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Mammograms Bad for Young Women with Breast Cancer Genes?

April 07, 2009
Contact: UCSF News Office (415) 476-2557

Mammography is widely used to screen for tumors in young women — even women in their 20s — who inherit a genetic mutation that confers a very high risk for breast cancer. But new research now suggests that exposing the youngest of these women to even small doses of radiation via screening mammograms might do more harm than good.

A research study that appeared in the Feb. 4, 2009, issue of the Journal of the National Cancer Institute (JNCI) concluded that among these high-risk women, annual mammograms are unlikely to be beneficial until age 35.

Dr. Mary Beattie, a primary care physician at the UCSF Women's Health Center and director of clinical research for the UCSF Cancer Risk Program, says the study is getting a lot of attention and may prove to be quite influential.

"This may result in a change in medical practice to benefit a small, but very important subset of women who are at high risk," she says. "The researchers concluded that starting mammograms when a woman is in her 20s or early 30s could be harmful." Screening via breast MRI exams may be more appropriate for this population, according to Beattie.

The mutations in question occur in the BRCA1 and BRCA2 genes. Women who carry deleterious mutations in one of these genes have up to an 80 percent likelihood of being diagnosed with breast cancer over the course of a lifetime. Breast cancer in these women often arises at very early ages.

The belief among health care professionals has been that BRCA1 and BRCA2 mutation carriers are likely to benefit from earlier and more frequent breast cancer screening in comparison with women who do not inherit deleterious BRCA mutations. Outcomes tend to be best for women whose cancers are detected early.

Women who carry deleterious BRCA mutations have an impaired ability to repair damage that arises in the DNA that makes up genes. The small amount of radiation exposure due to a mammogram — essentially an X-ray — can contribute to DNA damage. Women who have inherited a mutated version of the BRCA gene that weakens DNA repair are believed to be more vulnerable to the harmful effects of radiation in comparison with women who do not carry the mutation.

A common practice has been to recommend that a BRCA mutation carrier begin breast cancer screening at age 25. At UCSF's Cancer Risk Program, where counselors and doctors advise and care for women who carry these cancer risk genes, the recommended screening protocol is a mammogram, alternating with a breast MRI, at six-month intervals. Beattie says she and her colleagues are discussing the possibility of dropping the mammography component for women under 30 or 35.

MRI does not cause radiation exposure, and in younger women, who have denser breast tissue, it is better than mammography for detecting abnormal growth. While a breast MRI exam is many times more costly than a mammogram, insurers generally cover an annual breast MRI exam for BRCA mutation carriers, Beattie says.

Unfortunately, all available breast cancer screening strategies have a downside as well as benefits.

"Screening breast MRI should be reserved for women who truly are at high risk, namely BRCA carriers and their first-degree relatives who have not yet BRCA-tested," Beattie says. "Breast MRI is very sensitive, but it also detects many things that with follow-up turn out to be benign — false positives. Any woman who receives a screening breast MRI should be followed at a breast clinic where radiologists are highly experienced in interpreting breast MRIs."

For young women, the chance of a false positive during a first MRI is from one in five to one in 10, Beattie says, compared with about one in 20 for a mammogram.

Lead author of the JNCI study, Amy Berrington de Gonzalez of Johns Hopkins University, and her research colleagues estimated the breast cancer risk due to five annual mammograms in young BRCA carriers. The researchers extrapolated from data pooled from prior studies of excess breast cancer attributed to other medical procedures that exposed the breasts of young women to radiation.

The researchers also gathered information on breast cancer risk among young BRCA mutation carriers by reviewing cancer data from more than 8,100 individuals from families affected by these mutations.

Both the number of breast cancers prevented by mammography and the number of cancers caused by radiation exposure were estimated to be small. In BRCA mutation carriers who are screened starting between the ages of 25 and 29, up to 26 more breast cancers per 10,000 women might arise due to radiation exposure from mammography over the entire life span, the researchers concluded.

"It is not feasible to quantify the risk of radiation-induced breast cancer from mammography screening by studying the risks directly," the study authors reported, "because a study of thousands of women who were followed up for their entire lifetimes would be required."