For a sense of the future of personalized medicine, take a look at how breast-cancer treatment has evolved since scientists proved that the disease comes in more than one form. In 1987, researchers at the University of California at Los Angeles reported that roughly 25% of women with breast cancer had a genetic abnormality on the 17th chromosome that caused an extraordinary amount of human epidermal growth factor receptor 2, or HER2. These scientists also found that women with the HER2 marker were more likely to have a virulent form of cancer that spread quickly, making it deadlier than usual.
After cloning this aberrant protein, researchers at Genentech (DNA ) were able to develop an antibody that homes in only on these killer cells. In 1998, the U.S. Food & Drug Administration approved Herceptin for a subset of women with late-stage breast cancer, making it the first drug approved for a specific population.
Since Herceptin came on the market, more than 175,000 women in the U.S. with metastatic breast cancer have been treated with it, typically through once-a-week infusions over a 12-month period.
Genentech doesn't have data on survival rates for these women, but in its clinical trials, the South San Francisco-based company reported that women who were treated with conventional chemotherapy and Herceptin lived nearly five months longer than women who were given only chemotherapy.
Now, Genentech is in final-phase tests to prove that the compound is effective in halting breast cancer at earlier stages as well -- before the disease has spread to other organs. In the just-concluded experiment, cancer recurred within four years in just 15% of women treated with chemotherapy and Herceptin -- half the rate of women who received only chemotherapy.
Donna Henagin is one of the survivors. An operating engineer who runs cranes and other heavy equipment at construction sites in New York City, Henagin comes from a family with a history of breast cancer. Her mother underwent a mastectomy 12 years ago, and Henagin's aunt, her mother's sister, recently went through a course of radiation treatment after detecting a lump in one of her breasts.
Henagin was diagnosed with breast cancer four and a half years ago, when she was 37. A biopsy test, developed by Abbott Laboratories (ABT ) and now routinely given at many hospitals, showed her to be HER2 positive.
In June, 2001, she underwent 10 hours of surgery at Memorial Sloan-Kettering Cancer Center to remove her right breast and two dozen cancerous lymph nodes and to construct a new breast. She then began conventional chemotherapy.
After six months, she moved on to infusions of Herceptin every third Thursday for a year as part of Genentech's Phase III clinical trial. The treatment typically goes for $38,400, though in Henagin's case it was covered as part of the experiment.
With chemotherapy alone, Henagin says, doctors put her chances of living five years at 35% to 40%. By adding Herceptin to the treatment, they predicted her odds would improve to 50-50.
The compound actually snuggles into a tumor cell's surface. By doing this, it can drive the HER2 genes back inside. That effectively halts the cancer because without these external signposts, the cells no longer get a signal to multiply.
By planting itself on the tumor cell's exterior, Herceptin also paints each cancer cell with a bull's eye, spurring the body's immune system to attack and kill these cells as invaders. In addition, Herceptin hinders cancer cells from repairing themselves when they've been poisoned by chemotherapy, making that treatment more potent.
Today, Henagin says she feels fantastic. "I wasn't going to let this slow me down," she says. She worked throughout the therapy and recalls feeling no ill effects from Herceptin.
Better yet, her doctors have found no signs of cancer. "You cannot predict the future," says Dr. Andrew D. Seidman, her attending physician. "But so far, it has been a happy story for Donna."
Henagin's story also shows a shortcoming of predictive medicine, however. She has a 21-year-old daughter who already has been treated for thyroid cancer and, given the family history, may be likely to develop breast cancer before she turns 30.
Yet the daughter has held off on preventative treatment. The HER2 screening can be done only on cancerous tissue, since the marker isn't present in normal cells.
There are tests that can detect other biomarkers that predispose women to breast cancer, BRCA1 and BRCA2, but the options for those who test positive are a five-year course of tamoxifen or a preemptive mastectomy.
And those screenings cannot foretell all cancers. So Henagin's daughter goes in for more-frequent exams, and the family keeps their fingers crossed.
By Michael Arndt in Chicago
Edited by Patricia O'Connell