High-risk breast cancer surveillance with MRI: 10-year experience from the German consortium for hereditary breast and ovarian cancer

PurposeTo report on 10 years of high-risk service screening with annual MRI in the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC).MethodsA cohort of 4,573 high-risk, previously unaffected women (954 BRCA1 carriers, 598 BRCA2 carriers, 3021 BRCA1/2 non-carriers) participating in the GC-HBOC surveillance program was prospectively followed. Screening outcomes for 14,142 screening rounds with MRI between 2006 and 2015 were analyzed and stratified by risk group, type of screening round, and age.ResultsA total of 221 primary breast cancers (185 invasive, 36 in situ) were diagnosed within 12 months of an annual screening round with MRI. Of all cancers, 84.5% (174/206, 15 unknown) were stage 0 or I. In BRCA1 carriers, 16.9% (10/59, 5 unknown) of all incident cancers (screen-detected and interval cancers combined) and in BRCA2 carriers 12.5% (3/24, 4 unknown) were stage IIA or higher, compared to only 4.8% (2/42, 2 unknown) in high-risk BRCA1/2 non-carriers. Program sensitivity was 89.6% (95% CI 84.9–93.0) with no significant differences in sensitivity between risk groups or by age. Specificity was significantly lower in the first screening round (84.6%, 95% CI 83.6–85.7) than in subsequent screening rounds (91.1%, 95% CI 90.6–91.7), p < 0.001. Cancer detection rates (CDRs) and as a result positive predictive values were strongly dependent on type of screening round, risk group and patient age. CDRs ranged from 43.5‰ (95% CI 29.8–62.9) for the first screening round in BRCA2 carriers to 2.9‰ (95% CI 1.3–6.3) for subsequent screening rounds in high-risk non-carriers in the age group 30 to 39 years.ConclusionsHigh-risk screening with MRI was successfully implemented in the GC-HBOC with high sensitivity and specificity. Risk prediction and inclusion criteria in high-risk non-carriers need to be adjusted to improve CDRs and thus screening efficacy in these patients.

[1]  N. Risch,et al.  Autosomal dominant inheritance of early‐onset breast cancer. Implications for risk prediction , 1994 .

[2]  N. Karssemeijer,et al.  Influence of Risk Category and Screening Round on the Performance of an MR Imaging and Mammography Screening Program in Carriers of the BRCA Mutation and Other Women at Increased Risk. , 2017, Radiology.

[3]  T. Helbich,et al.  Magnetic Resonance Imaging of the Breast Improves Detection of Invasive Cancer, Preinvasive Cancer, and Premalignant Lesions during Surveillance of Women at High Risk for Breast Cancer , 2007, Clinical Cancer Research.

[4]  C. Gatsonis,et al.  Cancer yield of mammography, MR, and US in high-risk women: prospective multi-institution breast cancer screening study. , 2007, Radiology.

[5]  Ellen Warner,et al.  Contribution of mammography to MRI screening in BRCA mutation carriers by BRCA status and age: individual patient data meta-analysis , 2016, British Journal of Cancer.

[6]  Mithat Gönen,et al.  Breast cancer detection and tumor characteristics in BRCA1 and BRCA2 mutation carriers , 2017, Breast Cancer Research and Treatment.

[7]  Rongwei Fu,et al.  Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation , 2014, Annals of Internal Medicine.

[8]  Harry J de Koning,et al.  BRCA1-associated breast cancers present differently from BRCA2-associated and familial cases: long-term follow-up of the Dutch MRISC Screening Study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  T. Helbich,et al.  Triple-modality screening trial for familial breast cancer underlines the importance of magnetic resonance imaging and questions the role of mammography and ultrasound regardless of patient mutation status, age, and breast density. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  D Krebs,et al.  Breast MR imaging screening in 192 women proved or suspected to be carriers of a breast cancer susceptibility gene: preliminary results. , 2000, Radiology.

[11]  M. Yaffe,et al.  Improvement in DCIS Detection Rates by MRI Over Time in a High‐Risk Breast Screening Study , 2011, The breast journal.

[12]  H. D. de Koning,et al.  Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. , 2004, The New England journal of medicine.

[13]  R. Warren,et al.  Differences in Natural History between Breast Cancers in BRCA1 and BRCA2 Mutation Carriers and Effects of MRI Screening-MRISC, MARIBS, and Canadian Studies Combined , 2012, Cancer Epidemiology, Biomarkers & Prevention.

[14]  L. Cannon-Albright,et al.  Risk modifiers in carriers of brca1 mutations , 1995, International journal of cancer.

[15]  W. Chung,et al.  Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers , 2017, JAMA.

[16]  M. Hooning,et al.  Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BRCA1 and BRCA2 mutation carriers: a prospective analysis. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[17]  T. Helbich,et al.  Breast MRI: EUSOBI recommendations for women’s information , 2015, European Radiology.

[18]  Nina Ditsch,et al.  Hereditary breast and ovarian cancer: new genes, new treatments, new concepts. , 2011, Deutsches Arzteblatt international.

[19]  B. Karlan,et al.  An international survey of surveillance schemes for unaffected BRCA1 and BRCA2 mutation carriers , 2016, Breast Cancer Research and Treatment.

[20]  M. Yaffe,et al.  American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography , 2007 .

[21]  M. Hooning,et al.  Should we screen BRCA1 mutation carriers only with MRI? A multicenter study , 2014, Breast Cancer Research and Treatment.

[22]  D. Vanel The American College of Radiology (ACR) Breast Imaging and Reporting Data System (BI-RADS): a step towards a universal radiological language? , 2007, European journal of radiology.

[23]  Laura Cortesi,et al.  Multicenter Surveillance of Women at High Genetic Breast Cancer Risk Using Mammography, Ultrasonography, and Contrast-Enhanced Magnetic Resonance Imaging (the High Breast Cancer Risk Italian 1 Study): Final Results , 2011, Investigative radiology.

[24]  D. Plewes,et al.  Systematic Review: Using Magnetic Resonance Imaging to Screen Women at High Risk for Breast Cancer , 2008, Annals of Internal Medicine.

[25]  Harry J de Koning,et al.  Accuracy of screening women at familial risk of breast cancer without a known gene mutation: Individual patient data meta-analysis. , 2017, European journal of cancer.

[26]  A. Howell,et al.  Surveillance for familial breast cancer: Differences in outcome according to BRCA mutation status , 2007, International journal of cancer.

[27]  J. Klijn,et al.  Tumor characteristics and detection method in the MRISC screening program for the early detection of hereditary breast cancer , 2006, Breast Cancer Research and Treatment.

[28]  M. Yaffe,et al.  Long-term results of screening with magnetic resonance imaging in women with BRCA mutations , 2012, British Journal of Cancer.

[29]  Silke Coburger,et al.  Outcome of a structured surveillance programme in women with a familial predisposition for breast cancer , 2006, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[30]  Fh collaborative teams Mammographic surveillance in women younger than 50 years who have a family history of breast cancer: tumour characteristics and projected effect on mortality in the prospective, single-arm, FH01 study. , 2010, The Lancet. Oncology.

[31]  R. Newcombe Two-sided confidence intervals for the single proportion: comparison of seven methods. , 1998, Statistics in medicine.

[32]  E. R. van den Heuvel,et al.  Magnetic resonance imaging improves breast screening sensitivity in BRCA mutation carriers age ≥ 50 years: evidence from an individual patient data meta-analysis. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  U. Bick Intensified Surveillance for Early Detection of Breast Cancer in High-Risk Patients , 2015, Breast Care.