Surveillance of Women with the BRCA1 or BRCA2 Mutation by Using Biannual Automated Breast US, MR Imaging, and Mammography

Abstract

Purpose To evaluate a multimodal surveillance regimen including yearly full-field digital (FFD) mammography, dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) imaging, and biannual automated breast (AB) ultrasonography (US) in women with BRCA1 and BRCA2 mutations. Materials and Methods This prospective multicenter trial enrolled 296 carriers of the BRCA mutation (153 BRCA1 and 128 BRCA2 carriers, and 15 women with first-degree untested relatives) between September 2010 and November 2012, with follow-up until November 2015. Participants underwent 2 years of intensified surveillance including biannual AB US, and routine yearly DCE MR imaging and FFD mammography. The surveillance performance for each modality and possible combinations were determined. Results Breast cancer was screening-detected in 16 women (age range, 33-58 years). Three interval cancers were detected by self-examination, all in carriers of the BRCA1 mutation under age 43 years. One cancer was detected in a carrier of the BRCA1 mutation with a palpable abnormality in the contralateral breast. One incidental breast cancer was detected in a prophylactic mastectomy specimen. Respectively, sensitivity of DCE MR imaging, FFD mammography, and AB US was 68.1% (14 of 21; 95% confidence interval [CI]: 42.9%, 85.8%), 37.2% (eight of 21; 95% CI: 19.8%, 58.7%), and 32.1% (seven of 21; 95% CI: 16.1%, 53.8%); specificity was 95.0% (643 of 682; 95% CI: 92.7%, 96.5%), 98.1% (638 of 652; 95% CI: 96.7%, 98.9%), and 95.1% (1030 of 1088; 95% CI: 93.5%, 96.3%); cancer detection rate was 2.0% (14 of 702), 1.2% (eight of 671), and 1.0% (seven of 711) per 100 women-years; and positive predictive value was 25.2% (14 of 54), 33.7% (nine of 23), and 9.5% (seven of 68). DCE MR imaging and FFD mammography combined yielded the highest sensitivity of 76.3% (16 of 21; 95% CI: 53.8%, 89.9%) and specificity of 93.6% (643 of 691; 95% CI: 91.3%, 95.3%). AB US did not depict additional cancers. FFD mammography yielded no additional cancers in women younger than 43 years, the mean age at diagnosis. In carriers of the BRCA2 mutation, sensitivity of FFD mammography with DCE MR imaging surveillance was 90.9% (10 of 11; 95% CI: 72.7%, 100%) and 60.0% (six of 10; 95% CI: 30.0%, 90.0%) in carriers of the BRCA1 mutation because of the high interval cancer rate in carriers of the BRCA1 mutation. Conclusion AB US may not be of added value to yearly FFD mammography and DCE MR imaging surveillance of carriers of the BRCA mutation. Study results suggest that carriers of the BRCA mutation younger than 40 years may not benefit from FFD mammography surveillance in addition to DCE MR imaging. RSNA, 2017 Online supplemental material is available for this article.

Breast ultrasonography (BU) in the screening protocol for women at hereditary‐familial risk of breast cancer: has the time come to rethink the role of BU according to different risk categories?

“…The real US benefit was represented by the six-monthly examination; thus 29.4% of sensitivity was reached, without significant differences amongst the risk groups and age range. Also in this case, our US sensitivity in BRCA1/2 mutated patients (22.7%) compared to results of Van Zelst et al, 28 where total biannual ultrasound sensitivity was 32.1%. Once again, the real added value of US was the six-monthly examination by which 8 patients were found positive (5 aged ≤50 and 3 aged >50 years) with a DR equal to 1.2 × 1,000 person-years, in line with Brem et al that used three-dimensional US to improve the DR of mammographic screening in dense breasts.…”

“…On the other hand, in a previous study the MMG sensitivity increased to 34.6% in patients aged ≤50 years . In another paper, MMG performed on BRCA1/2 carriers showed a 37.2% of sensitivity . Our MMG sensitivity decreased slightly according to age, with a total sensitivity of 55%.…”

“…27 In another paper, MMG performed on BRCA1/2 carriers showed a 37.2% of sensitivity. 28 Our MMG sensitivity decreased slightly according to age, with a total sensitivity of 55%. Considering BRCA1/2 mutation carriers, the MMG sensitivity was very low being 25%, whereas in the HR population MMG alone reached 66% of sensitivity regardless of age.…”

Contrast‐enhanced MRI for breast cancer screening

“…47 In the study by van Zelst et al, two cancers were in retrospect visible at the 6-month interval, but missed due to their benign appearance. 48 The addition of ultrasound to MRI and mammography leads to a reduction of specificity of between 0% and 5.5%.…”

Abbreviated MRI Protocols in Breast Cancer Diagnostics

“…20 Conversely to ultrasound and DBT, the additional cancer yield of full diagnostic breast MRI was around 15 per 1000 in women with elevated risk 21 and around 23 per 1000 in an average risk screening setting, 22 with no cancer being detected during the screening interval and a reduction in sensitivity with decreasing biologic aggressiveness. 11,12 The results of breast MRI could not be increased by additional mammography or ultrasound [23][24][25] and a reduction of sequences resulting in an abbreviated breast MRI protocol did not significantly reduce the cancer yield compared with the full diagnostic MRI protocol with an additional cancer yield of 18 per 1000 in women who had already undergone mammography and breast ultrasound. 26 However the application of breast MRI in cancer screening is still impaired: in 2014, the breast cancer consortium reported that of around 25,600 women who met the 20% risk threshold in the U.S. and thereby qualified for breast MRI screening, only 2% had breast MRI performed.…”