Breast Cancer and Breast Screening

Breast cancer is the unregulated division and growth, due to genetic aberrations in the cells that make up either the ducts (which carry milk to the nipple) or lobules (glands which produce milk) of the breast. This results in the formation of carcinomas in situ (pre-cancerous lesions which remain within the compartment of their respective tissues), developing into invasive carcinomas (which can grow into neighbouring tissues) and potentially undergo metastasis and travel to other organs to form tumours via lymphatic system (or the bloodstream). The development of metastatic tumours means that there are fewer normal cells in the vital organs (such as lung, liver, brain) to carry out critical functions, hence can be fatal. Poorly differentiated breast cancers (the ones whose cells have the most different organisation to those in normal breast tissue), larger tumours and those which have spread to the lymph nodes and are able to metastasise have a worse prognosis. Some breast cells have cell surface protein receptors to which hormones bind and these may be found on cancerous cells. Importantly the presence of oestrogen (ER+), progesterone (PR+) and ERBB2 (HER2+) receptors mean that the cancer cells are dependent on these hormones for their growth, and so these receptors can be a target for treatment of the cancer, improving the prognosis. If we can prevent the supply of these hormones to the tumour, by blocking the receptors, so preventing the hormones from binding a producing a response in the cell, we can potentially destroy the tumour without harming other body cells. Those without any of these receptors present are known as triple-negative. Around 50,000 people are diagnosed with, and around 12,000 die from, breast cancer every year, the majority of those affected by the disease are women (usually postmenopausal), although it can also affect men.

Although 90% of breast lumps are benign (not cancer), one of the most common symptoms of breast cancer is a lump or thickened tissue in the breast (or potentially in the axillary lymph nodes, felt in the armpit). Other symptoms include any changes to the size, shape or the skin of the breast, discharge from the nipple or painful breasts or armpits. People with breast cancer symptoms then discuss them with their GP who can refer them for screening. The NHS also runs a screening programme where women aged 50 to 70 (the most at risk group) are invited for digital mammography. Screening involves either a mammogram or breast ultrasound to produce an image of the breast indicating any tumours. For younger women with denser breasts, ultrasound scans are more effective for indicating tumours. Biopsies are used to see if the lump is cancerous; either a few cells are removed either by using a vacuum to aspirate though a small needle without removing any tissue, or a sample of tissue is removed through a large needle. MRI scans can also be used to further identify the extent of the disease of the breast and to identify the area to be removed in surgery. Tests can also be carried out to check any metastasis to other vital organs (using CT scans or chest X-rays) or to identify the hormone receptor status of the tumour cells removed in biopsy.

The breast cancer screening programme has come under fire recently. A review published in the Lancet medical journal, showed that screening can lead to overdiagnosis, as each patient has a 1% chance of being overdiagnosed if they go for screening. Overdiagnosis is the screening which identifies a cancerous growth, but one which would not have been harmful. This means that patiuents have to unnecessairly undergo treatments (which can have dangerous side effects). There are also risks of false positives where women with no breat cancer at all are told that they have the disease, which leads to the anxiety of being diagnosed with cancer.

Screening is also associated with an increased breast cancer risk as X-rays (a type of ionising radiation) can cause genetic changes in cells. However, screening saves the lives of 1,307 people with breast cancer every year, by correctly idntifying cancer early enough for treatment to be effective. Women are encouraged by the NHS and cancer charities to still attend screening, despite controversy, but are now provided with more details about the risks involved.

Breast cancers are defined by their stage grade and receptor status. The stage of the tumour tells us its size and how far it has spread. TNM staging gives us staging bases on T, tumour size, N, whether the axaillary lymph nodes are affected and M, whether the tumour has metastised. Ductal carcinoma in situ is stage 0; if  the tumour measures less than 2cm and the lymph nodes in the armpit are not affected (also no metastasis) it is in stage 1; Stage 2 is when either the tumour measures between 2cm and 5cm or the lymph nodes in the armpit are affected, or both, with no sign that the cancer has spread elsewhere in the body; if there are still no signs of metastasis, but the tumour measures larger than 2cm and the lymph nodes in the axilla are affected, it is stage 3 (the tumour might be attached to structures in the breast, such as skin or surrounding tissue); Stage 4 describes tumours of any size where the cancer has spread to other parts of the body (metastasis). The grade of the cancer describes the appearance of the individual cancer cells that make up the tumour. If the cells are slow growing, even if they look abnormal, they are G1 (low grade); If the cells have poorer differentiation (and so look more abnormal) than G1 cells we describe them as G2 (medium grade); G3 (high grade) cells look very abnormal and proliferate quickly. 

Cancer develops due to changes to the genetic information in cells, mutations of oncogenes or tumour suppressor genes, which mean that there are changes to the proteins created within cells, which allows tumours to develop. These mutations are somatic which means they happen as the person is alive, rather than being present in the genetic information from conception (although some inherited alleles (versions of gene) are more likely to mutate than others). In cancer, cells are able to evade apoptosis (organised cell death) and anti-growth signals, or sustain their own growth and angiogenesis (formation of a blood supply to the tumour). An example of changes in cancer cells is a mutation causing the activation of the telomerase enzyme, which allows unlimited replication of the cell, as telomeres do not shorten, so the cell can undergo unlimited replications. In breast cancer, commonly inherited mutations include BRCA1, BRCA2, TP53 and PTEN which increase the risk of the disease. These are all tumour suppressor genes that when mutated may no longer be able to prevent excessive cell division and proliferation.

Currently breast cancer can be treated by: surgery to remove the tumour (breast-conserving surgey) or the entire breast (mastectomy) and in some cases the lymph nodes from the under arm (axilla); radiotherapy to destroy cancerous cells with targeted radiation (often used after other treatments to remove any remaining cancer cells); chemotherapy a treatment program which targets rapidly diving cells (such as cancer cells but also often affecting other cells in the body such as blood cells and hair follicles); Hormone therapy to target ER+ cancer cells with drugs to block oestrogen (such as Tamoxifen, aromatase inhibitors or goserelin) and biological therapy for HER2+ cancers through treatment with drugs such as the monoclonal antibody trastuzumab (Herceptin) in addition to chemotherapy. Cancer diagnosis is difficult to deal with and families are often offered counselling to learn more about the illness. Additionally breast removal surgery can be distressing for many women, as can the hair loss associated with chemotherapy, support is offered by charity groups.

Nice (the National Institute for Health and Care Excellence) have recently approved the Oncotype DX test to identify whether breast cancer will benefit from chemotherapy treatment. This will reduce unnecessary treatment as well as the stress and side-effects associated. The test  is used after surgery to see how likely a tumour is to recur (and if therefore chemotherapy needed) by looking at the activity of certain genes in the tumour. The test works best for those with ER+ cancer but HER2- cancers (without the ERBB2 receptors).

Radiotherapy can lead to skin irritation or lymphoedema (fluid build up due to the lymph nodes being blocked). Radiotherapy sessions only take a few minutes at a time, but are intensive for 3 to 5 days a week for 1 to 2 months. Chemotherapy drugs are usually administered intravenously (though in some cases they may be given in tablet form). Chemotherapy sessions usually last between 4 and 8 months, with sessions every 10-20 days. The main risks with chemotherapy is the risk of infection due to the effect on white blood cells which provide the immune response in the body, however other side effects include loss of appetite, nausea, tiredness and hair loss.

Hormone therapies are used in conjuncture with chemotherapy, or as an alternative to other treatments (which are too risky due to the general health of the person with breast cancer) or before surgery to shrink the tumour so that it is easier to remove. Hormone therapies can cause side effects like those associated with menopause such as hot flushes, tiredness, aching joints and weight gain. Tamoxifen and aromatase inhibitors are taken daily in tablet form, whereas goserelin is taken as an injection once a month. Tamoxifen prevents oestrogen binding to receptors; aromatase inhibitors prevented the production of oestrogen in women who have gone through menopause, for whom oestrogen is produced by aromatase; goserelin is an ovarian suppressor which prevents the production of oestrogen temporarily by the ovaries in pre-menopausal women. Ovarian ablation is a surgical or radiotherapeutic technique for permanent prevention of oestrogen production by the ovaries by inducing early menopause. Monoclonal antibodies work by binding to the HER2+ receptor protein, so indicating the HER2+ cancer cells which can then be destroyed. This treatment must be administered in hospitals via and intravenous drip; sessions take one hour and may be as regularly as once a week. Some side effects of trastuzumab include heart problems (so regular heart function tests are needed) and allergic reactions to the drug causing nausea. By identifying more genetic mutations in cancer cells we may find more ways in which we can treat patients, using targeted biological therapies, specific to the dependencies of their tumour.

http://www.nhs.uk/Conditions/Cancer-of-the-breast-female/Pages/Introduction.aspx

http://www.breakthrough.org.uk/

http://www.bbc.co.uk/news/health-20121043