New Approaches to Chemotherapy for Breast Cancer
From tweaking the size and timing of chemotherapy, to adjusting how it's administered, small improvements are making a big difference in women's lives.
Reviewed By Charlotte Grayson
The news just keeps getting better for women with breast cancer -- whether they're in the early or late stages of the disease.
While there hasn't been one particular breakthrough responsible for the change, Georgiana Ellis, MD, a professor of oncology at the University of Washington, Seattle, tells WebMD that "a number of small improvements seem to be adding up to a big improvement" in the prognosis for people battling breast cancer.
Some of the more interesting advances have been in chemotherapy -- the anti-cancer drugs that have been standard treatment for breast cancer for decades and are currently offered in combination with surgery and radiation. Chemotherapy remains a crucial component of breast cancer treatment and new techniques are making it more effective and easier to tolerate.
Old Drugs, New Tricks
Certainly, the discovery and use of new drugs has made a difference, but the biggest shift in chemotherapy may be in how these drugs are administered. "What we're trying to do is make relatively modest advances with the less-than-perfect medications we have now," says Andrew Seidman, MD, of Memorial Sloan-Kettering Cancer Center in New York. "We're teaching old dogs new tricks." The results, according to Seidman, are promising.
Ellis, from Seattle's Fred Hutchinson Cancer Research Center, agrees. For example, doctors are refining breast cancer chemotherapy by applying what they learn from treating patients with advanced cancer to those in earlier stages of the disease. If a medication works in slowing the growth of late-stage metastatic cancer, Ellis says, doctors now try to use it sooner because they want to use the best medications as early as possible.
New Ways to Administer Chemotherapy
Ellis and Seidman also see hope in a new approach to chemotherapy called dose density therapy, in which standard medications are administered more frequently than in the past. Although the idea is simple, its effects appear profound.
"For years we've been looking at dose intensity," says Seidman, which involves administering higher doses of chemotherapy medications than usual. "The results have been disappointingly negative, almost uniformly."
Using the standard or lower doses but giving them more often looks more promising. In addition to restricting the opportunity for cancer cells to become resistant to drugs, dose density therapy seems to constrict the blood supply to tumors, preventing their growth. This effect, called anti-angiogenesis, has been the focus of a great deal of research for years.
One recent study conducted by the Cancer and Leukemia Group B (CALGB) -- a research group sponsored by the National Cancer Society -- found that using dose density therapy could have dramatic effects. In women with breast cancer that had spread to the lymph nodes, researchers found that after surgical removal of the tumor, dose dense chemotherapy with various combinations of standard drugs -- Adriamycin, Taxol, and Cytoxan -- could reduce the risk of recurrence by 26%. Frequent dosing didn?t cause a greater number of side effects than traditional therapy, although the drug Neupogen was used to prevent the chemotherapy from causing neutropenia, a drop in the number of white blood cells. Seidman is currently leading another study for the CALGB of dose density therapy in 500 women with metastatic cancer using Taxol. He believes he will have results soon.
Ellis is optimistic about one variation of this approach called metronomic therapy, which focuses on making dose size tolerable and administering medicine orally when possible. Trials at Fred Hutchinson are going on now.
Another recent shift in treatment has been the increasing emphasis on neoadjuvant chemotherapy, the use of anti-cancer medications before surgery or radiation. While neoadjuvant therapy has not been shown to lengthen cancer patients' lives, it seems to have other benefits. For one, it decreases the odds that a patient will undergo a mastectomy and increases the odds that she will have less aggressive, breast-conserving surgery.
Of course, the significance of new medications shouldn't be underestimated. "One of the biggest changes we've had in chemotherapy is that we have new agents for breast cancer," says Ellis. Among them are Navelbine, Taxol, and Taxotere, which all work by disrupting the growth of cancer cells. While they've proved effective in women fighting advanced breast cancer, they are also currently being studied for use in early breast cancer.
Outside of chemotherapy in the strict sense, hormonal treatments are also having an impact. One of the most exciting developments, says Ellis, has been the development of aromatase inhibitors, including Arimidex, Femara, and Aromasin and the monoclonal antibody, Herceptin.
Combination or Monotherapy?
Experts have long debated whether combination chemotherapy, a number of drugs administered simultaneously, is more or less effective than monotherapy, a single drug given at a time. Recent evidence suggests that it depends on the stage of cancer.
"Clearly," Seidman tells WebMD, "combinations are superior to single agents in adjuvant chemotherapy, which is chemotherapy following radiation or surgery. Experts are constantly tinkering with variations in these combinations to make them more effective and less toxic.
But in cases of metastatic breast cancer, where the cancer has already spread to other parts of the body, Seidman points to numerous studies that indicate that using combination therapy is no better than using single drugs in a sequence. For instance, Seidman says that in the recent results of one study by the Eastern Cooperative Oncology group, using Taxol and doxorubicin Adriamycin together had no advantage over using them sequentially.
Despite the progress that's already been made, Ellis sees this as an area of great potential. "There's a lot more work to be done on dose scheduling and combinations," she says. But according to one theory, she says, "it's fiddling with all these little things that's contributing most to lowering the death rate."
The Future of Chemotherapy
Doctors and researchers are developing still other approaches to breast cancer chemotherapy. While drugs designed to prevent anti-angiogenesis originally attracted a great deal of attention in the press and inside pharmaceutical companies, studies have have been almost uniformly disappointing so far. The recent research into using Avastin, an anti-angiogenesis drug, in advanced breast cancer have not been encouraging, but further studies are planned. Other drugs and treatments are being developed and several institutions are looking into the possibility of a cancer vaccine.
Because of its toxicity and the harm it causes to both healthy and cancerous cells alike, traditional chemotherapy has inherent limitations. "Eventually, I think we'd like to get rid of chemotherapy as we know it," says Seidman. He hopes that as more is learned about breast cancer, experts will continue to develop more targeted approaches to systemic, or full-body, therapy.
One new approach being studied involves using liposomes, molecules that can be artificially filled with a chemotherapy drug and inserted into the body. These liposomes are essentially containers that carry a chemotherapy drug directly to the tumor, sparing the rest of the body unnecessary damage.
Treatment will also become more customized as researchers better understand the genetics of various subtypes of breast cancer. Different types of breast cancer respond better to different treatments. Drugs such as Herceptin -- which is designed to affect a specific type of cancer cell with high levels of the HER2 protein -- are the first new targeted medications. Researchers are also working on developing genetic tests for cancer cells that might allow doctors to identify the kind of cancer and thus determine a person?s ideal treatment from the outset.
Seidman reports that at Memorial Sloan-Kettering, breast cancer researchers have been studying the drugs geldanimycin and Gleevec -- the latter is currently used to treat certain types of abdominal cancer and leukemia -- for their targeted effects on cancer cells. Results are a ways off, but as more precise and focused ways of attacking cancer become possible, doctors may someday be able to stop relying on the generic, toxic chemotherapy agents that have been used for decades.
Separating Hype from Hope
While some of these new approaches are cause for hope, it's important to keep them in perspective.
"I think that we as oncologists, investigators, and journalists have to be very careful about separating hope from hype," says Seidman. "A lot of possibly exciting treatments are still years away from being used." Seidman cites as an example the great media excitement about anti-angiogenesis medications that was followed by disappointing results that dashed the hopes of patients.
Seidman stresses that while you should talk to your doctor about any new treatments you've heard of, you should also be aware that they may not be available to you. In some cases, you may be able to enroll in clinical trials of new types of chemotherapy.
But while a drug that can cure or prevent cancer may be far off, some approaches to chemotherapy, such as dose density, may be on the verge of becoming standard practice, says Seidman. While they may not provoke the excitement of a miracle drug, for now, these new ways of using old medications may offer the most hope.
Medically updated September 2003.
Originally published Sept. 27, 2002.
SOURCES: Georgiana Ellis, MD, the University of Washington. Andrew Seidman, MD, Memorial Sloan-Kettering Cancer Center in New York. The American Cancer Society web site. National Institutes of Health Medline web site. The U.S. Department of Health and Human Services web site. National Cancer Institute web site. Journal of Clinical Oncology, February 2003 (15): 577-9. Burstein, H. Medscape web site. "Targeted Therapies in Breast Cancer: the Champagne Has Lost Its Fizz." Hudis, C. Medscape web site. "Adjuvant Chemotherapy Overview: Old Drugs, New Tricks." Jones, S. Medscape web site. "What?s New in the Hormonal Treatment of Breast Cancer?" Miller, K. Medscape web site. "Clinical Status of Antiangiogenic Therapy -- Is There Still Reason to Hope?" Perez, E. Medscape web site. "Defining Regimens with Targeted and Novel Therapies for Breast Cancer." Pritchard, A. Medscape General Medicine, June 18, 2003; vol. 5. Pritchard, K. Medscape web site. "New Prognostic and Predictive Factors: Are They Ready for Clinical Use?" Sparano, P. Medscape web site. "Chemotherapy Options for Breast Cancer." WebMD Medical News: "Condensed Chemo Improves Cancer Outcome." "Frequent Chemo Ups Breast Cancer Survival." WebMD Medical News. "Arimidex Better than Tamoxifen Long Term."
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