In the mid-1990s, specific genetic mutations associated with lifetime breast cancer rates as high as 85% were discovered, leading to heightened interest in how to identify women at inherited risk for breast cancer and provide preventive and surveillance protocols appropriate to this elevated risk. However, clinicians were then faced with having to counsel women regarding options if a genetic mutation was identified, when few options were available at that time. Bilateral prophylactic mastectomies were associated with a 90% reduction in risk for mortality from breast cancer,1 but few women, particularly those of younger ages, chose that option.2 Risk reduction strategies were suggested and, even though based on sparse data, recommendations for intensive mammographic surveillance were supported. Several organizations recommended annual mammography starting at 25 years of age for women identified at high risk.
Eventually, it became clear that mammography was a poor method of screening for breast cancer in young, high-risk women with dense breast tissue. Sensitivity consistently less than 50% was observed in mammography screening trials. Furthermore, even in routinely screened high-risk patients, half of screen-detected breast cancers had already spread to the lymph nodes.3-5 Thus, not only was overall sensitivity poor, but sensitivity in detecting localized cancers was even worse, raising questions as to whether in fact more harm than benefit was provided to these young women at high risk.
Questions regarding risks associated with radiation from mammography in young women at high risk for breast cancer also were raised, and this has been an ongoing concern in terms of benefit and potential harm. In a recent study, a model was developed to estimate the lifetime risk for death from radiation-induced breast cancer caused by 5 annual mammograms among BRCA mutation carriers aged 40 years and younger. These estimates were used to determine in which age group mammography screening would be beneficial, assuming a 25% or less reduction in mortality from mammography in this age group. The authors found that, although screening mammography in high-risk women aged 35 to 39 years would have a net benefit, the estimated reduction in breast cancer mortality from screening women with BRCA mutations before 35 years of age was not substantially greater than the risk for radiation-induced breast cancer mortality.6
Given the limitations of mammography and concerns about the balance of benefits and harms, other methods for early detection of breast cancer in high-risk women were actively pursued. Several single and multicenter studies of screening MRI in high-risk women detected invasive breast cancers that were neither palpable nor visible on mammography (Figure 1). Based on published scientific evidence, in 2007 the American Cancer Society (ACS) recommended MRI be performed to improve early cancer detection in high-risk women.7 These recommendations, which are now supported by the NCCN Clinical Practice Guidelines in Oncology: Breast Cancer Screening and Diagnosis (in this issue; to view the most recent version of the these guidelines, visit the NCCN Web site at www.nccn.org), were intended to identify women at high risk and then provide more intensive and successful screening through MRI in addition to mammography.8
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