Development and Physiology During adolescence, the breast is composed primarily of dense fibrous stroma

and scattered ducts lined with epithelium.In the breast, this hormone-dependent maturation (thelarche) entails increased deposition of fat, formation of new ducts by branching and elongation, and the first appearance of lobular units.

The postpubertal mature or resting breast contains fat, stroma, lactiferous ducts, and lobular units. During phases of the menstrual cycle or in response to exogenous hormones, the breast epithelium and lobular stroma undergo cyclic stimulation. In the late luteal (premenstrual) phase, there is an accumulation of fluid and intralobular edema. It is probable that this edema produces both pain and breast engorgement.

With pregnancy, there is diminution of the fibrous stroma to accommodate the hyperplasia of the lobular units. This formation of new acini or lobules is termed the adenosis of pregnancy and is influenced by high circulating levels of estrogen and progesterone and by levels of prolactin that steadily increase during gestation.

After birth, there is a sudden loss of the placental hormones. A continued high level of prolactin is the principal trigger for lactation.

Milk line

The protuberant part of the human breast is generally described as overlying the second to the sixth ribs and extending from the lateral border of the sternum to the anterior axillary line.

Actually, a thin layer of mammary tissue extends considerably further, from the clavicle above to the seventh or eighth ribs below and from the midline to the edge of the latissimus dorsi posteriorly.

This fact is important when performing a mastectomy,the aim of which is to remove the whole breast.

The axillary tail of the breast is of surgical importance. In some normal subjects it is palpable and, in a few, it can be seen premenstrually or during lactation.

The lobule is the basic structural unit of the mammary gland.

The number and size of the lobules vary enormously: they are most numerous in young women.

From 10 to over 100 lobules empty via ductules into a lactiferous duct, of which there are 15–20.

The ligaments of Cooper are hollow conical projections of fibrous tissue filled with breast tissue; the apices of the cones are attached firmly to the superficial fascia and thereby to the skin overlying the breast. These ligaments account for the dimpling of the skin overlying a carcinoma.

The areola contains involuntary muscle arranged in concentric rings as well as radially in the subcutaneous tissue.

The areolar epithelium contains numerous sweat glands and sebaceous glands, the latter of which enlarge during pregnancy and serve to lubricate the nipple during lactation (Montgomery’s tubercles).

Near its apex lie the orifices of the lactiferous ducts. The nipple contains smooth muscle fibers arranged concentrically and longitudinally; thus, it is an erectile structure, which points outwards.

The lymphatics of the breast drain predominantly into the axillary and internal mammary lymph nodes. The axillary nodes receive approximately 85% of the drainage and are arranged in the following groups:

• lateral, along the axillary vein;• anterior, along the lateral thoracic vessels;• posterior, along the subscapular vessels;• central, embedded in fat in the centre of the axilla;• interpectoral, a few nodes lying between the pectoralis major and minor muscles;• apical, which lie above the level of the pectoralis minor tendon in continuity with the lateral

nodes and which receive the efferents of all the other groups.The apical nodes are also in continuity with the supraclavicular nodes and drain into the

subclavian lymph trunk, which enters the great veins directly or via the thoracic duct or jugular trunk.

The sentinel node is defined as the first lymph node draining the tumour-bearing area of the breast.

The internal mammary nodes are fewer in number. They lie along the internal mammary vessels deep to the plane of the costal cartilages, drain the posterior third of the breast and are not routinely dissected although they were at one time biopsied for staging.

Triple assessment

In any patient who presents with a breast lump or other symptoms suspicious of carcinoma, the diagnosis should be made by a combination of clinical assessment, radiological imaging and a tissue sample taken for either cytological or histological analysis the so called triple assessment.

Fine-Needle Aspiration

It can be done with a 22-gauge needle, an appropriate size syringe. Its main utility is the differentiation of solid from cystic masses, but it may be done whenever a new dominant, unexplained mass is found in the breast.

A cytologic examination of the aspirated material is performed

This simple procedure is postponed only if mammography is necessary and there is worry that a small hematoma, resulting from needle puncture, might confuse the radiographic evaluation.

Carcinoma will not be missed if a surgical biopsy is done when

(1) needle aspiration produces no cyst fluid and a solid mass is diagnosed,

(2) the cyst fluid produced is thick and blood tinged, and

(3) fluid is produced but the mass fails to resolve completely.

(4)rapid accumulation of fluid after initial aspiration (<2 weeks).

BREAST IMAGING• Breast radiographic imaging is used to detect small, nonpalpable breast

abnormalities, to evaluate clinical findings, and to guide diagnostic procedures.

• Mammography is the most sensitive and specific imaging test currently available, though 10% to 15% of clinically evident breast cancers have no mammographic correlate.

• Screening mammography is performed in efforts to detect breast cancer that is not clinically evident.

• Ultrasonography is not used as a screening tool or in the evaluation of mammographic microcalcifications, but in a directed fashion to evaluate a breast mass and characterize it as cystic or solid.

• Magnetic resonance imaging (MRI) is the imaging method of choice to evaluate implant rupture. It may be used in (occult breast cancer). MRI sensitivity for invasive cancers approaches 100% but is only 60% at best for DCIS.

• Computed tomography appears to be the best way to image internal mammary nodes and to evaluate the chest and axilla after mastectomy.

Mammogram

Magnetic resonance imaging (MRI) is of increasing interest tobreast surgeons in a number of settings:

• It can be useful to distinguish scar from recurrence in women who have had previous breast conservation therapy for cancer (although it is not accurate within 9 months of radiotherapy because of abnormal enhancement).

• It is the best imaging modality for the breasts of women with implants.

• It has proven to be useful as a screening tool in high-risk women (because of family history).

• It is less useful than ultrasound in the management of the axilla in both primary breast cancer and recurrent disease

Magnetic resonance imaging scan of the breasts showing carcinoma of the left breast (arrows). (a) Pre-contrast; (b) postgadolinium

contrast; (c) subtraction image.

Large-Core Needle Biopsy

• LCNB increasingly is the diagnostic method of choice to histologically evaluate nonpalpable mammographic abnormalities. In experienced centers, it is considered the standard of care

ABNORMAL DEVELOPMENT

• Absence of breast tissue (amastia) and absence of the nipple (athelia) are rare anomalies.

• Unilateral rudimentary breast development is much more common, as is adolescent hypertrophy of one breast with lesser development of the other. In contrast, accessory breast tissue (polymastia) and accessory nipples (supernumerary nipples) are both common. Supernumerary nipples are usually rudimentary and occur along the milk line from the axilla to the pubis in both males and females. They may be mistaken for a small mole. However, accessory nipples are removed only for cosmetic reasons.

• True polythelia refers to more than one nipple serving a single breast, which is rare.

Accessory breast• Accessory breast tissue is

commonly located above the breast in the axilla. Rudimentary nipple development may be present, and lactation is possible with more complete development. Accessory breast tissue, which may present as an enlarging mass in the axilla during pregnancy, is treated by surgical removal if it is large or cosmetically deforming, or it is removed to prevent enlargement during future pregnancy.

Supernumerary Nipples

• More common than supernumerary breasts

• Found along milk line• May darken during

pregnancy• Not dangerous

Inverted Nipples• This may occur at puberty or later in life.

Retraction occurring at puberty, also known as simple nipple inversion, is of unknown aetiology (benign horizontal inversion). In about 25% of cases it is bilateral. It may cause problems with breast-feeding and infection can occur, especially during lactation, because of retention of secretions.

• Recent retraction of the nipple may be of considerable pathological significance. A slit-like retraction of the nipple may becaused by duct ectasia and chronic periductal mastitis but circumferential retraction, with or without an underlying lump, may well indicate an underlying carcinoma

ANDI [Aberrations of Normal Development and Involution (ANDI)]

Aetiology

The breast is a dynamic structure that undergoes changes

throughout a woman’s reproductive life and, superimposed upon

this, cyclical changes throughout the menstrual cycle. The pathogenesis of ANDI involves disturbances in the breast physiology extending from a perturbation of normality to well-defined disease processes. There is often

little correlation between the histological appearance of the breast tissue and the symptoms.

Fibrocystic Changes• Fibrocystic condition (FCC), previously referred to as fibrocystic

disease in up to 90% of women. • FCC appears to represent an exaggerated response of breast

stroma and epithelium to anormal level of variety of circulating and locally produced hormones and growth.

• Symptomatically, the condition presents as premenstrual cyclical mastalgia with pain and tenderness .

• Breast examinations range from mild, bilaterally symmetrical alterations in texture ,to nodularity and dense, firm breast tissue with palpable lumps, to the frequent appearance of gross cysts.

• Mammographically, FCC is usually seen as bilaterally symmetrical diffuse or focal radiologically dense tissue.

• Ultrasonography alone may be used in women under 30 years of age.

• By ultrasound, cysts exist in up to one third of women 35 to 50 years of age, with most of these being nonpalpable.

• Because a mass due to fibrocystic condition may be difficult to distinguish from carcinoma on the basis of clinical findings, suspicious lesions should be biopsied.

Clinical presentation of FCC

Painful, often multiple, usually bilateral masses in the breast.

Rapid fluctuation in the size of the masses is common.

Frequently, pain occurs or worsens and size increases during premenstrual phase of cycle.

Most common age is 30–50. Rare in postmenopausal women not receiving hormonal replacement.

Treatment

• Breast pain associated with generalized fibrocystic condition is best treated by avoiding trauma and by wearing a good, supportive brassiere during the night and day.

• Hormone therapy is not advisable similarly, tamoxifen because of their side effects.

• Oil of evening primrose (OEP), a natural form of gamolenic acid, has been shown to decrease pain in 44–58% of users.

• Aspiration of a discrete mass suggestive of a cyst is indicated to alleviate pain and, more importantly, to confirm the cystic nature of the mass. The patient is reexamined at intervals thereafter. If no fluid is obtained by aspiration, if fluid is bloody, if a mass persists after aspiration, or if at any time during follow-up a persistent or recurrent mass is noted, biopsy should be performed.

Breast Cysts

• Cysts within the breast are fluid-filled, epithelium-lined cavities that may vary in size from microscopic to large, palpable masses .

• Cysts are generally discovered by physical examination and confirmed by ultrasound or needle aspiration.

• Most women with new cyst formation are first seen after the age of 35 and rarely before the age of 25 years. Cyst fluid can be straw colored, opaque, dark-greenish, and even contain flecks of debris.

• The only reliable indication for submitting fluid for cytology is the presence of a residual mass after aspiration of the fluid. If the cyst recurs multiple times (more than two times is a reasonable rule), cytology is justified. Finally, surgical removal of a cyst may be indicated if the cytology is suspicious or the cyst recurs multiple times.

Galactocele

• A galactocele is a milk-filled cyst, well circumscribed. It usually occurs after the cessation of lactation or when feeding frequency has been curtailed significantly.

• The pathogenesis of galactocele is not known, but it is thought that inspissated milk within ducts is responsible. The lump is usually located in the central portion of the breast or under the nipple. Needle aspiration produces thick, creamy material that may be tinged dark-green or brown.

• Although it appears purulent, the fluid is sterile. • Treatment is needle aspiration. Withdrawal of thick milky

secretion confirms the diagnosis; operation is reserved for cysts that cannot be aspirated or that become infected.

FibroadenomaFibroadenoma (adenofibroma) is a benign tumor composed of stromal

and epithelial elements.

Fibroadenomas appear in teenage girls and women during their early reproductive years.

Clinically, they present as firm well circumscribed ,highly mobile within the breast tissue , solitary tumors that may increase in size over several months of observation. At operation, fibroadenomas appear to be well-encapsulated masses that may easily detach from the surrounding breast tissue.

Ultrasound usually clearly shows the difference between cysts and fibro adenomas.

The treatment of fibroadenoma follows that for any unexplained solid mass within the breast. Most patients undergo excisional biopsy to remove the tumor and establish the diagnosis.

Cryoablation is not appropriate for all fibroadenomas because some are too large to freeze or the diagnosis may not be certain.

Phyllodes tumor

• Phyllodes tumor :It may reach a large size and, if inadequately excised, will recur locally. The lesion can be benign or malignant. If benign, phyllodes tumor is treated by local excision with a margin of surrounding breast tissue. The treatment of malignant phyllodes tumor is more controversial, but complete removal of the tumor with a rim of normal tissue avoids recurrence. Because these tumors may be large, simple mastectomy is sometimes necessary. Lymph node dissection is not performed, since the sarcomatous portion of the tumor metastasizes to the lungs and not the lymph nodes.

Milk engorgement Lactational mastitis and

Breast abscess Milk engorgement presented with dull aching pain associated with mild pyrexia , breast is

enlarged with no signs of inflammation

Mastitis describes a generalized cellulites of breast tissue that may involve a large area of the breast but may not form a true abscess.

Mastitis presents with erythema of the overlying skin, pain, and tenderness to palpation. There is induration of the skin and underlying breast parenchyma. Mastitis commonly complicates lactation, possibly as a result of bacteria( staph. Aurieus) ascending in ductal tree of the breast through the nipple.

Predisposing factors includes : milk engorgement ,nipple retraction , cracked nipple ,bad hygiene , DM

Local measures such as application of heat, or use of a mechanical breast pump on the affected side, administration of broad-spectrum antibiotics. In many situations, the differential diagnosis of acute mastitis includes inflammatory carcinoma.

Breast abscess present with , thropping pain associated with hectic fever ( never wait for fluctuation ) and signs of acute inflammation.

Treatment of breast abscise is drainage

Non lactating breast abscess and duct ectasia

• Commonly occurs in the subareolar breast tissue and may be recurrent. Subareolar duct ectasia and obstruction of major ducts may lead to proliferation of bacteria and subsequent abscess. Further destruction of the normal ductal openings leads to fistula formation and chronic recurrent abscess.

• Mammary duct ectasia, is an inflammatory condition that causes distortion and dilation of the lactiferous sinuses under the nipple. It is a common entity and is frequently responsible for nipple inversion in older women.

• The treatment is major duct excision .

Duct ectasia

Breast pain• Breast pain is common symptom.Usually it is of functional origin and

uncommonly is a symptom of breast cancer. • For those women with breast pain and an associated palpable mass, the

presence of the mass should be the focus of evaluation and treatment.• For patients without a mass, the evaluation should be guided by whether

the pain is cyclical or noncyclical.• Normal ovarian hormonal influences on breast glandular elements

frequently produce cyclical mastalgia. It is predominantly experienced in the luteal phase of the menstrual cycle and abates with menstruation.

• Noncyclical mastalgia is more likely to be the result of a non breast etiology or of a specific significant breast condition. A careful history and physical examination should eliminate musculoskeletal causes such as cervical radiculopathy, costochondritis, or intercostal muscle strain. Gastroesophageal reflux disorder, symptomatic gallstones, cardiovascular disease, and pulmonary pathology are fairly obvious after a brief patient interview.

• Breast cellulitis (mastitis), inflammatory breast cancer causes breast pain.

Investigation

• Women 30 years of age and older with cyclical or noncyclical mastalgia should undergo mammography. The exception to this rule is when the clinical breast examination reveals focal tenderness and breast ultrasound detects a simple cyst. In this instance the work-up can be terminated with reassurance and without a mammogram.

• If the mammogram is abnormal or the ultrasound reveals a complex cyst or solid lesion, further evaluation of the mass should commence.

• For patients younger than 30 years of age without focal breast pain, the initial management should be symptomatic.

Treatment • If the clinical breast examination and mammography are

normal, 85% of women respond to reassurance that mastalgia is a common, benign condition.

• For the 15% of women who do not, wearing a supportive brassiere and taking ibuprofen 600 to 800 mg every 8 hours during symptomatic days may be adequate to relieve symptoms.

• Primrose oil results in symptomatic relief in 58% of patients with cyclical and 38% of patients with noncyclical mastalgia.

• More aggressive therapies include danazol, a synthetic androgen that decreases ovarian function .

• Bromocriptine, a longacting dopaminergic drug that suppresses prolactin.

• Tamoxifen provided symptomatic relief in 75% of

Nipple Discharge

• Nipple discharge is common and is rarely associated with an underlying carcinoma.

• It is important to establish whether the discharge comes from one breast or from both breasts, whether it comes from multiple duct orifices or from just one, and whether the discharge is grossly bloody or contains blood.

• A milky discharge from both breasts is termed galactorrhea. In the absence of lactation or history of recent lactation, galactorrhea may be associated with increased production of prolactin. Serum prolactin is diagnostic.

• Unilateral, non milky discharge coming from one duct orifice is surgically significant and warrants special attention . However, the underlying cause is rarely a breast malignancy. The most common cause of spontaneous nipple discharge from a single duct is a solitary intraductal papilloma in one of the large subareolar ducts directly under the nipple. If an occult cancer is found, it is usually an intraductal carcinoma.

• Fibrocystic change, or cystic mastopathy, typically produces multiple-duct discharge and is another commonly associated finding.

• Subareolar duct ectasia, producing inflammation and dilation of large collecting ducts under the nipple, is a common finding that usually produces multiple-duct discharge.

Gynicomastia Hypertrophy of normal male breast tissue; can be divided into 2 categories:pubertal hypertrophy (ages 13–17),

senescent hypertrophy (age >50) Associated with some recreational and therapeutic drugs digoxin, thiazides, estrogens, phenothiazines, theophylline Marijuana

• Idiopathic Hypertrophy of the male breast may be unilateral or bilateral. The breasts enlarge at puberty and sometimes present the characteristic of female breasts .

• Hormonal Enlargement of the breasts often accompanied stilbestrol therapy for prostate cancer, now rarely used. It may also occur as a result of a teratoma of the testis, in anorchism and after castration.

• Rarely, it may be a feature of ectopic hormonal production in bronchial carcinoma and in adrenal and pituitary disease. Body builders may use steroids to improve their physique, which may cause gynaecomastia. Some even go so far as to take tamoxifen to mask this symptom.

• Associated with leprosy Gynaecomastia is very common in men suffering from leprosy. This is possibly because of bilateral testicular atrophy, which is a frequent accompaniment of leprosy.

• Associated with liver failure Gynaecomastia sometimes occurs in patients with cirrhosis as a result of failure of the liver to metabolise oestrogens. It is associated with drugs that interfere with the hepatic metabolism of oestrogens. It is also seen with certain drugs such as cimetidine, digitalis and spironolactone.

• Associated with Klinefelter syndrome Gynaecomastia may occur in patients with Klinefelter’s syndrome, a sex chromosome anomaly having 47XXY trisomy

Symptoms and signs include unilateral or bilateral breast enlargemen Surgery is indicated if enlargement is primary and does not regress and breast is cosmetically unacceptable

Fat NecrosisFat necrosis is a rare lesion of the breast but is of clinical importance

because it produces a mass (often accompanied by skin or nipple retraction) that is indistinguishable from carcinoma even with imaging studies.

Trauma is presumed to be the cause, though only about 50% of patients give a history of injury. Ecchymosis is occasionally present. If untreated, the mass effect gradually disappears.

The safest course is to obtain a biopsy. Needle biopsy is often adequate, but frequently the entire mass must be excised, primarily to exclude carcinoma.

Fat necrosis is common after segmental resection, radiation therapy, or flap reconstruction after mastectomy.

Risk Factors for Breast Cancer• Age: is probably the most important risk factor that clinicians use in everyday clinical practice. Breast cancer is rare in persons younger

than 20 years of age. Thereafter, the incidence increases to 1 in 93 by age 40, 1 in 50 by age 50, 1 in 24 by age 60, 1 in 14 by age 70, and 1 in 10 by age 80.

• Gender is also an important risk factor. Males are at risk for breast cancer, although the incidence in males is less than 1% of the incidence in females

• Histologic Risk Factors

■ Aytpia or Cancer on Previous Biopsy

■ Atypical ductal hyperplasia (ADH)

■ Atypical lobular hyperplasia (ALH)

■ Lobular carcinoma in situ (LCIS)

■ Previous history ductal carcinoma in situ (DCIS)

■ Previous history of invasive breast cancer• Thoracic Radiation Before Age 30

■ Infant thymus radiation

■ Frequent fluoroscopy for TB

■ Multiple x-rays for scoliosis• Family History—Three Generations Maternal and Paternal

■ Known or suspected gene mutation(BRCA1 and BRCA 2)

■ Early age onset <40

■ Bilateral breast cancer

■ Breast and/or ovarian cancer

■ Male breast cancer

■ Ethnicity , e.g., Jewish ancestry with family history

■ Cluster of rare tumors in a biological family• Reproductive Risk Factors

< ■ 5 years of combined estrogen/ progesterone hormone replacement therapy

■ Age at menarche <12

■ Nulliparity

■ Age at firstborn >30

■ Age at menopause >55

Pathology

• Breast cancer may arise from the epithelium of the duct system anywhere from the nipple end of the major lactiferous ducts to the terminal duct unit, which is in the breast lobule. The disease may be entirely in situ, an increasingly common finding with the advent of breast cancer screening, or may be invasive cancer.

• The degree of differentiation of the tumour is usually described using three grades: well differentiated, moderately differentiated or poorly differentiated.

• Previously, descriptive terms were used to classify breast cancer (‘scirrhous’, meaning woody, or ‘medullary’, meaning brain-like). More recently, histological descriptions have been used.

• Gene array analysis of breast cancers has identified five subtypes. Some of these correlate with known markers such as oestrogen receptor status. There are specific gene signatures that are said to correlate with response to chemotherapy or poor prognosis

Current nomenclature• Ductal carcinoma is the most common variant with lobular carcinoma

occurring in up to 15% of cases. • Rarer histological variants, usually carrying a better prognosis, include

colloid carcinoma, whose cells produce abundant mucin, medullary carcinoma, with solid sheets of large cells often associated with a marked lymphocytic reaction, and tubular carcinoma.

• Invasive lobular carcinoma is commonly multifocal and/or bilateral. • Cases detected via the screening programme are often smaller and better

differentiated than those presenting to the symptomatic service and are of a special type.

• Inflammatory carcinoma is a fortunately rare, highly aggressive cancer that presents as a painful, swollen breast, which is warm with cutaneous oedema. This is the result of blockage of the subdermal lymphatics with carcinoma cells. Inflammatory cancer usually involves at least one-third of the breast and may mimic a breast abscess. A biopsy will confirm the diagnosis and show undifferentiated carcinoma cells. It used to be rapidly fatal but with aggressive chemotherapy and radiotherapy and with salvage surgery the prognosis has improved considerably.

• In situ carcinoma is pre-invasive cancer that has not breached the epithelial basement membrane. This was previously a rare, usually asymptomatic, finding in breast biopsy specimens but is becoming increasingly common because of the advent of mammographic screening; In situ carcinoma may be ductal (DCIS) or lobular (LCIS), the latter often being multifocal and bilateral. Both are markers for the later development of invasive cancer, which will develop in at least 20% of patients.

• Staining for oestrogen and progesterone receptors is now considered routine, as their presence will indicate the use of adjuvant hormonal therapy with tamoxifen or the newer aromatase inhibitors. Tumours are also stained for c-erbB2 (a growth factor receptor) as patients who are positive can be treated with the monoclonal antibody trastuzumab (Herceptin), either in the adjuvant or relapse setting.

PATHOLOGY OF BREAST CANCER

Classification of Primary Breast Cancer

• Noninvasive Epithelial Cancers

Lobular carcinoma in situ (LCIS)

Ductal carcinoma in situ (DCIS) or intraductal carcinoma Papillary, cribriform, solid, and comedo types

• Invasive Epithelial Cancers (percentage of total)

Invasive lobular carcinoma (10–15)

Invasive ductal carcinoma

• Invasive ductal carcinoma, NOS (50–70) NOS, nothing otherwise specified

• Tubular carcinoma (2–3)

• Mucinous or colloid carcinoma (2–3)

• Medullary carcinoma (5)

• Invasive cribriform (1–3)

• Invasive papillary (1–2)

• Adenoid cystic carcinoma (1)

• Metaplastic carcinoma (1)

• Mixed Connective and Epithelial Tumors

Phyllodes tumors, benign and malignant

Carcinosarcoma

Angiosarcoma

.

PATHOLOGY OF BREAST CANCER (Spread)

• Local (direct)

Breast ,skin, pectoral fascia ,muscle ,rips

• Lymphatic to (axillary ,internal mammary ) lymph node

Embolization

Permeation

• Blood

Clinical picture

• Painless breast lump • Early findings: Single, nontender, firm to

hard mass with ill-defined margins;

or mammographic abnormalities and no palpable mass.

• Later findings: Skin or nipple retraction; axillary lymphadenopathy; breast enlargement, erythema, edema, pain; fixation of mass to skin or chest wall.

INVESTIGATIONS

• FNAC: Most experienced clinicians would not leave a suspicious dominant mass in the breast even when FNA cytology is negative unless the clinical diagnosis, breast imaging studies, and cytologic studies were all in agreement, such as a fibrocystic lesion or fibroadenoma.

• • Ultrasound: best for young women/ dense breasts. Ultrasonography is performed primarily to differentiate cystic from solid lesions but may show signs suggestive of carcinoma.

• Mammography

• Biopsy (‘Trucut’/open surgical): usually provides definitive histology (may be radiologically guided if lump is small or impalpable bdetected by mammography as part of breast screening programme).

• As an alternative in highly suspicious circumstances, the diagnosis may be made on frozen section of tissue obtained by open biopsy under general anesthesia. If the frozen section is positive, the surgeon can proceed immediately with the definitive operation.

This one-step method is rarely used today except when a cytologic study has suggested cancer but is not diagnostic and there is a high clinical suspicion of malignancy in a patient well prepared for the diagnosis of cancer and its treatment options.

In general, the two-step approach—outpatient biopsy followed by definitive operation at a later date—is preferred in the diagnosis and treatment of breast cancer, because patients can be given time to adjust to the diagnosis of cancer, can consider alternative forms of therapy, and can seek a second opinion if they wish. There is no adverse effect from the short delay of the two-step procedure.

Biomarkers• The ER and PR status and HER-2/neu status of the

tumor should be determined at the time of initial biopsy. • PR status may be more sensitive than ER status in

determining which patients are likely to respond to hormonal manipulation.

• The presence of HER-2/neu amplification predicts the response to trastuzumab (Herceptin), a monoclonal antibody that binds to the HER-2/neu receptors.

• Other studies such as proliferation indices may be performed.

• These markers may be obtained on core biopsy specimens, which will be necessary to institute neoadjuvant therapy.

• Once tissue diagnosis is reached we should stage the patient with

• a careful clinical examination, LFT’s, CXR bone scan and abdominal ultrasound

American Joint Committee on Cancer Staging System for Breast Cancer, 2002

• (p)T (Primary Tumor)

• Tis Carcinoma in situ (lobular or ductal)• T1 Tumor ≤2 cm• T1a Tumor ≥0.1 cm; ≤0.5 cm• T1b Tumor >0.5 cm; ≤1 cm• T1c Tumor >1 cm; ≤2 cm• T2 Tumor >2 cm; ≤5 cm• T3 Tumor >5 cm• T4 Tumor any size with extension to chest wall or skin• T4a Tumor extending to chest wall (excluding pectoralis)• T4b Tumor extending to skin with ulceration, edema, satellite nodules• T4c Both T4a and T4b• T4d Inflammatory carcinoma

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ

Tis (DCIS) Ductal carcinoma in situ

Tis (LCIS) Lobular carcinoma in situ

Tis (Paget) Paget disease of the nipple with no tumor

American Joint Committee on Cancer Staging System for Breast Cancer, 2002

• (p)N (Nodes)• N0 No regional node involvement, no special studies• N1 Metastasis to 1–3 axillary nodes and/or int. mammary positive by biopsy• N1(mic) Micrometastasis (>0.2 mm, none >2.0 mm)• N1a Metastasis to 1–3 axillary nodes• N1b Metastasis in int. mammary by sentinel biopsy• N1c Metastasis to 1–3 axillary nodes and int. mammary by biopsy• N2 Metastasis to 4–9 axillary nodes or int. mammary clinically positive, without axillary

metastasis• N2a Metastasis to 4–9 axillary nodes, at least 1 >2.0 mm• N2b Int. mammary clinically apparent, negative axillary nodes• N3 Metastasis to ≥10 axillary nodes or combination of axillary and int. mammary

metastasis• N3a ≥10 axillary nodes (>2.0 mm), or infraclavicular nodes• N3b Positive int. mammary clinically with ≥1 axillary node or >3 positive axillary nodes

with int. mammary positive by biopsy• N3c Metastasis to ipsilateral supraclavicular nodes

American Joint Committee on Cancer Staging System for Breast Cancer, 2002

• M (Metastasis)

• M0 No distant metastasis

• M1 Distant metastasis

American Joint Committee on Cancer Stage Grouping

• Stage TNM• 0 Tis, N0, M0• I T1, N0, M0• IIA T0, N1, M0

T1, N1, M0

T2, N0, M0• IIB T2, N1, M0

T3, N0, M0• IIIA T0, N2, M0

T1, N2, M0

T2, N2, M0

T3, N1, M0

T3, N2, M0• IIIB T4, N0, M0

T4, N1, M0

T4, N2, M0• IIIC Any T, N3, M0• IV Any T, any N, M1

Prognosis of breast cancer

• The best indicators of likely prognosis in breast cancer remain tumour size and lymph node status; however, it is realised that some large tumours will remain confined to the breast for decades whereas some very small tumours are incurable at diagnosis.

• Hence, the prognosis of a cancer depends not on its chronological age but on its invasive and metastatic potential. In an attempt to define which tumours will behave aggressively, and thus require early systemic treatment, a host of prognostic factors have been described. These include the histological grade of the tumour, hormone receptor status measures of tumour proliferation such as S-phase fraction, growth factor analysis and oncogene or oncogene product measurements.

Treatment of cancer of the breast

• The two basic principles of treatment are to reduce the chance of local recurrence and the risk of metastatic spread.

• Treatment of early breast cancer will usually involve surgery with or without radiotherapy. Systemic therapy such as chemotherapy or hormone therapy is added if there are adverse prognostic factors such as lymph node involvement, indicating a high likelihood of metastatic relapse.

• At the other end of the spectrum, locally advanced or metastatic disease is usually treated by systemic therapy to palliate symptoms, with surgery playing a much smaller role.

Algorithm for management of operable breast cancer

• Achieve local control• Appropriate surgery

■ Wide local excision (clear margins) and radiotherapy, or

■ Mastectomy ± radiotherapy (offer reconstruction – immediate or delayed)

■ Combined with axillary procedure

■ Await pathology and receptor measurements

■ Use risk assessment tool; stage if appropriate• Treat of risk of systemic disease

■ Offer chemotherapy if prognostic factors poor; include

Herceptin if Her-2 positive

■ Radiotherapy as decided above

■ Hormone therapy if oestrogen receptor or progesterone

receptor positive

The multidisciplinary team approach

• As in all branches of medicine, good doctor–patient communication plays a vital role in helping to alleviate patient anxiety.

• Participation of the patient in treatment decisions is of particular importance in breast cancer when there may be uncertainty as to the best therapeutic option and the desire to treat the patient within the protocol of a controlled clinical trial. As part of the preoperative and postoperative management of the patient it is often useful to employ the skills of a trained breast counsellor and also to have available advice on breast prostheses, psychological support and physiotherapy, when appropriate.

• In many specialist centres the care of breast cancer patients is undertaken as a joint venture between the surgeon, medical oncologist, radiotherapist and allied health professionals such as the clinical nurse specialist. This has been shown to be good for the patient, to lead to higher trial entry and to improve the mental health of the professionals in the breast team.

Local treatment of early breast cancer

Local control is achieved through surgery and/or radiotherapy

The aims of treatment are:

■ ‘Cure’: likely in some patients but late recurrence is possible

■ Control of local disease in the breast and axilla

■ Conservation of local form and function

■ Prevention or delay of the occurrence of distant metastases

Surgery

Surgery still has a central role to play in the management of breast cancer but there has been a gradual shift towards more conservative techniques, backed up by clinical trials that have shown equal efficacy between mastectomy and local excision followed by radiotherapy.

• It was initially hoped that avoiding mastectomy would help to alleviate the considerable psychological morbidity associated with breast cancer but recent studies have shown that over 30% of women develop significant anxiety and depression following both radical and conservative surgery. After mastectomy women tend to worry about the effect of the operation on their appearance and relationships, whereas after conservative surgery they may remain fearful of a recurrence.

Mastectomy

• Mastectomy is indicated for large tumours (in relation to the size of the breast), central tumours beneath or involving the nipple, multifocal disease, local recurrence or patient preference.

• The radical Halsted mastectomy, which included excision of the breast, axillary lymph nodes and pectoralis major and minor muscles, is no longer indicated as it causes excessive morbidity with no survival benefit.

• The modified radical (Patey) mastectomy is more commonly performed and is thus described below.The breast and associated structures are dissecte en bloc and the excised mass is composed of: the whole breast; a large portion of skin, the centre of which overlies the tumour but which always includes the nipple, all of the fat, fascia and lymph nodes of the axilla.

• Simple mastectomy involves removal of only the breast with no dissection of the axilla, except for the region of the axillary tail of the breast, which usually has attached to it a few nodes low in the anterior group.

Conservative breast cancer surgery

This is aimed at removing the tumour plus a rim of at least 1 cm of normal breast tissue.

This is commonly referred to as a wide local excision.

The term lumpectomy should be reserved for an operation in which a benign tumour is excised and in which a large amount of normal breast tissue is not resected.

• A quadrantectomy involves removing the entire segment of the breast that contains the tumour. Both of these operations are usually combined with axillary surgery, usually via a separate incision in the axilla.

• There is a somewhat higher rate of local recurrence following conservative surgery, even if combined with radiotherapy, but the long-term outlook in terms of survival is unchanged. Local recurrence is more common in younger women and in those with high grade tumours and involved resection margins.

• Patients whose margins are involved should have a further local excision (or a mastectomy) before going on to radiotherapy.

• Excision of a breast cancer without radiotherapy leads to an unacceptable local recurrence rate.

axillary surgery• There are various options that can be used to deal with the axilla,

including sentinel node biopsy, sampling, removal of the nodes behind and lateral to the pectoralis minor (level II) or a full axillary dissection (level III).

• The role of axillary surgery is to stage the patient and to treat the axilla. The presence of metastatic disease within the axillary lymph nodes remains the best single marker for prognosis; however, treatment of the axilla does not affect long-term survival, suggesting that the axillary nodes act not as a ‘reservoir’ for disease but as a marker for metastatic potential.

• Axillary surgery should not be combine with radiotherapy to the axilla because of excess morbidity.

• Removal of the internal mammary lymph nodes is unnecessary.

Radiotherapy

• Radiotherapy to the chest wall after mastectomy is indicated in selected patients in whom the risks of local recurrence are high. This includes patients with large tumours and those with large numbers of positive nodes or extensive lymphovascular invasion.

• There is some evidence that postoperative chest wall radiotherapy improves survival in women with node-positive breast cancer.

• It is conventional to combine conservative surgery with radiotherapy to the remaining breast tissue. Recurrence rates are too high for treatment by local excision alone except in special cases (small node-negative tumours of a special type).

Adjuvant systemic therapy

• It is now widely accepted that the outcomes of treatment are predetermined by the extent of micrometastatic disease at the time of diagnosis.

• Variations in the radical extent of local therapy might influence local relapse but probably do not alter long-term mortality from the disease. However, systemic therapy targeted at these putative micrometastases might be expected to delay relapse and prolong survival.

• Lymph node-positive and many higher risk node-negative women should be recommended adjuvant combined chemotherapy.

• Women with hormone receptor- positive tumours will obtain a worthwhile benefit from about 5 years of endocrine therapy, either 20 mg daily of tamoxifen if pre-menopausal or the newer aromatase inhibitors (anastrozole, letrozole and exemestane) if post-menopausal.

Hormone therapy

• Tamoxifen has been the most widely used ‘hormonal’ treatment in breast cancer. Reduce the annual rate of recurrence by 25%, with a 17% reduction in the annual rate of death. The beneficial effects of tamoxifen in reducing the risk of tumours in the contralateral breast have also been observed, as has its role as a preventative agent . 5 years of treatment is preferable to 2 years.

• Other hormonal agents that are also beneficial as adjuvant therapy have been developed.

• These include the

LHRH agonists, which induce a reversible ovarian suppression and thus have the same beneficial effects as surgical or radiation-induced ovarian ablation in pre-menopausal receptor-positive women, and the oral aromatase inhibitors for post-menopausal women. The latter group of compounds are now licensed for treatment of recurrent disease, in which they have been shown to be superior to tamoxifen.

Chemotherapy• Chemotherapy using a first-generation regimen such as a 6-monthly cycle of

cyclophosphamide, methotrexate and 5- fluorouracil (CMF) will achieve a 25% reduction in the risk of relapse over a 10- to 15-year period.

• CMF is no longer considered adequate adjuvant chemotherapy and modern regimens include an anthracycline (doxorubicin or epirubicin) and the newer agents such as the taxanes.

• Chemotherapy was once confined to pre-menopausal women with a poor prognosis (in whom its effects are likely to be the result, in part, of chemical castration effect) but is being increasingly offered to post-menopausal women with poor prognosis disease as well. Chemotherapy may be considered in node-negative patients if other prognostic factors, such as tumour grade, imply a high risk of recurrence. The effect of combining hormone and chemotherapy is additive although hormone therapy is started after completion of chemotherapy to reduce side-effects.

• Primary chemotherapy (neoadjuvant) is being used in many centres for large but operable tumours that would traditionally require a mastectomy (and almost certainly postoperative adjuvant chemotherapy). The aim of this treatment is to shrink the tumour to enable breast-conserving surgery to be performed.

• Newer ‘biological’ agents will be used more frequently as molecular targets are identified – the first of these, trastuzamab (Herceptin), is active against tumours containing the growth factor receptor c-erbB2.

• Other agents currently available include bevacizumab, a vascular growth factor receptor inhibitor, and lapitinab, a combined growth factor receptor inhibitor.

Follow-up of breast cancer

• Patients with breast cancer used to be followed for life to detect recurrence and dissemination. This led to large clinics with little value for either patient or doctor. It is current practice to arrange yearly or 2-yearly mammography of the treated and contralateral breast. There is a move to return the patient early to the care of the general practitioner with fast-track access back to the breast clinic if suspicious symptoms appear. There is currently no routine role for repeated measurements of tumour markers or imaging other than mammography.

Breast reconstruction• Despite an increasing trend towards conservative surgery, up to 50% of women still

require, or want, a mastectomy. These women can now be offered immediate or delayed reconstruction of the breast. Few contraindications to breast reconstruction exist.

• The easiest type of reconstruction is using a silicone gel implant under the pectoralis major muscle. This may be combined with prior tissue expansion using an expandable saline prosthesis first (or a combined device), which creates some ptosis of the new breast.

• If the skin at the mastectomy site is poor (e.g. following radiotherapy) or if a larger volume of tissue is required, a musculocutaneous flap can be constructed either from the latissimus dorsi muscle (an LD flap) or using the transversus abdominis muscle (a TRAM flap ). The latter gives an excellent cosmetic result in experienced hands but is a lengthy procedure and requires careful patient selection.

• To achieve symmetry the opposite breast may require a cosmetic procedure such as reduction or augmentation mammoplasty, or mastopexy.

• External breast prostheses that fit within the bra are the most common method of restoring volume fill and should be available for all women who do not have an immediate reconstruction.

MODERN TREATMENT FOR EARLY BREAST CANCER

• Shift from radical mastectomy to modified radical mastectomy to procedures that preserve the breast (conservative breast surgery ). Large size tumor is only a relative contraindication to breast conservation. Subareolar tumors, also difficult to excise without deformity, are not contraindications to breast conservation. Clinically detectable multifocality is contraindication to breast-conserving surgery. The patient—not the surgeon—should be the judge of what is cosmetically acceptable.

• The approach to the axillary nodes is also evolving. Many specialists are becoming more selective about the need for axillary dissection to axillary staging , and the use of sentinel node biopsy is replacing routine axillary dissection for women with clinically negative lymph nodes.

• Whole-breast radiation after surgical removal of the primary tumor. Radiotherapy after partial mastectomy consists of 5–7 weeks of five daily fractions to a total dose of 5000–6000 cGy.

• Adjuvant Chemotherapy: In practice, most medical oncologists are currently using systemic adjuvant therapy for patients with either node-negative or node-positive breast cancer.

• Targeted Therapy Her-2/Neu Overexpression :Trastuzumab (Herceptin), a monoclonal antibody that binds to the HER-2/neu receptors, when studied in the metastatic setting, has proved effective in combination with chemotherapy in patients with HER-2/neu overexpression.

Vascular Endothelial Growth Factor (VEGF) Bevacizumab (Avastin) is a monoclonal antibody directed against VEGF.

• Hormonal :decrease recurrence and mortality by 25% in women with ER-positive tumors regardless of menopausal status.

• Neoadjuvant Chemotherapy The use of chemotherapy or hormonal therapy prior to resection of the primary tumor (neoadjuvant) is gaining popularity.

EARLY INVASIVE BREAST CA • Discuss options with patient, based on pathology, size sit of the tumor, size of the

breasts, and patient desire .• Must: 1. Treat the entire breast and 2. Either assess (with SLN biopsy , and treat if

positive) or prophylactically treat / sample the axillary nodes. • The breast can be treated by lumpectomy (with a clearly negative margin) and 5,000

cGy breast radiotherapy(XRT). Breast XRT doesn’t impact survival, but it decreases local recurrence by 20%. This breast-conserving treatment is best if the tumor is < T3 (no extension and < 5 cm), it is unifocal, and the breast is not too small for an acceptable cosmetic result.

• Total mastectomy w/ or w/out immediate reconstruction is also acceptable. • The axillary nodes can be staged with axillary dissection of level 1 and 2 nodes or

SLN biopsy (s) SNL Bx is inappropriate for multiple CA's. • Add 5,000 cGy chest wall/axillary XRT for patients with > 3 positive nodes• Adjuvant Chemotherapy, Targeted Therapy ,. Hormonal and Neoadjuvant

Chemotherapy• All patients get routine flow up with CXR, exam for local recurrence, and bi- or

contra- lateral mammography

Treatment of Locally Advanced and Inflammatory Breast Cancer

The treatment of locally advanced breast cancer has been changing. The disease is heterogeneous and defies a uniform treatment approach. Prior to the 1970s, treatment included surgery and radiation, with little effect on survival. When surgery is used alone, local relapse rates in the range of 30% to 50% can be anticipated and the long-term cure rates rarely exceed 30%. Similar results are reported when radiation therapy is the sole modality of treatment. These poor results suggest that locally advanced disease is actually metastatic in most patients, emphasizing the role of chemotherapy in these patients. A trimodality approach with the addition of chemotherapy improved both disease-free and overall survivals.

Inflammatory breast cancer was once a uniformly fatal disease that claimed its victims after a median survival of 9 to 12 months. Current approaches emphasize aggressive use of combined modality treatment, which includes chemotherapy, mastectomy, and radiation therapy

Paget’s Disease• Paget’s disease of the breast clinically presents as nipple erythema and mild eczematous scaling

and flaking, progressing to nipple crusting, skin erosions, and ulceration. The condition spreads outward off the nipple and onto the areola and surrounding skin of the breast .

• The clinical differential diagnosis of scaling skin and erythema of the nipple-areolar complex includes eczema, contact dermatitis, postradiation dermatitis, and Paget’s disease.

• A skin specimen containing Paget’s cells and a lactiferous duct secures the diagnosis and can be obtained by nipplescrape cytology or biopsy.

• More than 97% of patients with Paget’s disease have an underlying breast carcinoma. Paget’s may present with (54%) or without (46%) a mass. Invasive breast cancer coexists with Paget’s disease in 93% of patients with a mass and in 38% of patients without a mass.

• For patients considering breast preservation, presurgical evaluation should include evaluation for occult multicentric disease with mammography with retroareolar spot compression views. Some advocate breast MRI. For patients with Paget’s disease confined clinically and radiologically to the nippleareolar complex, surgery may include excision of the nipple-areolar complex with at least a 2-cm cone of retroareolar tissue, encompassing all radiographic abnormalities.

• Alternatively, simple mastectomy with or without an axillary node procedure is probably the most common way Paget’s disease is treated in the United States. Nodal evaluation may be based on identification of an invasive component preoperatively or if invasive cancer is

Male Breast CancerThe majority of men with breast cancer (50% to 97%) present with a breast mass. In addition to local

pain and axillary adenopathy, other presentingnsymptoms include those of the nipple (retraction, ulceration, bleeding, and discharge). Evaluation includes breast imaging studies and, when there is uncertainty of a diagnosis of gynecomastia, needle or surgical biopsy.

The negative prognostic factors for breast cancer in men are the same as in women and The negative prognostic factors for breast cancer in men are the same as in women and include nodal involvement, tumor size, histologic grade, and hormone receptor statusinclude nodal involvement, tumor size, histologic grade, and hormone receptor status. When matched for age and stage, survival is similar to that in women.

The treatment of carcinoma in the male breast depends on the stage and local extent of the tumor.

Small tumors, movable across the chest wall, may be treated by local excision and radiation, if preferred and technically feasible, or by mastectomy. Nodal evaluation by sentinel node biopsy or axillary dissection is governed by the presence of invasive disease.

Breast tumors in men more commonly involve the pectoralis major muscle, probably because breast tissue in men is scant. If the underlying pectoral muscle is involved, modified radical mastectomy with excision of the involved portion of muscle is adequate treatment and may be combined with postoperative radiation therapy.

There is little experience with adjuvant chemotherapy or hormonal therapy in male breast cancer. Because most of these tumors are hormone sensitive, the use of adjuvant tamoxifen for node-positive and high-risk node-negative patients seems logical. For men at substantial risk for metastatic disease, adjuvant chemotherapy can be offered.

SCREENING

• Because the prognosis of breast cancer is closely related to stage at diagnosis it would seem reasonable to hope that a population screening programme that could detect tumours before they come to the patient’s notice might reduce mortality from breast cancer. Screening by mammography in women over the age of 50 years will reduce cause-specific mortality by up to 30%. A programme of 3-yearly mammographic screening for women between the ages of 50 and 64 years (now increased to 70 years).

Familial breast cancer• Recent developments in molecular genetics and the identification of a number of breast cancer

predisposition genes (BRCA1, BRCA2 and p53) have done much to stimulate interest in this area. Yet women whose breast cancer is due to an inherited genetic change actually account for less than 5% of all cases of breast cancer.

• A much larger number of women will have a risk that is elevated above normal because of an as yet unspecified familial inheritance. These women have a risk of developing breast cancer that is 2–10 times above baseline.

• Women who are thought to be gene carriers may be offered breast screening (and ovarian screening in the case of BRCA1, which is known to impart a 50% lifetime risk of ovarian cancer), usually as part of a research programme, or genetic counselling and mutation analysis. Those who prove to be ‘gene positive’ have a 50–80% risk of developing breast cancer, predominantly while pre-menopausal. Many will opt for prophylactic mastectomy. Although this does not completely eliminate the risk, it does reduce it considerably.

• For the great majority of women with a positive family history, who are unlikely to be carriers of a breast cancer gene, there are no currently proven breast cancer screening manoeuvres, although this is under investigation.

• Tamoxifen given for 5 years appears to reduce the risk of breast cancer by 30–50% and newer agents are currently under trial.

• Thus, these women are best served by being assessed and followed-up, preferably in a properly organised family history clinic.

PregnancyBreast cancer presenting during pregnancy or lactation tends to be at a later stage, presumably

because the symptoms are masked by the pregnancy; however, in other respects it behaves in a similar way to breast cancer in a nonpregnant young woman and should be treated accordingly.

Thus, treatment is similar with some provisos:

• radiotherapy should be avoided during pregnancy, making mastectomy a more frequent option than breast conservation surgery;

• chemotherapy should be avoided during the first trimester but appears safe subsequently;

• most tumours are hormone receptor negative and so hormone treatment, which is potentially teratogenic, is not required.

Becoming pregnant subsequent to a diagnosis of breast cancer appears not to alter the likely outcome, but women are usually advised to wait at least 2 years as it is within this time that recurrence most often occurs.

The risk of developing breast cancer with oral contraceptive use is only slight, and disappears 10 years after stopping the oral contraceptive pill.

Hormone replacement therapy does increase the risk of developing breast cancer if taken for prolonged periods and in certain high-risk groups.

HRT may also prolong symptoms of benign breast disorders such as cysts and mastalgia and make mammographic appearances more difficult to interpret.