Purpose To investigate the utility and accuracy of breast magnetic resonance (MR) imaging as a supplemental screening tool in women at average risk for breast cancer and to investigate the types of cancer detected with MR imaging screening. Materials and Methods This prospective observational study was conducted at two academic breast centers in women aged 40-70 years without breast cancer-associated risk factors (lifetime risk <15%). Between January 2005 and December 2013, women with at least minimal residual breast tissue (American College of Radiology categories A-D) and normal conventional imaging findings (screening mammography with or without screening ultrasonography [US]) were invited to undergo supplemental MR imaging screening. Outcome measures were supplemental cancer detection rates, interval cancer rates, and biologic profiles of MR imaging-detected additional cancers, as well as specificity and positive predictive value (PPV) of MR imaging screening. Tissue diagnoses or 2 years of follow-up were used to establish the reference standard. Results A total of 2120 women were recruited and underwent 3861 screening MR imaging studies, covering an observation period of 7007 women-years. Breast MR imaging depicted 60 additional breast cancers (ductal carcinoma in situ, n = 20; invasive carcinoma, n = 40) for an overall supplemental cancer detection rate of 15.5 per 1000 cases (95% confidence interval [CI]: 11.9, 20.0). Forty-eight additional cancers were detected with MR imaging at initial screening (supplemental cancer detection rate, 22.6 per 1000 cases). During the 1741 subsequent screening rounds, 12 of 13 incident cancers were found with MR imaging alone (supplemental cancer detection rate, 6.9 per 1000 cases). One cancer was diagnosed with all three methods (mammography, US, and MR imaging), and none were diagnosed with mammography only or US only. Cancers diagnosed with MR imaging were small (median, 8 mm), node negative in 93.4% of cases, and dedifferentiated (high-grade cancer) in 41.7% of cases at prevalence screening and 46.0% of cases at incidence screening. No interval cancers were observed. MR imaging screening offered high specificity (97.1%; 95% CI: 96.5, 97.6) and high PPV (35.7%; 95% CI: 28.9, 43.1). Conclusion In women at average risk for breast cancer, MR imaging screening improves early diagnosis of prognostically relevant breast cancer. © RSNA, 2017 Online supplemental material is available for this article.

Supplemental Breast MR Imaging Screening of Women with Average Risk of Breast Cancer

Multiple studies in the first decade of the 21st century have established contrast-enhanced breast MRI as a screening modality for women with a hereditary or familial increased risk for the development of breast cancer. In recent studies, in women with various risk profiles, the sensitivity ranges between 81% and 100%, which is approximately twice as high as the sensitivity of mammography. The specificity increases in follow-up rounds to around 97%, with positive predictive values for biopsy in the same range as for mammography. MRI preferentially detects the more aggressive/invasive types of breast cancer, but has a higher sensitivity than mammography for any type of cancer. This performance implies that in women screened with breast MRI, all other examinations must be regarded as supplemental. Mammography may yield ~5% additional cancers, mostly ductal carcinoma in situ, while slightly decreasing specificity and increasing the costs. Ultrasound has no supplemental value when MRI is used. Evidence is mounting that in other groups of women the performance of MRI is likewise superior to more conventional screening techniques. Particularly in women with a personal history of breast cancer, the gain seems to be high, but also in women with a biopsy history of lobular carcinoma in situ and even women at average risk, similar results are reported. Initial outcome studies show that breast MRI detects cancer earlier, which induces a stage-shift increasing the survival benefit of screening. Cost-effectiveness is still an issue, particularly for women at lower risk. Since costs of the MRI scan itself are a driving factor, efforts to reduce these costs are essential. The use of abbreviated MRI protocols may enable more widespread use of breast MRI for screening. Level of Evidence: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;50:377-390.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmri.26654

Contrast-enhanced MRI for breast cancer screening.

BACKGROUND Screening MRI is recommended for individuals at high risk for breast cancer, based on genetic risk or family history (GFH); however, there is insufficient evidence to support screening MRI for women with a personal history (PH) of breast cancer. We compared screening MRI performance in women with PH vs GFH of breast cancer. METHODS We analyzed case-series registry data, collected at time of MRI and at 12-month follow-up, from our regional Clinical Oncology Data Integration project. MRI performance was compared in women with PH with those with GFH. Chi-square testing was used to identify associations between age, prior history of MRI, and clinical indication with MRI performance; logistic regression was used to determine the combined contribution of these variables in predicting risk of a false-positive exam. All statistical tests were two-sided. RESULTS Of 1521 women who underwent screening MRI from July 2004 to November 2011, 915 had PH and 606 had GFH of breast cancer. Overall, MRI sensitivity was 79.4% for all cancers and 88.5% for invasive cancers. False-positive exams were lower in the PH vs GFH groups (12.3% vs 21.6%, P .99). Age (P < .001), prior MRI (P < .001), and clinical indication (P < .001) were individually associated with initial false-positive rate; age and prior MRI remained statistically significant in multivariable modeling (P = .001 and P < .001, respectively). CONCLUSION MRI performance is superior in women with PH compared with women with GFH. Screening MRI warrants consideration as an adjunct to mammography in women with a PH of breast cancer.

Screening MRI in Women With a Personal History of Breast Cancer

Purpose To compare the clinical, imaging, and histopathologic features of breast cancers detected at screening magnetic resonance (MR) imaging, screening mammography, and those detected between screening examinations (interval cancers) in women at high risk. Materials and Methods This retrospective institutional review board-approved, HIPAA-compliant review of 7519 women at high risk for breast cancer who underwent screening with MR imaging and mammography between January 2005 and December 2010 was performed to determine the number of screening-detected and interval cancers diagnosed. The need for informed consent was waived. Medical records were reviewed for age, risk factors (family or personal history of breast cancer, BRCA mutation status, history of high-risk lesion or mantle radiation), tumor histopathologic results, and time between diagnosis of interval cancer and most recent screening examination. The χ(2) test and logistic regression methods were used to compare the features of screening MR imaging, screening mammography, and interval cancers. The Wilcoxon signed-rank test was used to calculate P values. Results A total of 18 064 screening MR imaging examinations and 26 866 screening mammographic examinations were performed. Two hundred twenty-two cancers were diagnosed in 219 women, 167 (75%) at MR imaging, 43 (19%) at mammography, and 12 (5%) interval cancers. Median age at diagnosis was 52 years. No risk factors were associated with screening MR imaging, screening mammography, or interval cancer (P > .06). Cancers found at screening MR imaging were more likely to be invasive cancer (118 of 167 [71%]; P < .0001). Of the 43 cancers found at screening mammography, 38 (88%) manifested as calcifications and 28 (65%) were ductal carcinoma in situ. Interval cancers were associated with nodal involvement (P = .005) and the triple-negative subtype (P = .03). Conclusion In women at high risk for breast cancer who underwent screening with mammography and MR imaging, invasive cancers were more likely to be detected at MR imaging, whereas most cancers detected at screening mammography were ductal carcinoma in situ. Interval cancers were found infrequently and were more likely to be node positive and of the triple-negative subtype. (©) RSNA, 2016.

Breast Cancers Detected at Screening MR Imaging and Mammography in Patients at High Risk: Method of Detection Reflects Tumor Histopathologic Results

Background:We investigated the additional contribution of mammography to screening accuracy in BRCA1/2 mutation carriers screened with MRI at different ages using individual patient data from six high-risk screening trials.Methods:Sensitivity and specificity of MRI, mammography and the combination of these tests were compared stratified for BRCA mutation and age using generalised linear mixed models with random effect for studies. Number of screens needed (NSN) for additional mammography-only detected cancer was estimated.Results:In BRCA1/2 mutation carriers of all ages (BRCA1=1219 and BRCA2=732), adding mammography to MRI did not significantly increase screening sensitivity (increased by 3.9% in BRCA1 and 12.6% in BRCA2 mutation carriers, P>0.05). However, in women with BRCA2 mutation younger than 40 years, one-third of breast cancers were detected by mammography only. Number of screens needed for mammography to detect one breast cancer not detected by MRI was much higher for BRCA1 compared with BRCA2 mutation carriers at initial and repeat screening.Conclusions:Additional screening sensitivity from mammography above that from MRI is limited in BRCA1 mutation carriers, whereas mammography contributes to screening sensitivity in BRCA2 mutation carriers, especially those ≤40 years. The evidence from our work highlights that a differential screening schedule by BRCA status is worth considering.

/pdf/contribution-of-mammography-to-mri-screening-in-brca-4jdc41rgmc.pdf

Contribution of mammography to MRI screening in BRCA mutation carriers by BRCA status and age: individual patient data meta-analysis

Women with a genetic predisposition to breast cancer tend to develop the disease at a younger age with denser breasts making mammography screening less effective. The introduction of magnetic resonance imaging (MRI) for familial breast cancer screening programs in recent years was intended to improve outcomes in these women. We aimed to assess whether introduction of MRI surveillance improves 5- and 10-year survival of high-risk women and determine the accuracy of MRI breast cancer detection compared with mammography-only or no enhanced surveillance and compare size and pathology of cancers detected in women screened with MRI + mammography and mammography only. We used data from two prospective studies where asymptomatic women with a very high breast cancer risk were screened by either mammography alone or with MRI also compared with BRCA1/2 carriers with no intensive surveillance. 63 cancers were detected in women receiving MRI + mammography and 76 in women receiving mammography only. Sensitivity of MRI + mammography was 93 % with 63 % specificity. Fewer cancers detected on MRI were lymph node positive compared to mammography/no additional screening. There were no differences in 10-year survival between the MRI + mammography and mammography-only groups, but survival was significantly higher in the MRI-screened group (95.3 %) compared to no intensive screening (73.7 %; p = 0.002). There were no deaths among the 21 BRCA2 carriers receiving MRI. There appears to be benefit from screening with MRI, particularly in BRCA2 carriers. Extended follow-up of larger numbers of high-risk women is required to assess long-term survival.

Evans D. Gareth

Papers

MRI breast screening in high-risk women: cancer detection and survival analysis