Patient Info on Preventive Tamoxifen May Be ‘Too Complex’

BETHESDA, Md--National Cancer Institute officials have committed themselves to providing information to women and their physicians to help women make an informed decision whether to take tamoxifen (Nolvadex) to prevent breast cancer. But some members of the NCI’s own advisory board have questioned whether the information provided to date is too complex for most women to grasp.

"I’m not sure anyone will be able to understand the guidance," said Phillip A. Sharp, PhD, of the Massachusetts Institute of Technology’s Center for Cancer Research during a meeting of the National Cancer Advisory Board (NCAB). "It requires a PhD in statistics to figure out if you should be in this program or not," Dr. Sharp added.

When researchers announced the early termination of the Breast Cancer Prevention Trial (BCPT) in early April--after the study’s independent monitoring committee determined that women receiving tamoxifen had a 45% reduction in breast cancer, compared with placebo--the NCI pledged to develop information to help women considering prophylactic use of the drug determine their risk of breast cancer.

That same day, NCI opened a website with data from the BCPT, which included the finding that women taking tamoxifen, particularly those over age 50, had an increased risk of serious side effects, including endometrial cancer and pulmonary embolism. Since then, the agency has added material, including five pages of specific scenarios designed to help women determine if their risk of breast cancer matches those of the women admitted to the BCPT.

All the women in that study had a 3% to 4% risk of developing breast cancer over the next 5 years of their lives, noted Leslie G. Ford, MD, the NCI’s associate director for Early Detection and Community Oncology. The website risk profiles are meant to help women better determine their absolute risk. They rely on the same risk model used in admitting women to BCPT.

For example, Dr. Ford, said that a 45-year-old woman with two first-degree relatives with breast cancer or one first-degree relative with the cancer and a personal history of having undergone a breast biopsy, would have a risk that would indicate she might benefit from preventive tamoxifen.

Dr. Ford said the NCI estimates that 29 million women in the United States would meet these risk criteria: 26 million age 60 and older and 3 million between ages 35 and 59.

In her summary of what she called the Institute’s "first pass at advice to women," she noted that the balance of benefits and risks of taking prophylactic tamoxifen varied greatly by age and by hysterectomy status. "The choice to take tamoxifen ought to be a personal choice," she said. "We have been working hard to develop tools that will help women and their health care providers in making their decision."

The complexity of trying to decipher the information and list of scenarios provided by NCI left MIT’s Dr. Sharp and several other advisory board members questioning their value. Dr. Sharp asked if the Institute plans to produce guidelines "in which you can actually say, these are the people who, by and large, should be taking this treatment."

NCI director Richard D. Klausner, MD, answered with an unambiguous "No. We don’t do that for any treatment, and I think we shouldn’t." He said it is important that women and their doctors determine absolute risk and then consider other factors, including the treatment’s possible adverse effects. "This is a decision a woman makes with her physician," Dr. Klausner said. "I think we can create a simple model that will give a sense of an individual woman’s risk."

Frances M. Visco, JD, a member of the President’s Cancer Panel, noted that a previous study of breast cancer patients found that tamoxifen provided its benefits in 5 years, with no additional advantages after that. She asked if the NCI would offer guidance to women about which 5-year period in their life they should take tamoxifen to gain its greatest protective effect.

"I’ve talked to women who want their 12-year-old daughters to go on tamox-ifen," Ms. Visco said. "Which 5 years of a woman’s life is going to provide the most benefit and the least risk?"

Based on the BCPT, there is no answer to the question, said Barnett S. Kramer, MD, deputy director of the NCI’s Division of Cancer Prevention. "What we do know from the design of the trial is that if a woman enters at age 35, and meets the risk criteria, she would benefit, and at every age throughout the age range in the trial."

Acknowledging the complexity of the data, Dr. Klausner said: "I think the entire community needs some time to digest, to discuss, to argue about this, and, over time, to develop ways to evaluate how to use the data. It is not going to happen all at once."