Breast cancer

Epidemiology:

• Most commonest form of cancer to affect women in the Western world
• Directly responsible for 19% of all female cancer-related deaths
• Incidence of 30 per 100,000 population
• It is estimated that 1 in 9 women will develop the disease

Aetiology:

The risk factors include:

• Age:
• Rare <35 years of age
• Incidence increases with age
• Country of birth:
• High risk = northern Europe and north America
• Genetic factors:
• Hereditary and familial breast cancer can be described using the Lynch system of classification (see below)
• Early menarche/late menopause
• Nulliparity/late childbirth
• Obesity
• Exogenous hormones:
• High-dose OCP
• HRT

• Previous cancer
• Irradiation
• Previous benign disease (see below)

The lynch classification of inherited susceptibility to breast cancer:

Hereditary breast cancer:

• A family history of breast cancer and, sometimes, related cancers (colonic, endometrial) forming part of the Lynch syndrome type II
• This involves an autosomal dominant, highly penetrant cancer susceptibility factor
• These patients tend to be younger than average, have multiple primaries and may also have other tumours

Familial breast cancer:

• A family history of breast cancer including one or more first or second degree relative with breast cancer that does not fit the hereditary breast cancer definition

Relative risk of developing breast cancer in relation to previous benign beast disease:

No risk:

• Apocrine change
• Ductal ectasia
• Mild hyperplasia (no atypia)

Slight risk:

• Moderate or florid hyperplasia (no atypia)
• Sclerosing adenosis
• Papilloma

Moderate risk:

• Atypical ductal or lobular hyperplasia

TNM classification of breast cancer:

Tis Carcinoma in situ (pre-invasive)

T0 No clinical evidence of primary tumour

T1 Tumour <2cm

T2 Tumours 2-5cm

T3 Tumour >5cm

T4 Tumour of any size but with direct extension to chest wall or skin:

• (a) Fixation to chest wall
• (b) Oedema, lymphocytic infiltration or ulceration of skin
• (c) Both (a) and (b)

N0 No palpable ipsilateral axillary lymph nodes

N1 Palpable nodes not fixed:

• inflammatory only
• containing tumour

N2 Fixed ipsilateral lymph nodes

N3 Ipsilateral supraclavicular/infraclavicular nodes or oedema of the arm

M0 No evidence of distant metastasis

M1 Evidence of distant metastasis

Histology:

Are usually adenocarcinomas and are divided into 2 types:

• Ductal
• Lobular

There are 3 degrees of differentiation:

• Grade I – well differentiated
• Grade II – moderately differentiated
• Grade III – poorly differentiated

Carcinoma in situ:

This term refers to the period during which normal epithelial cells undergo apparent malignant transformation but do not invade through the basement membrane. There are 2 forms:

• Lobular (LCIS)
• Ductal (DCIS). DCIS represents all types of in situ carcinoma that are not identified as lobular. It can be further subdivided into:
• Comedo (a particularly menacing type of Tis)
• Solid
• Cribiform
• Micropapillary

The ratio of DCIS to LCIS is approximately 3:1 with 10-37% of those with LCIS and 30-50% of those with DCIS going on to develop invasive carcinoma

Types of invasive breast carcinoma:

Ductal 80%

Lobular/ductal combined 5%

Medullary 6%

Colloid 2%

Other 2%

Symptoms:

Lump 76%

Pain 5%

Nipple retraction 4%

Nipple discharge 2%

Skin retraction 1%

Axillary mass 1%

Paget’s disease:

• This condition presents clinically as a chronic, eczematoid eruption of the nipple
• The diagnosis may be confused with eczema
• It constitutes ~2% of the histological types
• Is almost always associated with an underlying intraductal or invasive carcinoma

Comparison of Paget’s disease and eczema of the nipple:

Paget’s disease Eczema

Unilateral Bilateral

Progressive/continuous Intermittent/variable

Moist or dry Moist

Irregular/discrete Indistinct

Nipple always involved Nipple sparing

Pruritus absent Pruritus present

Inflammatory breast carcinoma:

• Comprises ~1% of breast carcinomas
• Is rapidly progressive
• Characterised by:
• Erythema
• Peau d’orange
• Skin ridging
• May/may not be a palpable mass
• The commonest presenting feature is pain (unlike other breast cancers)
• The characteristic appearance of a diffusely enlarged breast is consequent upon the dissemination of tumour cells through the lymphatics of the dermis

Establishing the diagnosis of breast cancer:

Any palpable breast abnormality should be assessed by the process of triple assessment:

• Clinical evaluation
• Radiological evaluation
• Cytological/histological evaluation

During the consultation with the patient, it is important to convey that only 20% who consult have a breast carcinoma

Physical examination:

• The patient must be undressed to the waist and should sit facing the examiner
• The breast is initially examined from the front with the arms first at the side, then raised above the head and finally placed on the hips
• The patient is asked to point out the supposed area of abnormality and this is examined first
• The following must always be assessed:
• Asymmetry
• Visible lumps
• Erythema
• Peau d’orange (cutaneous oedema)
• Contour flattening
• Skin tethering (as identified by puckering, particularly when the arms are raised)
• Abnormal fixation
• Retraction and altered axis of the nipples

• After this, the patient is asked to lean forward, once again looking for skin retraction
• The supraclavicular, infraclavicular and axillary lymph nodes should be examined
• Further palpation of the breast is best performed in the supine position
• Should a mass be felt, one must assess its:
• Size
• Shape
• Location
• Fixation
• Consistency

Mammography:

Mammography is not useful in women <35 years of age:

• Dense breasts which may mask an underlying tumour
• Interpretation very difficult
• However, should be done if there is clinical suspicion of a malignancy

Mammographic abnormalities that warrant further investigation include:

• Radiological masses undetected on clinical examination
• Microcalcifications
• Stellate densities
• Architectural distortion
• Change from a previous mammogram

Mammography has a false-negative rate of 10-15%

Ultrasound:

• Very good at discriminating between solid and cystic masses
• Useful for guiding biopsy
• In younger women, ultrasound may reveal more information than mammography and most surgeons would perform this test first in women <35 years of age
• Masses in fatty breasts are difficult to assess

Aspiration cytology:

• Needle aspiration of a breast lump is dine with a 21-gauge needle
• The contents of the needle are expressed on to a slide, smeared and fixed (often in both air and alcohol) for cytological examination
• Is a false-negative rate of 1%

Wide-bore core needle biopsy:

• This method provides a sample of tissue for histological, rather than cytological examination
• Because the results are more reliable, this procedure is rapidly superseding aspiration cytology

Open biopsy – require a general anaesthetic:

Excision biopsy:

• Refers to the removal of all gross evidence of disease with a small rim of normal breast tissue

Incision biopsy:

• Similar to excision biopsy, except that only a part of the lump is removed
• It is generally felt that this is not good surgical practice and is, therefore, restricted to larger tumours
• Has largely been superseded by wide-bore core needle biopsy

Nipple biopsy:

• Conditions affecting the nipple (especially an eczema-like appearance) often warrant biopsy
• A wedge of nipple-areolar complex can be excised under local anaesthetic with minimal cosmetic disruption to confirm or refute a diagnosis such as that if Paget’s disease

Management of carcinoma in situ:

• DCIS is usually unilateral and is often treated by surgical excision and postoperative radiotherapy
• LCIS is a marker for a disease that is often bilateral and only sometimes progresses to invasive ductal carcinoma. Therefore, the patient can elect to be observed closely or undergo a curative bilateral mastectomy
• Less than 1% of axillary lymph nodes will be affected and clearance is not required

Management of invasive carcinoma:

This varies widely and is largely dependent on the size of the tumour and whether or not there is regional lymph node involvement

Generally:

Wide local excision of tumour, either a:

Lumpectomy

Quadrantectomy (removal of the involved breast quadrant)

Local radiotherapy

Possible axillary lymph node clearance

Possible adjuvant chemotherapy

For more advanced disease:

• Radical mastectomy with axillary node clearance
• Radiotherapy
• Adjuvant chemotherapy

Complications of surgery:

• Haemorrhage/haematoma formation
• Infection

Complications of radiotherapy:

• Cutaneous inflammation
• Photosensitisation
• Fibrosis and distortion of breast shape
• Shoulder stiffness
• Brachial plexus damage
• Lymphoedema of the arm

Adjuvant therapy:

This encompasses both cytotoxic and hormonal therapy

Cytotoxic therapy:

• Are 2 main regimens:
• CMF (cyclophosphamide, methotrexate and 5-fluorouracil)
• CAF (cyclophosphamide, adriamycin and 5-fluorouracil)
• Chemotherapy is given to all patients at a high risk of recurrence

Hormonal therapy:

• ~30% of all breast tumours respond to an anti-oestrogen such as tamoxifen 20mg od, this rises to 60% of oestrogen-receptor positive tumours

Some tumours are resistant to tamoxifen and even respond unfavourably, therefore, alternative hormonal therapies are available:

• Aromatase inhibitors (prevent the conversion of androgens to oestrogen) such as formestane and anastrozole
• Surgical oophorectomy
• Chemical oophorectomy (using Gn-RH agonists)