Breast cancer
Demographics
Breast cancer is the most common cancer among women and the second largest cause of cancer death. The incidence of breast cancer increases with age and peaks between the ages of 45-55 and plateaus from then onwards. The incidence of breast cancer is increasing due to increased screening.
Aeitiology and pathophysiology:
Breast cancer is caused by accumulation of genetic mutations leading to malignant growth.
- Risk factors of breast cancer include:
- Previous breast cancer
- Family history of breast cancer (if more than 2 first degree relatives have breast cancer, the risk to other members is doubled. )
- Age
- Genetical - individuals with 4 relatively common genes are more susceptible to developing breast cancer. This includes BRCA 1, BRCA 2, CHEK2 and FGFR2. In individuals with these genes, lifetime risk of developing cancer may be up to 80% with a 60% risk of developing ovarian cancer.
- Hormone replacement therapy with oestrogen or a combination of oestrogen and progesterone (increase in risk is proportional to duration of use)
- Previous pregnancy before the age of 30 reduces breast cancer risk
- Late menopause
- Lower socioeconomic class (class I and II)
- non vegetarian diet
Presentation
Women with breast cancer frequently present with a lump in their breast, although some may also present with changes to their nipples or the skin overlying the breast, or nipple discharge. Patients with breast cancer may also present with axillary or supra/infraclavicular lymphadenopathy, or with symptoms from metastatic disease such as bone pain. Some women may also present through routine screening.
Examination:
An examination should be performed of both breasts and for lymph nodes in the axilla, infra and supraclavicular regions and the cervical region. If the patient presents with symptoms of metastatic disease, other relevant systems should be examined as well (eg. bony tenderness, enlarged liver, focal neurological signs)
Cancerous lumps are more likely to be hard, and may be tethered to the skin or underlying structures. 85% of breast cancers present as a non-tender lump.
Referral:
Women are often referred to secondary breast services through screening, if they have symptoms suggestive of breast cancer or if they have significant family history of breast cancer.
In general practice, referral criteria for urgent (2 week) referral are:
- Woman of any age presenting with a discrete hard lump with fixation which may or may not be tethered to the skin.
- Woman over 30 with discrete lump which persists after next period or presents after menopause.
- Woman below 30 with a breast lump which enlarges, shows features of cancer (hard or fixed) or with other reasons of concern such as family history.
- Woman with previously confirmed breast cancer presenting with further lump or symptoms
- Patients with unilateral eczematous skin or nipple change which does not respond to topical treatment
- Patients with recent onset nipple distortion.
- Patients presenting with spontaneous unilateral bloody nipple discharge
- Man aged 50 or over with unilateral firm subareaolar mass.
A non urgent referral should be considered for women below 30 with breast lumps which feel typically benign.
Differential diagnoses
Breast lumps may be benign or malignant.
Benign causes of breast lumps include:
- Fibroadenomas - tend to be smooth and mobile, known as breast 'mouse' . occurs in young adults.
- Cyst - smooth, mobile, may be tender.
- Duct ectasia- retroareolar pain, nipple retraction and creamy nipple discharge.
- Sebaceous cyst - fixed to skin, may have a punctum.
- Galactocele- occurs in women who are lactating, smooth mobile swelling
- Fat necrosis - occurs after trauma - may be hard and irregular.
- Lipoma- Soft lobulated swelling, rare on breasts.
- Tuberculous abscess - rare in developed contries but may be prevalent in places where TB is endemic.
General swelling of the breast could be caused by:
- Pregnancy
- Lactation
- Puberty
- Mastitis - enlarged, red, tender and hot.
Investigations and management:
Patients referred via a 2 week wait referral will receive a triple assessment (usually on the same day by a multidisciplinary clinic) which includes:
- Examination by a breast clinician
- Imaging - mammogram usually for older women and ultrasound scan for younger women as they have denser breast tissue which is more difficult to image by mammography.
- Biopsy - usually by fine needle aspiration (which only yields cells and has a high false negative rate compared to other modes of biopsying) or core needle biopsy (which can be examined by pathologists).
If breast cancer is diagnosed, further investigations to stage and grade the cancer include:
- Routine bloods: Full blood count
- Liver function tests
- Renal function
- CA 15-3 tumour marker (useful for prognosis but not screening)
- Oestrogen and progesterone receptor status, HER 2 status.
- Chest X ray - may show lung metastases
- CT scan if signs of metastases is present
- Bone scan if patient presents with distant metastases, bone pain, lymph node involvement or advanced local disease
- PET scan - again used to detect metastases but may miss low grade tumours.
Breast cancer can be ductal arising from cells of the ducts of the breast, or lobular, arising from the terminal ducts and lobules.
Grading (bloom and richardson)
Preinvasive breast cancer is described as ductal or lobular carcinoma in situ.
G1- Well differentiated
G2- Moderately differentiated
G3- Poorly differentiated
Staging
T0 - no detectable primary tumour
T1- Tumour <2cm i="" nbsp="" p="" tage="">
T2- Tumour 2-5 cm (Stage II)
T3- Tumour >5 cm (Stage IIIA)
T4 Tumour of any size extending into the skin or chest wall (Stage IIIB)
N0- no nodes involved
N1- mobile axillary nodes (Stage II)
N2 Fixed axillary nodes (Stage IIIA)
N3 Supra or infraclavicular nodes (Stage IV)
M0 No distant metastases
M1 Distant metastases (Stage IV)
Treatment:
The choice of treatment in breast cancer depends primarily on the staging of the cancer, and molecular characteristics of the cancer such as the presence of oestrogen receptors, progesterone receptors and herceptin receptors, as well as other factors such as patient choice and fitness for surgery.
Local disease
Breast cancer which is confined to the breasts are often treated surgically. THis may be through a lumpectomy (also known as wide local excision), where part of the breast tissue is removed, or a full mastectomy where the whole breast is removed. This is often combined with sentinel node biopsy, where lymph nodes which the cancerous area drains to first are identified and biopsied. A lumpectomy is more appropriate for tumours less than 5 cm and not fixed, other considerations include the woman's breast size, and patient preference. Mastectomies are performed in patients with tumours between 5-10 cm, and may be combined with an axillary dissection to remove the axillary nodes.
Breast reconstructive surgery should also be considered by the patient. This may be performed at the time of the primary surgery or after this. This should be considered for both older and younger women as it may have huge psychological benefits.
Adjuvant radiotherapy is often given to many women after a lumpectomy . Adjuvant radiotherapy reduces recurrence rate from 40-60% to 4-6%.
In addition adjuvant hormonal therapy in patients with oestrogen positive tumours is often given to patients both pre and post menopausal as it is shown to improve survival and disease free period. This is often given for 5 years. Tamoxifen which is an oestrogen receptor antagonist is often given to premenopausal women, and aromatase inhibitors which block the conversion of androgens to oestrogen by fatty tissues is often used in post menopausal women.
In women with advanced local disease, neo-adjuvant chemotherapy may be used to reduce tumour size before surgery. This is usually with a FEC-T regime (5FU, epirubicin, and cyclophosphamide and taxanes)
Herceptin (Traztuzumab) is a monoclonal antibody which targets epidermal growth factor receptor 2 (known as HER2). This may be used in patients with HER2 positive disease although it may have significant side effects including effects on the heart.
Metastatic disease
Breast cancer most commonly metastasises to the lungs, liver, bone and brain. Metastatic disease is rarely curable. In older patients, hormonal therapy with tamoxifen and aromatase inhibitors are preferred. This is less effective in younger women (10% response in patients aged 30) and oestrogen levels can be reduced with leuteinizing hormone receptor hormone agonist which reduces ovary function. This is equally effective as surgical oophorectomy. Radiotherapy is ineffective at stopping ovary function.
Radiotherapy ma be used to control bone pain, and bisphosphanates may also be beneficial in this aspect. Bisphosphonates also reduce events such as fractures and spinal cord compression. Chemotherapy may be effective in prolonging survival in patients with liver and lung metastases.
Carcinoma in situ
CIS is diagnosed by excisional biopsy and is treated with mastectomy or radiotherapy.
Cancer in pregnancy:
Breast cancer may occasionally occur in patients who are pregnant. In these cases management should balance the risks to the fetus and risk to the mother. Radiotherapy and chemotherapy may harm the fetus, and may therefore be delayed. Termination of pregnancy may also be an option. lactation post partum should be stopped to allow surgery as lactation increases the vascularisation of the breast and some chemotherapeutic agents cross into the milk.
Prognosis:
Prognosis of breast cancer depends on the stage at which it presents. Recurrence typically peaks at 2 years, and is higher amongst women with node positive disease. 10 year survival of stage 1-2 disease is between 60-85% Stage 3 disease has a 10 year survival of around 40%, and average survival for patients with metastatic disease may vary depending on the site and grade of the metastases, and the presence of certain receptors. average survival is reported to be 18-24 months but may be many years for a small number of individuals.
Bower M, Waxman J, Oncology, Lecture notes, 2nd ed, Oxford;Wiley Blackwell;2010.
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