2 Clinical need and practice
2.1 Breast cancer is the uncontrolled, abnormal growth of malignant breast tissue. It is the most common type of cancer among women in the UK. The incidence of breast cancer in England and Wales in 2003 was 38,864, accounting for approximately 30% of all reported cancers in women. The age-standardised incidence rates in England and Wales are 144 and 113 per 100,000 population respectively, and women have a one in nine lifetime risk of developing breast cancer. Breast cancer is also the most common cause of cancer-related deaths in women. Approximately 10,500 women died from breast cancer in England in 2003.
2.2 Breast cancer incidence increases with age, and around 80% of breast cancers occur in women older than 50. Factors associated with increased breast cancer risk include previous breast cancer, early menarche, late menopause, hormone replacement therapy, oral contraception, obesity and alcohol consumption. It is also thought that breast cancer risk is increased in women who have not had children, or had children late, and women who have not breast-fed a baby. Family history and genetic predisposition also play an important role, because women who possess mutations of breast cancer susceptibility genes (BRCA1 or 2) are at a higher risk of developing breast cancer. However, the majority of breast cancers occur in women with no direct family history of the disease.
2.3 Once breast cancer is diagnosed, prognosis and treatment decisions depend on the extent of the disease. This is assessed by tumour staging, based on the size and nature of the primary tumour, the involvement of the regional lymph nodes and the presence of distant metastases. When the cancer remains localised in the breast ductules it is known as ductal carcinoma in situ (DCIS), or stage 0 of the Union Internationale Contre le Cancer (UICC) tumour, node, metastases (TNM) clinical staging system. Stages 1 to 3 of the UICC TNM clinical staging system describe cancer that has spread locally to the breast tissue and possibly the lymph glands in the armpit. If the cancer has spread to these local lymph glands, or nodes, it is called 'node-positive'. Stage 4 describes cancer in which the cancer cells have spread through the bloodstream and lymphatic system to other parts of the body. In stages 1 and 2 the tumour is smaller than 5 cm, and these stages are known as early breast cancer.
2.4 Breast tissue contains receptors for the female hormones oestrogen and progesterone. These receptors allow the breast tissue to grow or change in response to changing levels of those hormones. Approximately two thirds of women diagnosed with breast cancer have hormone-receptor-positive tumours; oestrogen or progesterone are the main hormones involved in the development and growth of this type of breast cancer. Hormone-receptor-positive tumours also tend to grow less aggressively, resulting in a better prognosis.
2.5 Current treatment options for early breast cancer depend on disease characteristics (such as stage and hormone-receptor status of the tumour), on patient characteristics (such as age and menopausal status) and on personal preferences.
2.6 Treatment can be divided into surgical treatment and adjuvant treatment after surgical removal of the primary cancer. The purpose of surgery is to control the disease locally (within the breast and axillary lymph nodes) and to determine the prognostic characteristics of the primary cancer. Adjuvant treatment may involve radiotherapy, chemotherapy, hormone therapy or molecular targeted therapy. The aim of adjuvant treatment is to prevent recurrence.
2.7 The aim of hormonal therapy is to deprive the tumour cells of the proliferative stimulus provided by oestrogen. This can be achieved by blocking the binding of oestrogen to its receptor in the nucleus of responsive cells, as with tamoxifen. In the UK, 5 years of tamoxifen therapy has become standard adjuvant hormonal treatment for postmenopausal women with early oestrogen-receptor-positive breast cancer. Tamoxifen also provides protection against bone fractures in postmenopausal women and it lowers serum cholesterol levels. However, long-term use of tamoxifen may be associated with vaginal bleeding, endometrial thickening, and increased risk of endometrial cancer and thromboembolic events.