HER-2/NEU: A CURE FOR BREAST CANCER?

The Cancer Chronicles Spring 1998
© 1998 by Ralph W. Moss, Ph.D.

Stories about progress in the war on cancer have been falling like artillery shells in recent months. The world had barely recovered from the Angiostatin/Endostatin flap,when news emerged of a sensational new drug called Herceptin. The story was announced at the American Society for Clinical Oncology (ASCO) meeting in Los Angeles and like the Angiostatin was ballyhooed in the New York Times (although not on the front page).

According to a University of California at Los Angeles news release, a new study on Herceptin represented "a significant medical breakthrough." Dr. Larry Norton, chief of the breast service at Memorial Sloan-Kettering Cancer Center in New York (the same scientist who claims that vitamin C is harmful to cancer patients undergoing chemotherapy) waxed enthusiastic about the treatment in the New York Times.

"This is the biggest difference I have ever seen in advanced breast cancer," he said. It is "a big effect, not a small, minor effect." This treatment "is not like anything we have ever seen before" in cancer therapy, he added. The Food and Drug Administration (FDA) has said that it will decide by November 4 whether or not to allow Genentech to market Herceptin. But Genentech mounted a huge display at ASCO, announcing that the drug would in fact be approved and available by November. This has created near pandemonium among breast and ovarian cancer patients desperate to get the latest "cure."

EXPERIMENTAL DRUG

So what's all the shouting about? Herceptin is an experimental immunological drug of a new and promising kind that homes in on a defect in one particular type of breast cancer. These are the cells that express the HER-2/neu gene. The gene is not inherited but develops for unknown reasons during a woman's lifetime. It then produces a protein which is present on the cell surface. HER-2/neu is found in about 30 percent of breast cancer cases and 20 percent of ovarian cancer cases. Weekly intravenous injections of Herceptin in a clinical trial were added to standard chemotherapy in women with stage IV breast cancer.

In the chemotherapy-alone group there were 32 percent remissions (partial or complete tumor shrinkages for a month or more). In the Herceptin-added group there were 49 percent remissions. After one year, there was an 11 percent difference: 67 percent of those receiving chemotherapy-alone were still alive while 78 percent of those also receiving Herceptin were still alive. About 14 percent of patients receiving chemo alone did not show evidence of progression compared with 28 percent of those receiving chemo plus Herceptin. The median duration of the response--which is a measurement from the time the cancer shrank to the time it began to enlarge or spread--was six months in the chemotherapy group compared to nine months in the chemo-plus-Herceptin group, a three month improvement.

Herceptin by itself had unspectacular effects. There were remissions (partial or complete) in 16 percent of patients. The median duration of responses was also nine months.

Scientists said that the side effects of Herceptin was minor, although they conceded that it could cause heart damage when combined with other drugs.

TELEVISED CURES

Before the meeting I was astounded to see on television a woman talking about her long-term cure following this treatment. It turns out that there are in fact precisely two cases in the country with apparently long-lasting effects of Herceptin. One of them is a patient of Dr. Dennis Slamon at UCLA, the other of Dr. Norton. The patient of Dr. Slamon has lived six years after taking Herceptin for 18 weeks, but none of the drug since. The patient of Dr. Norton is still on the drug five years out. According to Larry Altman, M.D. of the New York Times, "Statistically, the women would have been expected to die in less than a year without such treatment...." (May 18, 1998).

When such "poster child" cases are publicized by alternative practitioners they are universally derided as "mere anecdotes." But apparently a different standard applies when such stories are related by top doctors at major medical centers. Then they become valid case histories, worthy of publication in the New York Times.

The problem with such reasoning is this: no particular individual performs according to statistical norms. According to the government's own statistics (SEER Cancer Statistics Review, 1973-1991) the five-year relative survival rates for women with distant metastases (stage IV disease) ranged from 11.0 in older black women to 21.8 percent in younger white women. If we just look at the latter group for a moment, more than one out of five women with "incurable" breast cancer survives five years or more. These women, needless to say, did not receive Herceptin and some of them probably did not receive chemotherapy at all. So, if you treat a cohort of such women with Herceptin it is statistically inevitable that some of them are going to be alive at five years, as will untreated patients. We would expect, in fact, about a 20 percent survival. So how can you tell in the case of these particular individuals whether it was the Herceptin that caused the prolonged survival? Even if there is no sign of the tumor in their cases this fact may not be the cause of their prolonged survival, but merely an epiphenomenon. They might have survived anyway, with or without visible tumor.

PROBLEMS WITH CLINICAL TRIALS

Clinical trials theoretically offer a way out of this dilemma (although the ethics of having a control group are highly debatable). But such clinical trials have to be conducted by people who do not have any vested interest in the outcome of the trial. This is difficult, since a positive outcome alone is a tremendous career-booster.

There are many pitfalls to conducting clinical trials which I and many others have pointed out repeatedly (See my book Questioning Chemotherapy.) For example, it sometimes happens that patients receiving more toxic regimens seem to do better than those receiving less intensive treatments. Through a kind of medical Darwinism, the healthiest patients tend to survive the clinical trial itself, while sicker patients drop out due to toxicity or death. These patients are then sometimes eliminated from the final tally as "unevaluable." This bit of bookkeeping makes the intensive treatment look better than the control treatment, since it was precisely this hardy group of patients that was most likely to survive longer anyway. As a general rule, it takes great care and moral scruples to design a study in a way that does not bias the results in a direction that promotes the personal interests of the investigators.


Ralph W. Moss, Ph.D. is director of the The Moss Reports for cancer patients. Dr. Moss is the author of eleven books and three documentaries on cancer-related topics. He is or has been an advisor on alternative cancer treatments to the National Institutes of Health, the National Cancer Institute, the American Urological Association, Columbia University, the University of Texas, the Susan G. Komen Foundation and the German Society of Oncology. He wrote the first article on alternative medicine for the Encyclopedia Britannica yearbook. He is listed in Marquis Who's Who in America, Who's Who in the World, Who's Who in the East, and Who's Who in Entertainment (as a film documentarian). This Web site does not advocate any particular treatment for cancer. We urge you to always seek competent medical advice for all health problems, especially cancer. Before consulting our site please read our full Disclaimer statement.



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