State asks: is tamoxifen a carcinogen?

Numerous studies in the past 3 years have pointed to an elevated risk of several types of cancer among women taking tamoxifen, the world's leading drug to prevent breast cancer recurrence. Now, California regulators want to know whether tamoxifen's link to endometrial cancer--a uterine disease and the best-documented of these associations (SN: 4/16/94, p.247)--means the drug is a carcinogen. Such a determination would automatically require that warnings of the synthetic hormone's toxicity reach all California users. California's Proposition 65, passed 8 years ago, has gained national attention--some would say notoriety--for its attempt to compile a comprehensive list of chemicals that cause cancer or reproductive harm. But Catherine Caraway of the state's Environmental Protection Agency in Sacramento and head of Proposition 65's implementation, describes the statute as primarily a right-to-know initiative. Often, she says, it requires little more than labeling a listed chemical with a "clear and reasonable warning" of toxicity. To date, she notes, drugs account for more than one-quarter of the 403 carcinogens listed. On May 11, her agency convened a panel of scientific advisers to review data from animal and human studies of tamoxifen. By day's end, Carcinogen Identification Committee Chairman Thomas M. Mack of the University of Southern California School of Medicine in Los Angeles concluded that "evidence is convincing that tamoxifen does, in fact, produce endometrial carcinoma." When polled, the seven remaining committee members unanimously agreed that existing data offer sufficient evidence to call tamoxifen a carcinogen. Ordinarily, that vote would have ended the matter--and brought Proposition 65's carcinogen total to 404. But then Leslie G. Ford of the National Cancer Institute in Bethesda, Md., stepped in. In a June 23 letter to James W. Stratton, interim director of the Proposition 65 office, she argued, "It is premature to make a determination as to whether tamoxifen plays a causal role in the development of endometrial cancer." High rates of the disease in human trials, she said, may signify that women in the studies receive better medical surveillance than those in the general population or that they had been exposed to hormones or other risk factors for endometrial cancer. "This is the first time that we have had a last-minute call from a national agency saying that you need to review [a decision]," explains Caraway. Moreover, her agency's response--to delay listing tamoxifen as a carcinogen--"is unprecedented," she told Science News. In the interest of giving the matter a full and open hearing, the California EPA will convene a public forum this coming week. Zeneca Pharmaceuticals Group of Wilmington, Del. (the drug's manufacturer), NCI, tamoxifen researchers, and others will all get a chance to discuss the drug's alleged carcinogenicity in greater detail. Why all the fuss about tamoxifen? "That's a puzzle to me," Caraway says. "There appears to be a whirlwind storm around tamoxifen and [our consumers'] right to know." But John R. Valencia, an attorney representing Zeneca, observed during the May 11 hearing that "once news is conveyed to the general public that tamoxifen has been decided upon as a carcinogen, there's [likely to be] a natural public reaction." Indeed, Zeneca and NCI may fear that this reaction would jeopardize the recruitment and continuing participation of healthy women in a controversial tamoxifen trial to prevent breast cancer (SN: 2/26/94, p.133).

Mack points out, however, that many drugs cause cancer, have been listed under Proposition 65, yet continue in widespread use--because their therapeutic benefits outweigh their risks. As he told Science News, his committee's role was "not to make [such] cost-benefit judgments."