Start/Stop Music |
Music provided by Tony O'Connor - BioTrax recommends Tony's Private Collection for relaxation. Click Here. |
|
|
|
HEALTH ZONE - Breast Cancer Introduction |
Breast cancer is only one of more than 200 different kinds of cancer. Yet in women it accounts for almost one third of all cases, with a lifetime risk of one in nine.
 |
| If detected early, breast cancer can often be well treated |
Ask questions ?
Share views !
Share difficulties with your conditions !
Meet people with a similar condition !
Your not alone ! |
|
|
|
In the UK alone, there are over 40,000 new diagnoses of breast cancer each year - around 1% of which are men. The key to successful treatment is early detection. If left untreated, cancerous cells may break away from the primary lump and spread via the bloodstream or lymphatic system to other parts of the body. If diagnosis is made early enough, survival chances are high.
What is cancer?
Tissue mass is normally controlled by a precise and strongly regulated balance between cell proliferation and cell death. Following tissue damage proliferation is often increased to effect repair. So, to prevent unwanted proliferation, cells have a suicide or death programme. Cancer occurs when a cell loses the ability to control its growth and the balance between proliferation and cell death is lost. This cancer cell either proliferates more rapidly than normal cells or fails to respond to commands to initiate the death or suicide pathway. Cancerous cells keep on dividing and eventually form a lump or tumour.
~
Most cancers occur sporadically. Accumulation of damage to the DNA in our cells turns a normal cell into a cancerous one. Harmful chemicals in our environment, spontaneous errors in DNA replication, or a genetic mutation are possible causes.
Amazingly, much of the fundamental research into cancer-associated genes has been done using organisms such as yeast, sea urchin and frog eggs, tiny worms (called nematodes) and fruit flies. One of the advantages of using a ‘model’ organism, such as yeast, is that individual genes can be manipulated and the effects studied in successive generations relatively quickly and easily.
But to get a better understanding of the biology of breast cancer, and of how breast cancer cells differ from normal cells, it is necessary to use rodents as they, like us, have milk-producing mammary glands (breasts). In addition, some studies can and are conducted on human breast cancer cells grown in a laboratory.
What are the risk factors for breast cancer?
Most of the risk factors for breast cancer such as aging, late-onset menstruation, having dense breast tissue or a family history of the disease cannot be controlled. But, by studying different families who have a high incidence of breast cancer, scientists were able to track down mutations in two particular genes (BRCA1 and BRCA2) that are associated with an increased risk of developing breast cancer. It is now possible to test an individual to see if they have one of the identified mutations - although this does not make breast cancer inevitable. Environment and lifestyle also affect the outcome. Indeed, these known genetic mutations account for less than 1 in 20 cases of breast cancer.
Thanks are due to David Miles and Elaine Vickers (Cancer Research UK), Barry Furr (AstraZeneca), and Nick Wright (Barts and The London, Queen Mary's School of Medicine and Dentistry).
Breast Cancer - Current Treatment
If a patient is found to have an unusual mass or lump, the next step is to determine if it is cancerous. This is done by biopsy. Essentially, a needle is used to extract a small number of cells that are analysed under the microscope. Cancerous cells have a particular physical appearance that trained hospital technicians recognise. If the lump is cancerous it will need to be removed and/or destroyed. A range of treatments can achieve this goal. They include surgery, radiotherapy, chemotherapy, hormone treatment and immunotherapy.
Surgery
In the past, breast cancer patients would often have a whole breast removed (mastectomy). Nowadays, a lumpectomy followed by radiotherapy can often be an option, particularly if diagnosis is early and the tumour is small. Chemotherapy and/or hormone therapy may also be given. A mastectomy is generally only carried out when the tumour is large or involves the nipple.
Hormone therapy
 |
| The use of tamoxifen and other such medicines has dramatically reduced the death rate in women who have oestrogen-sensitive breast cancer. |
More than two thirds of breast cancers are oestrogen sensitive. That is, the hormone oestrogen stimulates the growth of the breast cancer by binding to specific receptors inside the cell. The drug tamoxifen is an antioestrogen that competes with natural oestrogen for these binding sites in many breast cancer cells. This impairs the normal effect of oestrogen, thus preventing cell proliferation and so slowing down tumour growth.
At menopause the ovaries stop producing oestrogen. But significant levels of this hormone still remain, particularly in breast tumours and fat tissue, because of the presence of the aromatase enzyme, which makes oestrogen from naturally occurring hormones. A form of medication called aromatase inhibitors can be given to post-menopausal women with oestrogen sensitive breast cancers to prevent oestrogen production and to stop the breast cancer growing. Aromatase inhibitors lower oestrogen levels more effectively after the menopause because at this time oestrogen values are much lower, the only source of oestrogen production being through peripheral tissues; the ovaries are no longer a primary source.
Chemotherapy
Chemotherapy is often used to treat breast cancer or to reduce the risk of recurrence after surgery. All chemotherapy drugs cause side-effects and a balance has to be struck between likely benefit and the level of toxicity.
Alkylating agents are among the most widely used in cancer chemotherapy. They act by damaging DNA, thus interfering with cell replication. The taxanes, administered by intravenous infusion, are also potent anti-cancer drugs. They affect cell structures called microtubules, which help cells keep their shape and are used to transport materials inside the cell. In a multiplying cell, the microtubules are rearranged to form a structure called the spindle. The spindle is broken down once cell division is complete. Taxanes prevent cells from breaking down the spindle, and the cancer cells become so clogged with microtubules that they cannot grow and multiply.
Chemotherapy can cause patients to have extreme nausea and vomiting. This can be so bad that the patients decide not to continue their course of treatment. Medicines have been developed to reduce this side effect; this has been done using ferrets, which, unlike most mammals, vomit in a similar way to people.
Radiotherapy
Radiotherapy for breast cancer is usually given using X-rays or cobalt irradiation. Researchers in the UK are currently testing the effectiveness of a new form of radiotherapy called Intensity Modulated Radiotherapy (IMRT) that they hope will be less damaging to the healthy tissue that surrounds the tumours.
Immunotherapy
The use of antibodies is a new approach to treating cancer, including breast cancer. Cancer cells often have cell surface molecules that are found in greater numbers than on normal cells, or are defective. One example is the HER-2 receptor, which is involved in transmitting growth signals from the cell surface to the cell nucleus. About one quarter of breast cancers have higher levels of HER-2 on their surface than normal. These cancers are often resistant to standard treatment and they correlate with poor patient survival. But antibodies to HER-2 are proving to be effective in blocking growth signal transmission and slowing the progression of advanced disease. Herceptin is the first antibody to be approved for the treatment of HER-2 positive breast cancer.
How did we get these treatments?
 |
| Chemotherapy agents are often derived from natural products, including the Yew tree [Currie ecology]. |
In the 1950s, scientists found that hormone changes could lead to breast cancer in rats, but it took many years before this pathway was considered for therapeutic approaches. Tamoxifen was discovered in the 1960s, but it took scientists about 15 years to realize its potential fully as a treatment for breast cancer partly because at the time most research was focused on chemotherapy. However, detailed studies in animals did indicate that it acted like an anti-oestrogen and so it was expected to be useful as both a contraceptive medicine and in the treatment of breast cancer. Although trials as a contraceptive were inconclusive, tamoxifen soon proved active in the treatment of advanced breast cancer. But at the time, there were neither human breast cancer cell lines nor good animal tumour models on which to evaluate tamoxifen. The data to support clinical trials of tamoxifen use alongside surgical intervention and in breast cancer prevention came later – following the availability of a chemically-induced rat mammary tumour model.
Screening thousands of natural compounds to find those that affect cell division led to the development of many current chemotherapy agents. One group, the vinca alkaloids, were derived from the common periwinkle Catharantus roseus e.g. vinorelbine. Others, for example Paclitaxel, were first isolated from the bark of the Pacific Yew tree. Once an effective compound has been discovered, scientists may use the structure of the molecule to design similar, but more potent versions.
Breast Cancer - Needs
 |
| Cells that grow uncontrollably often become cancerous [Harvard University]. |
The process by which our cells grow and multiply (called cell division) is normally tightly controlled. In embryos and young children, cell division is primarily needed for growth. However, its main role in adults is to repair and replace old cells.
Cell division is a very complex process, and it involves a very ordered sequence of events. Cancer occurs when a cell breaks free from normal constraints and starts multiplying uncontrollably. Tens, if not hundreds, of molecules are involved in cell division, and many of these have been implicated in cancer.
Cyclin D1
A study has revealed that one of these molecules, cyclin D1, is frequently found in very high amounts in breast cancer. It has now been demonstrated that the presence of too much cyclin D1 distinguishes malignant breast cancers (that are likely to grow and spread) from pre-malignant abnormal breast tissue, which is much less dangerous. Proof of principle has come from the breeding of mice that over-produce this cyclin in their mammary glands: they are prone to a type of cancer known as mammary adenocarcinomas.
p53
p53 belongs to a family of genes called the ‘tumour suppressors’. As their name suggests, these genes protect cells from becoming cancerous. p53 has been intensely studied, as it is altered in the majority of human cancers. This gene has been described as the ‘guardian of the genome’ because it scours the genetic material (the DNA) looking for faults. If it finds defects in the DNA, it will tell the cell to stop and repair them. However, if the faults are too serious to be repaired, p53 will trigger the cell to commit suicide. If p53 does not do its job, the damaged DNA will go unnoticed, and the cell may eventually become cancerous. When this gene was first discovered, scientists thought that it might actually be implicated in causing cancer. However, mice that lack p53 are extremely susceptible to cancer and thus its role as a tumour suppressor was confirmed. Now, the replacement of defective copies of p53 in cancer cells is one of the key areas of gene therapy research.
Tailoring the treatment of patients
An exciting development in recent years is the advent of technologies that allow scientists to study the thousands of genes present in cells and tissues in a single experiment. Using this technology, researchers can look for the genetic hallmarks of particular cancers. They can also look for specific genetic faults that might determine the cancer’s sensitivity to certain forms of treatment, or the aggressiveness of the disease. This information should eventually help doctors to tailor their patients’ treatment according to the genetic defects present in their cancer. Thus, the patient receives the treatment that is most likely to work for them.
Vaccine Research
A research group in London is aiming to develop a vaccine based on one of the molecules that distinguishes breast cancer cells from normal cells. By taking this approach they hope to make the patient’s immune system recognize and destroy the cancerous cells. To carry out a clinical study more than 900 women with advanced breast cancer were recruited. The vaccine was given randomly to women in each of two treatment groups: those who were having either chemotherapy or chemotherapy and hormone treatment. However, many in the chemotherapy-only group pulled out at twelve weeks as their cancer had returned. Only one subgroup had a statistically relevant change in survival time. It now seems that a longer time frame is needed to evaluate a vaccine’s true potential – as it takes 18 weeks to get high antibody levels - and that its administration should be done alongside the other treatment regimes, which include hormone therapy. But, the real difficulty will come later: in evaluating the effectiveness of a vaccine to prevent breast cancer. A better animal model would provide clinicians with a confidence of testing a vaccine on healthy individuals instead of trying to treat women with advanced disease where the benefits will always be limited. The availability of such a model, e.g. a transgenic mouse, will allow scientists to do the studies that can’t be done in patients. These include immunizing the animal and then giving them cancerous cells to see if they can destroy them.
The search for new cancer treatments must continue and researchers are now investigating many innovative ways of targeting cancer. For example, in order to grow beyond 1-2mm in size, a tumour must develop its own blood supply. Thus, some scientists are investigating this process and designing treatments that will stop blood vessel formation. Other research is based around modifying existing drugs, to increase their effectiveness or reduce side effects. Combination therapies, where several agents are used in conjunction with each other, are also being tested, as is the timing of chemo- and radiotherapies.
The discovery of new treatments and their benefits to patients suffering from this frightening disease emphasise the importance of such work.
|
|
 This information has been generously supplied to the BioTrax Volunteer Support Group by the :
Coalition for Medical Progress
Medical research studies may be conducted and are carefully designed to answer specific medical questions while protecting participants´ safety. Well conducted medical trials are the fastest and safest way to find improved treatments and preventions for diseases. Clinical trials or interventional trials determine whether experimental preventions, treatments, or new ways of using known therapies are safe and effective under controlled conditions. Observational or natural history studies examine health issues and disease development in groups of people or populations. For more information on current medical trials or to register on the BioTrax database, view the study section at www.biotrax.com .
Why not E-Mail this Health Zone News Letter to a friend who may benefit or print copies to give to your support groups or friends ? Click on the buttons below.
|
|
|
|
|
|
|
