Task Force Breaks New Ground With Breast Cancer Recommendations

While many of us were firing up our Weber grills on Labor Day, the Agency for Healthcare Research and Quality (AHRQ) announced that the United States Preventive Services Task Force (USPSTF) had recommended referrals for genetic counseling and evaluation for potential genetic testing for women who are at high risk for the breast cancer susceptibility gene 1 (BRCA1) or gene 2 (BRCA2) mutations.

This is the first time that the task force — the recommendations of which are considered the gold standard for clinical preventive services — has addressed the issue of genetic counseling and DNA-based genetic testing for any disease.

Though this may represent a milestone for genetic testing, it does not mean that all women will be tested. The task force recommended against routine genetic counseling or testing for clinically significant BRCA1 and BRCA 2 mutations in women without specific family-history patterns of breast or ovarian cancer. But women who have such a history — including those with a relative who has already tested positive for the mutations — should be referred for genetic counseling before a test is ordered.

“We debated the order for the BRCA recommendation and concluded that the most important message was that, for most women, referral for counseling and evaluation for testing was not recommended,” says task force Chairman Bruce Nedrow (Ned) Calonge, MD, MPH, chief medical officer and state epidemiologist in the Colorado Department of Public Health and Environment. “We then followed that with a recommendation that affected a much smaller percentage of women.”

What puts some women in the high-risk category are specific maternal and paternal family-history patterns associated with deleterious mutations in BRCA1 or BRCA2 genes.

Evaluating these family-history patterns determines a woman’s risk for deleterious BRCA1 or BRCA2 mutations, not for developing breast cancer. The task force therefore recommends that primary care physicians ask patients about family history, and when these patterns emerge, that they refer patients to genetic counselors for risk assessment, counseling, and evaluation for testing.

“Extracting a good family history, doing the analysis, and assessing the actual risk is an exacting task,” Calonge explains. “Our concern is that primary care providers aren’t well versed in pedigree evaluation.”

BEHIND THE DECISION

Why not routinely test all women for the BRCA mutations? Based on the evidence, the task force concluded that women without the suspect family history patterns have a low risk for developing breast or ovarian cancer associated with BRCA1 or BRCA2 mutations. “Thus,” states the recommendation, “any benefit to routine screening of these women for BRCA1 or BRCA2 mutations, or routine referral for genetic counseling, would be small or zero.”

The task force also concluded that the potential harm of routine referral for genetic counseling or BRCA testing outweighs potential benefits. Such harm encompasses the inconvenience and cost of frequent examinations and procedures, increased exposure to radiation from more frequent mammograms, the testing and biopsies resulting from false-positive test findings, and the false reassurance for women with increased risk for developing cancer between screenings.

“There are many unknowns,” adds Heidi Nelson, MD, MPH, professor of medical informatics and clinical epidemiology, and professor of medicine at Oregon Health and Science University in Portland. “There’s the potential impact on family members we revisit; all kinds of family things come out of these genetic tests.”

Nelson led investigators at the Oregon Evidence-based Practice Center, under contract to the AHRQ, which painstakingly marshaled evidence on which this task force recommendation is based (see “BRCA Recommendations,” next page).

BRCA recommendations: further reading.

The family-history patterns spelled out in the U.S. Preventive Services Task Force recommendation statement in the Sept. 6, 2005 issue of Annals of Internal Medicine, increase a woman’s lifetime risk for breast cancer to 60–85 percent, and increase ovarian cancer risks to 26 percent (BRCA1) and 10 percent (BRCA2) (USPSTF 2005).

The systematic evidence review that accompanies the task force recommendations are published in the same issue of Annals of Internal Medicine and includes 188 references. Essentially, the review poses seven key questions about prevention and screening, driven by what the task force needed to evaluate before making recommendations (Nelson 2005).

Nelson and colleagues sought answers in the medical literature. “Some questions are answered nicely,” she says, but sometimes “the literature is conflicting, confusing, or inadequate.”

To reflect variability in evidence, task force evaluations grade the strength of the supporting evidence (good, fair, poor) and the strength of the recommendations for providing a service (A, B, C, or D, or I [inconclusive]), based on the strength of the evidence and magnitude of net benefit (benefits minus harms).

In this case, the task force found “fair” evidence for not recommending routine BRCA testing and gave routine testing a “D” recommendation (i.e., the task force recommends against routinely providing the service). The evidence that women with specific family-history patterns may have increased risk for breast or ovarian cancer associated with BRCA mutations also was graded “fair,” as was evidence that prophylactic surgery significantly decreases the incidence of cancer in women who test positive. The task force found “insufficient” evidence to determine the benefits of chemoprevention or intensive screening for women who test positive, and also about important adverse ethical, legal, and social consequences of referral and testing of high-risk women. The recommendation for referring high-risk women for counseling and evaluation for testing is graded “B.”

EFFECT ON PAYERS

Much research is yet to be done, as Nelson and her colleagues point out in their evidence review. For example, not every woman who tests positive for deleterious BRCA1 and BRCA2 mutations will get cancer, and there are only limited data to describe risks linked to moderating factors outside the gene (which also is inclusive of unidentified genetic mutations). There are no data on the optimal age to test and how the age at testing influences benefits and adverse effects. It is unknown if testing for BRCA mutations saves lives or improves quality of life. There also are no data on how treatment effects are influenced by age at which initiated, type of mutation, adherence, and cost.

Yet, these and other data gaps have not kept physicians from ordering BRCA tests, genetic counselors from consulting with clients, or insurers from covering these services — often, for several years.

“We’ve never not covered them, to my knowledge,” says William Corwin, MD, medical director for utilization management and clinical policy at Harvard Pilgrim Health Care. “These recommendations, I think, have lagged what is fairly common practice already.”

But for payers who do not cover genetic counseling and BRCA testing, this task force recommendation may amount to an offer they can’t refuse.

“Many U.S. health plans rely on the U.S. Preventive Services Task Force as the gold standard for developing policies,” says Wade Aubry, MD, senior advisor at the Health Technology Center in San Francisco. “NCQA looks to the task force to develop performance measures, which then are used in plan accreditation. I think payers will respond well to this careful, evidence-based review.”

Which genetic test will the task force recommend next? Aubry, who served on the Blue Cross Blue Shield Association Technology Evaluation Center expert panel that evaluated BRCA testing in 1997, won’t name names, but allows that more than one could be next.