Posted on February 5th, 2009 by
It could be argued that “more is better” in breast cancer treatment, since more treatment seems to have led to better survival. However, since all cancer treatments are associated with side effects, aggressively treating all cancers may greatly compromise quality of life for many women. The side effects of chemotherapy are well-known: nausea, vomiting, hair loss, fatigue, and increased risk of infection and bleeding. Even hormonal therapies, the least toxic of the systemic breast cancer therapies, have implications for quality of life. Therefore, it is important to identify those patients that are most likely to benefit from aggressive treatment and spare others the discomfort and inconvenience of undergoing treatment that may not benefit them.
Many patients with early stage breast cancer can benefit from chemotherapy or hormonal therapy in addition to surgery and/or radiation. However, patients who have a worse prognosis or are at an increased risk for cancer recurrence may benefit the most. This is because treatment of breast cancer that has recurred is not as effective as initial treatment. Therefore, it is important that patients receive optimal treatment for breast cancer the first time around.
Over the last 20 years, doctors have learned that patients with one or more of the following characteristics are most likely to benefit from systemic therapy.
Some research suggests that the genetic makeup of the cancer may be even more important for determining prognosis than other factors, including size or stage of the cancer. The genetic makeup of cancer is a relatively new factor to be considered, but its importance for determining a patient’s prognosis—their probable outcome—is being increasingly recognized. The goal of determining the genetic makeup of a cancer is to identify whether particular genes are acting abnormally. Abnormal activity of some genes has been associated with an aggressive disease course or tendency to recur. Identifying increased or decreased activity of these certain genes may indicate a poor prognosis.
For example, breast cancers that have many estrogen receptors (ER) or the protein HER2 on their surface are know to be associated with a worse prognosis. These receptors are said to be “over-expressed” because the gene that encodes for the receptor protein is over-active, telling the body to produce more and more ER and HER2. Cancers over-expressing these proteins are called ER-positive or HER2-positive. Research has determined that patients with ER-positive breast cancer can be effectively treated with hormonal therapy and patients with HER2-positive breast cancer respond to treatment the anti-HER2 biological therapy, Herceptin®. Identifying the activity of these two genes, by identifying whether the cancer is ER- or HER2-positive, is already standard practice in determining prognosis and treatment in breast cancer.
It now appears that evaluating the activity of more than one or two genes involved in breast cancer may provide even more powerful information about the likely course of that cancer and possible treatments. Technology now exists to evaluate the activity of more than 10,000 genes in a single test. However, research shows that evaluating 20-200 genes that are critical to breast cancer appears to provide the most valuable information about prognosis and can help determine optimal and individualized therapy.
Oncotype DX TM is a new test that measures the expression, or activity, of 21 genes in a sample of early stage breast cancer cells. The test is used to calculate a Recurrence Score TM , which indicates the chance that a patient’s cancer will recur. In clinical trials, the Recurrence Score TM was found to be a better predictor of recurrence than standard measures such as patient age, tumor size, and tumor grade in women with node-negative breast cancer. Researchers from Italy have also reported that Oncotype DX™ helps predict response to chemotherapy for patients with early stage breast cancer.
Researchers also have found a test that evaluates the activity of 70 genes and can accurately determine which patients are likely to have a good outcome and those likely to have a poor outcome. Out of 295 patients with stage I or II breast cancer that were evaluated with this 70-gene test, those with a good-prognosis profile (115) lived nearly twice as long and were 35% less likely to have cancer spread to other locations in the body than those patients who tested in the poor-prognosis profile (180). This type of prognosis information may prove very useful for determining optimal treatment for each individual cancer.
While these initial results are exciting, the science of genomics is young and further research is always necessary to confirm early findings. Scientists have learned that technology that may appear exciting can yield different results when larger, and more carefully conducted studies are completed. The Oncotype DX™ test has already produced confirmatory findings, but a large trial in which patients are randomly assigned to the real test or a substitute is ongoing nonetheless. A large trial aimed at confirming the value of the 70-gene profile is ongoing in Europe .
1) Paik S, Shak S, Tang G, et al. Multi-gene PT-PCR assay for predicting recurrence in node negative breast cancer patients—NSABP studies B-20 and B-14. Proc of the 26th Annual San Antonio Breast Cancer Symposium. December 3-8, 2003; San Antonio, TX, Abstract #16.
2) Gianni L, Zambetti M, Clark K, et al. Gene expression profiles of paraffin-embedded core biopsy tissue predict response to chemotherapy in patients with locally advanced breast cancer. Proceedings from the 40th annual meeting of the American Society of Clinical Oncology 2004. Abstract #501.
3) Van de Vijver M, He YD, van’t Veer LJ, et al. A Gene-Expression Signature as a Predictor of Survival in Breast Cancer. New England Journal of Medicine 2002; 347(25):1999-2009.
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