Surgery (Dr.

Enriquez) Breast 2
December 10-13, 2007

BREAST CANCER Risk factors Hormonal  Inc exposure to estrogen – inc risk 1. Early Menarche 2. Nulliparity 3. Late pregnancy 4. Late menopause 5. HRT 6. obesity  Reduced exposure to estrogen – protective 1. Pregnancy 2. Longer lactation 3. exercise Nonhormonal  Radiation exposure  Alcohol intake  Diet  History of breast cancer
Table 16-8 Percent Incidence of Sporadic, Familial, and Hereditary Breast Cancer Sporadic breast cancer 75% Familial breast cancer 30% Hereditary breast cancer BRCA-1a BRCA-2

2. Breast and ovarian CA in the same individual 3. Male breast CA Screening recommendation 1. BSE every month 2. Clinical breast exam every 6 months 3. Mammography every 12 months beginning at 25 y/o 4. Transvaginal ultrasound/CA125 every 12 months beginning at 25 y/o Risk Management Strategies for BRCA – 1 and BRCA- 2 carriers 1. Prophylactic mastectomy w/ or w/o reconstruction 2. Prophylactic oophorectomy 3. Intensive surveillance for breast and ovarian CA 4. Chemoprevention

FEMALE/CANCER STATISTICS

65205-10% 45% 35%

BRCA – 1 and BRCA -2 - Tumor suppressor genes - Mutation, one becomes carriers of breast cancer susceptible gene • BRCA – 1 (chromosome 17q) - 45% of hereditary breast cancer - 90% lifetime risk of developing breast cancer - 40% lifetime risk of developing ovarian cancer - 50% of children of carriers inherit the trait • BRCA – 2 (chromosome 13q) - Biological function is not well defined, but plays a role in DNA damage response pathways - 35% of hereditary breast cancer - 85% lifetime risk of developing breast cancer - 20% lifetime risk of developing ovarian cancer - 50% of children of carriers inherit the trait Hereditary risk of breast cancer is considered 1. Family with 2 or more women developing breast/ovarian CA <50 y/o BATAS

BREAST CANCER  Multicentricity – second breast cancer outside the breast quadrant of the 1° cancer  Multifocality – second breast cancer within the same quadrant of the 1° cancer

NONINVASIVE BREAST CANCER (Do not post a risk for metastasis)  Lobular Carcinoma in situ (LCIS) - Proliferation of epithelial cells confined to the lobules without invasion through the basement membrane - Neighborhood calcification - 44-47 y/o - 25-35% becomes invasive and may develop in either breast 1 of 10

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65% invasive ductal CA, thus regarded as a marker for inc risk for invasive CA rather than a precursor Tx- observation/tamoxifen/bil mastectomy No benefit in excising LCIS as the dse diffusely involves both breast and risk of invasiveness is equal for both breast

INVASIVE BREAST CANCER  Paget’s Disease of the nipple - chronic, eczematous eruption of the nipple - associated with extensive DCIS or invasive CA - biopsy of the nipple - tx: surgical therapy

Ductal Carcinoma in situ (DCIS)/ Intraductal Carcinoma - Proliferation of epithelial cells confined to the mammary ducts without invasion through the basement membrane - High risk for progression to invasive CA - Tx- Mastectomy / BCS with post operative radiotherapy

BREAST CANCER - 33% of breast cancer cases – SBE

Table 16-10 Classification of Breast Ductal Carcinoma In Situ (DCIS) Determining Characteristics Histology Nuclear Grade Necrosis DCIS Grade Comedo High Extensive High Intermediate * Intermediate Focal or absent Intermediate Noncomedo ∞ Low Absent

Signs and Symptoms of Breast Cancer - Breast enlargement and assymetry - Nipple changes, retraction, or discharge(2° shortening of suspensory ligament of cooper) - Ulceration or erythema of the skin Peau d’ orange (localized edema 2° to disruption of skin lymphatics) - Satellite nodules - Axillary mass - Muskuloskeletal discomfort

Incidence of major histologic types

Breast inspection

Surgery – Breast 2 by Dra. Enriquez

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Breast palpation

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Ductography Nipple discharge

Regional nodes assessment

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Record the location, size, consistency, shape, mobility, fixation and other characteristic of any palpable mass or lymphadenopathy IMAGING TECHNIQUE o Mammography - 1960, 0.1 cGy - Screening mammography: used to detect unexpected breast CA in asymptomatic women - Diagnostic mammography: used to evaluate abnormal findings - views: CC,MLO, Spot compression(1.5x) - can be used to guide interventional procedures - False positive 10%, false negative 7% - Findings: o solid mass w/ or w/o stellate features, asymmetric thickening of breast tissue, clustered microcalcification, presence of fine stippled calcium in and around a suspicious lesion found in 50% of non palpable CA - 33% reduction in mortality in screening mammography - 40% reduction for stages II,III,IV - 30% increase in overall survival

Ultrasonography defines cystic masses w/c are well circumscribed, smooth margins and echo free center Benign solid masses has smooth contours round/oval shape with weak internal echoes, well defined ant and post margins Breast CA has irregular walls Used to guide interventional procedures

o 

MRI For young women who has dense breast Contralateral breast : 5.7% CA

BREAST BIOPSY o Nonpalpable Breast Lesions - Image guided breast biopsies 1. Ultrasound localization: no mass palpable 2. Stereotactic techniques: no mass only microcalcifications - combinations: 100% accurate - FNAB: cytological evaluation - CNB/Open Biopsy: analysis of breast tissue architecture, dx invasiveness o Palpable Breast Lesions - FNAB: 1.5 inch needle, 22-gauge needle on a 10cc syringe - CNB: 14-gauge needle FINE-NEEDLE ASPIRATION BIOPSY

Surgery – Breast 2 by Dra. Enriquez

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SURVIVAL BY STAGE

CNB

      

STAGE 0 STAGE I STAGE IIA STAGEIIB STAGE IIIA STAGE IIIB STAGE IV

      

98% 94% 85% 70% 52% 48% 18%

BREAST CANCER SCREENING PATH

STAGE I DISEASE

TNM STAGE GROUPING  STAGE IIA DISEASE

STAGE IIB DISEASE

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DISTAL SPREAD

STAGE IIIA DISEASE 

CRITERIA FOR STAGING

STAGE IIIB DISEASE CANCER PATIENT MANAGEMENT

STAGE IV DISEASE TUMOR EXTENT/STAGING

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        PRIMARY BREAST CANCER  Good prognostic factors

THERAPEUTIC OPTIONS Surgery Radiotherapy Chemotherapy Hormonal therapy Immunotherapy New therapies Supportive care

SURGICAL OPTIONS I

Poor prognostic factors  Spread to lymph nodes

BREAST CANCER DIAGNOSIS PATH

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SENTINEL LYMPH NODE BIOPSY - used in women with early breast cancers (T1, T2, T3 / N0) - contraindications: palpable lymphadenopathy, prior axillary surgery, chemotherapy, RT, multifocal breast cancers 1. Intraoperative gamma probe – for detection of radioactive colloid (technetium 99 sulfur colloid) 2. Intraoperative visualization of isosulfan blue dye

Stage II

SURGICAL OPTIONS II

Stage III

1. 2. 3. 4. 5. 

Skin sparing mastectomy Total (simple) mastectomy Extended simple mastectomy Modified Radical Mastectomy Halstead Radical Mastectomy Reconstruction (skin graft)

Stage IV

BREAST CANCER / SYSTEMIC TREATMENT  Stage 0 - Stage I PRINCIPLES OF RADIOTHERAPY  INDICATIONS 1. As adjunct to breast conservation surgery 2. Advanced locoregional breast CA (T>5cms)

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3. 4 or more positive axillary nodes o Principles of radiotherapy I

o

Principles of radiotherapy II

BREAST CANCER / HORMONAL THERAPY Regulation of cell proliferation

Adjuvant therapy: - Postoperative treatment in a patient - at high risk of microscopic metastases after - the removal of the primary tumor Neoadjuvant therapy: - Primary treatment of patients with a clinically - localized tumor

STANDARD CHEMOTHERAPY REGIMENS

Examples of Hormonal Therapy  Hormone receptors – detectable in more than 90% of well differentiated breast CA 1. Estrogen receptors 2. Progesterone receptors  TAMOXIFEN – binds to estrogen receptors in the cytosol to block uptake of estrogen by breast tissue - >60% clinical response if ER/PR + - <10% clinical response if ER/PR – - 25% risk reduction in recurrence - 7% reduction in mortality - 39% reduction in contralateral breast CA
49% reduction in incidence of breast CA in high risk patient

AROMATASE INHIBITORS - second line hormonal therapy - postmenopausal Relative Side Effects 

SIDE EFFECTS OF CHEMOTHERAPY

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Special Clinical Situations  NIPPLE DISCHARGE - Unilateral - Bilateral  AXILLARY LYMPH NODE METASTASES WITH UNKNOWN PRIMARY CANCER - 90% probability of harboring occult breast CA - Presenting sign in about 1% of breast CA - Biopsy - History and PE - Diagnostics  BREAST CANCER DURING PREGNANCY - 1:3000, 75% have axillary lymph node metastases - Average age 34 y/o - 25% of breast nodules will be cancerous - Biopsy - Treatment should not be delayed  MALE BREAST CANCER - 1% of breast CA occurs in men - Peak at 6th decade of life - Worse because of late diagnosis - Biopsy - Treatment: MRM - 80% are hormone receptor + , thus adjuvant tamoxifen is considered  PHYLLODES TUMORS (cystosarcoma phyllodes) - Connective tissue composes the bulk of these tumors, mixed with gelatinous, solid and cystic areas - Gross cut tumor shows classical leaf like appearance - Benign – w/c cannot be distinguished from fibroadenoma - Borderline-have a greater potential for local recurrence - Malignantliposarcomatous/rhabdomyosarcomatous , depends on the number of mitoses and presence of invasiveness - Treatment: wide excision with 1 cm margin mastectomy with/without axillary dissection  INFLAMMATORY BREAST CARCINOMA - Occurs in 3% of breast cancer - Mistaken for bacterial infection of the breast - 75% will have palpable axillary lymph nodes - 25% will have distant metastases - Treatment: neoadjuvant chemotherapy - 30% 5 year survival rates

RARE BREAST CANCERS  Squamous cell (epidermoid) CA - metaplasia within the duct system - regional mets: 25%, distant mets: rare  Adenoid cystic CA - 0.1% - 1-3 cms in dm, well circumscribed - Axillary lymph node metastases: rare - Death from pulmonary metastases reported  Apocrine CA - Well differentiated with aggressive growth pattern  Sarcomas - Large painless breast mass with rapid growth - CNB / open biopsy - Grade base on cellularity, degree of differentiation, nuclear atypia And mitotic activity - Primary tx: wide local excision, mastectomy with/without atypia - ANGIOSARCOMA – lymphangiosarcoma of the upper extremity in women with ipsilateral lymphedema following radical mastectomy / radiation - average time: 10.5 years - forequarter amputation  Lymphomas - Primary lymphoma of breast is rare - Diagnosed after a palpable axillary lymphadenopathy - Treatment: Lumpectomy / mastectomy with axillary dissection Recurrent or progressive locoregional dse: chemotherapy and RT - 74% - 5 year survival rate - 51% - 10 year survival rate 1. Histological features of burkitt lymphoma - <39 y/o, bilateral 2. B cell type - >40 y/o

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