This article reviews the relevant data on breast magnetic resonance imaging (MRI) use in screening, the short-term surgical outcomes and long-term cancer outcomes associated with the use of MRI in breast cancer staging, the use of MRI in occult primary breast cancer, as well as MRI to assess eligibility for accelerated partial breast irradiation and to evaluate tumor response after neoadjuvant chemotherapy. MRI for screening is supported in specific high-risk populations, namely, women with BRCA1 or BRCA2 mutations, a family history suggesting a hereditary breast cancer syndrome, or a history of chest wall radiation.
Key points
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Magnetic resonance imaging (MRI) screening is supported for specific high-risk populations.
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Data support the use of MRI for imaging women with occult breast cancer.
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MRI has not been shown to improve surgical outcomes in women undergoing breast-conserving surgery.
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Retrospective studies have failed to find significant improvements in breast cancer long-term outcomes with the addition of MRI.
Introduction
Mammography is the standard for breast cancer screening, and prospective randomized trials have shown reductions in breast cancer mortality from the implementation of screening mammography. However, screening mammography does have lower sensitivity in women with BRCA gene mutations, high lifetime risk of breast cancer due to family history, and dense breast tissue. Magnetic resonance imaging (MRI) has been evaluated as a screening adjunct given its improved sensitivity in specific subgroups of women and is recommended for screening in high-risk populations.
Significant controversy exists regarding the appropriate use of MRI in patients with breast cancer, particularly as part of the preoperative staging work-up. MRI is frequently obtained to exclude the presence of multicentric disease or an occult contralateral breast cancer (CBC) with the presumed benefit of improving patient selection for breast conservation as well as decreasing ipsilateral breast tumor recurrence (IBTR) and CBC rates. A survey sent to the American Society of Breast Surgeons in 2010 reported that 41% of responders routinely order breast MRI for newly diagnosed patients with breast cancer.
This article reviews the relevant data on MRI use in screening, the short-term and long-term outcomes associated with the use of MRI for cancer staging, the use of MRI in occult primary breast cancer, and MRI imaging to assess eligibility for accelerated partial breast irradiation (APBI) and to evaluate tumor response after neoadjuvant chemotherapy (NAC).
MRI for screening
MRI Screening in BRCA Mutation Carriers and Other High-Risk Women
Mammography remains the gold standard for breast cancer screening and is the only imaging modality to have shown a breast cancer mortality benefit. However, mammography has lower sensitivity in women with BRCA mutations, those with elevated lifetime risk based on family history, and those with dense breast tissue, whereas MRI has improved sensitivity for the detection of breast cancer regardless of breast density. Studies examining the use of MRI for screening have been done in high-risk women with a known or suspected BRCA mutation or those with a family history of breast cancer and an elevated lifetime risk of developing breast cancer. In 2008, in a systematic review, Warner and colleagues reported on 4983 women from 11 prospective MRI screening studies. There was substantial heterogeneity in the study inclusion criteria, including study design, number of screens, use of ultrasound or clinical breast examination, exclusion of patients with prior breast cancer, patient age, and method of risk assessment. The proportion of women in each study with a known BRCA mutation ranged from 8% to 100%, but all studies included women considered high risk because of an elevated annual or lifetime breast cancer risk. All studies reported improved sensitivity (with a positive test defined as Breast Imaging-Reporting and Data System [BIRADS] 4 or 5) with MRI (range 51%–100%) compared with mammography (range 14%–59%). A meta-analysis performed on 10 studies found an overall sensitivity of mammography of 32% (95% confidence interval [CI] 23–41) compared with 75% (95% CI 62–88) for MRI. Combining the 2 screening tests had the highest sensitivity for BIRADS 4 or 5 lesions at 84% (95% CI 70–97). Specificity of mammography (98.5%, 95% CI 97.8–99.2) was slightly higher than that of MRI (96.1%, 95% CI 93.7–96.6). Subsequently, similar results were reported from the multicenter high breast cancer–risk Italian 1 study, which prospectively enrolled 501 women with either a BRCA mutation, or a strong family history of breast or ovarian cancer, to undergo annual evaluation with clinical breast examination, mammography, ultrasound, and MRI. The median age of screened women was 45 years (range 22–79). A total of 52 cancers were identified: 94% screen detected, 6% interval cancers, and 28% node positive. The overall sensitivity of screening modalities was as follows: clinical breast examination 18% (95% CI 8.4–30.9), mammography 50% (95% CI 35.5–64.5), ultrasound 52% (95% CI 37.4–66.3), and MRI 91% (95% CI 79.2–97.6). The addition of mammography or ultrasound to MRI increased the sensitivity only slightly, to 93%. The specificity was again lower for MRI (96.7%, 95% CI 95.4–97.7) compared with mammography (99.0%, 95% CI 98.2–99.5).
Outcomes in BRCA carriers and high-risk women screened with MRI
Although the sensitivity of MRI exceeds that of mammography for cancer detection in these high-risk women, the ultimate goal of screening is to improve patient outcomes. Warner and colleagues examined the stage of breast cancer identified in 2 groups of BRCA-positive women: those screened with MRI (n = 445) and those who had conventional screening alone (n = 830). The cumulative incidence of invasive cancer at 6 years was not different between the MRI and no-MRI groups (10.6% and 12.2%, respectively; P = .7). However, the cumulative incidence of ductal carcinoma in situ (DCIS) or stage I breast cancer was significantly higher in the MRI-screened group (13.8%) compared with 7.2% in the conventional imaging group ( P = .01). Conversely, the incidence of stages II to IV breast cancer at 6 years was lower in the MRI-screened cohort (1.9%) compared with 6.6% in the conventional imaging group ( P = .02). Similarly, the average size of MRI detected invasive tumors was smaller (0.9 cm) than the conventional imaging group (1.8 cm) ( P <.001). On multivariate analysis, after controlling for age, oophorectomy, parity, prior history of breast cancer, tamoxifen use, oral contraceptive use, and hormone replacement therapy, the adjusted hazard ratio (HR) for the development of stage II to IV breast cancer in the MRI cohort was 0.30 (95% CI 0.12–0.72).
Whether MRI screening is associated with improved survival in BRCA mutation carriers remains unclear. The Dutch MRI screening study prospectively followed 2157 high-risk women, defined as BRCA mutation carriers or those with an estimated cumulative lifetime risk of breast cancer of 15% or more, in a screening program with clinical breast examination, annual mammography, and MRI. At a median follow-up of 4.9 years, significant differences in outcomes and tumor characteristics among the BRCA1, BRCA2, and non-mutation high-risk groups were noted. The BRCA1 group had the highest rate of interval cancer development (32.3%) compared with 6.3% for the BRCA2 group (high-risk group 3.7%, moderate-risk group 6.3%; P = .01). Patients with BRCA1-associated cancer were also diagnosed at younger ages, had fewer DCIS lesions, had larger tumor size at diagnosis, and had more grade 3 tumors and more hormone receptor-negative tumors. The cumulative distant metastasis–free survival at 6 years for the patients with BRCA cancer was 83.9% compared with 100% for the non-mutation high-risk patients. A Norwegian surveillance program for women with BRCA1 mutations followed 802 women screened with MRI and mammogram for a mean of 4.2 years. During the follow-up period, 68 women developed breast cancer and 10 patients died of their disease. The 5-year and 10-year breast cancer–specific survivals in this MRI-screened BRCA1 population were 75% and 69%, respectively. The 5-year survival for stage I breast cancer in this group was 82%, which is significantly lower than the 98% survival reported by the Norwegian Cancer Registry ( P <.05). These findings raise important questions regarding improvements in outcomes of BRCA1-associated cancers even when detected at smaller sizes with MRI screening. In contrast, Passaperuma and colleagues reported long-term outcomes in 496 BRCA mutation carriers followed in a prospective single-institution screening program of annual MRI, mammography, ultrasound, and clinical breast examination. Fifty-seven cancers were diagnosed, 65% invasive and 35% DCIS, with no statistically significant difference noted in tumor size (mean invasive cancer size, 1.02 cm), tumor grade, or nodal status between BRCA1 and BRCA2 cancers. Of those women with no prior history of breast or ovarian cancer, at a median follow-up of 8.4 years, there was 1 breast cancer-related death, for an annual breast cancer–specific mortality rate of 0.5%. With mixed data on survival benefit seen in women with BRCA mutations or familial risk screened with MRI, additional long-term follow-up is needed to determine the true added benefit of MRI screening in this population.
MRI Screening in Women with a History of Chest Irradiation
The current guidelines from the American Cancer Society and the American College of Radiology support the use of MRI screening in addition to mammography for BRCA mutation carriers and untested first-degree relatives of BRCA mutation carriers, those with a lifetime breast cancer risk estimated at 20% to 25% or more, as well as carriers of other genetic mutations associated with increased breast cancer risk or a history of chest wall irradiation between 10 and 30 years of age ( Box 1 ). The last group listed is based on expert opinion as women with a history of chest wall irradiation have a significantly elevated breast cancer risk, but there are limited data on the utility of MRI screening in this group.
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