21 Apr 2014/
The topic I’m going to address today is how treatment regimes for breast cancer are decided. You may be aware of different types of intervention, such as chemotherapy, radiotherapy, or various drug treatments, and may wonder how it is decided which strategy or combination of those, are planned for particular patients. The genetic makeup of a tumor is emerging as an important factor in planning cancer therapy.
Chemotherapy (often referred to as “chemo”) basically refers to a drug or cocktail of drugs that will kill cancerous cells. The problem with this approach is that it is not very specific, so some of the patient’s normal cells will also be affected. Chemotherapy targets cells that are dividing fast, including tumor cells, cells lining the stomach, hair follicles and others. This is why side effects of chemo can include nausea and hair loss. Chemo then, is like a ‘sledgehammer’ approach to cancer treatment.
Before surgery to remove a tumor, chemo and/or radiotherapy can be administered to a patient, to shrink the tumor and reduce the amount of breast tissue that needs to be removed surgically. In some cases this can help surgeons to avoid a full mastectomy, and conserve more of the patient’s breast.
Chemo and/or radiotherapy can also be used as treatment after surgery, to target cancer cells that may be remaining there. However, some treatments are more specific, called “targeted therapy”. One example is when a biopsy (sample of cells from the tumor) is taken, and when examined by pathologists (doctors who specialise in disease diagnosis) it shows that the cells have a type of protein called estrogen receptor (ER). Cells are then said to be ER-positive, meaning that they respond to the presence of estrogen in the body. If a tumour is ER-positive, doctors know that it would be worthwhile to try giving this patient anti-hormonal therapy, which will stop those ER-positive cells from growing. Tamoxifen is a drug against ER that has been used clinically for several decades. For post-menopausal patients, another option to target estrogen production is to use a drug called an aromatase inhibitor, which stops estrogen from being made before it can effect the ER-positive cells. Yet still, there are other types of breast cancer that grow despite not having the ER protein. For these cases, giving anti-estrogen therapy would not be beneficial. Pathologists can examine the tumour samples and determine whether the cells have any other proteins that make them grow; many such proteins have been discovered, and scientists have researched to produce drugs to target them.
One such protein is called HER-2. It is present in about 20% of breast cancers, and is associated with a bad disease outcome. Researchers found a way to target cells that have HER-2, creating an antibody called Herceptin, which when given as a drug treatment, binds to the HER-2 on the outside of cancer cells in the body, and stopping them from growing and dividing. Herceptin is a very successful treatment for HER-2-positive breast cancer.
The landscape of treatment for breast cancer is changing, with the realisation that there are so many different types of breast cancer. Even tumours that present the same way clinically can have very different genetic profiles. Genetic tests can be done on a patient biopsy, and many different genetic changes (mutations) can be observed. The combination of these mutations can give doctors and scientists information about the type of cancer, and how best to treat it. For example, OncoType DX is a gene test that can be used to predict whether a patient’s early-stage, ER-positive breast cancer is likely to spread (called metastasis). This prediction would be based on the mutations observed in the tumour. If the risk of spreading was high, chemotherapy might given alongside anti-estrogen therapy, to minimise spreading.
Treating an individual patient based on the genetic profile of their tumour is called “personalised medicine.” This is a fairly new idea, but has taken off in the scientific research world, and many new drugs are being tested in clinical trials to see whether tailored treatment for particular groups of people increases survival in that group. An example of success in personalised medicine (PM) is the antibody mentioned above, Herceptin, for HER-2-positive breast cancers. The goal of PM is to identify the right people to treat with particular drugs, and to also avoid unnecessary treatments (and their side effects) for people who will not respond to these drugs.