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The Breast Basic Science Conference Cindy M Deutmeyer MUSC Department of Surgery May 25 th, 2010.

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Presentation on theme: "The Breast Basic Science Conference Cindy M Deutmeyer MUSC Department of Surgery May 25 th, 2010."— Presentation transcript:

1 The Breast Basic Science Conference Cindy M Deutmeyer MUSC Department of Surgery May 25 th, 2010

2 Anatomy Develop along paired mammary ridges Primary bud secondary buds epithelial cords Major (lactiferous) ducts empty into shallow mammary pit mesenchyme proliferates elevation above skin nipple 4% Inverted nipples (pit not elevated above skin) Puberty: Estrogen & Progesterone proliferation of epithelial & connective tissue elements Polymastia: accessory breast Amastia: absence of breast Polands Sx: hypoplasia or absence of breast w/rib, chest wall, & upper extremity defects Polythelia: accessory nipples (1%)

3 Anatomy 3 tissue types: fatty, fibrous, glandular lobes composed of several Lobules Each lobe drains into Lactiferous Duct/Sinus, and eventually nipple Coopers suspensory ligaments: fibrous connective tissue bands, perpendicular to dermis, structural support

4 Breast Boundaries Superior Clavicle, 2 nd rib Inferior Inframammary Fold, 6 th rib Medial Sternum (lateral border) Lateral Anterior axillary line, Latissimus dorsi Posterior Pectoral fascia * Axillary tail of Spence

5 Blood Supply & Lymphatics Internal Mammary a. perforators Intercostal a. Axillary a. branches * Lateral thoracic * Highest thoracic Thoracoacromial a. branches 3 principal groups of veins * Internal thoracic v. perforators * Intercostal v. perforators * Axillary v. tributaries Batsons plexus: surrounds vertebral column 6 axillary lymph node groups Receive 75% lymph drainage 3 axillary lymph node levels * Level I: lateral to Pec minor * Level II: deep to Pec minor * Level III: medial to Pec minor

6 Cases

7 Case 1: Breast Pain 35 y.o. G1P1 presents with complaints of pain in breasts. Pain is bilateral, diffuse. Feels swollen. POBHx- SVD x 1 PGYNHx- regular menses PMHx/PSHx- negative MEDS- none FHx- noncontributory

8 Breast Pain Differential diagnosis Fibrocystic changes Mastalgia/mastodynia Cyst Duct obstruction Inflammation/infection- mastitis Trauma

9 Breast Pain Fibrocystic change Most common of benign breast conditions Replaces fibrocystic disease Multiple tender breast masses May be cyclic in nature May be exaggerated response to hormones Usually present as cyclic, bilateral pain and breast engorgement Pain diffuse, often radiates to shoulders or upper arms Prominent thickened plaques of breast tissue, often in upper outer quadrants

10 Breast Pain Fibrocystic change Management Fine-needle aspiration- diagnostic & therapeutic Ultrasound w/needle biopsy if bloody fluid, residual mass, cyst recurrence Restrict caffeine, foods containing methylxanthines OCPs Pain medications- ibuprofen, salicylates, acetaminophen Diuretics Danazol Bromocriptine

11 Breast Pain Infection/inflammation Presents with pain, erythema, fever Lactational mastitis- Occurs postpartum, Staph aureus or MRSA colonization Management- ultrasound, antibiotics (PCN), continue breast feeding or pumping (if not MRSA); incision and drainage of abscess if virulent strain/nosocomial Nonlactational abscess- Can be due to fistula, tuberculosis, fungi, carcinoma Mammo & Ultrasound req Zuskas Dz: recurrent retroareolar infections

12 Case 2: Nipple Discharge 35 y.o. G1P1 presents with complaints of spontaneous nipple discharge. Right breast, bloody discharge POBHx- SVD x 1 PGYNHx- benign PMHx/PSHx- negative MEDS- OCPs FHx- noncontributory

13 Nipple discharge Differential diagnosis Breast lesions- intraductal papilloma, ductal ectasia, fibrocystic changes, breast abscess Drug induced- phenothiazines, reserpine, methyldopa, imipramine, amphetamine, OCPs CNS lesions- pituitary adenoma, empty sella, hypothalamic tumor Medical conditions- Cushings, hypothyroid, chronic renal failure Carcinoma Idiopathic

14 Nipple discharge Workup Exam Labs- Prolactin, TSH Mammogram Cytologic evaluation of discharge- not very useful Ductography

15 Nipple Discharge Intraductal papilloma Epithelial tumors arising in ducts of breast Main cause of nipple discharge in nonpregnant or nonlactating women Usually women age Benign, extremely small increased cancer risk Size 2-5 mm, usually not palpable Present with spontaneous, bloody, serous or cloudy nipple discharge Management- excisional biopsy

16 Nipple Discharge Ductal ectasia Second most common cause of nipple discharge Older patients Increase in glandular secretion Discharge thick, gray/black color Can lead to nipple retraction and breast mass Management- medical, icepacks, anti-inflammatory agents, broad spectrum antibiotics, surgery if abscess or mass present

17 Nipple discharge *Bad signs Serous, serosanguinous, or watery discharge Associated with mass Unilateral Single duct Positive cytology Positive mammography Age >50 yrs old

18 Case 3: Breast Lump 45 y.o. G2P2 presents with complaints of mass in left breast. Noticed on self exam.

19 Breast Lump History Length of time present Presence of pain Change in size or texture Relationship to menstrual cycle Nipple discharge Family history of breast or ovarian cancer and ages Age at first live birth, menarche, menopause

20 Breast Lump Differential diagnosis Fibroadenoma Macrocysts Galactoceles Lipoma Abscess Rare causes- sclerosing adenosis, cystosarcoma phyllodes Malignancy

21 Breast Lump Work up Exam Imaging- Diagnostic mammogram- less sensitive in younger women due to breast density Ultrasound- can distinguish cystic lesions from solid masses (require further evaluation) Biopsy- GET A TISSUE DIAGNOSIS!! Fine needle aspiration, Core needle biopsy, Open biopsy


23 Breast Mass Fibroadenoma Second most common benign breast disease, most common benign solid tumor Firm, painless, mobile breast mass, 2-3 cm, commonly in upper outer quadrants Usually women aged Multiple in 15-20% of patients Slow growing, do not regress spontaneously Can be stimulated by exogenous estrogen, progesterone, lactation, pregnancy Management- watch & wait, biopsy, or excision

24 Breast Mass Macrocysts Most often women age Fluid-filled sac Often solitary but can be multiple Can have associated nipple discharge Aspiration for diagnosis and therapy Galactocoele Milk-filled cyst Usually follows lactation Firm, tender mass Usually in upper quadrants Diagnostic aspiration often curative Lipoma Nontender No associated skin or nipple changes Usually postmenopausal women Management- biopsy or excision

25 Breast cancer >180,000 new cases per year (estimated from 2008) 80% in women >50 yrs old, 20% in women <50 yrs old >40,000 deaths per year (estimated from 2008) Second leading cause of cancer-related death in women Lifetime risk of breast cancer 12% One in eight women will develop breast cancer Increasing incidence but decreasing mortality Lower incidence in Asian/Pacific Islanders, Hispanic/Latina, American Indian/Alaska natives Higher mortality in African Americans (though lower lifetime risk) Incidence & Mortality lowest in Asia/Africa, underdeveloped nations, those who have not adopted the Westernized reproductive & dietary patterns

26 Breast cancer Risk factors (21% of cases) FactorRelative Risk + FHx Menstrual Hx (menarche 40 yrs total) OCP useNo effect Estrogen replacement <10 yrsNo effect Pregnancy (1st >35 y.o., nulliparous) Contralateral breast cancer5.0 Ovarian/uterine cancer2.0

27 Breast cancer Classification Ductal carcinoma (>80% of cancers) In situ: progresses to invasive cancer; cribiform, solid, comedo types; classified by nuclear grade & necrosis; calcifications on mammo Medullary carcinoma: soft, hemorrhagic, BRCA1 Colloid/Mucinous carcinoma: elderly, bulky, gelatinous Tubular: peri- early menopausal, rarely metastasizes Papillary: 7 th decade, nonwhite women, small, rarely metastasize Inflammatory: dermal lymphatics invaded, erythema & warmth Pagets disease: eczematous lesion on nipple, usu assoc w/underlying malignancy, Apocrine duct

28 Breast Cancer Lobular carcinoma In situ: only in female breast; calcifications on mammo in adjacent tissue; 12x more common in white women; not premalignant lesion, but marker for future development of invasive cancer Infiltrative- multifocal, multicentric, bilateral; no distinct mass; signet-ring cell variant Rare variants Juvenile, epidermoid, carcinoid, squamous cell, spindle cell Sarcoma and carcinosarcoma Cystosarcoma phyllodes, angiosarcoma, malignant lymphoma

29 Breast cancer Symptoms 33% discovered by self-exam Breast enlargement or asymmetry Nipple changes, retraction, or discharge Ulceration or erythema of skin Axillary mass Musculoskeletal complaints Early- mammo abnormality, painless, mobile tumor

30 Breast cancer Screening Mammogram Annually every year >age 40, before age 40 in selected high-risk patients, w/annual clinical breast exam Start 5-10 yrs before age of affected family member Decreases mortality by up to 33% (not proven in women age 40-49) 10% False-positive rate 7% False-negative rate Clustered microcalcifications, fine/stippled calcium around a lesion, solid mass, & asymmetric tissue thickening are suspicious for cancer If equivocal findings on mammo, get ultrasound

31 Hereditary breast cancers Hereditary breast cancers 5-10% of breast cancers Appropriate counseling must be provided to patient and family before testing for BRCA mutations BRCA1 mutation (Breast & Ovary; some colon & prostate) AD inheritance, chromosome 17q21, thought to be tumor suppressor gene lifetime risk of breast cancer 90%, lifetime risk of ovarian cancer 40% Early age onset breast cancer Bilateral Usu invasive ductal CA, poorly differentiated, hormone receptor (-) BRCA2 mutation (Breast, less Ovary; some GI, Prostate, Melanoma, & Pancreas) chromosome 13q12, early age of onset, male breast cancer lifetime risk of breast cancer is 85%, lifetime risk of ovarian cancer 20% Well differentiated, hormone receptor (+) Ashkenazi Jews, Icelandic & Finnish populations Clinical breast exam Q6 mo, w/yearly mammo (MRI) & transvaginal ultrasound w/CA-125 level starting at age 25 (if options below not excercised) Prophylactic mastectomy after child-bearing Prophylactic oophorectomy after age 40

32 Breast Cancer Staging Clinical staging based on physical exam Pathological staging more accurate TNM Staging system T1: 2cm, T3:>5, T4: any size + involvement of chest wall or skin N0:0 nodes, N1:movable, N2:fixed, N3:infraclavicular, supraclavicular, internal mammary M0:no mets, M1:mets Most important predictor of survival is…

33 Breast Cancer Treatment In Situ (Stage 0) LCIS:observation, chemoprevention w/Tamoxifen, & bilateral total mastectomy DCIS: >4 cm disease or disease in >1quadrant = mastectomy Low-grade DCIS <0.5cm: Needle-localized Lumpectomy alone if margins are widely free of disease High-grade DCIS or larger size: Lumpectomy w/Adjuvant radiation tx, or Mastectomy Recurrence rate greater (9%) w/Lumpectomy + Rad, but mortality rate similar to mastectomy Risk for recurrence increases with: >2.5 cm size, comedo type, close margins

34 Breast Cancer Treatment Early Invasive (Stage I, IIA, or IIB) Mastectomy with assessment of axillary lymph node status Breast conserving surgery with assessment of axillary lymph node status + radiation (standard of care) Sentinel lymph node bx is now standard care for women with clinically negative nodes; metastatic disease in an axillary or sentinel lymph node requires full axillary dissection Contraindications to sentinel node bx: T3/T4, Inflammatory CA, palpable axillary nodes, pregnancy, DCIS without mastectomy, prior axillary surgery, after neoadjuvant chemo, prior nononcologic breast surgery Relative contraindications to breast conserving tx: prior radiation, positive surgical margins after re-excision, multicentric disease, scleroderma, lupus Chemo tx: for all node (+), cancers >1cm,and cancers >0.5cm with adverse prognostic features (BV or lymph invasion, high nuclear or histological grade, HER-2- neu amplification, & (-) hormone receptors Tamoxifen: for hormone receptor (+), >1cm; 5yr tx if premenopausal; 1-2 yr tx then aromatase inhibitor if menopausal Herceptin: for HER-2-neu (+) cancers

35 Breast Cancer Treatment Advanced Local-Regional (Stage IIIA or IIIB) No clinically detected distant mets Neoadjuvant chemo to shrink tumor & allow for breast conservation tx w/radiation (doxorubicin or taxane regimin Most get Mastectomy with evaluation of axillary status followed by radiation, +/- chemo SLNBx acceptable after neoadjuvant tx if no clinical nodes prior to chemo (need axillary dissection then) Distant Metastases (Stage IV) Tx mostly aimed at enhancing quality of life Hormonal therapy: bone or soft tissue mets only and receptor (+) Cytotoxic chemo: hormone receptor (-) or refractory, or symptomatic visceral mets Bisphosphonates: bony mets

36 Radiation Therapy Can be used for all stages of Breast cancer Reduces risk of local recurrence Standard in breast conservation tx Not needed for low-grade DCIS of the solid, cribiform, or papillary subtypes that is <0.5 cm & excised widely w/negative margins Mastectomy radiation: positive margins, 4 or more lymph nodes positive (or 3 or more in premenopausal woman) Chest wall & supraclavicular lymph nodes are radiated

37 Surgical Approach- Breast Conservation Resection of primary cancer with a 2mm margin of normal-appearing tissue + assessment of regional node status + radiation tx Segmental mastectomy, lumpectomy, partial mastectomy, wide local excision Use areolar incision when possible Should be able to encompass in mastectomy incision if completion mastectomy needed Upper breast lesion: follow lines of Zahn Lower breast lesion: radial incision Oncoplastic techniques if possible

38 Surgical Approach- Mastectomy Skin sparing: removes all breast tissue, NAC, & prev biopsy scars (recurrence rate 6-8%) Total (simple): all breast tissue, NAC, skin Modified radical: all breast tissue, NAC, skin & Level I & II axillary lymph nodes Halstead radical: same as modified, with pectoralis major & minor removed & Level III nodes Patey modification of MRM: removes pectoralis minor for dissection of Level III nodes Skin flap thickness usu 7-8 mm Complications: seroma (30%), hematoma, wound infection, skin flap necrosis Lymphedema w/MRM: 10-20% (tx w/compression sleeve)

39 Breast Reconstruction Immediate for prophylactic mastectomy or early invasive cancer Delayed for advanced cancer (radiation needed) Immediate: Expander/Implant, or Autologous tissue (latissimus dorsi myocutaneous flap; abdominal TRAM or DIEP flap) If 2 or less ribs resected, no recon needed (scar tissue provides stabilization)

40 Special Situations Breast CA in Pregnancy: usu present w/advanced disease; MRM in 1 st & 2 nd trimesters; lumpectomy w/axillary node dissection,radiation after delivery; chemo acceptable in 2 nd & 3 rd trimesters only Male Breast CA: <1% of all breast CA; usu invasive ductal; highest in Jewish & African-Americans; preceded by gynecomastia in 20%; similar survival rates as women; tx similar to women Phyllodes tumor: benign, borderline, or malignant; mammo findings cannot distinguish type; sharp demarcation from normal breast tissue; Tx w/lumpectomy or mastectomy; no axillary dissection needed Inflammatory Breast CA: induration, erythema, & edema; invasion of dermal lymphatics classic finding; 75% have palpable lymph nodes;Tx is neoadjuvant chemo w/MRM, radiation, +/- adjuvant chemo; poor prognosis

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