Beating The Odds
Finely tuned diagnoses and targeted drugs are creating optimism about surviving breast cancer
The crowd applauded wildly and wouldn't be quieted. The overflow audience in the Orlando hall was clearly grateful for what it had just heard. One person described it as "mind boggling," another as "jaw dropping," and several said they were on the verge of tears. "It was a Rolling Stones concert in terms of crowd response," says George Sledge, who was onstage. "Truth to tell, I had a hard time keeping my composure at the end."
But this was no rock concert. Not even close: It was the annual meeting of the American Society of Clinical Oncology, and Sledge, chair of the society's cancer education committee, was leading the discussion at a special session tacked on to the program at the last minute. The topic: a handful of studies looking at a new use of Herceptin, a breast cancer drug previously used to buy time for women whose cancer had spread elsewhere in the body. It was now being studied for use in the early stages of a particularly aggressive form of breast cancer that affects about 50,000 women a year, fully a quarter of women diagnosed with the disease. The Orlando session was the premiere for the kind of hard data that can turn skeptical oncologists into enthusiastic fans.
The researchers onstage got the Mick Jagger treatment for good reason. Herceptin helped a group of women with a specific type of cancer who previously had dim hopes. Science was able to single out these women, but it could offer little help beyond standard treatment. The new research showed that adding the drug to chemotherapy cut the recurrence of cancer by more than half. Put another way, that means that after four years, 15 percent of the women treated with chemo and Herceptin had a recurrence, compared with 33 percent of women treated with chemo alone. "This means major improvements in survival," says Robert Morgan, an oncologist at City of Hope Cancer Center in Duarte, Calif. The drug, he says, will immediately be used in the new way.
These women are not out of the woods yet. But the further good news for them is that the Herceptin findings come on the heels of other exciting developments in breast cancer treatment, including new and promising drugs and even news about therapeutic behavior changes, including diet. Add that to a growing understanding of the basic biology of breast cancer and incremental progress in treatment that has been made over the past few years, and the prospects for decreasing the mortality rate further are excellent. "This is a time for huge optimism," says Claudine Isaacs, an oncologist at the Lombardi Comprehensive Cancer Center at Georgetown University.
Challenges. Yet while there have been huge strides in treating breast cancer--the 10-year survival rate is now about 75 percent and will no doubt climb with the new treatments--challenges remain. A major one is pinpointing women with particular variations of the disease and matching them to the appropriate treatment. As drugs are given to women in earlier stages of their disease, the potential for harmful side effects must be even more carefully considered. And the array of new treatment options means more potential for confusion--and a greater need for women to be more assertive about getting the treatment they need.
Scientists were already on the right track and indeed reported recently in the Lancet that middle-aged women treated with chemotherapy and hormonal therapy had their risk of death cut in half over 15 years. The benefit of the chemo and drug therapy increased over time, suggesting that many of them may never have a recurrence. But that news doesn't include the newer variations in chemotherapy introduced over the past several years. Just last week, for example, researchers writing in the New England Journal of Medicine reported that replacing an older chemo drug, fluorouracil, with a new one, docetaxel, cut the risk of death by nearly 30 percent among breast cancer patients. Also not yet reflected: even newer drugs, some of which can target specific cancer cells, sparing the rest of the body.
New forms of treatment have now been added to the arsenal, most of them based on a fundamental shift in the way we think about the disease. With recent biological advances, especially in genetics, we now know that--as with other cancers--the term "breast cancer" has actually become somewhat quaint. More accurate, scientifically, would be "cancers that happen to be in the breast," some of them more aggressive than others.
A woman diagnosed with breast cancer today now faces a much different situation from one diagnosed 20, 10, or even five years ago. The debate used to be over which form of chemo to use or how often to use it. Says Sledge: "It was like arguing whether toothpaste A is better than toothpaste B." Doctors now use the "divide and conquer" approach, classifying breast cancers into specific categories and treating them accordingly. Women whose tumors are influenced by the hormones estrogen and progesterone, for example, can benefit from treatments that change the action of those hormones. Many of these women are still treated with tamoxifen--the former gold standard, but not without serious side effects. But a new class of drugs is gaining ground. Aromatase inhibitors, like Arimidex and Femara, were first examined for use after tamoxifen and are now candidates to replace it, at least in some women.
Indeed, one recent study showed that Femara is more effective than tamoxifen in preventing breast cancer recurrence. Those who took the newer drug had a 19 percent lower chance of a recurrence. Since the newer drug has only been in use for six years, it's still too early to know whether it will show a difference in overall survival, says David Epstein, president of the oncology division of Novartis, which makes Femara. One of the patients taking Femara is Joan Syron, a 72-year-old in Annandale, N.J., who was diagnosed with Stage II breast cancer. She started taking Femara in 2001, after five years on tamoxifen, and is still on it. "It's getting to be nine years [after diagnosis], and I'll never really stop worrying," she says, "but I feel comfortable with what I'm doing with my life."
Breast cancer tumors can also be classified by whether or not they make too much of a protein called HER2. Women with this type of cancer, who tend to be younger, until quite recently had little help specific to their cancer after completing chemotherapy. "We would see these women and we knew enough to tell them that they had aggressive disease, but we couldn't do anything for them," says Marisa Weiss, an oncologist in Philadelphia and founder of breastcancer.org. Herceptin targets this specific kind of cancer. It was first approved by the Food and Drug Administration for use in the latter stages of breast cancer but later was tested in women with an earlier stage of the disease. When the researchers checked the results after a few years, the successes were so dramatic that they halted the study, arguing it was unethical to deny any patient Herceptin.
That was good news for Marcia Rosenberg, who had been diagnosed with HER2-positive breast cancer after a routine mammogram. It was the first time Rosenberg, a 58-year-old Maryland attorney, had been seriously ill. She recalls hearing the diagnosis: "You could have knocked me over with a feather."
Rosenberg had a lumpectomy and then more surgery before doctors discovered the cancer had spread to her lymph nodes. Isaacs, her oncologist, suggested the Herceptin study, and Rosenberg trusted her. The trial was set up so that all the participants first got four cycles of chemo and then were told which arm of the study they'd been assigned to. Rosenberg learned she'd be assigned to the control group: She wouldn't be getting the drug.
Waiting. That was devastating news, since the word was out that Herceptin was showing encouraging early results. Isaacs told her to be patient, that some new findings were due out soon. Rosenberg didn't have to wait more than about 90 minutes: She was in the infusion room, having her chemo treatment, when a nurse handed her the phone and Isaacs told her the good news: The preliminary data looked so good that the patients in the trial, including her, would now be eligible for the drug. "It was one of the most dramatic days of my life," she says.
She's optimistic, and so are oncologists. "Probably thousands of women will be alive in a decade who wouldn't have been otherwise," says Sledge. Still, the study didn't extend long enough to tell if the early benefits will continue. "One must always be cautious looking into the future with these studies," says Len Lichtenfeld, deputy chief medical officer of the American Cancer Society. There are also questions about how long patients should take the drug and in what combinations with other medicines.
And there are still women sitting on the sidelines whose cancers do not fall into the categories treatable with new drugs. "HER2 is the engine that drives this cancer cell, but what are the engines, other than estrogen, that drive these other cells?" asks Karen Gelmon, an oncologist and head of the investigational drug program at the BC Cancer Research Centre in Vancouver.
A new group of women needing even newer treatments is now being talked about: so-called triple negatives, whose cancers aren't estrogen-receptor positive, progesterone-receptor positive, or HER2 positive. Lisa Carey, medical director of the Breast Center at the University of North Carolina, is studying whether this broad group can be subdivided into smaller groups, one of which may respond to drugs like Iressa and Tarceva, which target another receptor known as EGFR. African-American women fall disproportionately into this triple negative category, which may explain why breast cancer in those women tends to occur at younger ages and be more aggressive than in Caucasian women.
The science of classifying tumors this way is still in its rudimentary stage, and even if the statistics show an increase in survival, doctors cannot yet tell an individual patient that she'll survive her cancer for a determined period of time. So the challenge is not only coming up with new treatments but figuring out for whom they do and don't work. One drug that isn't limited to a specific tumor type is Avastin, a drug already shown to help in other cancers by choking off the tumor's blood supply. Genentech and Roche recently reported that in patients with advanced breast cancer, the drug, combined with chemo, doubled the time they lived without a recurrence compared with chemo alone, from six months to 11 months.
Heraleen Broome's breast cancer had spread to her lungs by 2003, and chemo wasn't working. "I was packing up everything to give it away," the 68-year-old remembers. "And then I decided to unpack and keep my stuff." She joined a trial of Avastin, and 11 tumors in her lungs became three. Every three weeks she drives from her home in Oakland, Calif., to San Francisco for treatment, and the people there are so familiar that it has become a social event.
It's not yet clear whether Avastin will ultimately improve survival rates in breast cancer, but the early reduction in recurrence reminds some of early data on Herceptin. The drug will also be studied in patients with earlier disease. In those early stages, it's not a case of throwing everything at a patient and seeing if it works. For one thing, chemo already has severe side effects. Even the new advance, docetaxel, increases the risk of diarrhea and mouth sores, though it produces less nausea and vomiting. And targeted drugs have their own downsides. Herceptin, for example, can cause heart problems in a small percentage of patients. That's important, since statistically many women who might take the drug would very likely have their cancer driven away by chemotherapy and surgery alone.
Lifestyle changes. The inevitable risk and expense of drugs explain why doctors were excited about another study, one that suggested for the first time that for some women a low-fat diet might actually reduce the odds that cancer will return. This is the first time that diet has been identified as a tool that survivors can use to protect themselves against the return of cancer; another study showed that even a little exercise can also extend survival (though a healthy lifestyle is no guarantee of beating the disease). "In general, I'm saying to a survivor: There's good data that you should clean up your act after a diagnosis," says Susan Love, a surgeon at the University of California-Los Angeles medical school and author of Dr. Susan Love's Breast Book. "Eat a low-fat diet with lots of fruits and vegetables that's low in animal fat." And unlike drugs, there are no potentially hazardous side effects. It's an easy thing for women to do. "To me, it's a no-brainer," says Larry Norton, deputy physician in chief for breast cancer programs at Memorial Sloan-Kettering Cancer Center in New York.
The flood of good news brings complexity to the field of breast cancer and to patients, making early detection and good care crucial. Right from the beginning, it's important to make sure that women have access to screening and proper treatment, says Lichtenfeld. There is also confusion for women struggling to figure out what it all means. Even beyond biology, says Weiss, every woman's breast cancer diagnosis is unique--who she is, how old she is, her social status, her education, her religious beliefs. Her style of making decisions is different, her insurance access is different, and her team of doctors is different.
With all the developments, "you now need an up-to-date doctor who knows the pros and cons of all these therapies," says John Mendelsohn, president of the M. D. Anderson Cancer Center in Houston. News filters down fast, but Weiss urges newly diagnosed patients to make sure their tumors are tested for hormone receptors and for HER2. Take the time to figure out the best course of treatment for your disease. "There is some sense of urgency, but you don't have to decide overnight what to do," says Weiss. And get a second opinion, suggests Rebecca McMenamin, 43, diagnosed with breast cancer last fall. "Even if you have a great doctor, it's reassuring to hear someone else tell you the same thing."
Whatever the status of the tumor, "patients should seek out opportunities to participate in clinical trials," says Harold Burstein of the Dana-Farber Cancer Institute in Boston. "Getting treated as part of a trial gives you better care--not just because the Herceptin studies were winners but because the care is carefully monitored, it reflects current thinking, and you're getting care that is state of the art." That's true even if you don't end up on the arm of the trial getting the drug--and trial participants will never be given no treatment at all for their cancer. Ask your doctor about trials you might be eligible for, or check out the National Cancer Institute's website for a list. "It's your body--you should learn as much as possible about what is happening and what your options are," advises McMenamin, who joined the Herceptin trial. "That can help to regain a sense of having some control over the situation." (Another benefit: While many women on the trial will now get the drug free, those who weren't may have difficulty being reimbursed for Herceptin, since it hasn't been approved by the FDA for its new use.)
Weeks after the scientific meeting that had cancer docs standing and cheering, most have returned home to the day-to-day dramas of treating cancer. But their optimism about progress in the field, though it comes with the caveats necessary in the uncertainty of medicine, lingers.
This story appears in the June 13, 2005 print edition of U.S. News & World Report.