Yesterday we learned that Elizabeth Edwards, John Edwards' remarkable and impressive 57-year-old wife, has suffered a return of the cancer for which she was treated just three years ago. What is this likely to mean for her?
When she was initially diagnosed, Edwards' breast cancer was treated with a combination of chemotherapy, surgery, and radiation, to which she seemed to respond well. The details of her cancer have not been made public, but we might expect roughly 90 percent of women with this diagnosis and with an apparently good response to treatment to be disease-free five years after treatment. Unfortunately, Edwards is among the roughly 5 percent of women in whom the disease reappeared more rapidly.
The recurrence was discovered almost by chance. She cracked a rib, and when she was X-rayed to evaluate that injury, the radiologist who read her film detected a "spot" on another rib, on the other side of her chest. The development of the new lesion in a location distant from the original tumor—a "metastasis"—dramatically worsened her prognosis. Edwards' likelihood of survival for five more years dropped from perhaps more than 85 percent to about 20 percent. And her illness went from one that might have been cured to one that might be, at best, controlled.
When breast cancer metastasizes, the new tumors that form are especially likely to be found in bone and typically lead to local pain and weakness of the affected bone. This causes a great risk of fractures. When the bone destruction from the cancer is extensive, dangerously—even fatally—high levels of calcium in the blood may result. For reasons that are not yet fully understood, the nests of breast cancer cells that grow in bone stimulate overactivity by the normal bone cells that are part of the remodeling and repair process by which we recover from fractures. Two kinds of bone cells are activated by nearby cancer cells: osteoclasts, which dissolve the hard mineral part of nearby bone, and osteoblasts, which rebuild it. The cancer usually more strongly stimulates the activity of the osteoclasts, which results in weakness and holes in the bone adjacent to the nests of tumor cells.
A number of treatments are available to help control metastatic breast cancer. One treatment depends on a biological characteristic of the tumor itself: receptors on the tumor cell surface that recognize estrogens, or female hormones. Many breast cancers are sensitive to—that is, are stimulated by—estrogens. So, using drugs like tamoxifen to block the cells' estrogen receptors is often helpful. In addition, drugs of a relatively new class, the aromatase inhibitors, have also been quite beneficial. These drugs inhibit an enzyme step that the body's natural estrogen production requires and so make much less estrogen available to stimulate the cancer. Another new drug, Herceptin, has been very useful for treating breast cancers that express on their surface a protein called HER2/neu. Edwards' doctors may try any of these treatments or more than one in combination.
Another important new treatment is specifically directed at metastases to bone. These drugs, called bisphosphonates, act by binding to the hard calcium-containing mineral in bone and then blocking the activity of the osteoclasts (the bone cells whose overproduction causes weakness and holes). Inhibiting or killing osteoclasts reduces the risk that bone close to the tumor will be eaten away and become dangerously weak. It is also likely that bisphosphonates sometimes kill tumor cells themselves. And the drugs may reverse the bone-weakening effect of osteoporosis, to which women with breast cancer are especially subject. Finally, local radiation to tumor-cell metastases in bone is sometimes used to kill nests of cancer cells and to relieve local symptoms, like bone pain.
In spite of the generally gloomy statistics for metastatic breast cancer, it is hard to predict how things will go for Elizabeth Edwards. Some patients, though never fully cured, still have a relatively good outcome, with their disease reasonably well-controlled, a high quality of life, and a good long time of survival. This group is a minority, to be sure. But let's hope Edwards is in it.