Sometimes it takes a stricken celebrity or two to bring home a new truth about a disease. In the course of a few days, both Elizabeth Edwards, wife of Presidential candidate John Edwards, and White House spokesman Tony Snow revealed that they are not just battling recurrences of cancer but also contending with malignancies that have spread and are no longer curable. Many Americans were stunned to hear that the Edwardses will continue their quest for the White House, with Elizabeth campaigning despite metastatic breast cancer. Snow, who was treated for colon cancer two years ago and now has tumor cells on his liver, will take time off but expects to return to his post.
Fellow cancer patients and their doctors are less surprised by such decisions to "push forward with the things you were doing yesterday," as Edwards put it in a 60 Minutes interview. Reason: in recent years the treatment of what used to be dismissed as terminal cancer has shifted from a win-or-lose battle against acute illness to something more akin to managing a chronic disease — in many cases with extended periods of feeling just fine, thanks.
"To us it's a great sea change in the way people look at cancer," says Dr. Daniel F. Hayes, clinical director of the breast oncology program at the University of Michigan Comprehensive Cancer Center. Hayes says that he and fellow oncologists are enthusiastic about the example Edwards is setting. "From our standpoint, we spend a lot of time trying to make it clear that while cancer — especially metastatic breast cancer — won't just go away, you can still live a long and productive life with it."
The change in managing cancer reflects a series of hard-won improvements in treatment — not, alas, for every form of cancer, but particularly for breast, colon, prostate and even lung. The gains include an explosion of new drugs that are more targeted and less toxic than old-school chemotherapeutic agents. In addition, new tests are beginning to help doctors match drugs more precisely to the genetic and molecular makeup of an individual tumor. Finally, there are remarkable advances in managing the side effects of treatment, which, in the past, could be as debilitating as cancer itself.
The payoff is being seen in longer and better-quality survival. According to the American Cancer Society, the percentage of people living five years after a diagnosis of any type of cancer barely budged from 50% in the mid-1970s to 52% in the mid-'80s, but it shot to 66% for patients with a diagnosis after 1995 and is continuing to rise. For breast cancer patients the five-year survival numbers leaped, from 75% in the '70s to nearly 90% by 2002. Receiving a diagnosis of cancer — and seeing that cancer return — is always a terrible blow. But in fact, there is no better time to be living with the disease.
The idea that we might one day find a cure for cancer seems axiomatic to anyone trying to understand the disease. That was the goal, after all, of the War on Cancer promoted by President Richard Nixon in 1971. But given the enormous complexity and variety of malignancies and the ways they can evolve and migrate in the body, an all-embracing cure is a naive hope. Instead, cancer doctors now appreciate that wayward cells may not necessarily have to be destroyed, just corralled and contained in a safe and tolerable way, often with drugs that are taken for the rest of the patient's life. "There was a mind shift that happened in the 1980s," says Dr. John Glaspy, professor of medicine at UCLA's Jonsson Comprehensive Cancer Center. "We realized that there is a power in the chronic-disease model where you can focus on a high quality of living with a disease instead of necessarily curing it. If we can have people alive, productive and happy, that's now viewed as a very wonderful outcome."
That new perspective provided fertile ground for the growth of new classes of cancer therapies. While older drugs were like heavy artillery — obliterating cancer cells but causing lots of collateral damage — newer drugs are more like smart bombs. Some of them target communication signals within malignant cells, some cut off supply lines by interfering with the growth of blood vessels around a tumor, and others block the chemical agents that enable tumors to expand into new territory. These more targeted therapies tend to focus on frantically proliferating cancer cells while leaving healthy cells intact.
Breast cancer is the model for treating cancer as a chronic disease, largely because it's the focus of so much research and drug development. "We have a ton of drugs that work for breast cancer — eight or nine — more than for any other cancer," says Dr. Christy Russell, co-director of the Norris Breast Center at the University of Southern California. The approach for someone with metastatic disease like Elizabeth Edwards, says Russell, is to use a drug until it stops working — as it almost inevitably will — and then switch to something else, possibly buying years of relatively good health.
Since 60% to 70% of breast cancers grow in response to estrogen, half a dozen drugs, beginning with tamoxifen, introduced in the late '70s, work by blocking that hormone. Such drugs prevent cancer recurrences for 10 years or more in 50% of women with estrogen-sensitive tumors. Even for those with metastatic disease, hormone therapy can lengthen life and frequently will be more effective than chemotherapy. (Edwards told TIME, however, that her cancer was only slightly sensitive to estrogen, though she's waiting for new biopsy results to reveal "what receptors and markers I have.")
Many newer drugs target other pathways for tumor growth. Herceptin, introduced in 1998, interferes with a protein called epidermal growth factor by blocking the her2 receptor, a binding site that is found on the surface of many cells but is overabundant in about 25% of breast cancers. Other smart drugs interfere with the same growth factor, using slightly different chemical strategies to do so, and some have proved useful in a range of cancers. Gleevec, for example, which was approved in 2001, prevents growth factors from attaching to cancer cells and activating an enzyme called tyrosine kinase, which regulates cell division.
Gleevec reversed the odds for patients suffering from two rare cancers — chronic myelogenous leukemia and gastrointestinal stromal tumors — for which there had been no effective treatments. In a matter of months, patients who were out of options had their lives back, and while their cancer was not cured, it was under control, at least for a while. Other new drugs, including Tarceva and Iressa, also halt tumor growth by messing with tyrosine kinase. The key to developing such drugs, says Glaspy, is "torturing cancer cells, and getting them to confess to us which pathways they are dependent on."
Researchers have wrung other kinds of information out of cancer cells, including the way they spur the formation of blood vessels, which nourish their growth. Avastin, approved in 2004, is the first drug to throw a wrench into the process by suppressing a tumor's ability to recruit vascular growth factors. As with many of the newer therapies, doctors have found that it works best as part of a cocktail of cancer drugs.
Newer additions to this growing arsenal are being developed at such a clip that "it's fun to be an oncologist right now," says Hayes, though he's worried about sharp cuts in federal research spending. Hayes remembers wincing a bit 25 years ago when patients wistfully hoped that "something new will come along" to save them. "Now there's something new coming down the pike all the time," he says. In fact, an alternative to Herceptin was approved this month, giving doctors something to try when Herceptin stops working.
Oncologists are also excited about a new generation of tests that enable doctors to do a better job of matching the treatment to the tumor. Oncotype Dx, introduced in 2004, looks at 21 genes in biopsied tissue to determine whether or not chemotherapy will be helpful for early breast cancer patients with recent diagnoses. At Duke University, molecular geneticist Joseph Nevins is testing a similar gene-based test for lung cancer. Researchers are aiming for tools that will tell them not only whether chemo is needed but also which specific drugs to use. Such a screen already exists for Herceptin, and many others are in development. Meantime, at the M.D. Anderson Cancer Center in Houston, Dr. Roy Herbst, chief of thoracic medical oncology, is looking for protein markers on lung tumors that will enable doctors to make the best choice among four different drug combinations.
None of these advances mean that living with cancer is easy, or even possible. A certain percentage of patients, as Snow and Edwards surely know, do not respond to any current treatments. And some types of cancer — particularly pancreatic, ovarian and stomach — continue to have high mortality rates, one reason cancer still kills 560,000 Americans every year. Side effects remain an issue as well, though antinausea medications are now so good that some doctors say it's rare for their patients to vomit. And drugs that prevent anemia and a drop in white blood cells mean patients can carry on with life's activities without the constant dread of contracting infections. Still, anxiety remains a steady companion for people living with cancer. "Dealing with the worry around tests and how well the drugs are working for recurrent cancer is one of the most emotionally challenging things that my patients experience," says Russell. "All medical oncologists must help patients manage this emotional roller coaster."
Edwards suspects she's better prepared than most, because she's already faced down death, not only with her first bout of cancer but also with the loss of her 16-year-old son Wade 11 years ago in a car accident. "When you lose a child through an accident," she says, "you discover that you only have an illusion of control over your own fate. I've already let go of that myth, and that makes this process a lot easier."
For now, Edwards is happy to be the public face of living with cancer and has enjoyed seeing fellow travelers at campaign stops, greeting her in headscarves or with thinly thatched noggins. She expects to begin a new round of treatment in mid-April, after a bit more campaigning and some time off to spend spring break with her kids. She's thinking less about how much time she may have and more about how she spends it. "I was cleaning my bathroom, and thinking, I really don't want to spend too much time doing this," she says. "Another thing I did was plant some lilacs and other flowers — something I hope to enjoy and I know my family will enjoy. That's work I'm happy to fill my days with."
Researchers from Harvard have shown that higher intakes of calcium and vitamin D may be reduce the risk of developing premenopausal breast cancer. The details of this study appeared in the May 28, 2007 issue of the Archives of Internal Medicine.
