COLUMN ONE : Feeling Betrayed by Science : A scandal over faked data in a breast cancer study has left patients reeling and a pioneering doctor in disgrace. It also has heightened fears about human experiments.
When she read the news, the patient burst into tears.
The story documented flaws in a study that had helped change the course of breast cancer treatment. Results had been falsified. What was worse, the researchers conducting the clinical trial--part of a long-running and extremely important series of breast cancer studies--knew about the doctored data but remained silent.
In an extraordinary reaction, the National Cancer Institute on Tuesday demanded--and got--the resignation of the man in charge of the massive $8-million-a-year project: Dr. Bernard Fisher, a pioneering 75-year-old surgeon who is a legend in breast cancer research. The NCI declared that no more women will be enrolled in the studies until an investigation is completed.
All of which left thousands of women who have breast cancer--and many of the doctors who treat them--feeling angry and betrayed.
The patient, a 60-year-old Los Angeles public relations specialist, had watched her mother die of the disease 30 years ago. In 1989, after receiving a diagnosis that she had breast cancer herself, she decided to have only the malignant lump removed--based in part on this project’s finding that lumpectomy was as effective as mastectomy, in which the entire breast is removed.
Now, she is wondering if she made the right choice, even though experts insist that she did. She has lost faith in those who do medical research. “If you can’t trust the people who are running this kind of trial,” she asked, “who can you trust?”
Indeed, there are many questions surrounding the National Surgical Adjuvant Breast and Bowel Project--a three-decade-long research effort that has involved 5,000 doctors, 484 hospitals and more than 44,000 patients throughout the United States and Canada. The scandal has rocked the breast cancer community and raised serious concerns about quality control in human experiments.
Specialists are hurrying to reassure patients that, despite the discrepancies in the data, the basic conclusion of the study stands: A woman’s entire breast need not be removed when she has cancer; lumpectomy is a safe alternative.
“It’s much ado about nothing,” said Dr. Susan M. Love, a nationally renowned expert who is director of the UCLA Breast Center. “There are multiple other studies showing the same thing. Even if you threw the whole study out, it still wouldn’t change the fact that lumpectomy is just as good as mastectomy.”
Even so, an undercurrent of doubt and anger has risen among patients, doctors and Congress. On April 13, the House Subcommittee on Oversight and Investigations will conduct a hearing on the project to determine, in the words of a spokesman, “how the system collapsed from beginning to end.”
“This is creating a substantial problem of trust and uncertainty,” said Dr. Harmon Eyre, chief medical officer of the American Cancer Society. “Women are challenging whether or not they had the right treatment, and doctors are concerned about how to respond.”
Said Jane Alsobrook, an independent film producer and breast cancer patient who serves on the board of a local advocacy group: “It makes us angry that . . . (authorities) think it’s not worth letting the general public know about unless somehow it leaks and creates a stir, and after the fact they say, ‘Oh, yes, that did happen, but don’t worry your little head about it.’ ”
The controversy comes on the heels of some widely publicized flaps that have undermined public confidence in the ability of scientists to police themselves.
Dr. Robert J. Levine, a professor of medicine at Yale University and an expert in the ethics of human experiments, points to two recent revelations: Cold War radiation experiments on humans without their knowledge and a study in which UCLA researchers were criticized for permitting schizophrenic patients to deteriorate before they were put back on medication that had been helping them.
“I think right now there is a tendency to have bad feelings about research on humans,” Levine said. “What people see is headlines, and it sows the seeds of some misgivings. They say, ‘There must be something wrong with research if that can go on.’ ”
Also at stake is the reputation of more than two dozen breast cancer studies, launched in 1958 and known collectively by the acronym NSABP. Paid for by the National Cancer Institute, the NSABP is coordinated out of the University of Pittsburgh, where Fisher is a professor.
The research has meant the difference between life and death for tens of thousands of women. In the United States alone, 182,000 women are expected to learn they have breast cancer this year, and 46,000 will lose their lives to the disease, which is the No. 1 cause of cancer in women.
The lumpectomy study was not the NSABP’s only significant accomplishment. Two other findings have been at least as instrumental in changing the course of breast cancer treatment. NSABP researchers provided the first proof that chemotherapy could help cure breast cancer. They also proved that “radical mastectomy,” in which the breast, lymph nodes and surrounding muscles are cut out, was not necessary; “total mastectomy,” in which only the breast and lymph nodes are removed, is just as effective.
The NSABP is running six breast cancer studies, and a seventh is about to start. Its major research project at the moment is another highly controversial study into whether the drug tamoxifen can prevent breast cancer among women who have never had the disease but are at high risk.
Researchers are trying to enroll 16,000 women in the study; half will receive tamoxifen for five years and the other half will receive a placebo. The scientists recently confirmed that the drug poses a slightly higher threat of causing uterine cancer than previously believed, and have changed the consent form accordingly--triggering a minor flap.
The uproar over the fraudulent data erupted March 13 when the Chicago Tribune reported that federal investigators had uncovered evidence that a Canadian surgeon, Dr. Roger Poisson of St. Luc’s Hospital in Montreal, had falsified records involving patient enrollment in NSABP studies between 1977 and 1990.
The newspaper went on to report that Fisher had failed to publish a promised reanalysis of the study and had never publicly acknowledged the fraud.
In 1991, Poisson was barred from further participation, and he has since been barred from receiving federal research money for the next eight years. At a Montreal news conference Thursday, Poisson admitted “faults of ethics and irregularities of principle” but said he had his patients’ best interests at heart.
The Chicago story generated a huge outcry, although the federal government had actually released the information nearly a year earlier. The Office of Research Integrity, the branch of the U.S. Department of Health and Human Services that monitors scientific misconduct and ran the investigation of Poisson, had published its findings last spring in three little-read federal publications.
The ORI found that Poisson had either fabricated or falsified data on 99 patients, including those who participated in the lumpectomy study. The phony data did not affect the outcome of the study; rather, Poisson enrolled women who were not eligible, presumably to impress the study’s organizers with a greater volume of data.
“In retrospect, maybe we should have raised a bigger flag,” said ORI Director Lyle Bivens. “It might have headed off the panic.”
Nor did the National Cancer Institute make the matter public. An article in this week’s issue of the journal Science was headlined: “How Not to Publicize a Misconduct Finding.” In an interview Wednesday, Dr. Dwight Kaufman, a top NCI official, said such criticism is legitimate.
“It was a serious oversight,” he said. “Frankly, we didn’t anticipate the level of anxiety and distrust that would emanate from these findings.”
But the flaws did not end with Poisson. On Tuesday, the cancer institute announced that ORI investigators had launched another investigation. The inquiry involves St. Mary’s Hospital in Montreal, where a discrepancy has been found in a date listed in a patient’s file.
Although the organizers of the NSABP were informed of the problem last September, they did not report it to the cancer institute until last week, Kaufman said.
That delay cost Fisher his job.
The NCI demanded that he be replaced, and the University of Pittsburgh immediately announced that he had requested a leave. Although Fisher will remain involved in the project, the NSABP will be headed on an interim basis by Dr. Donald Trump, deputy director of the Pittsburgh Cancer Institute.
“We’re insisting that they get their act together by changing the leadership and changing some of the procedures,” Kaufman said. He added that the NCI is stiffening the penalties for research groups that fail to report discrepancies promptly, and this week created an independent office whose sole job will be to monitor clinical trials.
Fisher’s ouster sent shock waves throughout medical science, especially the network of doctors participating in the NSABP.
Many are angry that Fisher was forced to take the fall for another researcher’s misdeeds and say that the cancer institute is guilty of the same offense it attributed to Fisher--not making the discrepancies public right away.
“It’s sad,” said Love, the UCLA professor. “Fisher has been a very important figure. He’s really been on the forefront of trying to figure out new ways of treating breast cancer. He’s one of the few creative thinkers that we have, and I don’t think he’s actually done anything terrible.
“I think that he should have released the information sooner, but my guess is that he probably didn’t think it would make any difference. And he was right. It didn’t.”
Others, however, are outraged that a scientist of Fisher’s stature did not report misconduct as soon as he knew about it.
“What was missing here was a sense of responsibility to all of the women whose lives have been, are and will be affected by breast cancer,” said Susan Tibbitts, executive director of the National Assn. of Women’s Health Professionals. “I think there was a lack of respect. Somebody made a judgment that we are not going to share this information.”
Justified or not, a forced departure of this magnitude is practically unheard of, said Levine, the Yale professor. He remembered only one--about a decade ago.
Although there are strict controls on the way research is conducted--every clinical trial must submit its findings to a “safety and data monitoring committee”--Levine said the system is not perfect.
“A skillful and dedicated data faker can beat almost any monitoring system,” Levine said. But, he added, such deception cannot go on indefinitely: “It’s very hard to catch them while it’s going on, but at the end of it all, when they . . . see center by center what the results were, if one of them is decidedly out of line there will be an investigation.”
Despite all indications that the fraud has not altered the validity of the NSABP research, patients and doctors have been left to cope with the fallout. Phones were active in the offices of breast surgeons and oncologists across the nation.
“I must have had 30 calls,” said Dr. Avrum Bluming, an Encino oncologist.
“It has all been sort of confusing and unsettling,” said Alsobrook, the film producer who had a lumpectomy three years ago. “To what purpose would somebody falsify results? For personal glory? I don’t really understand.
“This is our lives on the line.”
Making Progress
The National Surgical Adjuvant Breast and Bowel Project was begun in 1958 to evaluate the effectiveness of anti-cancer drugs used in conjunction with surgery for breast, colon and rectal cancer. Here are some of its major findings on breast cancer:
* Treatment: In 1961, the study found that a commonly accepted practice for treating breast cancer--removing the ovaries--was not justified in patients with operable breast cancer. Because the hormone estrogen is linked to breast cancer, and the ovaries produce estrogen, doctors often removed them. More recent research, however, has indicated that women who have had their ovaries removed may have less recurrence of breast cancer.
* Radical mastectomy: A 10-year study in the 1970s eliminated the particularly painful procedure in which the breast, lymph nodes and pectoral muscle were removed. The study proved that the far less drastic treatment called “total mastectomy,” in which only the breast and lymph nodes are removed, is just as effective. Today, radical mastectomy is considered barbaric.
* Chemotherapy: The project was the first research group to prove that chemotherapy could help cure breast cancer or delay its recurrence. Before this study in the 1970s, chemotherapy was not standard treatment for breast cancer.
* Tamoxifen: The study established that the use of the anti-estrogen agent is beneficial in breast cancer patients who are past menopause.
* Lumpectomy: The research group showed that the procedure whereby only the malignant tumor is removed, rather than the whole breast, is just as effective when combined with radiation treatment as mastectomy.
* Post-surgery: The study established that chemotherapy is beneficial to women who have had breast cancer surgery and show no sign of cancer in the lymph nodes under the arm.
* Prevention: In 1992, the research group began studies attempting to determine whether tamoxifen can prevent breast cancer in women who are at high risk of it.
