New Therapeutic Advancements — Precision Guided Cancer Treatment
Gene expression tests to help with treatment decisions are now available to women who have early-stage breast cancer. These tests identify whether a woman's tumor has an aggressive nature and therefore has a higher risk of recurring. Adjuvant chemotherapy decisions are now made easier by the recent development of the Oncotype DX and MammaPrint gene tests, which help weigh the benefits against the risks of chemotherapy for early-stage breast cancer. The tests work by measuring a woman's risk for recurrence by analyzing whether her gene expression patterns show she is more susceptible to aggressive cancers that are more likely to spread to distant sites in the body.
The tests help to refine the risk of recurrence with early stage breast cancer in estrogen receptor positive and node negative tumors, and have only been approved and used in recent years.
The Oncotype DX test analyzes a panel of twenty-one cancer genes from a small piece of tissue removed during surgery. This analysis helps determine the tumor's chance of coming back after treatment. It scores recurrence as low risk (1–17), intermediate risk (16–30), or high risk with (a score of 31 or above). The highest score possible is 100. Those with a low risk would receive no or little benefit from chemotherapy treatment and the benefit isn't clear for the intermediate-risk group. But for the high-risk group, where recurrence is likely, the benefit of chemotherapy significantly outweighs the risk.
The MammaPrint was approved last year by the Food and Drug Administration (FDA) and looks at 70 genes in a breast tissue sample that has been surgically removed. A clinical trial in Europe called MINDACT (Microarray In Node-negative Disease may Avoid Chemotherapy Treatment) is underway to study its use in the clinic. However, it requires fresh tissue, so it will likely never be used in the United States.
It is important to note that the use of molecular signatures, which is what is tested with the Oncotype DX test, is just starting. Some think this approach will be the future. At some point, we may be able to decide on the prognosis of a tumor and how effective treatment will be by using molecular typing of cancers rather than relying on traditional staging.
In Her Own Words
Amazing progress has been made over the last ten years, thanks to funding, brilliant scientists, and patients willing to be in clinical trials. I'm in a clinical trial because I want to be part of scientific advancement, and have a great deal of hope due to the dedication I see in the medical community to keep exploring new treatments.
— Nanci, age 55, 1-year survivor
Those women found to be at an intermediate risk will have another tool available to help refine their decision for adjuvant chemotherapy called TAILORx (Trial Assigning Individualized Options for Treatment). This study is sponsored by the National Cancer Institute (NCI) and will be available in several more years.
Targeted therapies are a classification of newer drugs that respond to specific gene changes that cause cancer.
Newer Imaging Tests
There are two recent developments in new imaging methods that are now being studied to detect breast cancers, especially in younger women who have denser breasts. Molecular breast imaging (MBI) is a technique that uses a special camera along with traditional mammography. Early studies presented at the Era of Hope meeting (which showcases new research findings supported by the Department of Defense Breast Cancer Research Project) suggested that it may be about as accurate as more expensive magnetic resonance imaging (MRI) and costs only $500.
Tomosynthesis (3D mammography) is an extension of digital mammography. The woman lies down on a table, her breast hangs through a hole, and the x-ray machine rotates around the breast to show a three-dimensional picture. This method is considered experimental and may help identify smaller tumors that may not be found with standard mammography.
Recently, two newer radiation therapy techniques have been used offering a more convenient schedule, with larger daily doses. One is hypofractionated radiation, in which radiologists give a larger dose of radiation over a few days with an overall radiation plan of three weeks, as opposed to the standard five-week plan. Other studies are looking at shortening the time even more.
Accelerated partial breast irradiation (APBI), another technique that minimizes the amount of radiation affecting normal tissue with a more targeted approach, is also being studied.
HER -2 Targeted Therapies
Drugs that target HER-2 (a gene that produces a protein that helps cancer grow), such as Herceptin (trastuzumab) and Tykerb (lapatinils), work by preventing the protein from helping breast cancer cells divide. They also help the immune system fight the protein's growth. This type of gene affects about 20 to 25 percent of patients. Tykerb is a pill recently approved by the FDA for this cancer when it is advanced and cancer cells have not responded to Herceptin.
Many of the drugs for this type of cancer were first approved for metastatic disease and then tested for use in early-stage disease. Other drugs are being tested that target the same protein. With all the different types of drugs available for different types of cancer, Adjuvant! Online is an Internet program that can help you make an early stage breast cancer treatment decision.
Anti-angiogenesis drugs are used to cut the blood supply that feeds cancer cells. An example of an anti-angiogenesis drug is Avastin (bevacizumab). There are some studies that have found that breast cancers surrounded by many new blood vessels are likely to be more aggressive. This is an area of research that needs further study before the theory can be validated.
One new discovery that shows promise, outlined in the January 2009 Cancer Cell, is the gene metaherin (also known as MTDH), which is found to be responsible for the aggressive nature of some tumors. Those tumors that express MTDH tend to be more resistant to chemotherapy and more likely to spread to other organs. Now that the gene has been identified, new drugs can be developed to counteract metaherin and prevent the cancer from spreading.
EGFR Targeted Drugs
Other drugs being worked on are those that target the epidermal growth factor receptor (EGFR) protein that is found in high amounts on the surface of some cancer cells. Two drugs that target EGFR, cetuximab (Erbitux) and eriotinib (Tarceva), are currently being used to treat other cancers. Studies are now looking at whether these drugs could also be used against breast cancers.
Biphosphonates are drugs used to reduce the risk of fractures in bones that have been weakened by metastatic disease. These drugs include pamidronate (Aredia) and zoledronic acid (zometa). The combination of hormone therapy and bisphosphonates is being studied for its treatment in early-stage breast cancer and its effect on reducing breast cancer risk.
There has recently been a study involving vitamin D and its relationship to early-stage breast cancer. The study suggested that women deficient in vitamin D had a poorer outcome with their cancer treatments. More research is needed in the study of vitamin D, but it is an area that should be brought up with your doctor. Vitamin D supplements can also be helpful in preventing bone loss.