Working Towards a Cure
Advances in Breast Cancer 2007
by William Hocking, M.D
In 2007, there will be approximately 180,000 new breast cancers diagnosed in the United States and about 40,000 deaths, representing the second most common cancer-related cause of death among women, after lung cancer. However, since 1991 there has been a 23% reduction in breast cancer mortality in the US, and over the past decade mortality has declined about 1% per year.
This is a striking turnaround in what previously had been a progressively rising death rate, and is due to improvements in screening resulting in earlier detection of cancers when they are most likely to be cured, and to rapidly improving treatments.
The widespread application of mammography has been primarily responsible for improvements in early detection. Recently, magnetic resonance imaging (MRI) has been shown to be highly sensitive and accurate in detecting breast cancers that may not be detected by mammography. Currently, MRI screening is recommended primarily for women with a genetic risk for breast cancer and women who have had previous radiation exposure such as for the treatment of Hodgkin’s disease, but this exciting technology may eventually play a broader role in early detection of breast cancer. For women at high risk of developing breast cancer, there are now 2 drugs, tamoxifen and raloxifene that have been shown to reduce the risk of breast cancer by about 50%.Many of the advances now occurring in breast cancer are based on a better understanding of the underlying biology of the cancer cell and the pathways within the cell that control cell growth and death. It has been known for many years that breast cancers that have receptors for estrogen are likely to respond to various hormonal treatments. We now also have the ability to study cancer cells from individual patients to detect patterns of gene activity (gene expression arrays) that can help predict who will benefit from chemotherapy and who is less likely to receive benefit. This movement toward “personalized medicine” is occurring in many areas, but is particularly exciting in cancer therapy, since it will eventually allow us to avoid toxic treatments for patients with little likelihood of benefit.
Adjuvant treatment refers to the use of either chemotherapy or hormonal therapies after the primary surgical treatment of breast cancer. The benefit from this approach in reducing breast cancer recurrence was first demonstrated in the 1970s, but over the last 3 decades there has been a progressive improvement of results that have occurred through the clinical trials process. In the past decade this progress has markedly accelerated with the addition of new drugs such as the taxanes and the discovery that chemotherapy can be given in a “dose dense” fashion (same doses at shorter intervals, with the use of growth factors to prevent lowering of the blood counts), each of which has resulted in a 20-30% reduction in the risk of recurrence. Perhaps the most excitement is related to the development of trastuzumab, a drug that targets the Her2-neu oncogene which is present in an elevated amount in about 25% of breast cancers. Her2-neu is an oncogene product that increases the growth of tumor cells, and in the past, women with this finding were known to have more aggressive cancers which were more likely to recur and spread to other organs. Treatment of these women with trastuzumab results in a 50% reduction in their risk of recurrence and 33% decrease in risk of death.
Another breakthrough has been the develop-ment of a new class of hormonal modulators known as aromatase inhibitors. Currently, there are 3 drugs available in this class, Anastrazole, Letrozole and Exemestane. In post-menopausal women, these drugs reduce the production of estrogen to a very low level, and this has a profound impact in reducing the risk of breast cancer relapse. These drugs also offer a new highly effective approach to treatment of post-menopausal women with recurrent breast cancer.
A number of new chemotherapy agents with activity against breast cancer have been developed, but increasingly our better understanding of the biology is leading to more “targeted therapies” such as trastuzumab. In the past year a new targeted agent, Lapatinib, has been shown to work in women after trastuzumab failure. Because of our expanding armamentarium and ability to treat breast cancer with a sequence of agents, even recurrent or metastatic breast cancer is now more like a chronic disease that can often be controlled for many years, than an immediately life-threatening disease. Ultimately, however, the goal is to find ways to prevent the development of breast cancer and to detect and treat at an early stage when less likely to recur.
The improvement in breast cancer survival is an illustration of the importance of investing in research into both the basic biology of disease and clinical trials to find better treatments.
William Hocking M.D., Hematologist-Oncologist, Marshfield Clinic