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BREAST DISEASES 1 Historical Perspective Ancient Egyptian references to both benign breast diseases and breast cancer in 1600 BC. In 1894, Halsted described the radical mastectomy A better understanding of breast physiology and endocrinology ----the use of systemic chemotherapy and hormonal agents Discovery of the BRCA-1 gene responsible for many instances of familial breast cancer 2 CHANGES IN BREAST CANCER SURGERY, 1972–1986 3 Anatomy On pectoral fascia and musculature of the chest wall Over upper anterior rib cage 2nd or 3rd to 6th Fat surrounding Skin envelope Axillary tail of Spencer Relation to pectoralis major muscle Lymph Pectoralis major → axillary → subclavicular → supra-clavicular Medial portion → intercostal lymphatic duct →para-mediastinum Subcutaneous lymphatic communication left→right Lymphatic plexus on the rectal sheath →falciform ligament→liver Some important structures Intercostobrachial nerve a sensory nerve supplying the underarm skin Long thoracic nerve of Bell a motor nerve to the serratus anterior and subscapularis muscles Thoracodorsal nerve a motor nerve to the latissimus dorsi adjacent to its accompanying artery and veins. Physiology Anterior pituitary hormones (prolactin) Adrenal corticoid hormones (Estrogen) Sexual hormones (Progesterone) Insulin Thyroid hormone Examination Inspection Overall inspection symmetry, size, shape, skin color, venous pattern, lump, local dimpling Nipple excoriation, inversion, discharge, edema and redness Skin redness, edema, Peau d’orange or pig-skin Palpation Gentle palpation, quadrant by quadrant Mass: number, size, consistency and mobility Lymph node: Central,pectoral,subscapular ,subclavicular and supra-clavicular group Character of the discharge is significant Milky, serous, or green-brown discharge are almost always benign in origin Bloody discharge most often results from an intra-ductal papilloma, it may mark an underlying cancer Imaging Study Mammography Thermography Ultrasound Ductogram Magnetic Resonance (MR) Positron Emission Tomography (PET) Evaluation of Breast Masses Biopsy FNA(0.7-0.9mm) Open biopsy Nipple discharge Serous,colorless normal menstrual cycle, intraductal papilloma or early pregnancy Bloody intraductal papilloma or ductal ca. Yellowish galactocele or cystic hyperplasia Ductogram 4 Acute Mastitis 1) Cause Lactic stasis Bacterial invasion (Staphylococcus aureus) 2)Manifestation Swelling pain Painful mass with reddish skin General features: Chill, fever, ipsilateral LN enlargement, bacteriaemia Abscess formation 3)Treatment General Thermo therapy: 25% Magnesium sulfate Antibiotic therapy: Local and general administration Drainage: Prevention 5 Cystic Hyperplasia 1) Cause Hormonal imbalance Excessive estrogen production and deficient corpus luteinum activity 2)Clinical manifestation Pain or lump, nipple discharge (15%) Bilateral invlvement Inseparable from other grandular tissue Tense cyst no fluctuant Tenderness Cyst may appear rapidly and then maintain their size or shrink after next menstraual flow Most painful in pre-menstraual period: mastodynia 3)Diagnosis Pain or lump FNA Management Hormonal therapy FNA, open biopsy, mastectomy 6 Fibroadenoma 1) Cause Estrogen may play an important role in its pathogenesis. 2) Manifestation Lump or mass Freely moveable, smooth, lobulated and independent from surroundings without fixation regardless the size. 3) Treatment Excision continued growth and need to be certain of the diagnosis 4)Mammographic appearance of a degenerating firoadenoma displaying a characteristic pattern of dense, popcorn-like calcification Histological appearance of a typical firoadenoma 7 Intraductal papilloma Woman of 40-50 years old. 6%-8% malignant tendency. Forming from the epithelial linings of the main ducts. Nodule at the areola margin. Pressure at that point reproduces the bloody discharge. Surgical excision (involved duct or radical resection if it is proved malignant by frozen section) 8 Breast Cancer 1)Etiology Estrogen as an important factor in pathogenesis of the breast cancer has been confirmed. Estron(E1) and estradiol (E2) carcinogenic Estriol (E3) non-carcinogenic Other various factors Cumulative risk of developing invasive beast cancer after a biopsy for benign breast disease. Women with proliferative disease with atypia are at significantly increased risk for developing invasive breast cancer Age-specific incidence curves for breast cancer The curve rises sharply after 30 years of age and continues to climb thereafter Demographic factor Age more than 30 yrs Female gender (130:1 female/male ratio) Greatly increased risk Known carrier of breast cancer susceptibility gene Strong family history—2 or more first-degree relatives with bilateral or premenopausal breast cancer Atypical ductal or lobular hyperplasia or lobular carcinoma in situ Ductal carcinoma in situ, risk limited to ipslateral breast Moderately increased risk Family history—1 or more first-degree relatives with not bilateral or premenopausal breast cancer Menstrual history—menarche before age of 12 yrs Parity—nulliparity or first live birth after age of 30 yrs Radiation– exposure o low-dose ionizing radiation in childhood or aldolescence Previous breast cancer—low-grade, node-negative, or receptor-positive, lobular history Other cancers—colon or endometrial cancer Diet—high-fat or high-calorie diet 2)Pathological procedure Tumor size Hormone receptor status Status of excision margins Histologic type Pathological classification Type 1 Non-metastasizing Inarticulate carcinoma Type 2 Rarely metastasizing 1.Pure extracellular mucinous or colloid Ca. 2.Medullary Ca. with lymphocyte infiltration 3.Well-differentiated adenocarcinomas Type 3 Moderately metastasizing 1. Adenocarcinoma 2.Intraductal Ca.with stromal invasion 3.Any other Ca. not specifically classified in other groups Type 4 Highly metastasizing 1.Undifferentiated Ca. 2.Any tumor that definitely invades blood vessels Breast cancer dissemination is not orderly and predictable but capricious Hematogenous spread is the primary mode of metastasis Blood-borne spread may occur in the absence of node involvement Hematogenous metastasis can occur at any time Regional lymph node metastases are a marker of tumor dissemination and not necessarily an intermediate step in the process of distant metastasis 3) Metastasis Metastasis routes: Direct invasion Skin, fascia, muscle Lymphatic metastasis of 4 routes Distant metastasizes Lung, bone, liver, adrenal glands, brain, ovarian Lymphatic metastasis Pectoralis major LN→ipslateral axillary LN→subclavicular →supra-clavicular →thoracic duct →venous stream Internal mammary nodes (para-sternal)→supra-clavicular lN Clinical manifestation Early manifestation is solid, painless mass, which is hard, not smooth, unmovable, usually found accidentally. Rapidly developing carcinoma invades surrounding tissue, changes the contour of the breast: Skin traction Nipple traction Peau d’orange or pig-skin Chest wall fixation. Inflammatory Carcinoma An acute onset of redness, pain and swelling of the breast due to lymphatic blockade and lymphangitis. Skin,surface veins and the axiallary nodes are involved. Poor prognosis and treatment is usually inadequate to control the disease. Paget’s Disease An unique form of breast cancer Weeping eczematous lesion of the nipple followed a sub-areolar mass develop beneath the nipple in most cases. Skin is merely involved and the prognosis is better. 4) Diagnosis Self-examination 60% cancer discovered by patients Physical examination Mammography Asymmetry, skin thicking, irregular masses or architectural distortions 5) Staging Primary tumor (p) TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ T1 Tumor 2 cm or less in greatest dimension T2 Tumor more than 2 cm but not more than 5 cm in greatest dimension T3 Tumor more than 5 cm in greatest dimension T4 Tumor of any size with direct extension into chest wall (not including pectoral muscles) or skin edema or skin ulceration or satellite skin nodules confined to the same breast or inflammatory carcinoma Regional Lymph Node Involvement NX Regional lymph nodes cannot be assessed N0 No regional lymph node involvement N1 Metastasis to movable ipsilateral axillary lymph node(s) N2 Metastasis to ipsilateral axillary lymph node(s) fixed to one another or to other structures N3 Metastasis to ipsilateral internal mammary lymph nodes Distant Metastasis MX Presence of distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis present Staging Stage1 T1-T2, N0, M0 Stage2 T1-T2, N1, M0 Stage3 T1-T2, N2-N3, M0 or T3-T4, N0-N3, M0 Stage4 Any combination of TN with M1 Examination Ultrasound Solid or cystic Needle aspiration Solid or cystic Cytology Excision biopsy Preferred method Treatment Surgical procedures Curative or palliative : Halsted radical mastectomy En bloc removal of breast, pectoralis muscle and axillary LN dissection (ALND) Extended radical mastectomy : Plus mediastinal LNs (2,3,4 rib cartilage and intra-thoracal A and V, LN) Modified radical mastectomy En bloc removal of breast and ALND Total mastectomy Breast conservation operation Lumpectomy, ALND and post-operative irradiation Breast conservation operation Factors favoring breat-conserving therapy are as followings: Patient preference for breast conservation Tumor size and location in breast favorable for good aesthetic result Unifocal tumor Small or absent intraductal component of tumor Postlumpectomy breast anticipated easy to follow by physical examination and mammography Patient inability to tolerate general anesthesia Breast Reconstruction Techniques A: Subpectoral prosthetic implant B: Pedicle transverse rectus abdominis myocutaneous (TRAM) flap Adjuvant Therapy Radiotherapy Pre-or post-operative reduce local recurrence rate and dissemination at the time of mastectomy Chemotherapy Breast cancer is considered relatively sensitive to chemotherapy. CMF: cyclophosphamide, methotrexate, and 5-fluorouracil leads to objective responses in more than half of premenopausal women with metastatic breast cancer. Other active regimens : CMFVP: CMF plus vincristine and prednisone AC: Adriamycin plus cyclophosphamide CAF: cyclophosphamide, Adriamycin, and 5-fluorouracil Numerous studies confirm : premenopausal, node-positive patients women have both longer disease-free survival and longer overall survival when treated with adjuvant CMF or CMFVP after “curative” surgery. Endocrinotherapy Both ER and PR at a level of at least 10 fmol/mg have the highest likelihood of response to hormonal intervention (60% to 70%). Hormonal interventions may be either ablative or additive. Ablative measures :oophorectomy or ovarian irradiation, adrenalectomy or hypophysectomy, and antiestrogenic drugs, such as tamoxifen. Additive measures : pharmacologic doses of female sex hormones, either estrogens or progestins, corticosteroids and testosterone derivatives Tamoxifen is by far the most commonly used hormonal intervention for both adjuvant and advanced disease treatment because of its ease of administration and minimal toxicity. 9 MALE BREAST DISEASES :Gynecomastia Gynecomastia is defined as palpable enlargement of the male breast. Nonspecific breast enlargement from fat deposition in obese patients must be differentiated At the onset of puberty, the estrogen/testosterone ratio may be high in some males, and this can persist for several years. Asymptomatic gynecomastia is a surprisingly common finding in adolescent males, probably because of this relative imbalance.