Anatomy• The breast is composed of 15–20 lobes, which are each composed of several

lobules. • Each lobe of the breast terminates in a major (lactiferous) duct (2–4 mm in

diameter), which opens through a constricted orifice (0.4–0.7 mm in diam- eter) into the ampulla of the nipple.

• Fibrous bands of connective tissue travel through the breast (suspensory ligaments of Cooper), which insert perpendicularly into the dermis and provide structural support.

• The axillary tail of Spence extends laterally across the anterior axillary fold. • The upper outer quadrant of the breast contains a greater volume of tissue

than do the other quadrants.

BLOOD SUPPLY, INNERVATION• Blood supply, innervation, and lymphatics. The breast receives its blood

supply from (1) perforating branches of the internal mammary artery; (2) lateral branches of the posterior intercostal arteries; and (3) branches from the axillary artery, including the highest thoracic, lateral thoracic, and pectoral branches of the thoracoacromial artery.

• The veins and lymph vessels of the breast follow the course of the arteries with venous drainage being toward the axilla. The vertebral venous plexus of Batson, which invests the vertebrae and extends from the base of the skull to the sacrum, can provide a

route for breast cancer metastases to the vertebrae, skull, pelvic bones, and central nervous system.

• Lateral cutaneous branches of the third through sixth intercostal nerves provide sensory innervation of the breast (lateral mammary branches) and of the anterolateral chest wall.

• The intercostobrachial nerve is the lateral cutaneous branch of the second intercostal nerve and may be visualized during surgical dissection of the axilla.

• Resection of the intercostobrachial nerve causes loss of sensation over the medial aspect of the upper arm.

LYMPHATICS• The boundaries for lymph drainage of the axilla are not well

demarcated, and there is considerable variation in the position of the axillary lymph nodes.

• The 6 axillary lymph node groups recognized by surgeons are (1) the axillary vein group (lateral); (2) the external mammary group (anterior or pectoral); (3) the scapular group (posterior or subscapular); (4) the central group; (5) the subclavicular group (apical); and (6) the interpectoral group (Rotter’s).

• The lymph node groups are assigned levels according to their relationship to the pectoralis minor muscle.

• Lymph nodes located lateral to or below the lower border of the pectoralis minor muscle are referred to as level I lymph nodes, which include the axillary vein, external mammary, and scapular groups.

• Lymph nodes located superficial or deep to the pectoralis minor muscle are referred to as level II lymph nodes, which include the central and interpectoral groups.

• Lymph nodes located medial to or above the upper border of the pectoralis minor muscle are referred to as level III lymph nodes, which make up the subclavicular group.

• The axillary lymph nodes usually receive more than 75 percent of the lymph drainage from the breast.

Selected Benign Breast Disorders and DiseasesCYSTS

• Cysts: In practice, the first investigation of palpable breast masses is frequently needle biopsy, which allows for the early diagnosis of cysts. A 21-gauge needle attached to a 10-mL syringe is placed directly into the mass. The volume of a typical cyst is 5–10 mL, but it may be 75 mL or more.

• If the fluid that is aspirated is not bloodstained, then the cyst is aspirated to dryness, the needle is removed, and the fluid is discarded as cytologic examination of such fluid is not cost-effective. After aspiration, the breast is carefully palpated to exclude a residual mass. If one exists, ultrasound examination is performed to exclude a persistent cyst, which is reaspirated if present.

• If the mass is solid, a tissue specimen is obtained. • When cystic fluid is bloodstained, 2 mL of fluid are taken for cytology. • The mass is then imaged with ultrasound and any solid area on the cyst wall is

biopsied by needle. • The two cardinal rules of safe cyst aspiration are (1) the mass must disappear

completely after aspiration, and (2) the fluid must not be bloodstained. If either of these conditions is not met, then ultrasound, needle biopsy, and perhaps excisional biopsy are recommended.

Selected Benign Breast Disorders and DiseasesFIBROADENOMAS

• Fibroadenomas: Removal of all fibroadenomas has been advocated irrespective of patient age or other considerations, and solitary fibroadenomas in young women are frequently removed to alleviate patient concern.

• Yet most fibroade- nomas are self-limiting and many go undiagnosed, so a more conservative approach is reasonable.

• Careful ultrasound examination with core-needle biopsy will provide for an accurate diagnosis.

• Subsequently, the patient is counseled concerning the biopsy results, and excision of the fibroadenoma may be avoided.

Selected Benign Breast Disorders and DiseasesSCLEROSING DISORDERS

• Sclerosing Disorders: The clinical significance of sclerosing adenosis lies in its mimicry of cancer.

• It may be confused with cancer on physical exam- ination, by mammography, and at gross pathologic examination.

• Excisional biopsy and histologic examination are frequently necessary to exclude the diagnosis of cancer.

• The diagnostic work-up for radial scars and complex scle- rosing lesions frequently involves stereoscopic biopsy.

• It is usually not possible to differentiate these lesions with certainty from cancer by mammography features, hence biopsy is recommended.

Selected Benign Breast Disorders and DiseasesPERIDUCTAL MASTITIS

• Periductal Mastitis: Painful and tender masses behind the nipple-areola complex are aspirated with a 21-gauge needle attached to a 10-mL syringe.

• Any fluid obtained is submitted for cytology and for culture using a trans- port medium appropriate for the detection of anaerobic organisms.

• Women are started on a combination of metronidazole and dicloxacillin while awaiting the results of culture.

• A subareolar abscess usually is unilocular and often is associated with a single duct system. Preoperative ultrasound will accurately delineate its extent

• The surgeon may either undertake simple drainage with a view toward formal surgery, should the problem recur, or proceed with definitive surgery.

• In a woman of childbearing age, simple drainage is preferred, but if there is an anaerobic infection, recurrent infection frequently develops.

• Recurrent abscess with fistula is a difficult problem and may be treated by fistulectomy or by major duct excision, depending on the circumstances.

• Antibiotic therapy is useful for recurrent infection after fistula excision, and a 2–4-week course is recommended prior to total duct excision.

Selected Benign Breast Disorders and DiseasesNIPPLE INVERSION

• Nipple Inversion: More women request correction of congenital nipple inversion than request correction for the nipple inversion that occurs secondary to duct ectasia.

• surgical complications of altered nipple sensation, nipple necrosis, and postoperative fibrosis with nipple retraction.

• Because nipple inversion is a result of shortening of the subareolar ducts, a complete division of these ducts is necessary for permanent correction of the disorder.

INFECTIOUS AND INFLAMMATORY DISORDERS OF THE BREAST

Bacterial Infection• Bacterial infection. Staphylococcus aureus and Streptococcus species are the organisms most

frequently recovered from nipple discharge from an infected breast. • Breast abscesses are typically seen in staphylococcal infections and present with point tenderness,

erythema, and hyperthermia. • These abscesses are related to lactation and occur within the first few weeks of breast-feeding.

Progression of a staphylococcal infection may result in subcutaneous, sub- areolar, interlobular (periductal), and retromammary abscesses (unicentric or multicentric),

• necessitating operative drainage of fluctuant areas. • Preoperative ultrasonography is effective in delineating the extent of the needed drainage

procedure, which is best accomplished via circumareolar incisions or incisions paralleling Langer lines.

• Although staphylococcal infections tend to be more localized and may be located deep in the breast tissues, streptococcal infections usually present with diffuse superficial involvement.

• They are treated with local wound care, including warm compresses, and the administration of intravenous antibiotics (penicillins or cephalosporins).

• Breast infections may be chronic, possibly with recurrent abscess formation. • In this situation, cultures are taken to identify acid-fast bacilli, anaerobic and aerobic bacteria, and

fungi. • Uncommon organisms may be encountered and long-term antibiotic therapy may be required.

INFECTIOUS AND INFLAMMATORY DISORDERS OF THE BREAST

Hidradenitis Suppurativa• Hidradenitissuppurativa. Hidradenitis suppurativa of the nipple-

areolacomplex or axilla is a chronic inflammatory condition that originates within the accessory areolar glands of Montgomery or within the axillary sebaceous glands.

• When located in and about the nipple-areola complex, this disease may mimic other chronic inflammatory states, Paget disease of the nipple, or invasive breast cancer.

• Involvement of the axillary skin is often multifocal and contiguous. • Antibiotic therapy with incision and drainage of fluctuant areas is

appropriate treatment.• Complete excision of the involved areas may be required and may

necessitate coverage with advancement flaps or split-thickness skin grafts.

INFECTIOUS AND INFLAMMATORY DISORDERS OF THE BREAST

Mondor's Disease• Mondor’s disease. This variant of thrombophlebitis involves the superficial veins

of the anterior chest wall and breast. • In 1939, Mondor described the condition as “string phlebitis,” a thrombosed vein

presenting as a tender, cord- like structure. • Typically, a woman presents with acute pain in the lateral aspect of the breast or

the anterior chest wall. • A tender, firm cord is found to follow the distribution of one of the major

superficial veins. • Most women have no evidence of thrombophlebitis in other anatomic sites. • When the diagnosis is uncertain, or when a mass is present near the tender cord,

biopsy is indicated. • Therapy for Mondor disease includes the liberal use of antiinflammatory

medications and warm compresses that are applied along the symptomatic vein. • Restriction of motion of the ipsilateral extremity and shoulder and brassiere

support of the breast are important. • The process usually resolves within 4–6 weeks. When symptoms persist or are

refractory to therapy, excision of the involved vein segment is appropriate.

RISK FACTORS FOR BREAST CANCER

Hormonal Risk Factors•Increased exposure to estrogen is associated with an increased risk for developing breast cancer, whereas reducing exposure is thought to be protective •Correspondingly, factors that increase the number of menstrual cycles, such as early menarche, nulliparity, and late menopause, are associated with increased risk•Moderate levels of exercise and a longer lactation period, factors that decrease the total number of menstrual cycles, are protective. •Older age at first live birth is associated with an increased risk of breast cancer.•There is an association between obesity and increased breast cancer risk

RISK FACTORS FOR BREAST CANCER

• Nonhormonal Risk Factors • Radiation (radiation therapy for Hodgkin's

lymphoma have a breast cancer risk that is 75 times greater)

• Studies also suggest that the risk of breast cancer increases as the amount of alcohol a woman consumes increases.

• high fat content diet

Risk Assessment

• The average lifetime risk of breast cancer for newborn U.S. females is 12%.

• A software program incorporating the Gail model is available from the National Cancer Institute at http://bcra.nci.nih.gov/brc.

• Claus and colleagues

Factors Associated with Increased Risk of Breast Cancer

• White • Older • Family history; Breast cancer in mother, sister, or daughter (especially

bilateral or premenopausal) • BRCA1 or BRCA2 mutation • Endometrial cancer• Proliferative forms of fibrocystic disease• Cancer in other breast • Early menarche (under age 12)• Late menopause (after age 50) • Nulliparous or late first pregnancy

screening mammography• Routine use of screening mammography in women 50 years of age

reduces mortality from breast cancer by 33%. • This reduction comes without substantial risks and at an acceptable

economic cost. • However, the use of screening mammography in women <50 years of age

is more controversial for several reasons: (a) breast density is greater and screening mammography is less likely to detect early breast cancer; (b) screening mammography results in more false-positive test findings, which results in unnecessary biopsies; and (c) younger women are less likely to have breast cancer, so fewer young women will benefit from screening.

• Current recommendations are that women undergo baseline mammography at age 35 and then have annual mammographic screening beginning at age 40.

Incidence of Sporadic, Familial, and Hereditary Breast Cancer

• Sporadic breast cancer 65–75%• Familial breast cancer 20–30%• Hereditary breast cancer 5–10%

BRCA1 a 45% BRCA2 35%

• p53a (Li-Fraumeni syndrome) 1%• STK11/LKB1a (Peutz-Jeghers syndrome) <1%• PTENa (Cowden disease) <1%• MSH2/MLH1a (Muir-Torre syndrome) <1%• ATMa (Ataxia-telangiectasia) <1%• Unknown 20% Both BRCA1 and BRCA2 function as tumor-suppressor genes, and for each gene, loss of both

alleles is required for the initiation of cancer.

BRCA MutationsBRCA1

• Five to 10% of breast cancers are caused by inheritance of germline mutations such as BRCA1 and BRCA2, which are inherited in an autosomal dominant fashion with varying penetrance

• BRCA1 is located on chromosome arm 17q, spans a genomic region of approximately 100 kilobases (kb) of DNA, and contains 22 coding exons

• Data accumulated since the isolation of the BRCA1 gene suggest a role in transcription, cell-cycle control, and DNA damage repair pathways.

• More than 500 sequence variations in BRCA1 have been identified.

• predisposing genetic factor in as many as 45% of hereditary breast cancers and in at least 80% of hereditary ovarian cancers.

• Female mutation carriers have up to a 90% lifetime risk for developing breast cancer and up to a 40% lifetime risk for developing ovarian cancer

• Approximately 50% of children of carriers inherit the trait.

• In general, BRCA1-associated breast cancers are invasive ductal carcinomas, are poorly differentiated, and are hormone receptor negative.

• BRCA1-associated breast cancers have a number of distinguishing clinical features, such as an early age of onset compared with sporadic cases; a higher prevalence of bilateral breast cancer; and the presence of associated cancers in some affected individuals, specifically ovarian cancer and possibly colon and prostate cancers.

BRCA2

• BRCA2 is located on chromosome arm 13q and spans a genomic region of approximately 70 kb of DNA. The 11.2-kb coding region contains 26 coding exons

• The biologic function of BRCA2 is not well defined, but like BRCA1, it is postulated to play a role in DNA damage response pathways.

• BRCA2 messenger RNA also is expressed at high levels in the late G1 and S phases of the cell cycle.

• The mutational spectrum of BRCA2 is not as well established as that of BRCA1. To date, >250 mutations have been found

• The breast cancer risk for BRCA2 mutation carriers is close to 85%, and the lifetime ovarian cancer risk, while lower than for BRCA1, is still estimated to be close to 20%.

• Breast cancer susceptibility in BRCA2 families is an autosomal dominant trait and has a high penetrance.

• Approximately 50% of children of carriers inherit the trait.• Unlike male carriers of BRCA1 mutations, men with germline

mutations in BRCA2 have an estimated breast cancer risk of 6%, which represents a 100-fold increase over the risk in the general male population.

• BRCA2- associated breast cancers are invasive ductal carcinomas, which are more likely to be well differentiated and to express hormone receptors than are BRCA1-associated breast cancers.

• BRCA2-associated breast cancer has a number of distinguishing clinical features, such as an early age of onset compared with sporadic cases, a higher prevalence of bilateral breast cancer, and the presence of associated cancers in some affected individuals, specifically ovarian, colon, prostate, pancreatic, gallbladder, bile duct, and stomach cancers, as well as melanoma.

• The 6174delT mutation is found in Ashkenazi Jews with a prevalence of 1.2%. Another BRCA2 founder mutation, 999del5, is observed in Icelandic and Finnish populations.

CANCER PREVENTION FOR BRCA MUTATION CARRIERS

• Risk management strategies for BRCA1 and BRCA2 mutation carriers include the following:

1. Prophylactic mastectomy and reconstruction2. Prophylactic oophorectomy and hormone

replacement therapy3. Intensive surveillance for breast and ovarian cancer4. Chemoprevention

Chemoprevention• Despite a 49% reduction in the incidence of breast cancer in high-risk

women taking tamoxifen, it is too early to recommend the use of tamoxifen uniformly for BRCA mutation carriers.

• Cancers arising in BRCA1 mutation carriers are usually high grade and are most often hormone receptor negative.

• Approximately 66% of BRCA1-associated DCIS lesions are estrogen receptor negative, which suggests early acquisition of the hormoneindependent phenotype. Tamoxifen appears to be more effective at preventing estrogen receptor–positive breast cancers.

EPIDEMIOLOGY AND NATURAL HISTORY OF BREAST CANCER

• Breast cancer is the most common site-specific cancer in women and is the leading cause of death from cancer for women aged 20 to 59 years

PRIMARY BREAST CANCER

• More than 80% of breast cancers show productive fibrosis that involves the epithelial and stromal tissues.

• With growth of the cancer and invasion of the surrounding breast tissues, the accompanying desmoplastic response entraps and shortens Cooper's suspensory ligaments to produce a characteristic skin retraction.

• Localized edema (peau d'orange) develops when drainage of lymph fluid from the skin is disrupted.

• With continued growth, cancer cells invade the skin, and eventually ulceration occurs. As new areas of skin are invaded, small satellite nodules appear near the primary ulceration.

• 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

AXILLARY LYMPH NODE METASTASES

• As the size of the primary breast cancer increases, some cancer cells are shed into cellular spaces and transported via the lymphatic network of the breast to the regional lymph nodes, especially the axillary lymph nodes. Lymph nodes that contain metastatic cancer are at first ill defined and soft but become firm or hard with continued growth of the metastatic cancer.

• the most important prognostic correlate of disease-free and overall survival is axillary lymph node status

DISTANT METASTASES• At approximately the twentieth cell doubling, breast cancers acquire their

own blood supply (neovascularization). • Thereafter, cancer cells may be shed directly into the systemic venous

blood to 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.

• These cells are scavenged by natural killer lymphocytes and macrophages. • Successful implantation of metastatic foci from breast cancer predictably

occurs after the primary cancer exceeds 0.5 cm in diameter, which corresponds to the twenty-seventh cell doubling.

• Common sites of involvement, in order of frequency, are bone, lung, pleura, soft tissues, and liver.

HISTOPATHOLOGY OF BREAST CANCER

• Carcinoma in Situ1. LOBULAR CARCINOMA IN SITU2. DUCTAL CARCINOMA IN SITU

• Invasive Breast Carcinoma1. Paget's disease of the nipple2. Invasive ductal carcinoma3. Adenocarcinoma with productive fibrosis (scirrhous, simplex, NST), 80% (invasive ductal

carcinoma of no special type)4. Medullary carcinoma, 4%5. Mucinous (colloid) carcinoma, 2%6. Papillary carcinoma, 2%7. Tubular carcinoma, 2%8. Invasive lobular carcinoma, 10%9. Rare cancers (adenoid cystic, squamous cell, apocrine)

Carcinoma in Situ• Cancer cells are in situ or invasive depending on whether or not they

invade through the basement membrane • Foote and Stewart published a landmark description of LCIS, which

distinguished it from DCIS • In the late 1960s, Gallagher and Martin published their study of whole-

breast sections and described a stepwise progression from benign breast tissue to in situ cancer and subsequently to invasive cancer. They coined the term minimal breast cancer (LCIS, DCIS, and invasive cancers smaller than 0.5 cm in size) and stressed the importance of early detection

• It is now recognized that each type of minimal breast cancer has a distinct clinical and biologic behavior.

Lobular Carcinoma In Situ• LCIS originates from the terminal duct lobular units and develops

only in the female breast. It is characterized by distention and distortion of the terminal duct lobular units

• LCIS may be observed in breast tissues that contain microcalcifications, but the calcifications associated with LCIS typically occur in adjacent tissues. This neighborhood calcification is a feature that is unique to LCIS and contributes to its diagnosis.

• The frequency of LCIS in the general population cannot be reliably determined because it usually presents as an incidental finding.

• The average age at diagnosis is 45 years, which is approximately 15 to 25 years younger than the age at diagnosis for invasive breast cancer.

Lobular Carcinoma In Situ• Invasive breast cancer develops in 25% to 35% of women with LCIS. • Invasive cancer may develop in either breast, regardless of which

breast harbored the initial focus of LCIS, and is detected synchronously with LCIS in 5% of cases.

• In women with a history of LCIS, up to 65% of subsequent invasive cancers are ductal, not lobular, in origin. For these reasons, LCIS is regarded as a marker of increased risk for invasive breast cancer rather than as an anatomic precursor.

• Individuals should be counseled regarding their risk of developing breast cancer and appropriate risk reduction strategies, including observation with screening, chemoprevention, and risk-reducing bilateral mastectomy.

Ductal Carcinoma In Situ.

• Published series suggest a detection frequency of 7% in all biopsy tissue specimens.

• DCIS, which carries a high risk for progression to an invasive cancer.• Histologically, DCIS is characterized by a proliferation of the epithelium that

lines the minor ducts, resulting in papillary growths within the duct lumina. • papillary growth pattern, cribriform growth pattern, solid growth pattern,

comedo growth pattern, • Calcium deposition occurs in the areas of necrosis and is a common feature

seen on mammography.

*Figure From: The Breast. Schwartz's Principles of Surgery, 10e, 2014

Ductal Carcinoma In Situ.

• The risk for invasive breast cancer is increased nearly fivefold in women with DCIS

• The invasive cancers are observed in the ipsilateral breast, usually in the same quadrant as the DCIS that was originally detected, which suggests that DCIS is an anatomic precursor of invasive ductal carcinoma

• DCIS is now frequently classified based on nuclear grade and the presence of necrosis

Invasive Breast Carcinoma

• Invasive breast cancers have been described as lobular or ductal in origin• About 80% of invasive breast cancers are described as invasive ductal

carcinoma of no special type (NST). These cancers generally have a worse prognosis than special-type cancers. • Foote and Stewart originally proposed the following classification for

invasive breast cancer.• Paget’s disease of the nipple• Invasive ductal carcinoma—Adenocarcinoma with productive fibrosis (scirrhous, simplex, NST), 80%• Medullary carcinoma, 4%• Mucinous (colloid) carcinoma, 2%• Papillary carcinoma, 2%• Tubular carcinoma, 2%• Invasive lobular carcinoma, 10%• Rare cancers (adenoid cystic, squamous cell, apocrine)

Paget’s disease of the nipple

• Paget’s disease of the nipple was described in 1874. • It frequently presents as a chronic, eczematous eruption of the nipple, which

may be subtle but may progress to an ulcerated, weeping lesion. • Paget’s disease usually is associated with extensive DCIS and may be

associated with an invasive cancer. • A palpable mass may or may not be present. • A nipple biopsy specimen will show a population of cells that are identical to

the underlying DCIS cells (pagetoid features or pagetoid change). Pathognomonic of this cancer is the presence of large, pale, vacuolated cells (Paget cells) in the rete pegs of the epithelium. Paget’s disease may be confused with superficial spreading melanoma. Differentiation from pagetoid intraepithelial melanoma is based on the presence of S-100 antigen immunostaining in melanoma and carcinoembryonic antigen immunostaining in Paget’s disease. • Surgical therapy for Paget’s disease may involve lumpectomy or mastectomy,

depending on the extent of involvement of the nipple-areolar complex and the presence of DCIS or invasive cancer in the underlying breast parenchyma.

Invasive ductal carcinoma

• Invasive ductal carcinoma of the breast with productive fibrosis (scirrhous, simplex, NST) accounts for 80% of breast cancers and presents with macroscopic or microscopic axillary lymph node metastases in up to 25% of screen-detected cases and up to 60% of symptomatic cases. • This cancer occurs most frequently in perimenopausal or

postmenopausal women in the fifth to sixth decades of life as a solitary, firm mass. • It has poorly defined margins and its cut surfaces show a central

stellate configuration with chalky white or yellow streaks extending into surrounding breast tissues. • In a large patient series, 75% of ductal cancers showed estrogen

receptor expression.

Invasive lobular carcinoma

• Invasive lobular carcinoma accounts for 10% of breast cancers. • Special stains may confirm the presence of intracytoplasmic mucin,

which may displace the nucleus (signet-ring cell carcinoma). • At presentation, invasive lobular carcinoma varies from clinically

inapparent carcinomas to those that replace the entire breast with a poorly defined mass. • It is frequently multifocal, multicentric, and bilateral. Because of its

insidious growth pattern and subtle mammographic features, invasive lobular carcinoma may be difficult to detect. • Over 90% of lobular cancers express estrogen receptor.

DIAGNOSIS OF BREAST CANCER

• In~30% of cases, the woman discovers a lump in her breast. Other less frequent presenting signs and symptoms of breast cancer include: • (a) breast enlargement or asymmetry; • (b) nipple changes, retraction, or discharge; • (c) ulceration or erythema of the skin of the breast; • (d) an axillary mass; and • (e) musculoskeletal discomfort.

• Breast pain usually is associated with benign disease.• Diagnosis of breast cancer;

• Examination• Imaging Techniques; Mammography, Ductography, Ultrasonography, Magnetic Resonance

Imaging

• Breast Biopsy;

Examination

• Symmetry, size, and shape of the breast are recorded, as well as any evidence of edema (peaud’orange), nipple or skin retraction, or erythema. • Careful palpation of supraclavicular and

parasternal sites also is performed. • A diagram of the chest and contiguous lymph

node sites is useful for recording location, size, consistency, shape, mobility, fixation, and other characteristics of any palpable breast mass or lymphadenopathy

Imaging Techniques; Mammography

• Mammography has been used in North America since the 1960s• Conventional mammography delivers a radiation dose of 0.1 cGy per study.

By comparison, chest radiography delivers 25% of this dose. However, there is no increased breast cancer risk associated with the radiation dose delivered with screening mammography. • Screening mammography is used to detect unexpected breast cancer in

asymptomatic women. In this regard, it supplements history taking and physical examination. • With screening mammography, two views of the breast are obtained, the

craniocaudal (CC) view and the mediolateral oblique (MLO) view. The MLO view images the greatest volume of breast tissue, including the upper outer quadrant and the axillary tail of Spence. • Compared with the MLO view, the CC view provides better visualization of

the medial aspect of the breast and permits greater breast compression. • Diagnostic mammography is used to evaluate women with abnormal findings

such as a breast mass or nipple discharge.

Imaging Techniques; Mammography

• Spot compression may be done in any projection by using a small compression device, which is placed directly over a mammographic abnormality that is obscured by overlying tissues.• The compression device minimizes motion artifact, improves

definition, separates overlying tissues, and decreases the radiation dose needed to penetrate the breast. • Magnification techniques (×1.5) often are combined with spot

compression to better resolve calcifications and the margins of masses. • Mammography also is used to guide interventional procedures,

including needle localization and needle biopsy.• Specific mammographic features that suggest a diagnosis of breast

cancer include a solid mass with or without stellate features, asymmetric thickening of breast tissues, and clustered microcalcifications

Imaging Techniques; Mammography

• These microcalcifications are an especially important sign of cancer in younger women, in whom it may be the only mammographic abnormality. • The clinical impetus for screening mammography came from the

Health Insurance Plan study and the Breast Cancer Detection Demonstration Project, which demonstrated a 33% reduction in mortality for women after screening mammography.• Current guidelines of the National Comprehensive Cancer Network

suggest that normal-risk women ≥20 years of age should have a breast examination at least every 3 years. • Starting at age 40 years, breast examinations should be performed

yearly and a yearly mammogram should be taken. • The benefits from screening mammography in women ≥50 years of

age has been noted above to be between 20% and 25% reduction in breast cancer mortality

Imaging Techniques; Mammography

• The use of screening mammography in women <50 years of age is more controversial again for reasons noted above: (a) reduced sensitivity; (b) reduced specificity; and (c) lower incidence of breast cancer. • For the combination of these three reasons targeting mammography

screening to women <50 years at higher risk of breast cancer improves the balance of risks and benefits and is the approach some health care systems have taken.

Imaging Techniques; Ductography

• The primary indication for ductography is nipple discharge, particularly when the fluid contains blood. • Radiopaque contrast media is injected into one or more of the major

ducts and mammography is performed. • A duct is gently enlarged with a dilator and then a small, blunt

cannula is inserted under sterile conditions into the nipple ampulla. • With the patient in a supine position, 0.1 to 0.2 mL of dilute contrast

media is injected and CC and MLO mammographic views are obtained without compression. • Intraductal papillomas are seen as small filling defects surrounded by

contrast media. • Cancers may appear as irregular masses or as multiple intraluminal

filling defects.

Imaging Techniques; Ultrasonography

• Second only to mammography in frequency of use for breast imaging, ultrasonography is an important method of resolving equivocal mammographic findings, defining cystic masses, and demonstrating the echogenic qualities of specific solid abnormalities.• Benign breast masses usually show smooth contours, round or oval

shapes, weak internal echoes, and well-defined anterior and posterior margins. Breast cancer characteristically has irregular walls but may have smooth margins with acoustic enhancement.• Ultrasonography is used to guide fine-needle aspiration biopsy, core-

needle biopsy, and needle localization of breast lesions.• Ultrasonography can also be utilized to image the regional lymph

nodes in patients with breast cancer.

Imaging Techniques; Magnetic Resonance Imaging

• In the process of evaluating magnetic resonance imaging (MRI) as a means of characterizing mammographic abnormalities, additional breast lesions have been detected. However, in the circumstance of negative findings on both mammography and physical examination, the probability of a breast cancer being diagnosed by MRI is extremely low. • There is current interest in the use of MRI to screen the breasts of high-risk

women and of women with a newly diagnosed breast cancer. 1) women who have a strong family history of breast cancer or who carry known genetic mutations require screening at an early age, because mammographic evaluation is limited due to the increased breast density in younger women. 2) an MRI study of the contralateral breast in women with a known breast cancer has shown a contralateral breast cancer in 5.7% of these women. • MRI can also detect additional tumors in the index breast (multifocal or

multicentric disease) that may be missed on routine breast imaging and this may alter surgical decision making. In fact, MRI has been advocated by some for routine use in surgical treatment planning based on the fact that additional disease can be identified with this advanced imaging modality and the extent of disease may be more accurately assessed.

Breast Biopsy, Nonpalpable Lesions.

• Image-guided breast biopsy specimens are frequently required to diagnose nonpalpable lesions.• Ultrasound localization techniques are used when a mass is present,

whereas stereotactic techniques are used when no mass is present (microcalcifications or architectural distortion only). • The combination of diagnostic mammography, ultrasound or

stereotactic localization, and fine-needle aspiration (FNA) biopsy achieves almost 100% accuracy in the preoperative diagnosis of breast cancer.• The advantages of core-needle biopsy include a low complication

rate, minimal scarring, and a lower cost compared with excisional breast biopsy.

Breast Biopsy, Palpable Lesions.

• FNA or core biopsy of a palpable breast mass can usually be performed in an outpatient setting.• A 1.5-in, 22-gauge needle attached to a 10-mL syringe or a 14 gauge core

biopsy needle is used.• The cellular material is then expressed onto microscope slides. Both air-

dried and 95% ethanol–fixed microscopic sections are prepared for analysis• Automated devices also are available. Vacuum assisted core biopsy devices

(with 8–10 gauge needles) are commonly utilized with image guidance where between 4 and 12 samples can be acquired at different positions within a mass, area of architectural distortion or microcalcifications. If the target lesion was microcalcifications, the specimen should be radiographed to confirm appropriate sampling. A radiopaque marker should be placed at the site of the biopsy to mark the area for future intervention• Tissue specimens are placed in formalin and then processed to paraffin

blocks

Examination

• INSPECTION • PALPATION

BREAST CANCER STAGING• The clinical stage of breast cancer is determined primarily through physical

examination of the skin, breast tissue, and regional lymph nodes (axillary, supraclavicular, and cervical).

• Mammography, chest radiography, and intraoperative findings (primary tumor size, chest wall invasion) also provide necessary staging information.

• Pathologic stage combines the findings from pathologic examination of the resected primary breast cancer and axillary or other regional lymph nodes.

• A frequently used staging system is the TNM (tumor, nodes, and metastasis) system.

• The single most important predictor of 10- and 20-year survival rates in breast cancer is the number of axillary lymph nodes involved with metastatic disease.

• Routine biopsy of internal mammary lymph nodes is not generally performed; however, with the advent of sentinel lymph node dissection and the use of preoperative lymphoscintigraphy for localization of the sentinel nodes, surgeons have begun to biopsy the internal mammary nodes in some cases

SURGICAL TECHNIQUES IN BREAST CANCER THERAPY

• Breast Conservation • Mastectomy and Axillary Dissection • MODIFIED RADICAL MASTECTOMY

Breast Conservation • Breast conservation involves resection of the primary breast cancer with a margin of

normal-appearing breast tissue, adjuvant radiation therapy, and assessment of regional lymph node status.

• Resection of the primary breast cancer is alternatively called segmental mastectomy, lumpectomy, partial mastectomy, wide local excision, and tylectomy. For many women with stage I or II breast cancer, breast-conserving therapy (BCT) is preferable to total mastectomy because BCT produces survival rates equivalent to those after total mastectomy while preserving the breast

• BCT allows for preservation of breast shape and skin as well as preservation of sensation, and provides an overall psychologic advantage associated with breast preservation.

• Breast conservation surgery is currently the standard treatment for women with stage 0, I, or II invasive breast cancer. Women with DCIS require only resection of the primary cancer and adjuvant radiation therapy without assessment of regional lymph nodes.

• Sentinel lymph node dissection is now the preferred staging procedure with a clinically node-negative axilla

Oncoplastic techniques are of prime consideration when

(a) a significant area of breast skin will need to be resected with the specimen to achieve negative margins; (b) a large volume ofbreast parenchyma will be resected resulting in a significant defect; (c) the tumor is located between the nipple and the inframammary fold, an area often associated with unfavorable cosmetic outcomes; or (d) excision of the tumor and closure of the breast may result in malpositioning of the nipple.

Mastectomy and Axillary Dissection

• A skin-sparing mastectomy removes all breast tissue, the nipple-areola complex, and scars from any prior biopsy procedures. There is a recurrence rate of less than 6 to 8%, comparable to the long-term recurrence rates reported with standard mastectomy, when skin-sparing mastectomy is used for patients with T1 to T3 cancers.

• A total (simple) mastectomy without skin sparing removes all breast tissue, the nipple-areola complex, and skin.

• An extended simple mastectomy removes all breast tissue, the nipple-areola complex, skin, and the level I axillary lymph nodes.

• The Halsted radical mastectomy removes all breast tissue and skin, the nipple-areola complex, the pectoralis major and pectoralis minor muscles, and the level I, II, and III axillary lymph nodes.

• The use of systemic chemotherapy and hormonal therapy as well as adjuvant radiation therapy for breast cancer have nearly eliminated the need for the radical mastectomy.

MODIFIED RADICAL MASTECTOMY

• A modified radical mastectomy preserves both the pectoralis major and pectoralis minor muscles, allowing removal of level I and level II axillary lymph nodes but not the level III (apical) axillary lymph nodes

• Anatomic boundaries of the modified radical mastectomy are the anterior margin of the latissimus dorsi muscle laterally, the midline of the sternum medially, the subclavius muscle superiorly, and the caudal extension of the breast 2 to 3 cm inferior to the inframammary fold inferiorly

• The most lateral extent of the axillary vein is identified and the areolar tissue of the lateral axillary space is elevated as the vein is cleared on its anterior and inferior surfaces.

• The long thoracic nerve of Bell is identified and preserved as it travels in the investing fascia of the serratus anterior muscle. Every effort is made to preserve this nerve, because permanent disability with a winged scapula and shoulder weakness will follow denervation of the serratus anterior muscle.

• Care is taken to preserve the thoracodorsal neurovascular bundle.

In Situ Breast Cancer (Stage 0)• Both LCIS and DCIS may be difficult to distinguish from atypical hyperplasia or from

cancers with early invasion. Expert pathologic review is required in all cases.• Bilateral mammography is performed to determine the extent of the in situ

cancer and to exclude a second cancer. Because LCIS is considered a marker for increased risk rather than an inevitable precursor of invasive disease, the current treatment options for LCIS include observation, chemoprevention with tamoxifen, and bilateral total mastectomy.

• There is no benefit to excising LCIS, because the disease diffusely involves both breasts

• in many cases and the risk of invasive cancer is equal for both breasts. The use of tamoxifen as a risk reduction strategy should

• be considered in women with a diagnosis of LCIS.

In Situ Breast Cancer (Stage 0)• Women with DCIS and evidence of extensive disease (>4 cm of disease or

disease in more than one quadrant) usually require mastectomy.• For women with limited disease, lumpectomy and radiation therapy are

recommended.• For nonpalpable DCIS, needle localization techniques are used to guide

the surgical resection. Specimen mammography is performed to ensure that all visible evidence of cancer is excised

• The gold standard against which breast conservation therapy for DCIS is evaluated is mastectomy. Women treated with mastectomy have local recurrence and mortality rates of <2%. Women treated with lumpectomy and adjuvant radiation therapy have a similar mortality rate, but the local recurrence rate increases to 9%.

• Forty-five percent of these recurrences will be invasive cancer when radiation therapy is not used.

Early Invasive Breast Cancer (Stage I, IIA, or IIB)

• the disease-free, distant disease-free, and overall survival rates for lumpectomy with or without radiation therapy were similar to those observed after total mastectomy.

• However, the incidence of ipsilateral breast cancer recurrence (in-breast recurrence) was higher in the lumpectomy group not receiving radiation therapy. (39.2% & 14.3%)

• These findings supported the use of lumpectomy and radiation therapy in the treatment of stage I and II breast cancer.

• Currently, mastectomy with assessment of axillary lymph node status and breast conserving surgery with assessment of axillary lymph node status and radiation therapy are considered equivalent treatments for patients with stage I and II breast cancer.

• Axillary lymphadenopathy confirmed to be metastatic disease or metastatic disease in a sentinel lymph node necessitates an axillary lymph node dissection.

Relative contraindications to breast conservation therapy

• (a) prior radiation therapy to the breast or chest wall,

• (b) involved surgical margins or unknown margin status after re-excision,

• (c) multicentric disease, and • (d) scleroderma or lupus erythematosus.

• Traditionally, dissection of the level I and II axillary lymph nodes has been performed in early invasive breast cancer.

• Sentinel lymph node dissection is now considered the standard for evaluation of the axillary lymph node status in women who have clinically negative lymph nodes.

• Candidates for this procedure have clinically uninvolved axillary lymph nodes with a T1 or T2 primary breast cancer. Controversy remains about the suitability of sentinel node dissection in women with larger primary tumors (T3) and those treated with neoadjuvant chemotherapy

Advanced Local-Regional Breast Cancer (Stage IIIA or IIIB)

• Women with stage IIIA and IIIB breast cancer have advanced local-regional breast cancer but have no clinically detected distant metastases.

• surgery is integrated with radiation therapy and chemotherapy

• Surgical therapy for women with stage III disease is usually a modified radical mastectomy, followed by adjuvant radiation therapy. Chemotherapy is used to maximize distant disease-free survival, whereas radiation therapy is used to maximize local-regional disease-free survival. In selected patients with stage IIIA cancer, neoadjuvant (preoperative) chemotherapy can reduce the size of the primary cancer and permit breast-conserving surgery.

Distant Metastases (Stage IV)• Treatment for stage IV breast cancer is not curative but may prolong

survival and enhance a woman's quality of life • Hormonal therapies that are associated with minimal toxicity are

preferred to cytotoxic chemotherapy. • Appropriate candidates for initial hormonal therapy include women with

hormone receptor–positive 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 receptor–negative cancers, symptomatic visceral metastases, and hormone-refractory metastases.

SPECIAL CLINICAL SITUATIONS• Nipple Discharge

UNILATERAL NIPPLE DISCHARGE BILATERAL NIPPLE DISCHARGE

• Axillary Lymph Node Metastases in the Setting of an Unknown Primary Cancer • Breast Cancer during Pregnancy • Male Breast Cancer • Phyllodes Tumors • Inflammatory Breast Carcinoma• Rare Breast Cancers

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

Nipple DischargeUNILATERAL NIPPLE DISCHARGE

• Nipple discharge is a finding that can be seen in a number of clinical situations. • It may be suggestive of cancer if it is spontaneous, unilateral, localized to a single

duct, present in women 40 years of age, bloody, or associated with a mass • mammography and ultrasound are indicated for further evaluation. • A ductogram also can be useful and is performed by cannulating a single discharging

duct with a small nylon catheter or needle and injecting 1.0 mL of watersoluble contrast solution.

• Nipple discharge associated with a cancer may be clear, bloody, or serous. Testing for the presence of hemoglobin is helpful, but hemoglobin may also be detected when nipple discharge is secondary to an intraductal papilloma or duct ectasia.

• Definitive diagnosis depends on excisional biopsy of the offending duct and any associated mass lesion

• Another approach is to inject methylene blue dye within the duct after ductography. • Needle localization biopsy is performed when there is an associated mass that lies

>2.0 to 3.0 cm from the nipple.

Nipple DischargeBILATERAL NIPPLE DISCHARGE

• Nipple discharge is suggestive of a benign condition if it is bilateral and multiductal in origin, occurs in women 39 years of age, or is milky or blue-green.

• Prolactin-secreting pituitary adenomas are responsible for bilateral nipple discharge in <2% of cases.

• If serum prolactin levels are repeatedly elevated, plain radiographs of the sella turcica are indicated and thin section CT scan is required.

• Optical nerve compression, visual field loss, and infertility are associated with large pituitary adenomas.

Axillary Lymph Node Metastases in the Setting of an Unknown Primary Cancer

• A woman who presents with an axillary lymph node metastasis that is consistent with a breast cancer metastasis has a 90% probability of harboring an occult breast cancer

• However, axillary lymphadenopathy is the initial presenting sign in only 1% of breast cancer patients.

• Fine-needle aspiration biopsy, core-needle biopsy, or open biopsy of an enlarged axillary lymph node is performed to confirm metastatic disease.

• When metastatic cancer is found, immunohistochemical analysis may classify the cancer as epithelial, melanocytic, or lymphoid in origin.

• The presence of hormone receptors (estrogen or progesterone receptors) suggests metastasis from a breast cancer but is not diagnostic.

Axillary Lymph Node Metastases in the Setting of an Unknown Primary Cancer

• The search for a primary cancer includes careful examination of the thyroid, breast, and pelvis, including the rectum.

• The breast should be examined with diagnostic mammography, ultrasonography, and MRI to evaluate for an occult primary lesion.

• Further radiologic and laboratory studies should include chest radiography and liver function studies. Chest, abdominal, and pelvic CT scans also are indicated, as is a bone scan to rule out distant metastasis.

• Suspicious findings on mammography, ultrasonography, or MRI necessitate breast biopsy.

• When a breast cancer is found, treatment consists of an axillary lymph node dissection with a mastectomy or preservation of the breast followed by whole-breast radiation therapy.

• Chemotherapy and endocrine therapy should be considered.

Breast Cancer during Pregnancy• Breast cancer occurs in 1 of every 3000 pregnant women, and axillary

lymph node metastases are present in up to 75% of these women • The average age of the pregnant woman with breast cancer is 34 years.• Fewer than 25% of the breast nodules developing during pregnancy and

lactation will be cancerous. • Ultrasonography and needle biopsy are used in the diagnosis of these

nodules. • Open biopsy may be required. • Mammography is rarely indicated because of its decreased sensitivity

during pregnancy and lactation; however, the fetus can be shielded if mammography is needed.

Breast Cancer during Pregnancy

• Approximately 30% of the benign conditions encountered will be unique to pregnancy and lactation (galactoceles, lobular hyperplasia, lactating adenoma, and mastitis or abscess).

• Once a breast cancer is diagnosed, complete blood count, chest radiography (with shielding of the abdomen), and liver function studies are performed.

Breast Cancer during Pregnancy

• Because of the potential deleterious effects of radiation therapy on the fetus, radiation cannot be considered until the fetus is delivered.

• A modified radical mastectomy can be performed during the first and second trimesters of pregnancy, even though there is an increased risk of spontaneous abortion after first-trimester anesthesia.

• During the third trimester, lumpectomy with axillary node dissection can be considered if adjuvant radiation therapy is deferred until after delivery.

• Lactation is suppressed.

Breast Cancer during Pregnancy• Chemotherapy administered during the first trimester carries a risk of

spontaneous abortion and a 12% risk of birth defects.• There is no evidence of teratogenicity resulting from administration of

chemotherapeutic agents in the second and third trimesters.• For this reason, many clinicians now consider the optimal strategy to be

delivery of chemotherapy in the second and third trimesters as a neoadjuvant approach, which allows local therapy decisions to be made after the delivery of the baby.

• Pregnant women with breast cancer often present at a later stage of disease because breast tissue changes that occur in the hormone-rich environment of pregnancy obscure early cancers.

• However, pregnant women with breast cancer have a prognosis, stage by stage, that is similar to that of nonpregnant women with breast cancer.

Male Breast Cancer

• Fewer than 1% of all breast cancers occur in men.• Breast cancer is rarely seen in young males and has a peak

incidence in the sixth decade of life. • A firm, nontender mass in the male breast requires

investigation. Skin or chest wall fixation is particularly worrisome.

• It is associated with radiation exposure, estrogen therapy, testicular feminizing syndromes, and Klinefelter's syndrome (XXY ).

• DCIS makes up <15% of male breast cancer, whereas infiltrating ductal carcinoma makes up >85%.

Male Breast Cancer• Male breast cancer is staged in the same way as female breast cancer, and stage

by stage, men with breast cancer have the same survival rate as women. • Overall, men do worse because of the advanced stage of their cancer (stage III or

IV) at the time of diagnosis. • The treatment of male breast cancer is surgical, with the most common procedure

being a modified radical mastectomy. • Sentinel node dissection has been shown to be feasible and accurate for nodal

assessment in men presenting with a clinically node-negative axillary nodal basin.• Adjuvant radiation therapy is appropriate in cases in which there is a high risk for

local-regional recurrence. • Eighty percent of male breast cancers are hormone receptor positive, and

adjuvant tamoxifen is considered. • Systemic chemotherapy is considered for men with hormone receptor–negative

cancers and for men with large primary tumors, multiple positive nodes, and locally advanced disease.

Phyllodes Tumors• These tumors are classified as

benign, borderline, or malignant. Borderline tumors have a greater potential for local recurrence.

• Phyllodes tumors are usually sharply demarcated from the surrounding breast tissue, which is compressed and distorted.

• The stroma of a phyllodes tumor generally has greater cellular activity than that of a fibroadenoma.

• Evaluation of the number of mitoses and the presence or absence of invasive foci at the tumor margins may help to identify a malignant tumor

Phyllodes Tumors

• Small phyllodes tumors are excised with a margin of normal-appearing breast tissue. When the diagnosis of a phyllodes tumor with suspicious malignant elements is made, re-excision of the biopsy site to ensure complete excision of the tumor with a 1-cm margin of normal-appearing breast tissue is indicated

• Large phyllodes tumors may require mastectomy. • Axillary dissection is not recommended because

axillary lymph node metastases rarely occur.

Inflammatory Breast Carcinoma• Inflammatory breast carcinoma

(stage IIIB) accounts for <3% of breast cancers.

• This cancer is characterized by the skin changes of brawny induration, erythema with a raised edge, and edema (peau d'orange)

• Permeation of the dermal lymph vessels by cancer cells is seen in skin biopsy specimens.

• The clinical differentiation of inflammatory breast cancer may be extremely difficult, especially when a locally advanced scirrhous carcinoma invades dermal lymph vessels in the skin to produce peau d'orange and lymphangitis

• Inflammatory breast cancer also may be mistaken for a bacterial infection of the breast. More than 75% of women who have inflammatory breast cancer present with palpable axillary lymphadenopathy, and distant metastases also are frequently present.

• Surgery alone and surgery with adjuvant radiation therapy have produced disappointing results in women with inflammatory breast cancer.

• However, neoadjuvant chemotherapy with a doxorubicin-containing regimen may effect dramatic regressions in up to 75% of cases. In this setting, modified radical mastectomy is performed to remove residual cancer from the chest wall and axilla.

• Adjuvant chemotherapy may be indicated depending on final pathologic assessment of the breast and regional nodes.

Evaluation of breast masses in premenopausal women

Evaluation of breast masses in postmenopausal women

The simplest biopsy methods

• Needle biopsy (FNA cytology, Large-needle (core needle) biopsy )

• Open biopsy IncisionalExcisional