Breast Cancer Drug To Be Approved For The Healthy But High Risk

Healthfacts, Oct 1, 1998 by Marya Napoli

Last month, a Food & Drug Administration (FDA) advisory committee voted to recommend approval of the breast cancer drug, tamoxifen, for the short-term reduction in the risk of breast cancer in high-risk populations. With this careful choice of words, the committee made a crucial distinction that may be lost once the prescription of tamoxifen to healthy women becomes widespread. Though the drug has already been hailed as a means of preventing breast cancer (see HealthFacts, May 1998), the Committee voted according to clinical trial results which merely indicate that tamoxifen can reduce the incidence of breast cancer. The 13,000 study participants were followed for only 4.5 years, so it is not known whether the 49% lower incidence of breast cancer in the tamoxifen-treated women represents true prevention or simply delayed onset of the disease. Furthermore, this benefit came at a high price. The older women in the trial who took tamoxifen developed uterine cancer and potentially fatal blood clots at 2-3 times the rate of those who didnt. Three women in the tamoxifen group died of pulmonary embolism. The FDA has the final say regarding approval, but the agency usually follows the advice of its advisory committees. Tamoxifen, a drug used for decades in the treatment of breast cancer, is expected to be approved for the new indication next month.

The committee members justified their decision by saying that they want to give women more options. But, in fact, women have no other options where it concerns breast cancer prevention. The lack of progress in learning the causes of breast cancer has left a vacuum filled by mammography screening which will, at best, benefit only about 30% of all older women destined to develop breast cancer. To fill this void, the Federal Government spent $70 million on a clinical trial to determine whether tamoxifen can prevent breast cancer in women at high risk for developing the disease. In April, the National Cancer Institute-sponsored Breast Cancer Prevention Trial (BCPT) was stopped 14 months early because of the dramatic difference in the rate of breast cancer in tamoxifen-treated women, as compared to those on the placebo, or dummy pill. The finding made headlines around the country, but enthusiasm waned by July when two European trials failed to confirm the BCPT results. Both studies, one in Britain and the other in Italy, found the same breast cancer rate among the tamoxifen-treated and the placebo-treated. The British trial followed its participants the longest--six years.

This did not stop the BCPT sponsors from pressing the FDA for the

approval of tamoxifen as a breast cancer preventive. Yet the opposition, most notably from the National Womens Health Network, that met the pla ing of the BCPT has escalated; in fact, it dominated the public comments portion of last months advisory committee meeting. Before the committee members voted to approve tamoxifen for risk reduction, they listened to representatives of eight advocacy organizations, including the Center for Medical Consumers. Virtually all opposed approval because there are too many unanswered questions about tamoxifens long-term safety for healthy women and about which women are at high risk enough to chance tamoxifens considerable side effects. (Tamoxifens non-life-threatening complications include vaginal discharge, hot flashes, and a 50% increase in cataract surgery.)

The advocates concerns were validated by Dr. Trevor Powles, who headed the British tamoxifen trial, which found no benefit to healthy but high-risk women. Dr. Powles told the advisory committee, I dont think were there yet. [The BCPT results] dont tell us much about the long-term incidence of breast cancer which is what we need to know. He went on to explain that breast cancer takes 10-15 years to develop, thus we need 10-15 years of follow-up before we know whether we had an effect. He pointed out that the type of breast cancer delayed by tamoxifen in the BCPT is estrogen-receptor positive cancer, which has always been the most curable. Dr. Powless trial differed in several respects from the BCPT: it had one-fifth the number of BCPT participants, a larger proportion of younger women (62% vs nearly 40% in the BCPT), and stricter criteria for high-risk factors. These differences may explain why Dr. Powles found no decrease in breast cancer incidence among the tamoxifen-treated participants.

The advisory committee came to an impasse over the question of which high-risk women should be given tamoxifen. The criteria for entry into the BCPT was so broad that just being over age 60 was enough to qualify. Women vastly overestimate their risk for developing breast cancer due to the last decades worth of breast cancer awareness activities. Scaring women with inflated importance of risk factors usually has the desired effect of selling everything from mammograms to more cancer research funding.

Much of the misinformation about risk factors comes from doctors. For example, a history of benign breast disease ranked high on the list until 1985 when the American College of Pathologists declared it a nondisease, thanks to the work of Dr. Susan Love. With colleagues at the Harvard Medical School, Dr. Love asked how benign cysts could be called a disease when they occur in 90% of the female population. (Breast cysts are palpably present in half of all women and microscopically present in 40%.) Throughout the 1970s women with benign breast disease, or fibrocystic breasts, were told they were at high risk for breast cancer, and, as a result, many were unable to get health insurance.