New drugs and surgical techniques have brought encouraging news in the battle against breast cancer during the past few months. Although no one has discovered a cure, taken together the developments represent a major step forward in the treatment of a disease that kills more than 40,000 women in the U.S. every year.
The latest drugs not only attack existing cancers but also may help women reduce the risk of getting the disease. On Sept. 25, the Food & Drug Administration approved the genetically engineered antibody, Herceptin, made by San Francisco-based Genentech. The drug works by attacking the proteins that trigger cell division in a particularly aggressive form of breast cancer. Although only 30% of breast cancers--those with the HER2 and HER2/NEU genes
--respond to Herceptin, cancer specialists call the drug exciting. Says Dr. Clifford Hudis, chief of the breast cancer service at Memorial Sloan-Kettering Cancer Center in New York: "Scientists not only found a target but were able to make a drug that homes in on it." As a gene therapy, Herceptin doesn't cause the kind of side effects, such as hair loss and nausea, that chemotherapy does.
More controversially, in early September, the FDA's oncologic drug advisory committee recommended expanding the label of tamoxifen to say that it reduces the risk of breast cancer in vulnerable populations--women who are over age 60 or have a close relative with the disease. Tamoxifen, made by Wilmington (Del.)-based Zeneca Pharmaceuticals under the trade name Nolvadex, is already approved for treating breast cancer and preventing its recurrence. The panel based its recommendation on a four-year study ended last April that showed a 49% reduction in the incidence of breast cancer among high-risk individuals taking the drug.
However, the study's short duration and the fact that its results conflict with those of European studies have alarmed some experts and advocacy groups. "For this drug to be recommended for use in healthy women is appalling," says Barbara Brenner, executive director of Breast Cancer Action in San Francisco. Brenner faults the uncertainty of tamoxifen's benefits and the "undisputed evidence of serious side effects." According to the U.S. study, tamoxifen doubles a woman's chances of developing uterine cancer and triples the risk of blood clots in the lungs. For someone with breast cancer, this may be a risk worth taking. But it is questionable whether a healthy woman should take the chance. Moreover, other possible side effects include eye damage, depression, irritability, and hot flashes.
"OFF-LABEL" USE. Even so, the FDA is expected to follow the panel's advice and expand tamoxifen's indications by the end of the month. Indeed, many physicians are already prescribing it for prevention in a practice known as "off-label" use. Dr. Gabriel Hortobagyi, chairman of the department of breast medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston, says women should carefully assess their individual risk of getting breast cancer and "balance that risk with the dangers inherent in taking tamoxifen." Tamoxifen costs $100 per month and insurance companies will probably begin to reimburse patients for the drug as a preventative treatment after FDA approval. According to hospital administrators, insurance companies typically follow the FDA's lead.
Some researchers suggest there is a safer alternative to tamoxifen. A study reported in May at a meeting of the American Society of Clinical Oncologists indicates that raloxifene, approved last year for preventing osteoporosis, may reduce the risk of breast cancer by as much as 70% in postmenopausal women who are at normal-to-low risk for the disease. Raloxifene, made by Eli Lilly of Indianapolis under the name Evista, doesn't appear to increase the risk of uterine cancer, while it carries about the same risk of clotting as tamoxifen. The research has yet to appear in a peer-reviewed medical journal, but the lead investigator, Dr. Steven Cummings, professor of epidemiology at the Univer-sity of San Francisco School of Medicine, expects publication by yearend. Because the FDA has not approved raloxifene to prevent breast cancer, insurancecom- panies are not likely to pay for it.
Cancer patients may also attempt to bolster their chance of beating the disease by adding Taxol, a drug derived from the Pacific yew tree, to the
standard regimen of chemotherapy drugs following breast cancer surgery. Using Taxol as a supplement increases the survival rate and decreases the risk of recurrence, according to results released in May from a multicenter trial overseen by the National Cancer Institute. Although the addition of Taxol, which is taken intravenously, has only a modest benefit (3% to 6% over chemotherapy alone), says Hortobagyi, "any improvement is very good news." Also, Taxol, made by Bristol-Myers Squibb in Princeton, N.J., works on patients who have not responded to other forms of chemotherapy, indicating the drug does something "above and beyond everything else we've got," says Dr. William Peters, director of Wayne State University's Barbara Ann Karmanos Cancer Institute in Detroit.
The standard surgical approach to breast cancer may soon change as well, thanks to a technique known as sentinel-node biopsy. The usual procedure following discovery of a cancerous growth in the breast is to remove the growth in a lumpectomy, along with a section of lymph nodes under the armpit to gauge whether the cancer has spread. Half the time it hasn't, says Sloan-Kettering's Hudis, and women are left with an unnecessarily sore arm prone to swelling and nerve irritation.
To avoid this, doctors now may inject the tumor with blue dye or a radioactive isotope and follow the liquid's progression to the lymph nodes. They then remove the first node in which the dye or isotope appears. "If there's no cancer in that first, or sentinel node, then we don't take the section from under the arm," says Hudis. Like all new surgical techniques, doctors may be reluctant to perform sentinel-node biopsy until more research is available. The NCI is currently organizing a multicenter trial comparing the effectiveness of sentinel-node biopsy to wholesale lymph-node removal.
To make any kind of breast cancer surgery less painful, researchers at Duke University Medical Center in Durham, N.C., are using an alternative to general anesthesia known as paravertebral block. It entails a series of injections near the spine to block the sensation of pain in the chest area during and up to 30 hours after surgery. The technique, which usually involves mild sedation, makes women far less likely to require narcotic pain relievers and medication for nausea following the procedure, Duke doctors say. "This means patients are able to leave the hospital sooner," says Dr. Roy Greengrass, co-director of regional anesthesia at Duke. Some patients, he says, are up and about within an hour of surgery. Not yet widespread, the technique requires "highly specialized anesthesiologists," he says.
SCANNING TECHNIQUES. And for all those who have ever dreaded the squeezing, pushing, and poking of a mammogram, there may soon be an easier way. The recently patented computed tomography laser mammography test (CTLM), manufactured by Imaging Diagnostic Systems of Plantation, Fla., calls for patients to lie face-down on a table, allowing one breast to slip through an opening. A laser underneath the table then painlessly creates cross-sectional pictures of the breast.
No comparative studies have been released to determine if the CTLM test is more accurate. Dr. Richard Reitherman, a radiologist and director of the Hill Breast Center in Glendora, Calif., says CTLM is just one of several technologies expected to emerge during the next few years that will make breast cancer examinations less disagreeable. Magnetic resonance imaging, thermography, and positron electron topography are all scanning techniques that are being refined and investigated as alternatives to traditional X-ray mammography. So, although the war against breast cancer is far from over, there is new weaponry that promises to increase a patient's chances of survival.