In this Dutch study, women whose family history suggested they were at moderate or high risk of developing cancer were studied; women who were known carriers of the BRCA1 or BRCA2 mutation, and are at the highest risk of developing breast cancer, were also included. The BRCA genes help prevent cancer when they are functioning normally. However, inherited mutations in these genes give women a 60% to 70% chance of developing breast cancer by age 70. Other women considered at high-risk of breast cancer are those with two or more close relatives (mother, sister, daughter) who have had breast or ovarian cancer; or, with one relative who had such cancer before age 40.

The researchers looked at the records of 1,198 women followed at a cancer clinic in the Netherlands between 1978 and 1999. In this clinic, screening recommendations included monthly breast self-examination, twice-yearly clinical breast exams, and annual mammography. There was an optional addition of MRI beginning in 1995 for women with BRCA mutations or very dense breasts.

The women were divided into three groups: moderate risk, high risk, and those with the BRCA mutations. Within a median follow-up period of three years, 26 cancers were detected by screening and nine "interval" cancers were diagnosed between screening appointments. As expected, the rates were highest in the BRCA mutation carriers — nine breast tumors were detected with the average age of 40 at diagnosis. Also, the sensitivity of screening was lowest in the BRCA mutation carriers, meaning that more of these women had cancers that were discovered in the interval between screening.

Why these women with the BRCA mutation had a higher frequency of interval cancer detection wasn’t clear. The authors suggest that it may have been related to the fact that the women in this group were younger and had denser breast tissue, which makes it more difficult to see breast cancer on mammograms, or because the cancers in this group were particularly aggressive.

"It is clear that mammography is not effective enough in this group," says the lead author of the study, Cecile Brekelmans, MD, PhD, a doctor and epidemiologist at the Dr. Daniel den Hoed Cancer Center in the Netherlands. But she says it is too early to recommend any screening strategy for high-risk women under the age of 40. "We have to await results from current MRI trials. There are several MRI studies going on in Europe for high-risk young women," notes Brekelmans.

American Cancer Society (ACS) guidelines currently encourage any high-risk women to talk to their health care provider about starting screening earlier than the typically recommended age 40 for the first mammogram. Experts, including those cited in this study, say screening for BRCA mutation carriers should begin at age 25 to 35, or five years prior to the youngest age of diagnosis in that family. However, there are no large studies to prove this recommendation is effective.

"(People) need to keep in mind that only 5% to 10% of breast cancers are associated with a BRCA mutation, so for most women, this discussion is not relevant. They need to get annual mammograms starting at age 40," says Debbie Saslow, PhD, director of breast and cervical cancer for the ACS. "Unfortunately, however, most young women overestimate their risk of breast cancer."

Saslow says any woman who thinks she is at high risk should have a risk assessment done. Many doctors currently use the National Cancer Institute’s Breast Cancer Risk Assessment Tool to make those calculations. "Many of these women might find out their risk is really lower than they think," she says. .

Brekelmans also cautions that rushing into an intensive screening program could have a downside. "Screening — apart from possible benefit such as mortality reduction, earlier detection and less aggressive therapy — always can bring harm; for instance, false positives, over-diagnosis and over-treatment, and psychological side effects such as fear of cancer," she says.

Brekelmans suggests young women who are proven at high-risk of getting breast cancer ask their doctor about taking part in clinical trials of more aggressive screening techniques, or await the results of the European MRI trials for high-risk young women. Saslow concurs that it is too early to make a definitive recommendation. "So far the follow-up is only about three years — not long enough to make recommendations one way or the other."

To access the National Cancer Institute’s Breast Cancer Risk Assessment Tool, click here.