Hope for A Cure
After years of baby steps in the march against breast cancer, new research has resulted in a giant leap forward. Doctors who once hoped, at best, to minimize the devastation of this disease are now peppering their conversations with that four-letter word—cure.
"We’re very careful about using words like cure, but I think it’s time to go back to those words," says Eric P. Winer, M.D., director of the breast oncology center at Boston’s Dana-Farber Cancer Institute. Among the changes doctors expect in the next decade: targeted therapies that attack cancer without harming healthy cells, better detection methods, and treatments to prevent the disease entirely. "Breast cancer is going to be different in five to ten years," says Winer. "I believe we could see a 75 percent reduction in death rates, meaning that instead of 40,000 women dying annually, it will be more like 10,000."
The mood of the cancer-research community has shifted noticeably since May, with news of two drugs. While the compounds themselves (Herceptin and Avastin) are promising, it’s the scientific theory behind the drugs that researchers feel will unlock the secrets of breast cancer.
The Breast Cancer Breakdown
Until recently, breast cancer was seen as a single disease, and many woman were treated the same: "Slash, burn and poison," says Los Angeles breast surgeon Susan Love, M.D., referring to surgery, radiation and chemotherapy.
Now scientists believe that the disease should never have been named after body parts in the first place. Cancer, it turns out, is defined by its genetic blueprint, not just its location. Breast cancer is really a collection of a half-dozen, and possibly more, diseases. Some can be defined by their hormonal activity; estrogen and progestin receptor positive cancers may have three or more distinct forms. Another is distinguished by multiple copies of a particular gene, HER2. Finally, a "basal-type cancer"—linked neither to hormones nor HER2—has also been identified.
Pinpointing the specific type of cancer in the breast will allow researchers to develop new drugs that fight tumor cells with fewer side effects or the collateral damage of chemotherapy.
Such therapies are already being prescribed. Herceptin, used in women with HER2-positive breast tumors (particularly aggressive when untreated), binds to certain proteins, blocking tumor growth and harnessing the body’s own immune system to heal itself. In a study by Mayo Clinic researchers, Herceptin plus chemotherapy prevented recurrences in about half of women who would have had a recurrence. But the true potential of this research goes beyond the drug itself. "The fact that we have identified this key pathway implies to me that other agents will be available in the future that may do even better," says Winer.
The war against breast cancer will be won or lost in a Petri dish, as laboratories identify exactly what type of cancer a woman has, so the most effective agents can be prescribed to combat it. "We used to blanket the whole Amazon rain forest with chemicals," says Larry Norton, M.D., deputy physician-in-chief, Memorial Hospital at Memorial Sloan- Kettering Cancer Center in New York. "Now we design molecules to hit a single tree. It’s a new level of detail."
New Avenues of Attack
Recent findings on Avastin have boosted the profile of anti-angiogenesis drugs, which choke off the blood supply to tumors. This drug, FDA-approved to treat advanced colorectal cancer, is showing promise in breast cancer, too. Theoretically, all cancers produce proteins that direct the formation of new blood vessels that ultimately feed tumors. Studies of Avastin plus chemo showed that blocking those signals could starve colon cancer cells, so researchers began to study the drug for treating other solid tumors. A National Cancer Institute study showed that among women with advanced breast cancer, Avastin plus chemo slowed cancer progression by half. Researchers are now looking at long term survival as well as whether the drug can also benefit women with early stage disease.
New Drug-Delivery Systems
Nanotechnology is a term you’ll hear more of when it comes to breast (or any) cancer research. Basically, nanotech involves devices 80-100,000 times smaller than the width of a human hair. Since cancer happens at the cellular level, these tiny technologies have the potential to prevent, detect and treat cancer in ways never before imagined.
Earlier this year, one nanotech drug, Abraxane by American BioScience, was approved for advanced breast cancer. The active ingredient is Paclitaxel, also found in the chemo drug Taxol, but Abraxane’s tiny particles ferry the therapy right to the tumor, so patients don’t need extra drugs or ingredients to dampen down side effects.
Nanotechnology can also make drugs more effective. Initial studies have found that Abraxane may allow patients to safely receive 50 percent more active ingredient per dose than the traditional delivery method, shrinking tumors faster and to a greater degree. The verdict is still out on whether this will affect survival rates, but models developed by Larry Norton and his colleagues at Sloan-Kettering already support the idea that "dose-dense" treatment—delivering the most doses possible in the shortest period of time—is the most effective way to stop cancer. This treatment is based on the notion that tumors grow and die according to predictable patterns. The trick is frequency; giving a small dose more often means more medicine can be administered over the same time period with less toxicity, so the drug knocks out as much cancer as possible without taking as great a toll on the patient. "Now that we know certain patterns of growth are important, finding the molecules responsible for them may lead us to the cure," says Norton.
Better, Earlier, Detection
Nanotechnology may also be used to detect cancer at earlier stages. Launched into the breast or elsewhere, such particles will act as tiny probes, taken into cancer cells too small to be detected by conventional methods. These anocrystals may be used to bind to cancer or normal cells, making them more visible with MRI or other types of scans.
It’s not nearly as futuristic as it sounds. In March, the FDA moved a step closer to approving a nanoparticle known as Combidex, developed by Advanced Magnetics, Inc., which, when used with an MRI, will help distinguish normal from cancerous cells. Right now, the only way for doctors to find out if cancer has spread is to remove or biopsy one or several lymph nodes. The nanoparticles have the potential to detect cancers accurately without the removal of even a single lymph node. Soon, nanoscale devices may allow doctors to multitask, both detecting cancer at its earliest stages and simultaneously delivering anticancer agents.
Other new detection methods identify the growth of new blood vessels that could signal the emergence of cancer. Clinical trials have begun on ComfortScan, a new device from DOBI Medical International that detects increased blood-vessel creation. The ten-minute scan won’t be dramatically different from a mammogram
Another tool, iFind, may revolutionize breast self exams. The handheld device responds to the higher level of hemoglobin found in cancer tissues, which require more blood and oxygen than surrounding tissues. In a small study, the device was96 percent reliable in detecting cancer. Although larger trials are needed, developers say the device, expected to cost less than a few hundred dollars, could be available in as few as two years. It won’t replace mammograms, but it will give women a useful tool for monitoring their breasts between screenings.
New Tools to Prevent Cancer
Drugs are also being studied for their prevention potential. Aromatase inhibitors, such as AstraZeneca’s Arimidex, Novartis’ Femara and Pfizer’s Aromasin, dramatically reduce recurrence in women with early stage disease; now investigators hope to design studies to determine if the drugs can just as dramatically cut the rate of occurrence in women at high risk for the disease.
Just as a colonoscopy can now detect and remove polyps before they become cancerous, researchers are working to develop methods that will allow them to seek out and destroy precancerous breast changes. Already, researchers at Sloan-Kettering are studying the use of focused ultrasound to eradicate precancerous breast lesions. Unlike the ultrasound used to scan for irregularities, this technology uses focused, high-energy sound beams to destroy suspicious cells, leaving healthy tissue untouched. "It’s like a Flash Gordon ray gun," says Norton. "It’s possible that we’ll find tiny lesions, diagnose them and destroy them so they never grow into cancers."
Originally published in More magazine, October 2005.