Using Lifetime Risk Estimates to Recommend Magnetic Resonance Imaging Screening for Breast Cancer Survivors

Abstract

There are millions of breast cancer survivors in the United States currently, and expectations are that the number will continue to increase in the years to come. Survivors of early-stage breast cancer are at increased risk for developing second primary breast cancers. Data regarding the effectiveness of surveillance mammography among survivors of early-stage breast cancer are limited, but suggest that mammography may reduce breast cancer mortality for this cohort as it does when used to screen the general population. Although national guidelines recommend annual mammographic surveillance for survivors of early-stage breast cancer, studies suggest surveillance mammography is underutilized. Mammography is not a perfect test. In fact, it may be particularly insensitive at detecting breast cancer among selected high-risk populations, such as BRCA carriers, young women, and women with dense breast tissue. Magnetic resonance imaging (MRI) has consistently demonstratedgreatersensitivityversusmammographyinthesepopulations. However, MRI screening is more costly and time consuming, requires the injection of intravenous contrast, generates more false-positive results, and has not been shown to impact breast cancer mortality. Debate regarding the role of MRI as a screening test led the American Cancer Society to convene an expert panel to develop guidelines in 2007. The panel recommended breast MRI screening as an adjunct to mammography for: BRCA mutation carriers and their first-degree relatives; women with a lifetime breast cancer risk 20% to 25%; women with a history of chest radiation between ages of 10 and 30 years; and women with predisposing genetic syndromes (eg, Li-Fraumeni, Cowden). The group felt there was insufficient evidence to recommend for or against MRI screening among women with a personal history of invasive breast cancer or ductal carcinoma in situ. On one hand, MRI surveillance may seem appropriate for breast cancer survivors. Compared to women with a higher than 20% lifetime risk of primary breast cancer as defined by BRCAPRO or other family history–based models, many survivors of early-stage breast cancer could experience an even greater risk of second primary breast cancer. In addition, the sensitivity of mammography among survivors could be impaired by changes in the breast caused by previous treatments. In contrast, no studies have explored the utility of surveillance MRI among survivors. Moreover, this cohort also faces a competing risk of mortality from the primary breast cancer diagnosis. Based on personal observations, use of surveillance MRI among women with a personal history of early-stage breast cancer appears to be increasing. These issues raise serious questions regarding the appropriate use of surveillance breast MRI among survivors of early-stage breast cancer. To explore the implications of applying the American Cancer Society risk threshold to women with a personal history of breast cancer who are not BRCA carriers, we constructed an analytic model to calculate lifetime risk of developing a second breast cancer after diagnosis of an initial breast cancer. Specifically, we sought to determine which subsets of breast cancer survivors met a 20% or 25% lifetime risk threshold of having a new cancer, taking into account the competing risk of cancer mortality from the first diagnosis and agedependent noncancer mortality. The model was designed to provide customized values for lifetime risk of developing breast cancer for each year after diagnosis, as a function of the initial cancer (hormone receptor–positive v –negative, mortality risk), its treatment (breastconserving surgery v mastectomy, and tamoxifen v not for hormone receptor–positive cancers), and age at initial diagnosis. Our model assumed the risk of developing a second breast cancer was constant over time, not related to a patient’s age, and the same for the ipsilateral versus contralateral breast—as demonstrated in multiple prospective and retrospective studies. Adjuvant tamoxifen therapy was associated with a 47% reduction in the risk of developing a new breast cancer over the 10-year period after the primary cancer diagnosis. Therefore, the risk of developing a second breast cancer was only a function of the number of intact breasts and use of tamoxifen. No assumptions were made regarding the sensitivity or specificity of MRI screening in women with a personal history of breast cancer. Mortality risk from the initial diagnosis was assumed to be constant and completed within 7 years for hormone receptor–negative cancers and 15 years for hormone receptor–positive cancers. Patients with an initial diagnosis of ductal carcinoma in situ were assumed to have no mortality risk associated with their primary breast cancer diagnosis. Nonbreast cancer mortality was determined using 2004 United States female life-tables. The annual likelihood of a survivor developing a second breast cancer was determined by multiplying the per year probability of developing a new breast cancer with the per year probability of being alive (ie, not dying from the primary breast cancer or a nonbreast cancer cause). The lifetime risk of developing a JOURNAL OF CLINICAL ONCOLOGY COMMENTS AND CONTROVERSIES VOLUME 28 NUMBER 27 SEPTEMBER 2