SACRAMENTO — Quietly last spring, a panel of state-appointed scientists unanimously concluded that one of the world's most widely prescribed anti-cancer drugs, tamoxifen, can itself cause cancer.
This finding would normally mean that tamoxifen, which has been prescribed worldwide to about 3 million women with breast cancer, would be added to the governor's list of 404 chemicals "known to the state to cause cancer."
But the drug has not been listed. Instead, under pressure from the drug maker and the National Cancer Institute and after personal intervention by the governor, the Wilson Administration has delayed a decision indefinitely.
The listing by the state could have major economic consequences for the drug manufacturer and possibly a psychological impact on women taking the drug as well.
It also comes at a time when a National Cancer Institute study is under way to see if the drug is helpful not just in treating breast cancer but in preventing it. For that, investigators need to enroll healthy women, and some scientists believe that they would be scared away if the drug were declared a carcinogen.
Wilson intervened in the case just days before the July 1 deadline to add chemicals to the list.
Wilson became involved in the issue after he "was contacted by breast cancer patients, who informed him that this [scientific] advisory committee had made the recommendation," said Paul Kranhold, the governor's press secretary. The patients told Wilson that the scientists--along with the staff of the agency that reviewed the drug--had failed to consult with the NCI. "And it turned out they had not," Kranhold said.
The governor did not decide to delay the listing and call the added hearings, Kranhold said. That decision was left to the Office of Environmental Health Hazard Assessment, which does the staff work on suspect chemicals.
The office delayed a final decision, called for two days of additional hearings that were held Oct. 10-11, and unleashed a passionate debate that has split the scientific community and raised questions about the wisdom of the state publicly listing any prescription drug as a carcinogen.
A spokesman for Zeneca, the sole manufacturer of the drug in the United States, credits Wilson with the delay.
"We had to get more aggressive to get a hearing," said Zeneca's Steve Lampert. "The governor was quite gracious making sure there was a public hearing and not just listing."
Proponents of listing the drug say it is vital to alert women to the risks--particularly the healthy women enrolled in the nationwide trial to see if tamoxifen can prevent breast cancer. They also say that such a listing is required under Proposition 65, the anti-toxics initiative approved by voters in 1986.
Opponents argue that proof that the drug causes cancer is not clear-cut, that the drug is never issued without complete warnings about possible effects and that the listing is unnecessarily alarmist.
"What proportion of the women in the general population are sufficiently sophisticated to understand benefit versus risk, when all they're told by the state is risk?" asked Dr. Sydney Salmon of the Arizona Cancer Center, one of a long list of scientists who testified against listing tamoxifen as a carcinogen.
The eight scientists on the state's Carcinogen Identification Committee based their May vote largely on a string of scientific reports linking tamoxifen to a small but troubling increase in uterine cancer.
In almost every case, the decisions of the scientists have been followed and the substances added to the governor's list of cancer-causing chemicals required under Proposition 65.
California's listing of the drug could jeopardize the NCI-sponsored breast cancer prevention trial, said Dr. Phillip Bretz, director of the Breast Institute in Rancho Mirage. The trial hopes to enroll 16,000 women, half of whom will be given tamoxifen and the other half a placebo.
But the study was briefly suspended last year amid allegations that investigators had not fully informed patients about uterine cancer risks.
"Any further bad publicity, especially coming out of an important state as California, may sound the death [knell] for this trial and with it the hopes of Zeneca that tamoxifen will be the biggest selling drug in history," Bretz said.
As those remarks show, the delay in the state's decision whether to list tamoxifen as a carcinogen has kicked off a maelstrom of scientific, political and ethical debate. Among the developments:
* The chairman of the Carcinogen Identification Committee and six other members threatened to resign if their decision on tamoxifen is arbitrarily overturned by the Wilson Administration.
* Zeneca Pharmaceuticals launched an extensive campaign to keep the drug off the cancer list, circulating petitions among physicians, scientists and breast cancer activists to prevent the listing. The company reports $550 million a year in sales of the drug, which it markets under the brand name Nolvadex.
