HEALTH & SCIENCE

Level of risk from breast cancer gene questioned

Counseling patients about the implications of predictive genetic tests may prove to be one of the trickiest aspects of treatment.

By Victoria Stagg Elliott, AMNews staff. Sept. 16, 2002. Additional information

The decision about whether to get tested for a genetic predisposition to breast and ovarian cancer is already a tough one for many women. And physicians say recent studies questioning the level of risk currently associated with BRCA1 and BRCA2 mutations will make it even more complicated.

The most recent study suggests that the design of the earlier studies, which focused on high-risk families, may be biased and that the risk for gene carriers without a family history may not be quite as high as the generally accepted 85%.

The families who participated in the initial research may have additional genetic or environmental risks that turn them into cancer clusters, and those risks may not necessarily be relevant to women with the gene but not the family history, according to the new study, published in the Aug. 21 Journal of the National Cancer Institute and authored by a statistician at Memorial-Sloan Kettering Cancer Center in New York.

"There's an impression out there that anyone who has the mutation has a very high lifetime risk of breast cancer, but, on average, among all mutation carriers, it's really much lower," said Colin Begg, PhD, study author and chair of the center's Dept. of Epidemiology and Biostatistics.

Testing and treatment for ovarian cancer is poor. Screening protocols for women who are at high risk of breast cancer are better but far from perfect.

And with clinical trials of pharmaceutical preventives still in the early days, some women have chosen the radical option of prophylactic removal of their breasts and ovaries rather than live with the anxiety.

"It's a minefield because of how drastic the treatments are for the woman," said Jay Brooks, MD, chief of hematology/oncology at Ochsner Foundation Clinic in Baton Rouge, La. "But for women who have seen so many family members die of breast cancer, they're very pleased with it."

Now with the new data, decision-making will be even harder.

"Individual patients have to ask themselves: 'Well, if I had a 75% risk of breast cancer but now it's reduced to 50%, will I do something different?' " Dr. Brooks said. "I don't know. That depends on the individual patient."

Inexact science

Experts stress that risk assessment has never been an exact science -- with or without genetic testing -- but that in the age of increasingly available genetic tests, it will have to get better.

Risk assessment also will have to start dealing with the question of when. A positive test for a gene linked to breast cancer only indicates a lifetime risk, but it does not indicate whether the disease will hit at age 70 or 25. And it may not hit at all.

"If the risk of breast cancer by age 70 is 40% to 50%, then the risk at young ages is probably relatively low," Dr. Begg said. "You should probably be concerned about breast cancer when you're young, and only really contemplate prophylactic measures as you get older."

Those who counsel patients about their risks say that genetic makeup is just one part of the risk puzzle they consider, but they add that there is no cutoff point for when a woman should consider radical steps. That is left up to the patients.

"What is appropriate is what the woman chooses," said Jeffrey N. Weitzel, MD, director of the Dept. of Clinical Cancer Genetics and the Cancer Screening and Prevention Program at the City of Hope Comprehensive Cancer Center in Los Angeles. "We don't tell them what to do."

Experts also add that genetic testing can deliver good news as well as bad, and that this also helps women negotiate their risks.

"These are great tools," Dr. Weitzel said. "I can't tell you how many families I've found with the high-risk mutation, and then found out that their sister or their daughter doesn't carry it."

But as genetic testing begins to enter medicine's mainstream, experts say much more research is needed in how to assess risk, communicate it and deal with it.

"Genetic testing is the future and will become more widespread," Dr. Begg said. "It's going to be increasingly important to have a sound knowledge of the risks if you are a mutation carrier, but my concern is that risks will be calculated based on studies of high-risk families. That would be improper."

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Objective: To test the theory that the design of trials to determine the risk of breast and ovarian cancer linked to BRCA1 and BRCA2 gene mutations has caused the actual risk to be overstated.
Method: Eight published case-controlled studies were reviewed.
Results: Women with genetic abnormalities and a strong history of breast cancer are likely to possess a much higher risk for breast cancer than women with abnormalities but without a strong family history.
Conclusion: Methodologic techniques to improve the prediction of cancer risk are needed.

Source: Journal of the National Cancer Institute, Aug. 21

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Article, "On the Use of Familial Aggregation in Population-Based Case Probands for Calculating Penetrance" abstract, Journal of the National Cancer Institute, Aug. 21 (http://jncicancerspectrum.oupjournals.org/cgi/content/abstract/jnci;94/16/1221)

Summary, "BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer," GeneReviews (http://www.geneclinics.org/profiles/brca1/)

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Copyright 2002 American Medical Association. All rights reserved.