Breast

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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

 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

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

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

B A T A S 1 of 10

Table 16-8 Percent Incidence of Sporadic, Familial, and Hereditary Breast Cancer

Sporadic breast cancer 65-75%

Familial breast cancer 20-30%

Hereditary breast cancer 5-10% BRCA-1a 45% BRCA-2 35%

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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

 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

 Incidence of major histologic types

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

BREAST CANCER

- 33% of breast cancer cases – SBE

 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

 Breast inspection 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

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 Breast palpation

 Regional nodes assessment

 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

o Ductography

- Nipple discharge

o 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

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 CNB

 BREAST CANCER SCREENING PATH

 TNM STAGE GROUPING  SURVIVAL BY STAGE  STAGE 0  98%  STAGE I  94%  STAGE IIA  85%  STAGEIIB  70%  STAGE IIIA  52%  STAGE IIIB  48%  STAGE IV  18%  STAGE I DISEASE

 STAGE IIA DISEASE

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 STAGE IIIA DISEASE

 STAGE IIIB DISEASE

 STAGE IV DISEASE

 DISTAL SPREAD

 CRITERIA FOR STAGING

CANCER PATIENT MANAGEMENT

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PRIMARY BREAST CANCER  Good prognostic factors

 Poor prognostic factors

 BREAST CANCER DIAGNOSIS PATH

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

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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 SURGICAL OPTIONS II

1. Skin sparing mastectomy 2. Total (simple) mastectomy 3. Extended simple mastectomy 4. Modified Radical Mastectomy 5. Halstead Radical Mastectomy  Reconstruction (skin graft)

BREAST CANCER / SYSTEMIC TREATMENT  Stage 0 - Stage I  Stage II  Stage III  Stage IV PRINCIPLES OF RADIOTHERAPY  INDICATIONS

1. As adjunct to breast conservation surgery 2. Advanced locoregional breast CA

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

o Principles of radiotherapy II

 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

SIDE EFFECTS OF CHEMOTHERAPY

BREAST CANCER / HORMONAL THERAPY Regulation of cell proliferation

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

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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

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Malignant-liposarcomatous/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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