While some promising new treatments for breast cancer are years away from regular treatment regimens, others are on the market or just around the corner.
Still on the horizon for treating breast cancer are anti-angiogenesis drugs. They block the formation of new blood vessels that feed tumors and help them grow. These drugs have shown promise in treating colon cancer and are now being studied in patients with advanced breast cancer. But it may be some time before these drugs have been studied enough to make the leap to treating early-stage breast cancer.
Even so, new breast cancer treatments are available now. Over the past year, doctors have learned a lot more about many targeted therapies that very soon may be helping millions of women live longer and healthier lives after learning they have breast cancer.
Abraxane and Albumin-Bound Nanoparticle Drugs
In January, headlines trumpeted the release of a new chemotherapy drug for breast cancer called Abraxane. Technically, Abraxane isn't a new drug -- it's an exciting new way of delivering an existing drug.
Paclitaxel, commonly marketed as Taxol or Taxotere, is part of many chemotherapy drug regimens, but it has one big problem, says Clifford Hudis, chief of the Breast Cancer Medicine Service at New York's Memorial Sloan-Kettering Cancer Center. "It doesn't dissolve in water, which means we have to put the drugs in solvents to deliver them to patients." Those solvents can cause a number of side effects, including severe allergic reactions. Patients taking paclitaxel have to receive heavy doses of other medications first, such as steroids and antihistamines, before getting their chemotherapy.
Abraxane does a neat end run around that problem. A process called protein-bound nanoparticle technology creates tiny particles that bind the paclitaxel to a naturally occurring protein called albumin. "The binding makes little packets of paclitaxel -- think of them as little bubbles -- that can be dissolved in water," says Hudis. This means no more solvent, which in turn means no more medications before chemotherapy, and no more of the side effects that go along with them. It's also shortened the chemotherapy's infusion time from more than three hours to around half an hour.
These practical pluses would be enough to make anyone receiving chemotherapy rejoice. But there may also be a bonus in terms of the drug's effectiveness. In one of the major clinical trials that led to Abraxane's FDA approval, women who got this drug had almost twice the response rate to chemotherapy compared with women who received regular Taxol. This may be in part because without the need for solvents, higher doses of paclitaxel could be delivered to the women getting Abraxane.
Or another factor could be involved. Because albumin, which normally transports nutrients to cells, accumulates in rapidly growing tumors, it's possible that the bundles of Abraxane in their albumin "envelopes" are sent by express delivery directly to cancer cells. "There are signs indicating that albumin receptors in breast cancer and other cancer cells would preferentially pick up these albumin-bound packets," says Hudis.
If so, that may have exciting implications for other chemotherapy drugs used in breast and other cancers, says Claudine Isaacs, MD, director of the Clinical Breast Cancer Program at the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center in Washington, D.C. "This delivery system probably will not be limited to paclitaxel. Theoretically, you could put any number of chemotherapy drugs in these packets, not just paclitaxel." And years of experience with chemotherapy show that delivery matters. "The same drug can have a very different side effect profile, as well as potentially different benefits and response rates, based on how it's delivered."
So far, Abraxane has only been FDA-approved for use in patients with breast cancer that has recurred or metastasized. Still, many drugs that are first approved for use in this stage of the disease later prove to be effective for women with earlier-stage breast cancer.
Aromatase inhibitors aren't new. The FDA approved the first, Arimidex, in September 2000. Many large trials have recently confirmed that these hormone therapies outperform the more commonly used tamoxifen to prevent tumor recurrence in women who had hormone-positive breast cancers (cancers that are fed by estrogen).
Because they act only on estrogen that's produced outside the ovaries, aromatase inhibitors are only effective in postmenopausal women. (Before menopause, most of the body's estrogen is produced in the ovaries.) But for these women, Arimidex and its sister drugs, like Aromasin and Femara, offer a small but crucial advantage over tamoxifen -- 4% to 5% -- in preventing cancer recurrence.
"What's important is that these drugs significantly reduce late recurrences," says Isaacs. But she notes that researchers still don't know which strategy works best: taking an aromatase inhibitor instead of tamoxifen, as the first course of therapy after surgery for breast cancer (called adjuvant therapy) or beginning treatment with tamoxifen and switching to an aromatase inhibitor after two to five years.
Major trials are looking at these questions now, Isaacs says. For the moment, know that aromatase inhibitors should be a part of the equation for any postmenopausal woman with hormone-positive breast cancer. That's the new recommendation from the American Society for Clinical Oncology.
"There definitely are side effects, such as osteoporosis and muscle and joint achiness, and others could always emerge. Aromatase inhibitors may not be right in all of these cases," Isaacs says. "But they should be seriously considered."
About 25% of breast cancers have too many copies of a gene called HER2neu, which helps control how cells grow, divide, and repair themselves. When there are extra copies of this gene, the body often makes too much of the HER2neu protein, and cells can grow out of control. HER2-positive breast cancers can be very aggressive.
For several years, the drug Herceptin has been used to treat women with HER2-positive breast cancer that has metastasized or recurred. It's a kind of drug known as a monoclonal antibody. It works like a heat-seeking missile, homing in on cells that make too much HER2neu protein. Used either with chemotherapy or alone, Herceptin can reduce tumor size and increase a woman's chances of both overall survival and disease-free survival.
But the trials that led to Herceptin's FDA approval were all in women with advanced breast cancer. Would Herceptin work as well in women with early-stage disease? Within the last year, promising research has indicates the answer may be yes.
In a study released last June, scientists at the University of Texas M.D. Anderson Cancer Center in Houston looked at women with early-stage, HER2-positive breast disease. They found that more than twice as many women who received Herceptin as part of their presurgical chemotherapy had their tumors completely disappear compared with women who received chemotherapy alone. Indeed, the results were so striking that the researchers stopped the study early, after enrolling only 42 of a planned 164 patients.
"More than 65% of the Herceptin patients had a complete response rate, as compared with only 26% of patients who received chemotherapy only," says Aman Buzdar, MD, deputy chair of the department of breast and medical oncology at the M.D. Anderson Cancer Center.
So why hasn't Herceptin been approved for use in early-stage HER2-positive breast cancer yet? First, because of the relatively small size of the trial, and second, because of concerns about its side effects. In a small percentage of patients, Herceptin can cause heart damage and sometimes even heart failure. (Some common chemotherapy drugs can as well.)
Four large-scale, randomized clinical trials are now under way to better identify the benefits and risks of Herceptin. "It's very likely that Herceptin will be an effective therapy in early-stage disease, based on what we've seen in metastatic breast cancer," says Sloan-Kettering's Hudis. "But what's not so clear yet is how big an impact it will have on survival and recurrence rates, and what the price might be for a broad population in terms of heart failure. If we improve survival rates by 2%, but it causes 4% of patients to have significant heart failure, then you'd have a hard time figuring out what to do next."
In the small group of study patients at M.D. Anderson who received Herceptin, says Buzdar, none so far has developed any heart problems almost two years after treatment. Some doctors have prescribed Herceptin "off-label" for women with non-metastatic breast cancer, but both Hudis and Isaacs are cautious. They recommend women with early-stage breast cancer only take Herceptin if they are in a clinical trial until more questions are answered about the drug's risks and benefits.
When it comes to responding to chemotherapy, not all breast cancers are created equal. So far, doctors have not been able to accurately predict which women would derive added benefits from chemotherapy and which ones wouldn't. So the policy has often been, "When in doubt, get chemotherapy."
Now, studies show that a new genetic test, known as the Oncotype DX 21-gene assay, not only assesses the likelihood of breast cancer recurrence for many early-stage breast cancer patients, but also predicts how much chemotherapy will help these women. This new test may give some low-risk women the option of skipping the rigors of chemotherapy, while reassuring others that the often-difficult treatment they're receiving has a clearly defined benefit.
For women who have hormone-positive breast cancer that has not yet spread to the lymph nodes, the Oncotype assay analyzes 21 genes related to breast cancer in the body that breast cancer cells depend on, including the estrogen receptor, HER2 and proliferation genes. It then divides the results into low-, medium-, and high-risk scores.
Women in the low-risk group, about half the patients studied, would get only a minimal, if any, benefit from chemotherapy. Women in the high-risk group would be very likely to benefit from chemotherapy.
"What this suggests is that for women with node-negative, hormone-positive breast cancer, we'll be able to use this test to help determine who will do very well with tamoxifen alone and may not need chemotherapy, and who will benefit from additional treatment with chemotherapy," says Isaacs.