Tumors Of The Breast PDF

TUMORS OF THE BREAST Tumors are the most important lesions of the female breast. may arise from either : 1. connective tissue or 2. epithelial structures (most common). Breast tumors: 1. fibroadenoma, 2. carcinoma of the breast Fibroadenoma Introduction the most common benign neoplasm of the breast...

TUMORS OF THE BREAST Tumors are the most important lesions of the female breast. may arise from either : 1. connective tissue or 2. epithelial structures (most common). Breast tumors: 1. fibroadenoma, 2. carcinoma of the breast Fibroadenoma Introduction the most common benign neoplasm of the breast An increase in estrogen activity is a contributing factor the peak incidence is in the third decade of life. Morphology firm, solitary, freely movable nodule, 1 to 10 cm in diameter. Rarely, multiple rarely, they may exceed 10 cm in diameter (giant fibroadenoma). white color on cut section, surrounded by yellowpink specks representing the glandular areas Fibroadenoma. This well Circumscribed and mobile nodule was Removed surgically Fibroadenoma. The lesion consists of a proliferation of intralobular stroma surrounding and often pushing and distorting the associated epithelium. The border is sharply delimited from the surrounding tissue. Fibroadenoma. A, The radiogram shows a characteristically wellcircumscribed mass. B, Grossly, a rubbery, white, well-circumscribed mass is clearly demarcated from the surrounding yellow adipose tissue. The absence of adipose tissue accounts for the radiodensity of the lesion. C, The proliferation of intralobular stroma surrounds, pushes, and distorts the associated epithelium. The border is sharply delimited from the surrounding tissue. Clinical Features present as solitary, discrete, movable masses. They may enlarge late in the menstrual cycle and during pregnancy. After menopause they may regress and calcify. Breast Carcinoma Introduction Commonest cancer in women 40,940 deaths per year second cause after lung cancer as a cause of cancer death in women. Epidemiology and Risk Factors Well-Established Influences Well-Established Influences Less Well-Established Influences Geographic factors Menstrual history Oral contraceptives Age Age at menarche 55yr High-fat diet First-degree relative with breast cancer Pregnancy Alcohol consumption Premenopausal First live birth from ages 25 to 29yr Cigarette smoking Premenopausal and bilateral First live birth after age 30yr Exogenous estrogens Postmenopausal First live birth after age 35yr Postmenopausal and bilateral Nulliparous Benign breast disease Proliferative disease without atypia Proliferative disease with atypical hyperplasia Lobular carcinoma in situ Geographic Variations The risk is significantly higher in North America and northern Europe than in Asia and Africa. reproductive patterns, and nursing habits are thought to be involved Age Breast cancer is uncommon in women younger than age 30. the risk steadily increases throughout life, but after menopause the upward slope of the curve almost plateaus. Genetics and Family History 5% to 10% of breast cancers are related to specific inherited mutations. BRCA1 & BRCA2 50% of women with hereditary breast cancer have mutations in gene BRCA1 (on chromosome 17q), 30% have mutations in BRCA2 (on chromosome l3q). Genetic testing is available, their exact role in carcinogenesis of breast cancer is not fully understood both of these genes are thought to function in DNA repair They act as tumor suppressor genes, since cancer arises when both alleles are inactive or defective most carriers will develop breast cancer by the age of 70 years, as compared with only 7% of women who do not carry a mutation. Other Risk Factors Prolonged exposure to exogenous estrogens postmenopausally, known as hormone replacement therapy, prevents or at least delays the onset of osteoporosis. short-term use of combined estrogen plus progestin hormone therapy is associated with an increased risk of breast cancer, Oral contraceptives have also been suspected of increasing the risk of breast cancer. the newer formulations of balanced low doses of combined estrogens and progestins seem to be safe. Hormonal Influences Endogenous estrogen excess, or more accurately, hormonal imbalance, clearly has a significant role. Many of the risk factors mentioned (long duration of reproductive life, nulliparity, and late age at birth of first child) imply increased exposure to estrogen peaks during the menstrual cycle Functioning ovarian tumors that elaborate estrogens are associated with breast cancer in postmenopausal women. Estrogens stimulate the production of growth factors by normal breast epithelial cells and by cancer cells. hypothesis estrogen and progesterone receptors normally present in breast epithelium, often present in breast cancer cells, may interact with growth promoters, such as: transforming growth factor α, platelet-derived growth factor, and fibroblast growth factor elaborated by human breast cancer cells, to create an autocrine mechanism of tumor development. Ionizing radiation to the chest increases the risk of breast cancer. Only women irradiated before age 30, during breast development, seem to be affected. For example, 20% to 30% of women irradiated for Hodgkin lymphoma in their teens and 20s develop breast cancer, but the risk for women treated later in life is not elevated. less well-established risk factors, such as obesity, alcohol consumption, a diet high in fat Obesity is a recognized risk factor in postmenopausal women. Pathogenesis As is the case with all cancers, the cause of breast cancer remains unknown. However, three sets of influences seem to be important: (1) genetic changes, (2) hormonal influences, (3) environmental variables Genetic Changes genetic changes have also been implicated in the genesis of sporadic breast cancer. breast cancers are heterogeneous at the molecular level. mutations affecting proto-oncogenes and tumor suppressor genes in breast epithelium contribute to the oncogenic transformation process. HER2/NEU proto-oncogene, Among the best characterized is overexpression of the HER2/NEU proto-oncogene, which has been found to be amplified in up to 30% of invasive breast cancers. its overexpression is associated with a poor prognosis. Also Mutations of suppressor genes RB and p53 Gene expression profiling can stratify breast cancer into five subtypes: 1. luminal A (estrogen receptor positive), 2. luminal B (estrogen receptor positive), 3. HER2/NEU overexpressing (estrogen receptor negative), 4. basal-like (estrogen receptor and HER2/NEU negative), and 5. normal breast like. Morphology Cancer of the breast affects the left breast slightly more often than the right. 4% of women with breast cancer have bilateral primary tumors or sequential lesions in the same breast Greater than 95% of breast malignancies are adenocarcinomas, Breast cancers are classified into those that have not penetrated the limiting basement membrane (noninvasive) and those that have (invasive). A- Noninvasive 1. Ductal carcinoma in situ (DCIS; intraductal carcinoma) 2. Lobular carcinoma in situ (LCIS) B- Invasive (infiltrating) 1. 2. 3. 4. 5. 6. Invasive ductal carcinoma ("not otherwise specified") Invasive lobular carcinoma Medullary carcinoma Colloid carcinoma (mucinous carcinoma) Tubular carcinoma Other types Total Cancers CARCINOMA IN SITU[*] Percentage 15–30 Ductal carcinoma in situ 80 Lobular carcinoma in situ 20 INVASIVE CARCINOMA 70–85 No-special-type carcinoma (“ductal”) 79 Lobular carcinoma 10 Tubular/cribriform carcinoma 6 Mucinous (colloid) carcinoma 2 Medullary carcinoma 2 Papillary carcinoma 1 Metaplastic carcinoma 10 positive LNs Absent Any size invasive carcinoma Negative or positive lymph nodes Present III IV 46 13 MALE BREAST Gynecomastia enlargement of the male breast, may occur in response to absolute or relative estrogen excesses. Gynecomastia, then, is the male analogue of fibrocystic change in the female. cirrhosis of the liver, with consequent inability of the liver to metabolize estrogens Other causes include : Klinefelter syndrome, estrogen-secreting tumors, estrogen therapy,. Physiologic gynecomastia often occurs in puberty and in extreme old age.