Cutting-Edge Breast Cancer Therapy
Reviewed By Michael Smith
There's no doubt that breast cancer treatment has made great strides in recent years. A diagnosis of breast cancer is no longer a death sentence, and the treatment is no longer more painful than the disease. Today, women with breast cancer live longer -- and better -- than ever before. Many are completely cured. And the future looks even brighter, with individualized, cutting-edge therapies being tested and developed right now.
Hitting the Target
Future breast cancer treatments will be a lot smarter about the cells they target. Older approaches -- standard chemotherapy and radiation -- tend to attack all rapidly dividing cells throughout the body. That includes healthy cells lining the hair follicles and the intestines, as well as cancer cells. Yes, the approach can work, but it also causes many of traditional chemotherapy's infamous side effects.
But researchers have learned that breast cancers, like people, are not identical. And they've been using this knowledge to develop more effective, less toxic drugs. By discovering precisely how tumors differ from person to person, they've begun creating treatments that seek out and destroy specific types of cancer cells, and only those cancer cells -- leaving healthy cells alone.
"Why is it that in one patient, breast cancer acts one way -- after chemotherapy, the cancer never recurs -- while in another patient with the same [size and type of tumors], after surgery and chemotherapy, the cancer comes back? It's probably due in large part to fundamental genetic differences in the tumors," says Eric Winer, MD, head of the Dana-Farber Cancer Institute's Breast Oncology Program in Boston.
We've already learned, for example, that some breast cancers rely on the female hormones estrogen and progesterone to grow. In women with these so-called estrogen- and progesterone-receptor (ER and PR) positive cancers, blocking the activity of the hormones can stop growth or even shrink the tumor. Examples of successful hormone-blocking drugs include tamoxifen, Arimidex, Aromasin, and Femara.
Some cancers, on the other hand, have particularly high levels of a protein called HER2. The drug Herceptin attacks this protein and effectively fights the cancer.
And experts predict that these targeted therapies are just the beginning. "There's much more beyond HER2 and ER-PR status," says Winer. "The hope is that we'll be able to identify a greater number of subtypes of breast cancer, and ... we'll have a much clearer sense of the benefits of different kinds of treatments. At the same time, that information is going to allow us to develop new and more targeted treatments."
Search and Destroy
One of the most promising areas of breast cancer research is targeted therapeutics. These treatments send toxic cancer-killing agents directly to tumor cells, avoiding the "fallout" damage to healthy cells that happens with broad-range chemotherapies and radiation. The more that's known about the differences in genetic makeup among cancers, the more targets can be identified.
Researchers at the University of California San Francisco's Comprehensive Cancer Center are beginning clinical trials with a new technology called immunoliposomes, developed by researchers John Park, MD, and Christopher Benz, MD.
"It's a molecule comprised of a lipid [fat] ball containing a therapeutic agent, such as a chemotherapy drug," explains study leader Joe Gray, PhD, professor of laboratory medicine. According to Gray, the approach will use an antibody that seeks out a specific protein found only on the surface of cancer cells. The antibody will deliver the lipid ball into the cancer cell, where it will release its toxic contents -- the drug -- and kill the cancer.
The first trial of the immunoliposome approach will focus on the HER2 protein. "But that's just a prototype," says Gray. "You can change the antibody and target different tumor types depending on what cancer protein is present, and you can also change the toxin. Within five years, we're hoping to generate half a dozen different therapeutics that target different subtypes of breast tumors."
Duke researchers are taking the liposome approach in a different direction. In a recent trial, 21 women with especially hard-to-treat breast cancers received a treatment the women jokingly refer to as the "booby Jacuzzi." The affected breast is immersed in salt water for an hour while radio frequency energy warms the tumor to 104 degrees Fahrenheit. At this temperature, the liposomes melt, releasing their potent drugs directly into the tumor. Not only did all the women see some degree of improvement, none experienced the typical side effects of chemotherapy.
Cells are constantly sending and receiving messages to and from other cells. Some signals stimulate the cell to grow and reproduce; others direct it to stop growing. The signaling process involves proteins on the surface of cells as well as genes within the cells. When the signaling process goes awry, cell growth can spin out of control, leading to tumors -- a process called deregulation.
Scientists are working to identify -- and stop -- the genes that cause deregulation in breast tissue. Though they've "already generated a long list of candidate targets," it's particularly challenging to intervene in the cell-signaling process, says Gray. "If a protein is on the surface of a cell, it's easy to get therapeutics to it. But if we're targeting [something within the cell, such as a gene], it's much harder to attack that." His team is looking at how the faulty genes affect cell function, in hopes of finding "a target either upstream or downstream of the signaling process to attack with therapeutics."
And these are just a few of the many new approaches being investigated right now. According to Winer, "Breast cancer treatment is already more than 'one size fits all.' We don't treat all patients with the same therapies." Now, that individualized approach needs to be taken to the next level, especially among women with early-stage disease. With continued research, he says, "we'll understand how each treatment works, and be much more selective picking and combining them for different patients."
Originally published Sept. 23, 2002.
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