incidence is rising, but mortality is not rising because they are diagnosed at earlier stages;
 * peak incidence is around age 57;
 * In men, it occurs at a ratio of 1:140.

Etiology

 * Age is the most serious risk (incidence rises from 30 years of age, with 85% of tumours above 45 years of age);
 * Sporadic carcinomas - dysplastic changes of epithelialcells (carcinoma in situ) occur until cancer develops;
 * but also involves the activity of stromal cells, which produce proteolytic enzymes and angiogenic factors-facilitating growth and metastasis;
 * hormonal effects - long-term effects of estrogens;
 * genetic carcinomas - occurrence in direct relatives (mother, sister, daughter) or accumulation of tumors within syndromes (Li-Fraumeni syndrome - mutation of one p53 allele, Cowden syndrome - rare, associated with hamartomas);
 * the gene BRCA 1 and 2 is of greatest importance for the detection of genetic susceptibility;
 * a woman with a BRCA 1 mutation has a lifetime risk of 55-85% for cancer (15-45% for ovarian cancer);
 * common in the Jewish population;
 * male BRCA carriers are in turn at risk for prostate cancer and colorectal cancer;
 * hereditary cancer is often bilateral;
 * BRCA 2 positive carcinoma is usually very poorly differentiated, aggressive.

Risk factors:

 * 1) length of exposure to estrogens - early menarche, late menopause, nulliparity;
 * 2) other breast disease - cystic adenomas, ductal papillomas (risk of missed carcinoma);
 * 3) effects of ionizing radiation - also mammography;
 * 4) obesity, increased fat intake and lack of exercise;
 * 5) the effect of smoking, chemicals, hormonal contraceptives has not been clearly documented.

Clinical manifestations

 * Most commonly, it is a palpable, painless lump in the breast (in 75% it is the first manifestation of the disease);
 * Optimally, however, a non-palpable lesion should be found on mammography;
 * other symptoms (less common) - breast pain (5%), breast enlargement (1%), skin or nipple retraction (5%), discharge (2%), superficial changes on the nipple (1%);
 * enlargement of axillary nodes - regional spread;
 * at advanced stage - bone pain, weight loss,...
 * paraneoplasia - dermatomyositis, neuromuscular syndrome, acanthosis nigrans, hypercalcemia in bone metastases.

Clinical examination:

 * Careful personal, family and gynecological medical history;
 * appearance - symmetry of the breasts, symmetry with breathing, nipple regularity, skin color, vein enlargement may indicate tumor activity;
 * palpation - systematically all quadrants, size of resistance, mobility, border, consistency;
 * frequency of findings of carcinomas in each quadrant - most often HZK (47%), nipple (22%) and HVK (14%), lower quadrants few;
 * palpation of nodes axillary, above the germ.

Imaging methods:

 * mammography is dominant - the yield is up to 90%;
 * finding - microcalcifications are usually visible, solid lesion with serrated edges;
 * ultrasound - usually complementary to mammography, has high sensitivity (95%) but limited specificity, preferred in women under 40 years of age;
 * CT, MRI, less so ductography, PET.

Biochemical testing:

 * standard - liver tests, urea, creatinine, electrolytes, ...
 * tumor markers - CEA, CA 15-3, TPA;
 * of particular importance is the determination of hormone receptors - by immunohistochemistry in tissue sections; the influence of estrogen and progesterone on tumor growth is assumed
 * molecular biology - especially determination of HER-2/neu - causes increased proliferative activity (prognostic and predictive significance);
 * biopsy - fine needle aspiration (FNA) - more important to differentiate between cystic and solid masses;
 * histology is only possible with a self-cutting needle (core biopsy) under anaesthesia (local or general).

Screening:

 * early diagnosis is the basis for successful treatment;
 * mammography screening for women 45 and older (once every two years).

Histopathology

 * Carcinoma most commonly arises from the terminal ductal lobular unit (TDLU);
 * It is usually preceded by a non-invasive form - carcinoma in situ.

Carcinoma in situ

 * Lobular carcinoma in situ' - from mammary lobule cells, proliferation of cells in lobules that dilate;
 * not detectable mammographically (unlike the previous one);
 * 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, may form microcalcifications (detectable mammographically), may progress to 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 carcinoma

 * There are different forms, infiltrating is divided into 2 forms - lobular and ductal.
 * Lobular:
 * about 10%, often in the HZK (upper outer quadrant);
 * often metastasizes to serous membranes, meninges, ovaries, retroperitoneally.
 * Ductal:
 * the most common (75%), often tubular, accompanied by reactive fibrosis - the tumour has a 'skirhotic' form where it is hard as a stone;
 * metastasizes to bone, liver and lungs;
 * Inflamatory (erysipeloid) carcinoma:
 * rare (1-3%), the most aggressive form;
 * infiltration of the entire breast, diffuse erythema, skin induction (typical orange peel appearance);
 * 50-70% of tumours have nodal metastases at the time of diagnosis.

Treatment
The final treatment is the result of a joint decision by a multidisciplinary team.

Surgical treatment

 * Since 1882, radical mastectomy with exenteration of the axilla (pectoral muscles, nerves, ...) has been performed;
 * Nowadays, modified radical mastectomy is more commonly performed - the breast is separated from the pectoralis fascia, the nodes are removed from the superficial stages, the nodes below the m. pectoralis minor are usually not removed;
 * another variant - sentinel node;
 * salvage procedures - quadrantectomy, tumorectomy;
 * necessary to complement radiotherapy, reconstructive surgery is performed;
 * also as a modality of hormonal treatment - ovarectomy;
 * for BRCA, surgery can also be used as prophylaxis.

Radiotherapy

 * Carcinoma has limited radiosensitivity;
 * it is indicated after salvage surgery, the result is then identical to ablation;
 * it is therefore given adjuvantly;
 * brachyradiotherapy - application of iridium wires;
 * palliative treatment - for bone metastases.

Chemotherapy

 * Breast cancer is relatively sensitive to a range of cytostatics, and combinations are mainly used;
 * the basic combination is CFM - cyclophosphamide, methotrexate, 5-FU, or combination with anthracyclines;
 * monotherapy - in older women with limited marrow reserve;
 * adjuvantly - before menopause always when lymph nodes are involved, not given for carcinoma in situ or for tumors under 1 cm;
 * neoadjuvant - for large tumours;
 * palliation - the main treatment method for disseminated disease, can significantly prolong survival.

Hormone Therapy

 * Adjuvant, neoadjuvant and palliative treatment;
 * in premenopausal - castration - surgical or pharmacological.
 * SERM - Tamoxifen
 * Aromatase inhibitors - reduction of female sex hormone synthesis

Biological treatments

 * Membrane receptor inhibition - Ig against HER-2/neu receptors - Herceptin.

Related articles

 * Breast
 * Hereditary cancer syndromes
 * Benign breast disease
 * Tabar classification of breast cancer
 * Breast Cancer Classification BI-RADS
 * Diagnostic Imaging in Senology
 * Infiltrating Mammary Carcinoma (slide)

Source

 * ws:Nádory prsu