New Day, New Hope
Leave it to the outspoken breast surgeon Susan Love to sum up the state of breast cancer treatment these days. “If you think you know what’s going on, you don’t.”
It’s been that kind of year in the field of breast cancer. Several major announcements of promising prevention avenues and treatments have given patients and doctors something to celebrate--and much to absorb. And, with additional advancements on the horizon, things will continue to be confusing for a while.
Over the years, it was Love who reminded everyone of the dismal state of breast cancer treatment by referring to surgery, radiation and chemotherapy as “slash, burn and poison.”
The recent advances, however, would appear to escape that tart description. They include a new medication for women with severe breast cancer (Herceptin) and evidence that two medications already available may work to prevent breast cancer (tamoxifen and raloxifene).
Moreover, there is major research aimed at understanding the genetic underpinnings of breast cancer that could lead to additional new treatments within just a few years, says Dr. Dennis Slamon, director of the Revlon/UCLA Women’s Cancer Research Program and a principal investigator of Herceptin.
“In the next 24 to 48 months, how we treat many of our cancers is going to change dramatically,” Slamon says.
Increasingly, researchers are unlocking the secrets of particular genes that play a role in the development of breast cancer, says Anna Wu, a research scientist at the Beckman Research Institute at City of Hope National Medical Center in Duarte.
“We are on the verge of an explosion in understanding these genes,” says Wu, who predicts there will be a range of “biologically based therapies,” those based on the role genes play, within the next five to 10 years.
However, with each new discovery, researchers become more enlightened and confounded by the genes involved in cancer development. Some genes, called oncogenes, are involved in unregulated cell growth, while tumor suppressor genes are involved in regulation of cell growth.
Herceptin, the drug approved by the Food and Drug Administration last month, is based on the idea that a protein called HER-2/neu causes the unchecked growth of cancer cells. Another exciting area of research involves medications that address angiogenesis, which can cause a tumor to develop new blood cells, allowing it to grow and spread.
Random Mutation Complicates Things
“Cancer is a disease of unregulated growth,” Wu says. “Of key importance in the development of cancer is the presence of cells that decide to divide or not to divide. But there are so many genes involved. It’s very complex. That is why there is no one cure. One hundred women with breast cancer will have 100 different pathways of disease because of random mutations of genes.”
Thus, there is no talk these days of a “cure” for cancer. Indeed, there may be many ways to contain the disease and limit cells from growing and metastasizing, which is when the cancer spreads from its site of origin to other organs of the body.
“I think we’re moving into a new paradigm of breast cancer,” says Love, adjunct professor at the UCLA School of Medicine and the author of several women’s health books. “The new idea is to control cells instead of kill them. It’s a shift of mind-set.”
But where does that leave women with breast cancer--or those at high risk for the disease--now?
“All this news is exciting, but a lot of women are faced with questions,” Love says. “So much of this is a work in progress.”
With each new advance, she adds, “People say, ‘This is the answer.’ But these aren’t the answers. This is our best guess at the moment. So stay tuned, because there is a lot of stuff going on.”
For now, women and their doctors need to be aware that there are more options in fighting the disease--and that there is a greater need than ever before to keep pace with current thinking.
One of the most urgent controversies in breast cancer now centers on whether women who are at high risk for the disease should begin taking either tamoxifen or raloxifene to prevent the disease.
Tamoxifen (Nolvadex is the brand name) has long been used to treat women with breast cancer. A five-year study to examine whether it could prevent the disease in high-risk women was halted this year--one year early--after collecting ample evidence that the drug reduced the risk of breast cancer by 49%. This is the first study to show that a drug may be effective in preventing the disease.
Last month, an FDA advisory panel urged the agency to approve tamoxifen for prevention. The FDA, however, has not ruled on the matter, and controversy over tamoxifen’s role in prevention is very much alive.
Experts have raised such questions as:
* Do the risks of tamoxifen outweigh the potential benefits? The drug increases the risk of blood clots and uterine cancer, although uterine cancer is considered easier to successfully treat than breast cancer.
* Since the study lasted only four years, is tamoxifen really preventing breast cancer, or simply delaying it? Previous studies indicate that prolonged use of the drug (10 years) increases the risk of developing breast cancer.
* Who should take it for prevention? High-risk women are typically defined as those who have a mother, sister or daughter with breast cancer. But there are several other risk factors (such as never having borne a child), and there is debate over which of those factors would constitute sufficient risk to consider drug therapies to prevent the disease.
Study Not Geared to Address Race
In addition, the recently halted study did not include enough nonwhite women to know whether the effect is similar for women of all races.
“There are still a lot of questions,” Love says. “Is it just subduing breast cancer? Tamoxifen is not the prevention drug. It probably reduces the risk of breast cancer short-term.”
The National Cancer Institute recently released a computer program for doctors that will help them determine whether a particular patient is a candidate for preventive medications. Called the Breast Cancer Risk Assessment Tool, the program estimates a woman’s risk in the following five years and over her lifetime.
But since the FDA has not yet approved tamoxifen for prevention, physicians may be reluctant to administer it, Love says.
“I think most physicians are still feeling very confused about who should be on it,” she says.
And consumers, too, are apt to be perplexed by the intense publicity surrounding the tamoxifen prevention study and the many issues it raised. According to Fran Visco, president of the National Breast Cancer Coalition, an advocacy organization, one caller to her office wondered whether it was OK to give tamoxifen to her 12-year-old daughter.
“The attention this trial has gotten concerns us,” Visco says.
However, others say that the value of tamoxifen for cancer prevention is established despite the unresolved issues.
Balancing One Set of Risks Against Another
“Women whose breast cancer risk is sufficiently high to offset the potential detrimental effects of tamoxifen would be candidates for the drug. However, women whose breast cancer risk is not as high should evaluate their individual benefits and risks with their physicians in order to make an informed decision with regard to the use of tamoxifen,” stated the authors of the study, in a recent Journal of the National Cancer Institute.
Complicating the prevention question is the information, released in May, that a drug called raloxifene may also prevent breast cancer. The FDA approved raloxifene, which is sold under the brand name Evista, several years ago for the prevention of osteoporosis. But a study found that postmenopausal women taking the medication reduced their risk of breast cancer by about 70% without the serious side effects seen with tamoxifen use.
However, the study had followed the women for only two years, considered a very short time to assess a medication’s long-term impact.
“People are being put on raloxifene for breast cancer assuming that this is perfectly fine,” says Love. “But we have no information on that. These prevention drugs are still really up in the air.”
While tamoxifen was tested on women as young as 35 with a high risk of breast cancer, raloxifene was studied only on older women with average to low risk of breast cancer.
An important new study, the Study of Tamoxifen and Raloxifene, will begin early next year to compare medications in preventing breast cancer. About 22,000 high-risk, postmenopausal women will be recruited at 193 institutions nationwide and in Canada. The women will be given either 20 milligrams of tamoxifen or 60 milligrams of raloxifene daily for five years.
Perhaps the best thing about the trove of new information on breast cancer is where it will lead in the years to come, experts note.
“We have a better sense of how to focus those research dollars that are so hard to get,” Visco says. “We are at the next level of cancer research.”
Want to Know More?
For more information on emerging news, studies and information on breast cancer:
* Health professionals who wish to order the Breast Cancer Risk Assessment Tool can call the NCI’s Cancer Information Service at (800) 4-CANCER or visit the NCI Web site at https://cancertrials.nci.nih.gov.
* Women interested in participating in the Study of Tamoxifen and Raloxifene can obtain information at https://www.nsabp.pitt.edu; or by mail to NSABP, Box 21, Pittsburgh, PA 15261. Or fax: (412) 330-4660.
Local participating study investigating groups include Cedars-Sinai Medical Center, City of Hope National Medical Center in Duarte, Los Angeles Oncologic Institute, San Gabriel Valley Clinical Oncology Research Program in Pasadena, St. Mary Medical Center in Long Beach, UCLA Cancer Prevention Network at UCLA, UC Irvine Medical Center in Orange and USC/Norris Comprehensive Cancer Center.
* The National Alliance of Breast Cancer Organizations is offering additional information this month including an expanded online calendar listing year-round meetings and events and a national survey on women’s attitudes about breast biopsy. Call (888) 80-NABCO or visit https://www.nabco.org.
