‘Dishing’ out a new test to improve breast cancer treatment
Friday, November 07, 2014
Excluding cancers of the skin, breast cancer is the most common cancer among women in the United States, accounting for 29 percent of newly diagnosed cancers. Breast cancer incidence and death rates generally increase with age, and 79 percent of new cases and 88 percent of breast cancer deaths occur in women 50 years of age and older.
Early detection of breast cancer by mammography leads to a range of treatment options, including less-extensive surgery (e.g., breast-conserving surgery like lumpectomy vs. mastectomy) and the use of chemotherapy with fewer serious side effects — or even, in some cases, the option to forgo chemotherapy. But often, chemotherapy is the best option.
Chemotherapy for breast cancer uses powerful drugs to target and destroy breast cancer cells. Unfortunately, chemotherapy can be highly toxic, carrying risks of side effects — some temporary and mild, others more serious or permanent.
When breast cancer is diagnosed, the drug regimen the patient receives is based primarily on the results of a biopsy that is used to identify the type of tumor. The effectiveness of the initial treatment is assessed after 2-3 months by determining whether the tumors are shrinking or continuing to grow.
According to several studies, in more than 100,000 cases each year, the breast cancers never respond to the standard drugs, either initially or after repeated doses. As a result, 33 percent to 43 percent of patients must be switched to different drug combinations.
New on the horizon is "tumor in a dish," a new technology that may change the harsh reality of chemotherapy treatment. This new method rapidly assesses how effective specific anti-cancer cocktails will be on a patient's cancer before chemotherapy begins.
A team of biomedical engineers at Vanderbilt University, led by Assistant Professor Melissa Skala, has developed the technique, which uses fluorescence imaging to monitor the response of 3-D chunks of tumors removed from patients and exposed to different anti-cancer drugs. The engineers applied the technique to three major forms of cancerous breast tissue removed during the biopsy, cutting the tissue up into small pieces and putting them in a special collagen gel.
This gel maintains them as "organoids" that retain the 3-D structure of the original tumor and include supporting cells from the tumor's environment. The technique uses a laser, tuned to the frequencies that cause two key enzymes in the cells to fluoresce. Measuring the variations in the intensity of the resulting fluorescence provides a dynamic readout of cellular metabolism, which is a sensitive biomarker of drug response.
Human tumor organoids that respond to an anti-cancer drug begin shrinking within 72 hours, while those that resist treatment to the drug continue to grow. The test also measures the responses of all the individual cells in the organoid, which is critical because tumors respond differently to different drugs.
If a given drug cocktail kills 90 percent of the cancer cells but doesn't affect the remaining 10 percent, the resistant tumor cells can take over and cause the tumor to grow back. Hopefully, the test will make it possible to find drug combinations that kill all the cancerous cells in a tumor.
In their lifetimes, 1 in 8 women will develop invasive breast cancer. That's a staggering average.
This is the first time the 3-D culturing method has been used to predict the effectiveness of different drug on tumors from individual patients. The next step is testing tumors from more patients to see how the results compare to the response that the patients have to chemotherapy.
If these experiments validate the test results, researchers estimate that the test could become available clinically within 5-10 years.
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