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rate from breast cancer has been decreasing in the United States by about 2 percent per year over the last decade, suggesting that early detection and improved therapy are both having an impact on the disease.

Mammography is not perfect, however. Routine screening in clinical trials resulted in a 25 to 30 percent decrease in breast cancer mortality among women between the ages of 50 and 70. A lesser benefit was seen among women ages 40 to 49. The benefit of screening mammography for women over age 70 is more difficult to assess because of a lack of data for this age group from randomized clinical trials. Screening mammography cannot eliminate all deaths from breast cancer because it does not detect all cancers, including some that are detected by physical examination. Some tumors may also develop too quickly to be identified at an early, “curable” stage using the standard screening intervals. Furthermore, it is technically difficult to consistently produce mammograms of high quality, and interpretation is subjective and can be variable among radiologists. Mammograms are particularly difficult to interpret for women with dense breast tissue, which is especially common in young women. The dense tissue interferes with the identification of abnormalities associated with tumors, leading to a higher rate of false-positive and false-negative test results among these women. These difficulties associated with dense tissue are especially problematic for young women with heritable mutations who wish to begin screening at a younger age than what is recommended for the general population.

Mammography can also have deleterious effects on some women, in the form of false-positive results and overdiagnosis and overtreatment. As many as three-quarters of all breast lesions that are biopsied as a result of suspicious findings on a mammogram, turn out to be benign; that is, the mammographic findings were falsely positive. (Many tissue biopsies performed on lumps found by physical examination are also benign, but the false-positive rate for physical examination has not been carefully studied.) “Overdiagnosis” is the labeling of small lesions as cancer or precancer when in fact the lesions may never have progressed to a life-threatening disease if they had been left undetected and untreated. In such cases, some of the “cures” that occur after early detection may not be real, and thus, such women are unnecessarily “overtreated.” Technical improvements in breast imaging techniques have led to an increase in the rate of detection of these small abnormalities, such as carcinoma in situ, the biology of which is not well understood. Currently, the methods for classification of such lesions detected by mammography are based on the appearance of the tissue structure, and the ability to determine the lethal potential of breast abnormalities from this classification is crude at best.

The immense burden of breast cancer, combined with the inherent limitations of mammography and other detection modalities, have been the driving forces behind the enormous efforts that have been and that