MRI versus mammography for breast cancer screening in women with familial risk (FaMRIsc): a multicentre, randomised, controlled trial

Abstract

Background: Screening guidelines for women at familial risk of breast cancer without a known causative gene mutation differ internationally. To our knowledge, no randomised controlled MRI-screening trial has been performed. The FaMRIsc-study aims to assess the efficacy of MRI versus mammography screening for familial risk and furthermore assesses the influence of breast density. Methods: In 12 Dutch hospitals, 1355 women aged 30-55 years with a cumulative lifetime risk of ≥20% without a BRCA1/2 mutation were randomised with a web-based computer generated hospital sequence, concealed for participants, physicians and researchers, in either the MRI-group with yearly MRI, clinical breast examination and mammography biennially, or the Mammography-group with yearly mammography and clinical breast examination. Breastfeeding, pregnancy, previous screening and previous ductal carcinoma in situ were permitted, but no previous invasive cancer. Primary outcomes were number, size and nodal-stage of breast cancers. Secondary outcomes were sensitivity, specificity and positive predictive value. Results were also stratified by mammographic density (BI-RADS AD). Intention to screen analyses were performed. This trial was registered with the Netherlands Trial Register, NTR2789. Findings: Between Jan 1 2011, and Dec 31 2017 in the MRI-group (674 women) compared to the Mammographygroup (680 women) with a median follow-up of 5.2 years for both groups, more breast cancers were detected (40 versus 15, p<0•001), invasive cancers were smaller (median size 9 versus 17 mm, p=0•010) and less frequently node positive (4/24, 17% versus 5/8, 63%, p=0•023). In the MRI-group, specificity was significantly lower compared to the Mammography-group (83•8% versus 91•0%, p<0•001), while sensitivity hardly differed (97•5% versus 86.7%, p=0.18). Clinical breast examination contributed hardly to detection (1/55). In incident cancers, tumour stage was better in the MRI-group (p=0•035), with lower numbers of node positive and ≥T2 tumours, while specificity improved in both arms (MRI-group: 87•4%, Mammography-group: 92•6%, p<0•001). All tumours ≥T2 were in the two highest density categories. In BI-RADS density A-C MRI was most effective. Interpretation: The earlier detection by MRI screening and especially the fewer late-stage cancers in incident rounds, may reduce adjuvant chemotherapy and mortality. However, especially for women with the highest breast density at the cost of more false positive results.

Establishment and validation of an immunodiagnostic model for prediction of breast cancer

“…The sensitivity was lower than those of the 50-69 and >70 age groups, with 85% and 80% sensitivity, respectively. 44 High density of breast tissue impairs the sensitivity of mammography, especially in women between 40 and 49 years of age (about 74% of them with high breast density) and 45% of women in their 60s have high breast density 6 Therefore, the immunodiagnostic model could make up the low sensitivity of mammography in young women, especially at high breast density. 2,4,6 Furthermore, the results of this study demonstrated that at stage I of BC, the level of anti-p16 autoantibody was significantly higher than that in stage II, stage III and stage IV.…”

“…44 High density of breast tissue impairs the sensitivity of mammography, especially in women between 40 and 49 years of age (about 74% of them with high breast density) and 45% of women in their 60s have high breast density 6 Therefore, the immunodiagnostic model could make up the low sensitivity of mammography in young women, especially at high breast density. 2,4,6 Furthermore, the results of this study demonstrated that at stage I of BC, the level of anti-p16 autoantibody was significantly higher than that in stage II, stage III and stage IV. The anti-p16 autoantibody was firstly reported by our group in 2006 45 The p16 protein is a cyclin-dependent kinase inhibitor, and also a negative regulator of the mammalian cell cycle 46 Despite it is not specific for BC, the finding indicates that the anti-p16 antibody could be a biomarker in the early detection of BC.…”

“…3,4 Therefore, it is not recommended for women with average risk and under the age of 50 years 5 In addition, mammography can not only lead to overdiagnosis, but also makes women experience the harms and side effects of treatment. 6,7 In comparison, serological tests based on the tumor-associated biomarkers could be a good way to remedy some defects of mammography. 8 Recently, with the development of proteomic technologies, a variety of tumor-associated antigens (TAAs) have been identified and employed in immunoassay.…”

SEOM clinical guidelines in hereditary breast and ovarian cancer (2019)

“…For those women with a positive family history of BC and no mutation in a high/moderate penetrance gene, BC risk can be estimated by predictive models, such as BOADICEA or Tyrer-Cuzyck. In women with a cumulative lifetime BC risk of 25-30%, both annual mammography and breast MRI should be offered (IIB) beginning at the age when their 10-year BC risk reaches 5% (IIIC) [25,26].…”

Diffusion Weighted Imaging of Different Breast Cancer Molecular Subtypes. A Systematic Review and Meta Analysis.

“…Magnetic resonance imaging (MRI) has become a cornerstone for the diagnosis of breast cancer (BC) [1][2][3][4]. It has the highest sensitivity of all imaging modalities but is confronted with lacks in speci city [5].…”