The Breast

COMPARATIVE AND SURGICAL ANATOMY

INVESTIGATION OF THE BREAST

THE NIPPLE

BENIGN BREAST DISEASE

CONGENITAL ABNORMALITIES

CARCINOMA OF THE BREAST

TREATMENT OF CANCER OF THE BREAST

SCREENING FOR BREAST CANCER

FAMILIAL BREAST CANCER

HORMONE-REPLACEMENT THERAPY

TREATMENT OF ADVANCED BREAST CANCER

THE MALE BREAST

OTHER TUMOURS OF THE BREAST

The Breast

Subjects covered in this chapter include anatomy, investigations of the breast, the nipple, benign and malignant disorders of the breast, breast reconstruction, screening for breast cancer, breast cancer genetics and the male breast.

Comparative and surgical anatomy

The protuberant part of the human breast is generally described as overlying the 2nd to the 6th ribs, and extending from the lateral border of the sternum to the anterior axillary line. Actually, a thin layer of mammary tissue extends considerably farther from the clavicle above to the 7th or 8th ribs below, and from the midline to the edge of 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 considerable surgical importance. In some normal cases it is palpable, and in a few it can be seen premenstrually or during lactation. A well-developed axillary tail is sometimes mistaken for a mass of enlarged lymph nodes or a lipoma.

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 from 15 to 20. Each lactiferous duct is lined by a spiral arrangement of contractile myoepithelial cells and is provided with a terminal ampulla — a reservoir for milk or abnormal discharges.

The ligaments of Cooper are hollow conical projections of fibrous tissue filled with breast tissue, the apices of the cones being 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).

The nipple is covered by thick skin with corrugations. Near its apex lie the orifices of the lactiferous ducts. The nipple contains smooth muscle fibres arranged concentrically and longitudinally; thus is an erectile structure which points outwards. Lymphatics of the breast drain predominantly into the axillary and

internal mammary lymph nodes. The axillary nodes receive approximately 75 per cent 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 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 sentinal node is that lymph node designated as the first axillary node draining the breast.

The internal mammary nodes are fewer in number and lie along the internalmammary vessels deep to the plane of the costal cartilages.

Investigation of the breast

Although an accurate history and clinical examination are still the most important methods of detecting breast disease there are a number of investigations which can assist in the diagnosis as follows

Mammography

Soft tissue X-rays are taken by placing the breast in direct contact with ultrasensitive film and exposing it to low-voltage, high-amperage X-rays. The dose of radiation is approximately 0.1 Gy and therefore mammography is a very safe investigation.

Ultrasound

Ultrasound is particularly useful in young women with dense breasts in whom mammograms are difficult to interpret, and in distinguishing cysts from solid lesions. It can also be used to localise impalpable breast lumps.

Magnetic resonance imaging

Magnetic resonance imaging (MRI) is of increasing interest to breast 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 gold standard for imaging the breasts of women with implants; it may prove useful as a screening tool in high-risk women; and it is being evaluated in the management of the axilla in both primary breast cancer and recurrent disease.

Needle biopsy/cytology

Histology can be obtained using a fine needle such as a Trucut or Corecut biopsy device under local anaesthesia. Cytology is obtained using a 21 or 23 Gauge needle and 10-ml syringe with multiple passes throughout the lump without releasing the negative pressure in the syringe. The aspirate is then smeared on to a slide which is air dried. Fine needle aspiration cytology (FNAC) is the least invasive technique of obtaining a cell diagnosis and is very accurate if both operator and cytologist are experienced. However, false negatives do occur, mainly through sampling error, and invasive cancer cannot be distinguished from in situ disease.

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.

The nipple

Absence of the nipple is rare, and usually associated with amazia (congenital absence of the breast).

Supernumerary nipples not uncommonly occur along a line extending from the anterior fold of the axilla to the fold of the groin. This constitutes the milk line of lower mammals.

Nipple retraction

This may occur at puberty or later in life. Retraction occurring at puberty, also known as simple nipple inversion, is of unknown aetiology. In about 25 per cent of cases it is bilateral. It may cause problems with breastfeeding and infection can occur, especially during lactation, owing to retention of secretions.

Treatment

Treatment is usually unnecessary, and it may spontaneously resolve during pregnancy or lactation. Simple cosmetic surgery can produce an adequate correction but has the drawback of dividing the ducts. Mechanical suction devices have been used to attempt to evert the nipple with some effect. Recent retraction of the nipple may be of considerable pathological significance. A slit-like retraction of the nipple may be due to duct ectasia and chronic periductal mastitis, but circumferential retraction, with or without an underlying lump, may well indicate an underlying carcinoma.

Cracked nipple

This may occur during lactation and be the forerunner of acute infective mastitis. If the nipple becomes cracked during lactation, it should be rested for 24—48 hours and the breast emptied with a breast pump. Feeding should be resumed as soon as possible.

Papilloma of the nipple

Papilloma of the nipple has the same features of any cutaneous papilloma and should be excised with a tiny disc of skin.

Retention cyst of a gland of Montgomery

These glands, situated in the areola, secrete sebum, and if they become blocked a sebaceous cyst forms.

Chancre of the nipple

This very rare condition usually occurs by infection from a syphilitic buccal ulcer in the mouth of the partner, although can be seen in the wet-nurse of a syphilitic baby. The mother of such an infant is immune to reinfection from her own child.

Eczema

Eczema of the nipples is a rare condition and is bilateral, and usually associated with eczema elsewhere on the body.

Paget’s disease

Paget’s disease of the nipple must be distinguished from the eczema.

Abnormal discharges from the nipple

Discharge can occur from one or more lactiferous ducts. Management depends on the presence of a lump (which should always be given priority in diagnosis and treatment) and of the presence of blood in the discharge or discharge from a single duct. Mammography is rarely useful except to exclude an underlying impalpable mass. Cytology may reveal malignant cells but a negative result does not exclude a carcinoma.

A clear, serous discharge may be ‘physiological’ in a parous woman or may be associated with a duct papilloma or mammary dysplasia.

A blood-stained discharge may be caused by duct ectasia or less commonly a duct papilloma or carcinoma. A duct papilloma is usually single and situated in one of the larger lactiferous ducts and is sometimes associated with a cystic swelling beneath the areola.

A black or green discharge is usually due to duct ectasia and its complications.

Treatment

Treatment must firstly be to exclude a carcinoma by occult blood test and cytology. Simple reassurance may then be sufficient, but if the discharge is proving

intolerable an operation to remove the affected duct or ducts can be performed. Microdochectomy. It is important not to express the blood before the operation as it may then be difficult to identify the duct in theatre. A lacrimal probe or length of stiff nylon suture is inserted into the duct from which the discharge is emerging. A tennis raquet incision can be made to encompass the entire duct, or a periareolar incision used and the nipple flap dissected to reach the duct. The duct is then excised. A papilloma is nearly always situated within 4—5 cm of the nipple orifice.

Cone excision of the major ducts (after Hadfleld). When the duct of origin of nipple bleeding is uncertain or when there is bleeding or discharge from multiple ducts, the entire major duct system can be excised for histological examination without sacrifice of the breast form. A periareolar incision is made and a cone of

the pectoral fascia. The resulting defect is obliterated by a series of purse-string sutures. It is important to warn the patient that she will be unable to breast feed after this and may lose nipple sensation.

tissue is removed with its apex just deep to the surface of the nipple and its base on

Benign breast disease

This is the most common cause of breast problems — up to 30 per cent of women will suffer from a benign breast disorder requiring treatment at some time in their lives. The most common symptoms are pain, lumpiness or a lump. The aim of treatment is to exclude cancer and, once this has been done, to treat any remaining symptoms.

Benign breast disorders can be classified in the following way:

• ANDI (lumpy breasts, tenderness or a smooth lump):

cyclical nodularity and mastalgia, cysts, fibroadenoma;

• Duct ectasia/periductal mastitis;

• Pregnancy related:

galactocoele,

peurperal abscess;

• Congenital disorders:

inverted nipple,

supernumary breasts/nipples;

• Nonbreast disorders:

Tietze’s disease;

sebaceous cysts and other skin conditions.

Congenital abnormalities

Amazia

Congenital absence of the breast may occur on one or both sides. It is sometimes associated with absence of the sternal portion of the pectoralis major (Poland’s syndrome). It is more common in males.

Polymazia

Accessory breasts have been recorded in the axilla (the most frequent site), groin, buttock and thigh. They have been known to function during lactation.

Mastitis of infants

Mastitis of infants is at least as common in the male as in the female. On the 3rd or 4th day of life, if the breast of an infant is pressed lightly, a drop of colourless fluid can be expressed; a few days later there is often a slight milky secretion, which disappears during the 3rd week. This is popularly known as ‘witch’s milk’. It is due to stimulation of the foetal breast by maternal prolactin, thus is essentially physiological.

Diffuse hypertrophy

Diffuse hypertrophy of the breasts occurs sporadically in otherwise healthy girls at puberty and, much less often, during the first pregnancy. The breasts attain enormous dimensions and may reach the knees when the patient is sitting. The condition is rarely unilateral. This tremendous overgrowth is apparently due to an alteration in the normal sensitivity of the breast to oestrogenic hormones, and some success in treating it with antioestrogens has been reported. Treatment is otherwise by reduction mammoplasty.

Injuries of the breast

Haematoma

Haematoma, particularly a resolving haematoma, gives rise to a lump which, in the absence of overlying bruising, is difficult to diagnose correctly unless it is aspirated or incised.

Traumatic fat necrosis

Traumatic fat necrosis may be acute or chronic, and usually occurs in stout, middle-aged women. Following a blow, or even indirect violence (e.g. contraction of the pectoralis major), a lump, often painless, appears. This may mimic a carcinoma, even displaying skin tethering and nipple retraction, and biopsy is required for diagnosis. A history of trauma is not diagnostic as this may merely have drawn the patient’s attention to a pre-existing lump.

Acute and subacute inflammations of the breast

Bacterial mastitis

Bacterial mastitis is the commonest variety of mastitis and nearly always commences acutely. Although associated with lactation in the majority of cases, it is not necessarily so. Of 100 consecutive cases of breast abscess, 32 occurred in women who were not lactating (De Jode). Some of these will be associated with an infected haematoma or with periductal mastitis and this will be discussed later.

Aetiology. Lactational mastitis is seen far less frequently than in former years. Most cases are caused by Staphylococcus aureus and, if hospital-acquired, are likely to be penicillin resistant. The intermediary is usually the infant; after the second day of life 50 per cent of infants harbour staphylococci in the nasopharynx.

‘Cleansing the baby’s mouth’ with a swab is also an aetiological factor. The delicate buccal mucosa is excoriated by the process; it becomes infected, and organisms in the infant’s saliva are inoculated on to the mother’s nipple.

Whilst ascending infection from a sore and cracked nipple may initiate the mastitis, in many cases the lactiferous ducts will first become blocked by epithelial debris leading to stasis — this theory is supported by the relatively high incidence of mastitis in women with a retracted nipple. Once within the ampulla of the duct, staphylococci cause clotting of milk and within this clot organisms multiply.

Clinical features. The affected breast, or more usually a segment of it, presents the classical signs of acute inflammation. Early on this is a generalised cellulitis, but later an abscess will form.

Treatment. During the cellulitic stage the patient should be treated with an appropriate antibiotic, e.g. flucloxacillin, and the breast rested, with feeding on the opposite side only. The infected breast should be emptied of milk using a breast pump. Support of the breast, local heat and analgesia will help to relieve pain.

If an antibiotic is used in the presence of undrained pus, an ‘antibioma’ may form. This is a large, sterile brawny oedematous swelling which takes many weeks to resolve.

The breast should be incised and drained if the infection does not resolve within 48 hours, or if, after being emptied of milk, there is an area of tense induration or other evidence of an underlying abscess.

The presence of pus can be confirmed with a needle aspiration, and the pus analysed for the infection and for cytology. This has the advantage of allowing diagnosis on the smear of a rare inflammatory carcinoma. In contrast to the majority of localised infections, fluctuation is a late sign and incision must not be delayed until it appears. Usually the area of induration is sector-shaped, and in early cases about one-quarter of the breast is involved; in many late cases the area is more extensive. When in doubt an ultrasound scan may clearly define an area ‘ripe’ for drainage.

Drainage of an intramammary abscess. The usual incision is sited in a radial direction over the affected segment, although if a circumareolar incision will allow adequate access to the affected area this should be preferred because of a better cosmetic result. The incision passes through the skin and the superficial fascia. A long haemostat is then inserted into the abscess cavity. Every part of the abscess is

can be felt are entered.

Finally, the haemostat having been withdrawn, a finger is introduced and any remaining septa are disrupted. The wound may then be lightly packed with ribbon gauze or a drain inserted to allow dependent drainage.

Mastitis from milk engorgement

Mastitis from milk engorgement is liable to occur around weaning time, and sometimes in the early days of lactation when one of the lactiferous ducts becomes blocked with epithelial debris. In the latter instance only a sector of the breast becomes indurated and tender.

Chronic intramammary abscess

Chronic intramammary abscess which follows inadequate drainage or injudicious antibiotic treatment is often a very difficult condition to diagnose: when encapsulated within a thick wall of fibrous tissue, the condition cannot be

palpated against the point of the haemostat and its jaws are opened. All loculi that

distinguished from a carcinoma without the histological evidence from a biopsy.

Tuberculosis of the breast

Tuberculosis of the breast, which is comparatively rare, is usually associated with active pulmonary tuberculosis or tuberculous cervical adenitis.

Tuberculosis of the breast occurs more often in parous women and usually presents with multiple chronic abscesses and sinuses and a typical bluish attenuated appearance of the surrounding skin. The diagnosis rests on bacteriological and histological examination. Treatment is with antituberculous chemotherapy. Healing is usual although often delayed, and mastectomy should be restricted to patients with persistent residual infection.

Actinomycosis

Actinomycosis of the breast is rarer still. The lesions present the essential characteristics of faciocervical actinomycosis.

Syphilis of the breast

A primary chancre of the nipple has been referred to (above). Secondary lesions of syphilis include diffuse syphilitic mastitis.

Mondor’s disease

Mondor’s disease is thrombophlebitis of the superficial veins of the breast and anterior chest wall although it has also been encountered in the arm.

In the absence of injury or infection, the cause of thrombophlebitis —like that of spontaneous thrombophlebitis in other sites — is obscure. The pathognomonic feature is a thrombosed subcutaneous cord, usually attached to skin. When the skin over the breast is stretched by raising the arm, a narrow, shallow subcutaneous groove alongside the cord becomes apparent. The differential diagnosis is lymphatic permeation from an occult carcinoma of the breast. The only treatment required is restricted arm movements, and in any case the condition subsides within a few months without recurrence, complications or deformity.

Duct ectasia/periductal mastitis

Pathology

This is a dilatation of the breast ducts associated with periductal inflammation, the pathogenesis of which is obscure and almost certainly not uniform in all cases, although the disease is much more common in smokers.

The classical description of the pathogenesis of duct ectasia asserts that the first stage in the disorder is a dilatation in one or more of the larger lactiferous ducts which fill with a stagnant brown or green secretion. This may discharge. These fluids then set up an irritant reaction in surrounding tissue leading to periductal mastitis or even abscess and fistula formation. In some cases a chronic indurated mass forms beneath the areola which mimics a carcinoma.

Fibrosis eventually develops which may cause slit-like nipple retraction.

An alternative theory suggests that periductal inflammation is the primary condition and anaerobic bacterial infection is found in some cases.

An association between recurrent periductal inflammation and smoking has been demonstrated which may suggest that arteriopathy is a contributing factor in its aetiology.

Clinical features

Nipple discharge (of any colour), a subareolar mass, abscess, mammary duct fistula and/or nipple retraction are the commonest symptoms.

Treatment

In the case of a mass or nipple retraction, a carcinoma must be excluded by obtaining a mammogram and negative cytology or histology. If any suspicion remains the mass should be excised.

Antibiotic therapy may be tried, the most appropriate agents being flucloxacillin and metronidazole. However, surgery is often the only option likely to bring about cure of this notoriously difficult condition, and consists of excision of all of the major ducts (the Hadfield’s operation).

Aberrations of normal development and involution (ANDI)

Nomenclature

The nomenclature of benign breast disease is very confusing. This is because over

the last century a variety of clinicians and pathologists has chosen to describe a mixture of physiological changes and disease processes according to a variety of clinical, pathological and aetiological terminology. As well as leading to confusion, patients were often unduly alarmed or overtreated by ascribing a pathological name to a variant of physiological development. To sort out this confusion, a new system has been developed and described by the Cardiff Breast Clinic — ANDI. (Many alternative terms have been applied to this condition including fibrocystic disease, fibroadenosis, chronic mastitis and mastopathy.)

A etiology

The breast is a dynamic structure which 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 an extreme of normality to well-defined disease processes. There is often little correlation between the histological appearance of the breast tissue and the symptoms.

Risk of malignancy developing in association with benign breast pathology

These relative risks according to different histological features found at biopsy.

Pathology

The disease consists essentially of four features which may vary in extent and degree in any one breast.

1.

2.Fibrosis. Fat and elastic tissue disappears and is replaced by dense white fibrous trabeculae. The interstitial tissue is infiltrated with chronic inflammatory cells.

3.Hyperplasia of epithelium in the lining of the ducts and acini may occur with or without atypia.

4. Papillomatosis. The epithelial hyperplasia may be so extensive that it results in papillomatous overgrowth within the ducts.

Clinical features

The symptoms of ANDI include an area of lumpiness (seldom discrete) and/or

Cyst formation. Cysts are almost inevitable and very variable in size.

breast pain (mastalgia).

A benign discrete lump in the breast is commonly a cyst or fibroadenoma. True lipomas occur rarely.

Lumpiness may be bilateral, commonly in the upper outer quadrant, or less commonly confined to one quadrant of one breast. The changes may be cyclical, with an increase in both lumpiness and often tenderness before a menstrual period.

Noncyclical mastalgia is commoner in perimenopausal and postmenopausal women. It may be associated with ANDI or with periductal mastitis, or referred from, for example, a musculoskeletal disorder. About 10 per cent of breast cancers exhibit pain at presentation.

Treatment of lumpy breasts

If the clinician is confident that he or she is not dealing with a discrete abnormality (and clinical confidence may be buttressed by mammography or ultrasound scanning if appropriate), then initially the woman can be offered firm reassurance. It is perhaps worthwhile reviewing the patient at a different point in the menstrual cycle, say 6 weeks after the initial visit, and often the clinical signs will have resolved by that time. There is a tendency for women with lumpy breasts to be rendered unnecessarily anxious and to be submitted to multiple random biopsies because the clinician lacks the courage of his or her convictions.

Treatment of mastalgia

Pronounced cyclical mastalgia may become a significant clinical problem where the pain and tenderness interfere with the woman’s life, disturb her sleep and impair sexual activity. Initially, firm reassurance that the symptoms are not associated with cancer will help the majority of women. A patient symptom diary will help her to chart the pattern of pain throughout the month and thus determine whether this is cyclical mastalgia. If reassurance is inadequate, then a planned escalation of treatment could be advised. Oil of evening primrose, in adequate doses given over 3 months, will help more than half of these women. For those with intractable symptoms a prolactin inhibitor such as danazol may be given. Very rarely it is necessary to prescribe an antioestrogen, e.g. tamoxifen or a luteinizing hormone-releasing hormone (LHRH) agonist, to deprive the breast epithelium of oestrogenic drive.

For noncyclical mastalgia it is important to exclude extramammary causes such as

chest wall pain, and it may be necessary to carry out a biopsy on a very localised tender area which might be harbouring a subclinical cancer. Treatment may be with nonsteroidal analgesics or by injection with local anaesthetic of a ‘trigger spot’.

Breast cysts

These occur most commonly in the last decade of reproductive life due to a nonintegrated involution of stroma and epithelium. They are often multiple, may be bilateral and can mimic malignancy. Diagnosis can be confirmed by aspiration and/or ultrasound.

Treatment

A solitary cyst or small collection of cysts can be aspirated. If they resolve completely, and if the fluid is not bloodstained, no further treatment is required. However, 30 per cent will recur and require reaspiration. Cytological examination of cyst fluid is no longer practised routinely. If there is a residual lump or if the fluid is bloodstained, a local excision for histological diagnosis is advisable, as is also the case if the cyst repeatedly reforms.

Galactocele

Galactocele, which is rare, usually presents as a solitary, subareolar cyst, and always dates from lactation. It contains milk and in longstanding cases its walls tend to calcify. It can become enormous.

Fibroadenoma

These usually arise in the fully developed breast during the 15—25-year period, although occasionally they occur in much older women. They arise from hyperplasia of a single lobule, and usually grow up to 2—3 cm in size. They are surrounded by a well-marked capsule and can thus be enucleated through a cosmetically appropriate incision. However, in a patient under 30 years these donot require excision unless associated with suspicious cytology, or if they become very large, or if the patient expressly desires the lump to be removed. Giant fibroadenomas occur occasionally during puberty. They are over 5 cm in diameter and are often rapidly growing, but in other respects are similar .to smaller fibroadenomas and can be enucleated through a submammary incision.

Phyllodes tumour

These benign tumours, previously sometimes known as serocystic disease of Brodie or cystosarcoma phyllodes, usually occur in women over the age of 40 but can appear in younger women. They present as a large, sometimes massive tumour, with an unevenly bosselated surface. Occasionally ulceration of overlying skin occurs owing to pressure necrosis. In spite of their size they remain mobile on the chest wall. Histologically there is a resemblance to a fibroadenoma, but despite the name of cystosarcoma phyllodes they are rarely cystic and only very rarely develop features of a sarcomatous tumour. These may metastasise via the bloodstream.

Treatment

Treatment for the benign type is enucleation in very young women or wide local excision. Massive tumours, recurrent tumours and those of the malignant type will require mastectomy.

When the diagnosis of carcinoma is in doubt

There will always be cases where the clinician cannot be sure whether a particular lump in the breast is an area of mammary dysplasia, a benign tumour or an early carcinoma.

If there is doubt on either clinical, cytological or radiological examination it is essential to obtain a tissue diagnosis. This is often possible by needle biopsy. In the advent of a negative result, open biopsy of the mass is necessary. Because of the possibility of reporting errors, the authors suggest that frozen section reporting should rarely be used and certainly should not form the basis for a decision to undertake a mastectomy.

Carcinoma of the breast

Breast cancer is the commonest cause of death in middle-aged women in Western

Aetiological factors

1.Geographical. It occurs commonly in the Western world accounting for 3—5 per cent of deaths, yet is a rare tumour in Japan. In developing countries it accounts for 1—3 per cent of deaths.

2.Age. Carcinoma of the breast is extremely rare below the age of 20, but thereafter the incidence steadily rises so that by the age of 90 nearly 20 per cent of women are affected.

By age 25 1 in 19608 By age 60 1 in 24By age 30 1 in 2525 By age 65 1 in 17By age 35 1 in 622 By age 70 1 in 14By age 40 1 in 217 By age 75 1 in 11

By age 55 1 in 33 Ever 1in 81987—1988 Cancer incidence rates, NCI, USA.

3.Gender. Less than 1 per cent of patients with breast cancer are male.

4.Genetic. It occurs more commonly in women with a family history of breast cancer than in the general population. Breast cancer related to a specific mutation accounts for about repercussions in terms of counselling and attempted prevention in these women. This will be discussed more fully in a subsequent section.

5.Diet. Because breast cancer so commonly affects women in the ‘developed’ world, dietary factors may play a part in its causation. There is some evidence that there is a link between diets low in phyto-oestrogens. A high intake of alcohol is associated with an increased risk of developing breast cancer.

6.Endocrine. Breast cancer is commoner in nulliparous women and breastfeeding in particular appears to be protective. Also protective is having a first child at an early age, especially if associated with late menarche and early menopause. It is

countries.

By age 45 1 in 93 By age 80 l in 10By age 50 l in 50 By age 85 l in 9

5 per cent of breast cancers, yet has far-reaching

known that in postmenopausal women, breast cancer is more common in the obese. This is thought to be because of an increased conversion of steroid hormones to oestradiol in the body fat. The role of exogenous hormones, in particular the oral contraceptive pill and hormone replacement therapy, in the development of breast cancer is more controversial, but it can be said with some authority that for most women the benefits of these treatments will far outweigh the small putative risk.

The increase in the likelihood of developing breast cancer associated with the above risk factors is usually quantified in terms of the relative risk (RR). Thus a RR of 2.0 means that the individual has twice the chance of developing breast cancer as the average for the population, whilst a RR of 0.5 indicates a risk reduction of 50 per cent.

Pathology

Breast cancer may arise from the epithelium of the duct system anywhere from the nipple end of major lactiferous ducts to the terminal duct unit which is in the breast lobule. It may be entirely in situ — an increasingly common phenomenon with the advent of breast cancer screening — or may be invasive cancer. The degree of differentiation of the tumour is usually described by three grades — well differentiated, moderately or poorly differentiated. Ductal carcinoma is the most common variant, but lobular carcinoma occurs in up to 10 per cent of cases, although this may be mixed. 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 multi-focal and/or bilateral.

Inflammatory carcinoma is a fortunately rare, highly aggressive cancer which presents as a painful, swollen breast, which is warm with cutaneous oedema. This is due to 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.

In situ carcinoma is preinvasive cancer which has not breached the epithelial basement membrane. This was previously a rare, usually asymptomatic finding in breast biopsy specimens but is becoming increasingly common owing to the advent of mammographic screening — it accounts for 20 per cent of cancers detected by

screening. In situ carcinoma may be ductal (DCIS) or lobular (LCIS), the latter often multifocal and bilateral. Both are markers for the later development of invasive cancer which will go on to develop in at least 20 percent of cases. Although mastectomy is curative, this is overtreatment in many cases and the best treatment for in situ carcinoma is the subject of a number of clinical trials.

Paget’s disease of the nipple

Paget’s disease of the nipple is a superficial manifestation of an underlying breast carcinoma. It presents as an eczema-like condition of the nipple and areola which persists in spite of local treatment. The nipple is eroded slowly and eventually disappears. If left, the underlying carcinoma will sooner or later become clinically evident. Thus nipple eczema should be biopsied if there is any doubt about its

ovoid cells with abundant, clear, pale-staining cytoplasm in the Malpighian layer of the epidermis.

The spread of mammary carcinoma

1. Local spread. The tumour increases in size and invades other portions of the breast. It tends to involve the skin and to penetrate the pectoral muscles, and even the chest wall.

2. Lymphatic metastasis occurs primarily to the axillary lymph nodes and to the internal mammary chain of lymph nodes. The site of the tumour within the breast does not dictate which nodes will be involved, e.g. medial tumours spread just as readily to the axillary nodes as do lateral tumours. The involvement of lymph nodes is not necessarily a chronological event in the evolution of the carcinoma, but rather a marker for the metastatic potential of that tumour. In advanced disease there may be involvement of supraclavicular nodes and of any contralateral lymph nodes.

3. Spread by the bloodstream. It is by this route that skeletal metastases occur (in order of frequency) in the lumbar vertebrae, femur, thoracic vertebrae, rib and skull; they are generally osteolytic. Metastases may also occur in the liver, lung and brain, and occasionally the adrenal glands and ovaries.

Clinical presentation

While any portion of the breast, including the axillary tail, may be involved, breast cancer commences most frequently in the upper, outer quadrant. Most breast

cause. Microscopically Paget’s disease is characterised by the presence of large,

cancers will present as a hard lump, which may be associated with indrawing of the nipple. As the disease advances locally there may be skin involvement with peau d’orange or frank ulceration and fixation to the chest wall. This is described as cancer-encuirasse. About 5 per cent of breast cancers in the UK will present with either locally advanced disease or symptoms of metastatic disease. This figure is nearer 20 per cent in the developing world. These patients must then undergo a staging evaluation so that the full extent of their disease can be ascertained. This will include a careful clinical examination, chest X-ray, serum alkaline phosphatase and gamma glutamine transaminase (GGT), with liver ultrasound if these are abnormal, and an isotope bone scan. This is important for both prognosis and treatment — a patient with widespread visceral metastases may obtain anincreased length and quality of survival from systemic hormone or chemotherapy, but she is not likely to benefit from surgery as she will die from her metastases before local disease becomes a problem. In contrast, patients with relatively small (less than 5 cm in diameter) tumours confined to the breast and ipsilateral lymph nodes rarely need staging beyond a good clinical examination as the pick-up rate for distant metastases is so low.

Phenomena resulting from lymphatic obstruction in Staging of breast cancer

advanced breast cancer

Peau d’orange is due to cutaneous lymphatic oedema. Where the infiltrated skin is tethered by the sweat ducts it cannot swell, leading to an appearance like orange skin. Occasionally the same phenomenon is seen over a chronic abscess.

Late oedema of the arm is a troublesome complication of breast cancer treatment fortunately seen less often now that radical axillary dissection and radiotherapy are rarely combined. It does however occasionally still occur after either modality of treatment alone and appears anytime from months to years after treatment. There is usually no precipitating cause but recurrent tumour should be excluded as neoplastic infiltration of the axilla can cause arm swelling due to both lymphatic and venous blockage. This neoplastic infiltration is often painful due to nerve involvement.

An oedematous limb is susceptible to bacterial infections following quite minor trauma, and these require vigorous antibiotic treatment. Treatment of late oedema is difficult but limb elevation, elastic arm stockings and pneumatic compression devices can be useful.

Cancer-en-cuirasse. The skin of the chest is infiltrated with carcinoma and has

been likened to a coat. It may be associated with a grossly swollen arm. This usually occurs in cases with local recurrence after mastectomy, and occasionally is seen to follow the distribution of irradiation to the chest wall. The condition may respond to palliative systemic treatment but prognosis in terms of survival is poor.

Lymphangiosarcoma is a rare complication of lymphoedema with an onset many years following the original treatment. It takes the form of multiple subcutaneous nodules in the upper limb and must be distinguished from recurrent carcinoma of the breast. The prognosis is poor but some cases respond to cytotoxic therapy or irradiation. Interscapulothoracic (forequarter) amputation is sometimes indicated.

There are two traditional systems of classification for breast carcinoma which predominantly rely on clinical staging of the disease. These are the Manchester system and the International Union Against Cancer TNM (tumour, nodes, metas-tases) staging system.

The TNM system was an attempt to allow a common language amongst oncologists world-wide, thus allowing accurate information exchange and evaluation of studies of treatment, as well as providing prognostic information to aid in the planning of treatment for the individual patient. However, this refinement of taxonomy in fact contributes little to any of these activities.

Further subdivisions in the TNM system now mean that there are seven T-stages, four N-stages and three M-stages, allowing for 180 possible combinations. Pathological lymph node staging depends on both the number of lymph nodes removed, thus the extent of surgery, and how assiduous the pathologist is in looking for deposits of tumour within the nodes. ‘M’ staging depends on what investigations have been performed — thus will vary between centres. Consequently staging is observer biased.

Although prognosis broadly correlates with stage, other factors also influence prognosis and should be assessed, for example the Nottingham Prognostic Index includes not only tumour size and lymph node status but tumour grade.

Conventional staging will indicate broadly which treatment is required but again other factors may be equally important. For example, surgical treatment of a small stage I, or II (T1 or T2) breast tumour usually requires only wide local excision rather than mastectomy — but the latter may have to be performed if the breast is very small, the tumour is central or multifocal, or for patient preference. Equally the use of adjuvant systemic therapy is decided on not only tumour size and lymph node status but also biological measures such as oestrogen receptor status, patient

age and menopausal status, and in the case of tamoxifen this can be recommended irrespective of clinicopathological variables.

Thus as we gain more knowledge of the biological variables which affect prognosis it becomes increasingly clear that it is these factors (discussed in more detail below) rather than anatomical mapping which influence outcome and treatment. Perhaps a more pragmatic approach would be to classify patients according to the treatment that they require.

Prognosis of breast cancer

The best indicators of likely prognosis in breast cancer are still tumours 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 has been described. These include histological grade of the tumour, hormone receptor status, measures of tumours proliferation such as 5-phase fraction and thymidine-labelling index, growth factor analysis and oncogene or oncogene product measurements. Many others are under investigation but have proved of little practical value in patient management.

Treatment of cancer of the breast

As has been indicated above, treatment will largely depend upon clinical stage of the disease at presentation including not only classical TMN staging but often other tumour characteristics such as tumour grade. 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 invasion 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.

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 where 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, where 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.

Treatment of early breast cancer

The aims of treatment are:

1 ‘cure’: possible in some patients but recurrence up to 20 years after initial

2.control of local disease in the breast and axilla;

3. conservation of local form and function;

4. prevention or delay of the occurrence of distant metastases.

Local treatment of early breast cancer

treatment is nor uncommon;

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 which have shown equal efficacy between mastectomy and local excision followed by radiotherapy. This followed a change in the model of breast cancer spread, which is no longer thought of as a centrifugal anatomical spread but rather that it is the presence of micrometastases which predetermines the outcome of the disease.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 per cent of women develop significant anxiety and depression following both radical and conservative surgery. After mastectomy they rend to worry about the effect of the operation on their appearance and relationships whilst after conservative surgery women may remain fearful of a recurrence.

Mastectomy is now only strictly indicated for large tumours (in relation to the size of the breast), central tumours beneath or involving the nipple, multifocal disease, local recurrence or for patient preference. The radical Halstead mastectomy which included excision of the breast, axillary lymph nodes, pectoralis major and minor muscles is no longer indicated as it causes excessive morbidity with no survival benefit. Modified radical (‘Patey’) mastectomy is more commonly performed and thus is described below. Simple mastectomy involves removal of the breast only 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. Because no pathological staging of the axilla is performed with a simple mastectomy, it is often followed by radiotherapy to the axilla.

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 always includes the nipple;

• all of the fat, fascia and lymph nodes of the axilla. The pectoralis minor muscle is either divided or removed to gain access to the upper two-thirds of the axilla. The axillary vein and nerves to serratus anterior and latissimus dorsi should be

Local control is achieved through surgery and/or radiotherapy.

Patey’ mastectomy. The breast and associated structures are dissected

preserved.

The wound is drained using a wide-bore suction tube.

Early mobilisation of the arm is encouraged and physiotherapy helps normal function to return very quickly — most patients are able to resume light work or housework within a few weeks. Conservative breast cancer surgery 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 or lumpectomy. A quadrantectomy involves removing the entire segment of the breast which contains the tumour. These are usually combined with axillary surgery, usually via a separate incision in the axilla, to either sample the axilla, remove nodes behind and lateral to pectoralis minor (level II) or perform a full axillary dissection (level III). A quadrantectomy, axillary dissection and radiotherapy is known as QUART and has been popularised by Professor Umberto Veronesi from Milan. Whilst it is recognised that there is a somewhat higher rate of local recurrence following conservative surgery, even if combined with radiotherapy, the long-term outlook in terms of survival is unchanged.

The role of axillary surgery is still debated, but it is accepted that the presence of metastatic disease within the axillary lymph nodes is still the best 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. An acceptable way to approach this problem in premenopausal women is to stage the axilla by operation as there is a good case for giving chemotherapy to lymph node-positive patients. In postmenopausal patients, tamoxifen is usually given regardless of axillary lymph node status. If mastectomy is performed it is reasonable to clear the axilla as part of the operation, but if a wide local excision is planned the surgeon may choose either operative dissection or postoperative radiotherapy. Axillary surgery should not be combined with radiotherapy to the axilla because of excess morbidity. Removal of the internal mammary lymph nodes is unnecessary.

Sentinal node biopsy is a technique currently under evaluation which may well prove the way forward in the future in the management of the axilla in patients with clinically node-negative disease. The sentinal node is localised perioperatively by the injection of patent blue dye and/or radioisotope-labelled albumin near the tumour. The marker will pass to the primary node draining the area, be detected visually or with a hand-held gamma camera, and sent for frozen section histological analysis. In patients in whom there is no tumour involvement

of the sentinal node, it is hoped that further axillary dissection can be avoided as skip lesions are thought to occur in less than 3 per cent of patients.

Radiotherapy

Radiotherapy to the chest wall after mastectomy has been largely abandoned except in cases of extensive local disease with infiltration of the chest wall. It is conventional to combine conservative surgery with radiotherapy to the remaining breast tissue. However, there is currently doubt as to whether all patients undergoing conservative surgery should receive radiotherapy as most will not develop local recurrence and thus will be overtreated by adjuvant radiotherapy, which is not without morbidity and even long-term mortality from inadvertent irradiation to the myocardium. A UK national clinical trial is currently underway to try to ascertain whether there is a survival advantage with radiotherapy and to identify which patients are at highest risk of local relapse, and thus would benefit most from postoperative breast irradiation. Currently those thought to be at highest risk include those with extensive in situ carcinoma (or of course invasive cancer) at the margins of excision, patients under 35 years and those with multifocal disease.

Adjuvant systemic therapy

Over the last 25 years there has been a revolution in our understanding of the biological nature of carcinoma of the breast. 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. As a result of many international clinical trials and recent world overview analyses, it can be stated with extreme statistical confidence that the appropriate use of adjuvant chemotherapy or hormone therapy will improve relapse-free survival by approximately 30 per cent, which ultimately translates into an absolute improvement in survival of the order of 10 per cent at 15 years. Bearing in mind how common the disease is in Northern Europe and the USA, this translates into figures of major public health importance.

Who to treat and with what are still questions for which absolute answers have yet to found, but the data from an overview of recent trials suggest that lymph node-positive and poor prognosis node-negative premenopausal women should be recommended adjuvant combined chemotherapy and that postmenopausal women

will obtain a worthwhile benefit from about 5 years of tamoxifen, 20 mg daily.

Hormone therapy

Tamoxifen is the most widely used ‘hormonal’ treatment in breast cancer. Its efficacy as an adjuvant therapy was first reported in 1983 and it has now been shown to reduce the annual rate of recurrence by 25 per cent, with a 17 per cent reduction in the annual rate of death. The effect of tamoxifen is favourable in most cases except for oestrogen receptor ER-negative premenopausal women; postmenopausal women with oestrogen receptor-rich (positive) tumours achieve a greater reduction in the relative risk of relapse than oestrogen receptor-negative cases. The beneficial effects of tamoxifen in reducing the risk of tumours in the contralateral breast have also been observed. Trials studying the optimal duration of treatment are close to maturity and suggest that 5 years of treatment may be preferable to 2 years.

Other hormonal agents are being developed which may prove beneficial as adjuvant therapy, such as the LHRH agonists which induce a reversible ovarian suppression and thus are hoped to have the same beneficial effects as surgical or ~radiation-induced ovarian ablation in premenopausal women, and the oral aromatase inhibitors for postmenopausal women.

Chemotherapy

Chemotherapy using a regimen such as a 6-monthly cycle of cyclophosphamide, methotraxate and 5-fluorouracil (CMF) will achieve a 30 per cent reduction in the risk of relapse over a 10—15-year period. This treatment has been confined to premenopausal poor prognosis women (where its effects are likely to be due in part to a chemical castration effect) but is being increasingly offered to postrnenopausal women with poor prognosis disease as well. Chemotherapy may be considered in node-negative patients if other prognostic factors such as tumour grade infer a high risk of recurrence. The effect of combining hormone and chemotherapy is still under investigation and is beginning to look promising.

High-dose chemotherapy with stem cell rescue for patients with heavy lymph node involvement is still considered experimental and should not be offered outside controlled trials.

Primary chemotherapy is being used in many centres for large hut 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. This approach is successful in up to 80 per cent of cases, but is not associated with improvements in survival compared with conventionally timed chemotherapy.

Breast reconstruction

Despite an increasing trend toward conservative surgery, up to 50 per cent 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 — even those with a limited life expectancy may benefit from the improved quality of life, however patients do require counselling before this procedure so that their expectations of cosmetic outcome are not unrealistic.

The most common 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 (for example following radiotherapy) or if a larger volume of tissue is required, a musculocutanous flap can be constructed from either the latissimus dorsi muscle (an LD flap) or the contralateral 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.

Nipple reconstruction is a relatively simple procedure which can be performed under a local anaesthetic. Alternatively the patient can be fitted with a prosthetic nipple. To achieve symmetry, the opposite breast may require a cosmetic procedure such as reduction or augmentation mammoplasty, or mastopexy. A breast reconstructive service can be offered by a suitably trained breast surgeon, a plastic surgeon or ideally a combined oncoplastic approach.

External breast prostheses which fit within the bra may also be recommended.

Screening for breast cancer

Because the prognosis of breast cancer is closely related to stage at diagnosis, it would seem reasonable to hope that a population screening programme which could detect tumours before they come to the patient’s notice may reduce mortality from breast cancer. A number of studies has indeed shown that breast screening by mammography in women over the age of 50 will reduce cause-specific mortality by up to 30 per cent. Following the publication in 1987 of the Forrest report the National Health Service in the UK has launched a programme of 3-yearly mammographic screening for women between the ages of 50 and 64. The introduction of this programme has undoubtedly improved the quality of breast cancer services but a number of questions remains unanswered including the value of screening women under 50 and the ideal interval between screenings. The psychological consequences of false alarms or false reassurances still need to be addressed and self-examination programmes which have failed to show any benefit for the population in terms of earlier or decreased mortality from breast cancer still remain controversial.

Familial breast cancer

Recent developments in molecular genetics and the identification of a number of breast cancer predisposition genes (BRCA1, BRCA2 and TPS3) have done much to stimulate interest in this fascinating area. Yet women whose breast cancer is due to an inherited genetic change actually account for less than 5 per cent of all breast cancers — that is about 1250 cases per year in the UK and 9000 cases in the USA. A much larger number of women will have a risk elevated above normal due to an as yet unspecified familial inheritance. These women have a risk of developing breast cancer two to 10 times above baseline.

The BRCAI gene has been cloned and is located on the long arm of chromosome 17 (17q). The gene frequency in the population is approximately 0.0006. BRCA2 is located on chromosome 13q. Women who are thought to be gene carriers may be offered breast screening (and ovarian screening in the case of BRGA1, which is known to impart a 50 per cent lifetime risk of ovarian cancer), usually as part of a research programme, or may be offered generic counselling and mutation analysis. Those who prove to be ‘gene positive’ have an 80 per cent risk of developing breast cancer, predominantly whilst premenopausal. Many will opt for prophylactic mastectomy, although this does not completely eliminate the risk.

For,those with a positive family history who are unlikely to be carriers of a breast cancer gene, which will comprise the great majority of women, there is no currently proven preventive or screening manoeuvre, although these are under investigation. Thus these women are best served by being assessed and followed up, if necessary, in a properly organised research family history clinic.

Pregnancy

The effects of pregnancy on breast cancer are not well studied but it is thought that breast cancer presenting during pregnancy or lactation tends to be at a later stage — presumably because the symptoms are masked by the pregnancy — but 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 is probably 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 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 Pill.

Hormone-replacement therapy

Hormone-replacement therapy (HRT) does not appear to increase significantly the risk of developing breast cancer unless taken for prolonged periods (over 10 years), and perhaps in certain high-risk groups. HRT may, however, prolong symptoms of benign breast disorder and make mammographic appearances more difficult to interpret.

Patients who develop breast cancer whilst on HRT appear to have a more favourable prognosis. The consequences in terms of recurrence in women using HRT following breast cancer are unknown.

Treatment of advanced breast cancer

Breast cancer may occasionally present as metastatic disease without evidence of a primary tumour (that is with an occult primary). The diagnosis is made partly by exclusion of another site for the primary and may be confirmed by histology of the metastatic lesions. Treatment should be aimed at palliation of the symptoms and treating the breast cancer, usually by endocrine manipulation.

Locally advanced inoperable breast cancer

Locally advanced inoperable breast cancer, including inflammatory breast cancer, is usually treated with systemic therapy

—either chemotherapy or hormone therapy.

Occasionally ‘toilet mastectomy’ or radiotherapy is required to control a fungating tumour, but often incision through microscopically permeated tissues makes the outcome worse than the original.

Metastatic carcinoma of the breast

Metastatic carcinoma of the breast will also require some form of palliative systemic therapy to alleviate symptoms. Hormone manipulation is often the first line because of its minimal side effects. It is particularly useful for bony metastases. However, only about 30 per cent of these tumours will be hormone responsive, and unfortunately even these will in time become resistant to this treatment. First-line hormone therapy for postmenopausal women is tamoxifen, and for premenopausal women ovarian suppression, but where resistance to these has developed, other hormonal agents can prove useful, with about half of the response rate seen in the first-line therapy. Synthetic progestagens such as medroxyprogesterone acetate (‘Provera’) aromatase inhibitors or the newer agents such as antiprogestins and pure antioestrogens are all candidates for this role.

Cytotoxic therapy is used, particularly in younger women or those with visceral metastases and rapidly growing tumours. A variety of regimens is available and although none prolongs survival, contrary to expectations quality of life and symptom control is often better with more aggressive treatments, responses being seen in up to 70 per cent of patients.

Local treatment may also prove useful for some metastatic disease such as radiotherapy for painful bony deposits and internal fixation of pathological

fractures.

The male breast

Gynaecomastia

Idiopathic

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

Hormonal

Enlargement of the breasts often accompanied stilboestrol 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.

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 due to failure of the liver to metabolise oestrogens. It is associated with drugs that interfere with the hepatic metabolism of oestrogens, such as cimetidine.

Gynaecomastia may occur in patients with Klinefelter’s syndrome, a sex chromosome anomaly having XXY trisomy. It is also seen with certain drugs such as cimetidine, digitalis and spironolactone.

Treatment

Provided the patient is healthy and comparatively young, reassurance may be sufficient. If not mastectomy with preservation of the areola and nipple can be performed.

Carcinoma of the male breast

Carcinoma of the male breast accounts for less than 2 per cent of all cases of breast cancer. The known predisposing causes include gynaecomastia and excess

endogenous or exogenous oestrogen. As in the female it tends to present as a lump and is most commonly an infiltrating ductal carcinoma.

Treatment

Stage for stage the treatment is the same as for carcinoma in the female and prognosis depends upon stage at presentation. Adequate local excision, because of the small size of the breast, should always be with a mastectomy

Other tumours of the breast

Lipoma

A true lipoma is very rare.

Sarcoma of the breast

Sarcoma of the breast is usually of the spindle-cell variety, and accounts for 0.5 per cent of malignant tumours of the breast. Some of these growths arise in an intracanalicular fibroadenoma or may follow previous radiotherapy, e.g. for Hodgkin’s lymphoma many years previously. It may be impossible to distinguish clinically a sarcoma of the breast from a medullary carcinoma, hut areas of cystic degeneration suggest a sarcoma and on incising the neoplasm it is pale and friable. Sarcoma tends to occur in younger women between the ages of 30 and 40. Treatment is by simple mastectomy followed by radiotherapy. The prognosis depends on the stage and histological type.

Metastases

On rare occasions, cancer elsewhere may present with a metastasis in the breast. The breast is also occasionally infiltrated by Hodgkin’s disease and other lymphomas.