You are on page 1of 45

BREAST

HOUSSAM OSMAN

A BRIEF HISTORY OF BREAST CANCER THERAPY


Tumor resection. Lymph node dissection Radiotherapy Chemotherapy Hormonal therapy Integrated therapy with breast conservative surgery.

EMBRYOLOGY AND FUNCTIONAL ANATOMY OF THE BREAST


Embryology:
Develop from thickened ectoderm (mammary ridges, milk lines) extending from the base of the forelimb (future axilla) to the region of the hind limb (inguinal area). Male and female breasts are identical at birth. Proliferation start with puberty and development is completed with pregnancy. Congenital anomalies: Amastia : arrest in mammary ridge development. Polymastia : failure of normal regression. Polythelia, other congenital association. Inverted nipple : failure of a pit to elevate above skin level. Poland's syndrome . Turner's syndrome and Fleischer's syndrome. Witch's milk

Functional Anatomy :
Location. Structure. Nipple areola complex. Blood supply: internal mammary artery, posterior intercostal arteries, axillary artery, and lateral thoracic artery . Veins: internal thoracic vein, posterior intercostal veins, and axillary vein.

vertebral venous plexus of Batson.

Lymphatic: the axillary vein group (lateral), the external mammary group (anterior or pectoral group), the scapular group (posterior or subscapular), the central group , the subclavicular group (apical), the interpectoral group (Rotter's). Level I : located lateral to or below the lower border of the pectoralis minor muscle. Level II : located superficial or deep to the pectoralis minor muscle. Level III : located medial to or above the upper border of the pectoralis minor muscle.

PHYSIOLOGY OF THE BREAST


Breast Development and Function
Estrogen initiates ductal development progesterone is responsible for differentiation of epithelium and for lobular development. Prolactin is the primary hormonal stimulus for lactogenesis in late pregnancy and the postpartum period. It upregulates hormone receptors and stimulates epithelial development.

Pregnancy, Lactation, and Senescence


In response to estrogen and progesterone the breast tissues proliferate , skin darken, and Montgomery glands become more prominent. In late pregnancy prolactin stimulates the synthesis of milk with full expression of the lactogenic action after delivery of the placenta (low estrogen). Oxytocin initiates contraction of the myoepithelial cells resulting in compression of alveoli and expulsion of milk into the lactiferous sinuses. With menopause there is a decrease in the secretion of estrogen and progesterone by the ovaries and involution of the ducts and alveoli of the breast. The surrounding fibrous connective tissue increases in density, and breast tissues are replaced by adipose tissues

Gynecomastia
enlarged breast in the male. Physiologic gynecomastia: the neonatal period, adolescence, and senescence. (excess of circulating estrogens in relation to circulating testosterone) In the nonobese male, breast tissue measuring at least 2 cm in diameter must be present before a diagnosis of gynecomastia may be made does not predispose the male breast to cancer. clinical classification of gynecomastia: Grade I : Mild breast enlargement without skin redundancy Grade IIa : Moderate breast enlargement without skin redundancy Grade IIb : Moderate breast enlargement with skin redundancy Grade III : Marked breast enlargement with skin redundancy and ptosis, which simulates a female breast

The pathophysiologic mechanisms: I. Estrogen excess states A. Gonadal origin B. Nontesticular tumors C. Endocrine disorders D. Diseases of the livernonalcoholic and alcoholic cirrhosis E. Nutrition alteration states II. Androgen deficiency states A. Senescence B. Hypoandrogen states (hypogonadism) C. Renal failure III. Drug-related IV. Systemic diseases with idiopathic mechanisms Therapy.

INFECTIOUS AND INFLAMMATORY DISORDERS OF THE BREAST


Bacterial Infection :
Staphylococcus aureus and Streptococcus species. related to lactation . US Abx and I&D.

Mycotic Infections :
blastomycosis or sporotrichosis.. Amphotrericin.

Hidradenitis Suppurativa :

chronic inflammatory condition that originates within the accessory areolar glands of Montgomery or within the axillary sebaceous glands. Antibiotic therapy with incision and drainage. Excision may be required which may necessitate coverage with flaps or STSG.

Mondor's Disease
thrombophlebitis involves the superficial veins of the anterior chest wall and breast. present as a tender, cord-like structure. ? Biopsy anti-inflammatory medications, warm compresses, restriction of motion, and brassiere support of the breast. When symptoms persist or are refractory to therapy, excision of the involved vein segment is appropriate.

COMMON BENIGN DISORDERS AND DISEASES OF THE BREAST


ANDI:
Early reproductive years (age 1525) Normal Disorder Lobular development Fibroadenoma Stromal development Adolescent hypertrophy Nipple eversion Nipple inversion
Later reproductive years (age 2540) Normal Disorder Cyclical changes of Cyclical mastalgia menstruation Nodularity Epithelial hyperplasia Bloody nipple discharge of pregnancy

Disease Giant fibroadenoma Gigantomastia Subareolar abscess Mammary duct fistula Disease Incapacitating mastalgia

Involution (age 3555):


Normal Lobular involution Disorder Macrocysts Sclerosing lesions Disease

Duct involution Dilatation Sclerosis Epithelial turnover

Duct ectasia Nipple retraction


Epithelial hyperplasia

Periductal mastitis

Epithelial hyperplasia with atypia

Cancer Risk Associated with Benign Breast Disorders and In Situ Carcinoma of the Breast:

Nonproliferative lesions of the breast Sclerosing adenosis Intraductal papilloma Florid hyperplasia Atypical lobular hyperplasia Atypical ductal hyperplasia Ductal involvement by cells of atypical ductal hyperplasia Lobular carcinoma in situ Ductal carcinoma in situ

No increased risk No increased risk No increased risk 1.5 to 2-fold 4-fold 4-fold 7-fold 10-fold 10-fold

Classification of benign breast disorders:


Nonproliferative disorders of the breast : Cysts and apocrine metaplasia Duct ectasia :dilated subareolar ducts, palpable , thick nipple discharge. Calcifications Fibroadenoma and related lesions Proliferative breast disorders without atypia Sclerosing adenosis Radial and complex sclerosing lesions Ductal epithelial hyperplasia Intraductal papillomas Atypical proliferative lesions Atypical lobular hyperplasia (ALH) Atypical ductal hyperplasia (ADH)

Treatment of Selected Benign Breast Disorders and Diseases: Cysts:


Aspiration If the mass did not disappear or if the fluid is blood stained -> US, needle biopsy, and possible excisional biopsy. ultrasound examination with core-needle biopsy. Counseling Excision. mimic cancer. Excisional biopsy and histologic examination are frequently necessary to exclude the diagnosis of cancer Aspiration If no pus -> Abx Purulent -> surgery

Fibroadenoma:

Sclerosing disorders:

Periductal mastitis:

RISK FACTORS FOR BREAST CANCER


Hormonal and Nonhormonal Risk Factors :
Estrogen: : early menarche, nulliparity, and late menopause, older age at first live birth, obesity. : exercise, longer lactation period, full-term pregnancy . Nonhormonal: radiation exposure, alcohol, high fat diet.

Risk-Assessment Models :
The average lifetime risk of breast cancer for newborn U.S. females is 12%. Two risk-assessment models are currently used to predict the risk of breast cancer.

Risk Management :
Postmenopausal hormone replacement therapy. screening mammography in women age 50 years and older reduces mortality from breast cancer by 33%. Tamoxifen: *Gail relative risk of 1.70 or greater -> reduce the incidence of breast cancer by 49%. *DVT, PE, endometrial CA, cataract.

BRCA Mutations:
BRCA-1 and BRCA-2, autosomal dominant, tumor-suppressor genes. BRCA-1 : *chromosome 17q *90% lifetime risk for developing breast cancer and up to a 40% lifetime risk for developing ovarian cancer. *invasive ductal carcinomas, are poorly differentiated, and are hormone receptor negative.

BRCA-2: chromosome 13q The breast cancer risk for BRCA-2 mutation carriers is close to 85% and the lifetime ovarian cancer risk Identifying carriers: (1) obtaining a complete, multigenerational family history. (2) assessing the appropriateness of genetic testing for a particular patient (3) counseling the patient (4) interpreting the results of testing Cancer prevention measures: *Prophylactic mastectomy and reconstruction; *Prophylactic oophorectomy and hormone replacement therapy; *Intensive surveillance for breast and ovarian cancer; and *Chemoprevention.

EPIDEMIOLOGY AND NATURAL HISTORY OF BREAST CANCER


Epidemiology:
the most common site-specific cancer in women and is the leading cause of death from cancer for women age 40 to 44 years. increase in incidence and decrease in mortality rate. The 5- and 10-year survival rates for these women were 18.0 and 3.6%, respectively.

The primary breast cancer:


productive fibrosis that involves the epithelial and stromal tissues. . (peau d'orange). The size of the primary breast cancer correlates with disease-free and overall survival, but there is a close association between cancer size and axillary lymph node involvement. up to 20% of breast cancer recurrences are locoregional, more than 60% are distant, and 20% are both locoregional and distant.

Axillary lymph node metastases:


Typically, axillary lymph nodes are involved sequentially from the low (level I) to the central (level II) to the apical (level III) lymph node groups. The most important prognostic correlate for disease-free and overall survival.

Distant metastases:
Hematogenously seed the pulmonary circulation via the axillary and intercostal veins or the vertebral column via Batson's plexus of veins, which courses the length of the vertebral column. the most common cause of death in breast cancer patients. bone, lung, pleura, soft tissues, and liver.

HISTOPATHOLOGY OF BREAST CANCER


Carcinoma In Situ:
Basement membrane involvement Diagnosis necessitates the analysis of multiple microscopy sections to exclude invasion Multicentricity; occurrence of a second breast cancer outside the breast quadrant

of the primary cancer


Multifocality; occurrence of a second cancer within the same breast quadrant as the primary cancer 2 types:

Lobular carcinoma in situ


Ductal carcinoma in situ

Lobular Carcinoma in Situ (LCIS):


Multicentricity; 60 to 90% of cases Bilaterally in 50 to 70% of cases

The age at diagnosis is 44 to 47 years 12 times more frequently in white women than in African American women Cytoplasmic mucoid globules; distinctive cellular feature Neighborhood calcification Invasive breast cancer develops in 25 to 35% of cases; either breast, regardless of which breast harbored the initial focus of LCIS 65% of subsequent invasive cancers are ductal, not lobular in origin A marker of increased risk for invasive breast cancer rather than an anatomic precursor

Ductal Carcinoma in Situ (DCIS):


Multicentricity; 40 to 80% of cases Bilaterally in 10 to 20% of cases Accounts for 5% of male breast cancers Early development; no cancer cell cytological features Mammography: Calcium deposition occurs in the areas of necrosis Classified based on nuclear grade and the presence of necrosis (comedo, noncomedo..etc) Fivefold increase in the risk of invasive breast cancer (ipsilateral breast, same quadrant) An anatomic precursor of invasive ductal carcinoma

Invasive Breast Carcinoma :


I. Paget's disease of the nipple II. Invasive ductal carcinoma A. Adenocarcinoma with productive fibrosis (scirrhous, simplex, NST) 80% B. Medullary carcinoma 4% C. Mucinous (colloid) carcinoma 2% D. Papillary carcinoma 2% E. Tubular carcinoma (and ICC) 2% III. Invasive lobular carcinoma 10% (signet-ring cell carcinoma) IV. Rare cancers (adenoid cystic, squamous cell, apocrine)

DIAGNOSING BREAST CANCER


History and Physical Examination

Imaging Techniques: Mammography Screening mammography ;


unexpected, asymptomatic

Diagnostic mammography (more views)


false-positive rate of 10% false-negative rate of 7%

Xeromammography Ductography
Primary indication: nipple discharge

Ultrasonography Magnetic Resonance Imaging (MRI) Strong family history of breast cancer MRI of the contralateral breast in women with a known breast cancer (5.7% positive)

Breast Biopsy: Nonpalpable Lesions


Image-guided Fine-needle aspiration (FNA) biopsy
cytologic evaluation

Core-needle biopsy
alternative to open biopsy low complication rate, avoidance of scarring, and a lower cost.

Open biopsy
breast tissue architecture invasive cancer is present

Palpable Lesions
Fine-needle aspiration (FNA) biopsy Core-needle biopsy (sampling error)

BREAST CANCER STAGING AND BIOMARKERS


Breast Cancer Staging :
TNM: TX T0 Tis T1 T2 T3 T4 NX N0 N1 N2 MX M0 M1 Primary tumor cannot be assessed No evidence of primary tumor Carcinoma in situ 2 cm or less more than 2 cm but not more than 5 cm more than 5 cm direct extension to (a) chest wall or (b) skin cannot be assessed No regional lymph node metastasis movable ipsilateral axillary lymph node ipsilateral axillary lymph nodes fixed or matted cannot be assessed No distant metastasis Distant metastasis

Staging: Stage 0 Stage I Stage IIA

Tis
T1 T0 T1 T2 T2 T3 T0 T1 T2 T3 T3 T4 T4 T4 any T any T

N0
N0 N1 N1 N0 N1 N0 N2 N2 N2 N1 N2 N0 N1 N2 N3 any N

M0
M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M1

Stage IIB

Stage IIIA

Stage IIIB

Stage IIIC Stage IV

Traditional Prognostic and Predictive Factors for Invasive Breast Cancer:


Tumor Factors Nodal status Tumor size Histologic/nuclear grade Lymphatic/vascular invasion Pathologic stage Hormone receptor status DNA content (ploidy, S-phase fraction) Extensive intraductal component Host Factors Age Menopausal status Family history Previous breast cancer Immunosuppression Nutrition Prior chemotherapy Prior radiation therapy

OVERVIEW OF BREAST CANCER THERAPY


In Situ Breast Cancer (Stage 0):
Bilateral mammography is performed to determine the extent of the in situ cancer and to exclude a second cancer. LCIS: observation with or without tamoxifen. DCIS: *widespread disease (two or more quadrants)-> require mastectomy. *limited disease-> lumpectomy and radiation therapy are recommended. *Low-grade DCIS of the solid, cribriform, or papillary subtype, which is less than 0.5 cm in diameter, may be managed by lumpectomy alone. *Nonpalpable -> needle localization techniques to guide the surgical resection. *Adjuvant tamoxifen therapy is considered for all DCIS patients.

Early Invasive Breast Cancer (Stage I, IIa, or IIb) :


(1) (2) (3) (4) mastectomy with assessment of axillary lymph node status and breast conservation (lumpectomy with assessment of axillary lymph node status and radiation therapy) are considered equivalent. Axillary lymphadenopathy or metastatic disease in a sentinel axillary lymph node necessitates an axillary lymph node dissection. contraindications to breast conservation therapy include : prior radiation therapy to the breast or chest wall. involved surgical margins or unknown margin status following re-excision. multicentric disease. scleroderma or other connective-tissue disease. Adjuvant chemotherapy for early invasive breast cancer is considered for all nodepositive cancers, all cancers that are larger than 1 cm in size, and node-negative cancers larger than 0.5 cm in size when adverse prognostic features are present. Tamoxifen therapy is considered for hormone receptorpositive women with cancers that are larger than 1 cm in size. . HER2/neu expression is determined for all newly diagnosed patients with breast cancer and may be used to provide prognostic information, predict the relative efficacy of various chemotherapy regimens, and predict benefit from Herceptin in women with metastatic or recurrent breast cancer.

Advanced Locoregional Regional Breast Cancer (Stage IIIa or IIIb):


surgery is integrated with radiation therapy and chemotherapy. operable stage IIIa : modified radical mastectomy, followed by adjuvant chemotherapy, followed by adjuvant radiation therapy. Neoadjuvant can be considered. inoperable stage IIIa and for stage IIIb: neoadjuvant chemotherapy is used to decrease the locoregional cancer burden and may permit subsequent surgery to establish locoregional control. In this setting, surgery is followed by adjuvant chemotherapy and adjuvant radiation therapy.

Internal Mammary Lymph Nodes:


Systemic chemotherapy and radiation therapy are used in the treatment of grossly involved internal mammary lymph nodes.

Distant Metastases (Stage IV) :


hormonal therapy for women with hormone receptorpositive cancers; women with bone or soft tissue metastases only; and women with limited and asymptomatic visceral metastases. Systemic chemotherapy is indicated for women with hormone receptornegative cancers, symptomatic visceral metastases, and hormone refractory metastases. anatomically localized problems may benefit from individualized surgical treatment

Locoregional Recurrence:
Women with a previous mastectomy undergo surgical resection of the locoregional recurrence and appropriate reconstruction. Chemotherapy and antiestrogen therapy are considered and adjuvant radiation therapy is given if the chest wall has not previously received radiation therapy. Women with previous breast conservation undergo a mastectomy and appropriate reconstruction. Chemotherapy and antiestrogen therapy are considered.

NONSURGICAL BREAST CANCER THERAPIES


Radiation Therapy :
used for all stages of breast cancer. reduce the risk of local recurrence.

Adjuvant chemotherapy:
reduce in the odds of recurrence and of death in women age 70 years or younger with stage I, IIa, or IIb breast cancer. age 70 years or older, adjuvant chemotherapy is recommended those with blood vessel or lymph vessel invasion, high nuclear grade, high histologic grade, HER2/neu overexpression, and negative hormone receptor status.

Neoadjuvant chemotherapy:
For operable advanced locoregional breast cancer . inoperable stage IIIa and for stage IIIb breast cancer, neoadjuvant chemotherapy is used to decrease the locoregional cancer burden.

Chemotherapy for distant metastases:


women with hormone receptornegative cancers with symptomatic visceral metastasis or with hormone refractory cancer may receive systemic chemotherapy.

Antiestrogen Therapy :
all women with in situ cancer, reduce in the incidence of invasive breast cancer. Node-negative women with hormone receptorpositive breast cancers that are 1 to 3 cm in size. Node-positive women and for all women with a cancer that is more than 3 cm in size. Can be added to the neoadjuvant therapy regimen for women with advanced locoregional breast cancer, especially for women with hormone receptorpositive cancers.

Anti-HER2/Neu Antibody Therapy :


Patients with cancers that overexpress HER2/neu .

SPECIAL CLINICAL SITUATIONS


Nipple Discharge: Unilateral
Suggestive of cancer: Spontaneous Localized to a single duct 40 years or more Bloody Associated with a mass

Bilateral
Suggestive of a benign condition: Multiductal in origin 39 years or less Milky or blue green in color

Axillary Lymph Node Metastases with Unknown Primary Cancer :


Consistent with a breast cancer metastasis; 90% occult breast cancer Axillary lymphadenopathy is the initial presenting sign in only 1% of breast cancer patients Metastatic disease cannot be excluded; fine-needle biopsy and/or open biopsy of an enlarged axillary lymph node Metastatic cancer found; immunohistochemical analysis

Breast Cancer During Pregnancy:


1 of every 3000 pregnant women (axillary lymph node metastases are present in up to 75% of them) Average age is 34 years Less than 25% of the breast nodules developing during pregnancy and lactation will be cancerous Ultrasonography and needle biopsy (decreased sensitivity of mammography during pregnancy) 30% of the benign conditions encountered will be unique to pregnancy and lactation First and second trimesters: modified radical mastectomy Third trimester: lumpectomy with axillary node dissection Radiation & Chemotherapy are considered in special situations

Male Breast Cancer:


Less than 1% of all breast cancers North Americans and the British (Jewish and African American) Preceded by gynecomastia in 20% of men Radiation exposure, estrogen therapy, testicular feminizing syndromes, Klinefelter's syndrome (XXY) Peak incidence in the sixth decade of life 85%: Infiltrating NST 15%: DCIS Modified radical mastectomy (adjuvant radiotherapy and chemotherapy can be considered) Men do worse (advanced stage of their cancer at the time of diagnosis)

Phyllodes Tumors : Benign, borderline, or malignant Borderline tumors have a greater potential for local recurrence Sharply demarcated from the surrounding breast tissue Always monoclonal (fibroadenomas are either polyclonal or monoclonal) Small: excised with a 1-cm margin of normal-appearing breast tissue Large phyllodes tumors may require mastectomy Axillary dissection is not recommended

Inflammatory Breast Carcinoma:


Stage IIIb Less than 3% of breast cancers Skin changes: brawny induration erythema with a raised edge edema (peau d'orange) Mistaken for a bacterial infection of the breast 75% have palpable axillary lymphadenopathy Distant metastases at diagnosis in 25% of white women Surgery +/- radiation therapy Neoadjuvant chemotherapy

Rare Breast Cancers :


SQUAMOUS CELL (EPIDERMOID) CARCINOMA ADENOID CYSTIC CARCINOMA APOCRINE CARCINOMA SARCOMAS

LYMPHOMAS