Group Cancels $100M Breast Cancer Drug Study

The National Cancer Institute on Tuesday canceled a five-year, $100 million study designed to test the new class of breast cancer prevention drugs known as aromatase inhibitors, the Washington Post reports.

According to the Post, a committee appointed by NCI Director John Niederhuber last week decided not to endorse the study, citing the cost and questions concerning its usefulness and safety. In addition, the committee said that two large U.S. and Britain-based studies of the drugs are under way.

Tamoxifen, which blocks the production of estrogen, is the only FDA-approved drug for reducing breast cancer risk, but it increases risk for uterine cancer and blood clots, according to the Post.

Another estrogen-blocking drug, called raloxifene, has been shown to be equally as effective as tamoxifen at reducing breast cancer risk, but it increases risk of hot flashes and other menopause-related symptoms. Aromatase inhibitors work by blocking the production of estrogen.

The study would have involved administering either raloxifene or the aromatase inhibitor letrozole to 12,800 women at high risk of developing breast cancer at 500 sites in the U.S. and Canada, the Post reports.

"The numerous scientific concerns ... are sufficiently formidable that the NCI will not commit to the funding of this particular trial," the agency wrote. It added, "While the ... study may provide another possible option for women at risk for breast cancer, the dangers of introducing these drugs, with their many known side effects, outweighs their potential until we are better able to determine who will benefit from these interventions and what the longer-term effect may be."

Some proponents of the study criticized the decision, saying the study would have helped determine the best drugs to prevent breast cancer.

Lawrence Wickerham of the National Surgical Adjuvant Breast and Bowel Project in Pittsburgh, which was organizing the study, said, "We feel this trial is scientifically valid and one that has the potential to impact the health of thousands of women in this country and around the world."

Some breast cancer advocacy groups who lobbied against the study said that more research is needed to better identify the women who would benefit most from the drugs.

Barbara Brenner, executive director of Breast Cancer Action, said, "We're talking about giving very powerful drugs to healthy women who have not had breast cancer."

She added, "We know there are lots of side effects in the short term. We have no idea what they would do in the long term" (Stein, Washington Post, 6/20).

In related news, a study published Wednesday in the Journal of the American Medical Association found that genetic links to breast and ovarian cancers might be hidden on the paternal side and in some families where there are few female relatives, the Long Island Newsday reports (Ricks, Long Island Newsday, 6/19).

Jeffrey Weitzel of the City of Hope cancer center in Duarte, Calif., and colleagues between 1997 and 2007 evaluated 306 women who were diagnosed with breast cancer before age 50 to determine if risk assessment tools used by insurance companies to dictate reimbursement for genetic screening were underestimating breast cancer risk for some women, Reuters reports.

Women with two or fewer close female relatives on either side who lived past the age of 45 were considered to have a "limited family structure," according to Reuters.

About 50% of the participants fell into this category. The study found that participants with less family information to evaluate were at a higher risk of having BRCA1 or BRCA2 mutations, which are believed to increase the chance of developing breast and ovarian cancers.

The mutations were found in 13.7% of participants with limited family structure, compared with 5.2% of participants with an adequate family structure.

Weitzel said the findings challenge the accuracy of the probability models used to determine the need for genetic tests (Steenhuysen, Reuters, 6/19).

"A lot of people -- doctors included -- forget that [the father] can be the contributor" of the genetic mutations, and "a patient can be blinded as to what's happening on the paternal side," Weitzel said (Long Island Newsday, 6/19). He added, "Half of genetic breast cancers are inherited from a woman's father, not her mother. But unless [the father] has female relatives with breast cancer, the faulty gene may have been passed down silently, without causing cancer."

Weitzel said guidelines used by insurance companies to decide coverage for genetic testing should change in light of the study's findings. Noah Kauff, a cancer geneticist at Memorial Sloan-Kettering Cancer Center in New York City, in a related JAMA editorial wrote that women with few female relatives who develop breast cancer before age 50 should get a genetic test (AP/Baltimore Sun, 6/20). An abstract of the study and the editorial are available online.