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

1. The BreastBasic Science ConferenceCindy M DeutmeyerMUSC Department of SurgeryMay 25th, 2010

2. Anatomy • Develop along paired mammary ridges • Primary bud  15-20 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 • Poland’s 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 • 15-20 lobes composed of several Lobules • Each lobe drains into Lactiferous Duct/Sinus, and eventually nipple • Cooper’s suspensory ligaments: fibrous connective tissue bands, perpendicular to dermis, structural support

4. Breast Boundaries • Superior Clavicle, 2nd rib • Inferior Inframammary Fold, 6th 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 • Batson’s 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 PainFibrocystic 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 PainFibrocystic 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 PainInfection/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 • Zuska’s 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 40-45 • 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 DischargeDuctal 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 MassFibroadenoma • 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 20-40 • 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 35-50 • 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) Factor Relative Risk + FHx 1.2-3.0 Menstrual Hx (menarche <12, >40 yrs total) 1.3-2.0 OCP use No effect Estrogen replacement <10 yrs No effect Pregnancy (1st >35 y.o., nulliparous) 2.0-3.0 Contralateral breast cancer 5.0 Ovarian/uterine cancer 2.0

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: 7th decade, nonwhite women, small, rarely metastasize • Inflammatory: dermal lymphatics invaded, erythema & warmth • Paget’s 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, T2:>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 1st & 2nd trimesters; lumpectomy w/axillary node dissection,radiation after delivery; chemo acceptable in 2nd & 3rd 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