If It Works For Breast Cancer...

The challenge: To use promising strategies against this disease to fight other killers

It's the year for women in the oncology world. The most encouraging cancer-related headlines in recent months have all trumpeted the advantages of a new generation of breast cancer treatments. Genentech Inc.'s (DNA ) Avastin is able to extend survival for breast cancer patients. A group of estrogen-blocking drugs called aromatase inhibitors have proven effective in preventing breast cancer from recurring after surgery. And in late April the National Cancer Institute (NCI) reported that Herceptin, another Genentech drug, cuts the risk of breast cancer recurrence by 52% for certain patients. "These results are one more example that we are at a major turning point in the use of targeted therapies to eliminate suffering and death from cancer," said NCI director Dr. Andrew C. von Eschenbach.

At least these results will improve the odds of eliminating suffering and death from breast cancer. The number of breast cancer patients still alive five years after diagnosis, a key milestone in cancer survival, had already risen from 78% in 1985 to 88% in 2000, according to the American Cancer Society (ACS), and the newer treatments are sure to push that rate higher. The latest breast cancer studies are expected to generate the most buzz at the world's largest cancer research meeting, sponsored by the American Society of Clinical Oncology (ASCO) in Orlando, May 13-17. It is there that the details on the recent Avastin and Herceptin breast cancer trials will be released, as well as more information on aromatase inhibitors and improvements in breast cancer screening. There will also be data on other experimental drugs, among them GlaxoSmithKline's (GSK ) lapatinib, which targets two genetic abnormalities found in breast tumors.

Unfortunately, these breast cancer advances stand out in part because they stand alone. No comparable improvements will be reported for lung, colon, or prostate cancers, all of which are diagnosed in more people each year than breast cancer. The outlook for lung cancer, by far the nation's biggest cancer killer, is particularly dismal: Over the same 15-year period that survival rates in breast cancer climbed 10 points, lung cancer's five-year survival rate went from 14% to 15%. Two new lung cancer drugs, Iressa from AstraZeneca (AZN ) and Tarceva from Genentech, Roche Holding (RHHVF ), and OSI Pharmaceuticals (OSIP ), work on only a small percentage of patients. Studies to date have found that Tarceva and Avastin, also tested against lung cancer, increase average survival by just a few months; Iressa, not at all.

To the public, this does not sound like progress. But cancer specialists say the advances in breast cancer point the way toward strategies that might be equally effective against lung, colon, and prostate cancer. Large clinical trials, widespread and early screening, a focus on preventing tumor recurrences after initial treatment, and carefully matching up the proper patients with the proper treatment have all paid off in breast cancer. Those same techniques are already being tested against the three other major cancer killers. "We're making steady progress in all cancer types," says Dr. Larry Norton, head of breast cancer research at Memorial Sloan-Kettering Cancer Center in New York. "The interval between advances is getting shorter and shorter."

Progress in breast cancer came first in part because it followed the money. In the 1980s women started pressuring private and public entities for more funding, and the current annual NCI budget is proof of their success: $566 million for breast cancer research, compared with $308 million for prostate cancer, $276 million for lung, and $262 million for colon. The ACS estimates that prostate cancer will be diagnosed in 232,000 U.S. men this year, yet the Defense Dept. has spent a total of $1.83 billion researching breast cancer and $565 million on prostate cancer.

Some heavy cultural baggage may be limiting activism by other cancer patients. Lung cancer carries a "blame the victim" burden, because some 85% to 90% of patients are former or current smokers. Prostate cancer is an embarrassing topic for many men, while colon cancer suffers from the public's discomfort over screening -- even though colon cancer is almost always cured if detected early.

By contrast, there's no consensus in the medical community about whether early breast cancer detection improves survival, but that hasn't slowed the widespread use of mammography. What has certainly improved survival is the deciphering, decades ago, of the biology of breast cancer and the rapid introduction of therapies tailored to that biology. Most breast tumors depend on the female hormone estrogen for growth, so the estrogen-blocking drug Tamoxifen has been the gold standard in treatment for more than 30 years. It was the first drug used to reduce the risk of deadly tumor recurrences after surgery and the first approved to prevent cancer in high-risk women.

THE PREVENTIVE ROUTE

As good as Tamoxifen is, aromatase inhibitors, introduced in the late 1990s, are proving better. AstraZeneca's Arimidex, Novartis' (NVS ) Femara, and Pfizer's (PFE ) Aromasin are already common treatments for early stage breast cancer, and clinical trials reported over the past year found that they can be better than Tamoxifen at preventing tumor recurrence. As a result, ASCO recently recommended aromatase inhibitors for use after surgery for postmenopausal women with hormone-positive breast cancer.

To target an even narrower slice of breast cancer patients, the NCI reported in April that Herceptin, which knocks out the Her-2/neu gene that causes some 25% of breast cancers, can also sharply cut down the risk of recurrence. Breast cancer patients now have at least five different drugs that can actually prevent disease, not just treat it.

Duplicating that success in other cancers will require the same biologically specific treatments -- posing a tough challenge. Many lung and colon tumors, for example, depend on high levels of a blood enzyme called epidermal growth factor (EGF). EGF receptors on the tumor cell's surface are blocked by Iressa, Tarceva, and several other drugs, but those receptors are a much more complex target than estrogen. "In lung cancer it is not just the presence or absence of EGF receptors but the establishment of a mutation within the receptor that determines the tumor's responsiveness" to a certain drug, says Dr. William J. Slichenmyer, Pfizer's vice-president for oncology development.

Just as there is a test for Her-2/neu, lung cancer specialists need a test that can pinpoint which tumors depend on EGF. They've made some progress. Genzyme Corp. (GENZ ) announced on May 2 that it licensed a test from scientists at Dana-Farber Cancer Institute and Massachusetts General Hospital that detects genetic mutations likely to respond to Iressa.

Such tests will go a long way toward helping the cancer community realize its longtime dream of creating personalized treatments for each and every cancer patient. That dream is closest to coming true for breast cancer patients. And although it's not a cure, it's at least a partial payoff for all those dollars spent.

By Catherine Arnst in New York

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