From: Reuters
Published February 26, 2008 09:05 PM

Breast cancer gene carriers need dual screening

By Anthony J. Brown, MD

NEW YORK (Reuters Health) - Among women with BRCA1 gene mutations, which are known to increase the risk of breast cancer, annual screening with both mammography and MRI is associated with better survival when compared with screening with either method alone, new research indicates.

The trade-offs, however, are a high rate of false-positive results, which lead to unnecessary biopsies.

The findings were based on data from 22 studies that included 8,139 women who carried the BRCA1 gene. In addition, the researchers developed a prediction model based on data from the Surveillance Epidemiology and End Results (SEER) Program (1975-1980) and the Breast Cancer Surveillance Consortium.

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The results indicated that annual combined screening with mammography plus MRI increased the average life expectancy by 1.38 years compared with follow-up only without screening tests (clinical surveillance). The false-positive rate was 84.0 percent.

"For women who carry BRCA1 gene mutations, adding annual MRI to annual mammography has a clear benefit in terms of projected life expectancy and breast cancer mortality reduction," lead author Dr. Janie M. Lee told Reuters Health. "Whether the trade-offs related to MRI screening are acceptable to women at increased risk of developing breast cancer is still being investigated."

In the general population, the lifetime risk of breast cancer for women is 13 percent. In BRCA1 mutation carriers, by contrast, this risk can be as high as 80 percent. Strategies to reduce this high risk have included preventative mastectomy, removal of the ovaries (to lower levels of estrogen which can encourage breast cancer growth), preventive chemotherapy, and more frequent office visits, according to the report in the journal Radiology.

Younger women, especially those of childbearing age, are often reluctant to undergo preventative mastectomy, the investigators point out. Preventative chemotherapy might be a suitable choice, but unfortunately no studies to date have shown it to reduce breast cancer mortality. That leaves increased surveillance.

According to the report, mammography is not nearly as sensitive at detecting breast cancers in BRCA1 mutation carriers as it is in the general population. Previous research has shown that MRI can achieve higher sensitivity than mammography, but whether this translates into reduced breast cancer mortality is unclear.

Due to the long length of follow-up and the large number of patients required, the authors note that it is unlikely that any trial will ever investigate whether MRI screening can reduce breast cancer mortality. This prompted Lee, from Massachusetts General Hospital in Boston, and colleagues to conduct the current decision analysis.

The average life expectancy was 71.15 years, the report indicates, and with clinical surveillance alone, the average diameter of breast cancers at diagnosis was 2.6 centimeters. Using annual screening with mammography, MRI, or both, the average tumor diameter at diagnosis fell to 1.9, 1.3, and 1.1 centimeters, respectively.

Compared with clinical surveillance, all three imaging-based screening strategies increased life expectancy and reduced mortality from breast cancer. Again, the most pronounced benefit was with mammography plus MRI.

In addition to the high false-positive rate seen with mammography plus MRI screening, nearly one in three women underwent one or more biopsies for what turned out to be benign disease. The false-positive rates and negative biopsy results with the other screening strategies were also increased, but not as high as that seen with the combined approach.

More research is required to find the optimal sequence and frequency for screening tests for breast cancer, and to "minimize the potentially negative effects on women's health-related quality of life when screening with increased intensity is pursued," Lee noted.

She added that her team is "currently working to extend our model of breast cancer natural history and screening in BRCA1 gene mutation carriers to women who carry BRCA2 mutations, and women whose lifetime risk of breast cancer exceeds 20 percent -- these women are defined by the American Cancer Society as being at 'high-risk' of developing breast cancer."

SOURCE: Radiology, March 2008.

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