Advances in the medical management of breast cancer
Drug treatments play an important role in the treatment of the majority of women with invasive breast cancer and complement surgery and radiotherapy. These treatments can be broadly divided into three groups: chemotherapy, endocrine therapy (sometimes referred to as hormonal therapy) and finally targeted or biological therapies.
Wednesday 9th March 2011
Chemotherapy is a general term that has come to describe a group of 'cytotoxic' drugs that have the ability to kill dividing cells. Chemotherapy can be given for early breast cancer and can also be given for cancer that has spread to other parts of the body (metastasised). In the setting of early disease, chemotherapy given after surgery is referred to as adjuvant and if given before surgery is referred to as neo-adjuvant treatment.
Who should receive chemotherapy?
The most recent advances in chemotherapy have not only been to do with the drugs themselves but also refinements in understanding as to who should receive chemotherapy. There is an international consensus that some breast cancers are of such a low risk, for example, they are very small in size and low in grade, that there is no need for chemotherapy drugs. However, for many tumours there will at least be some small benefit in the addition of chemotherapy either before or after surgery.
A large amount of research, over the years, has resulted in analyses of many clinical studies that enable us to best predict, for a given stage and grade of breast cancer the average benefit for a course of chemotherapy. There are now widely used predictive computer programmes that allow us to enter individual patient and tumour characteristics and give an approximation of the additional benefit of chemotherapy in improving outcome. A commonly used programme is called "Adjuvant on-line".
More recently research has looked at actually tailoring prediction to the individual tumour. One such approach is called Oncotype DX. A sample of the tumour from the biopsy or definitive surgery can be sent for genetic analysis and a gene profile score called a recurrence score determined for the individual tumour. This will then give a much better predictive score for the benefit of treatment for an individual. The Oncotype DX is not for all breast cancers as it has only been validated in tumours which are oestrogen receptor positive and largely lymph node negative.
The optimal chemotherapy regimens
Much research has gone on recently into optimising the chemotherapy treatment regimen. Recent advances include accelerating the speed of chemotherapy and also the addition of new drugs including Taxanes. The Taxanes are compounds that come from the Yew Tree.
Many new drugs are being developed for breast cancer chemotherapy. These include drugs for advanced disease, where new medicines such as Abraxane, a Taxane which does not require any pre-medication or steroid, has recently been evaluated. Other new drugs include Eribulin.
Chemotherapy will still be offered to a significant proportion of patients with breast cancer. Some of the greatest fears around chemotherapy have been alleviated over recent years with better use of better supportive therapies.
(i) Nausea and vomiting
New anti-sickness drugs including Granisetron, Aprepitant and Paleonsetron, have been developed. It is now thankfully unlikely that women experience significant vomiting following chemotherapy.
(ii) Low blood counts
Many chemotherapy drugs can lower the white cell count. Now there are new growth factors which can be given as a single subcutaneous injection often the day after chemotherapy and this will significantly reduce the risk of a low white cell count and therefore prevent the delays and infections that used to occur for patients receiving chemotherapy.
(iii) Hair loss
Hair loss remains a major challenge for women undergoing breast cancer treatment. Many of our most active chemotherapy drugs cause hair loss. The cold-cap system remains the only proven strategy to try and reduce the risk or delay hair loss in a proportion of women. However, this only effective in some cases and better research into this side effect is ongoing. Meanwhile the wigs and hairpieces provided continue to improve.
The traditional drugs that block the oestrogen receptor for breast cancer include Tamoxifen. This drug which has been available for many decades, was a major advance in treatment of the disease and is one of the first targeted treatments being used in cancer. Tamoxifen still remains a gold standard for pre-menopausal women with oestrogen receptor positive breast cancer.
Recently the Aromatase inhibitors have been developed. These drugs block the peripheral conversion of the male hormones (androgens) to oestrogens and these medicines are probably slightly more effective than Tamoxifen in post menopausal women. However, they do have an additional side effect profile.
Fulvestrant is a new anti-oestrogen in the same family as tamoxifen. This comes as an intra-muscular injection given once a month and probably has fewer side effects than the Aromatase inhibitors. As yet, Fulvestrant is used only in women with more advanced stages of breast cancer.
Herceptin is a very specific treatment, a monoclonal antibody that targets a protein on the surface of about 20% of breast cancer cells. This target is HER2. This drug is ineffective in other forms of breast cancer. Herceptin has been available for the treatment of breast cancer for nearly a decade. Since 2005 its use has included women with HER2 positive early breast cancer.
Therefore, breast cancers are always tested for the HER2 protein. Herceptin significantly adds to the benefit of chemotherapy in HER2 positive breast cancer and will be routinely discussed with women with this type of breast cancer.
Herceptin has to be monitored carefully and can cause side effects including effect on the heart muscle. It is now understood much better how to amange such effects and to be able to continue with herceptin in the majority of cases.
Newer drugs, for example Lapatinib and other such HER2 targeted therapies are being developed which may have less in the way of this side effect.
Bevacizumab is a monoclonal antibody that targets new blood vessel formation. Blood vessels are required when a tumour grows above a millimetre in size and this process can be blocked by certain medication. Anti-androgenic drugs have had a mixed history in breast cancer and their use remains somewhat controversial. Nevertheless, for a small proportion of patients with advanced breast cancer they may be useful.
Most recently Dr Andrew Tutt and colleagues based at the Breakthrough Unit at Guy's Hospital have evaluated a new class of anti-breast cancer drug called Parp inhibitors. So far these seem to be active in a genetically inherited form of breast cancer associated with BRCA1 and BRCA2 mutations. These drugs have a novel mechanism of action with few side effects. They may well be useful in other forms of breast cancer, for example, cancer that do not have oestrogen or HER2 receptors and this hypothesis is going to be tested in further clinical studies.
In summary the medical treatment of breast cancer is improving all the time. There is a better understanding of which tumours requires treatment, better predicting of benefit for individual patients, more effective drugs, new targeted therapies and better supportive treatments to help with side effects. Such advances, together with improved surgery and radiotherapy are leading to major improvements in the survival from breast cancer.
Mark Harries - March 2011