Differences in natural history between breast cancers in BRCA1 and BRCA2 mutation carriers and effects of MRI screening - MRISC, MARIBS and Canadian studies combined
A partir des données de trois études incluant au total 1 275 participantes porteuses d'une mutation du gène BRCA1 ou BRCA2 et à l'aide de deux modèles mathématiques, cette étude évalue, en fonction du gène muté et de la catégorie d'âge des patientes, l'intérêt de combiner ou non une IRM et une mammographie pour détecter un cancer du sein
Background: It is recommended that BRCA1/2 mutation carriers undergo breast cancer screening using Magnetic Resonance Imaging (MRI) because of their very high cancer risk and the high sensitivity of MRI in detecting invasive cancers. Clinical observations suggest important differences in the natural history between breast cancers due to mutations in BRCA1 and BRCA2, potentially requiring different screening guidelines. Methods: Three studies of mutation carriers using annual MRI and mammography were analysed. Separate natural history models for BRCA1 and BRCA2 were calibrated to the results of these studies and used to predict the impact of various screening protocols on detection characteristics and mortality. Results: 1,275 BRCA1/2 mutation carriers participated in the studies and 124 cancers (99 invasive) were diagnosed. Cancers detected in BRCA2 mutation carriers were smaller (80% DCIS or ≤ 10mm versus 49% for BRCA1, p<0.001). Below age 40, 1 (invasive) cancer of the 25 screen-detected cancers in BRCA1 mutation carriers was detected by mammography alone, compared with 7 (3 invasive) of 11 screen-detected cancers in BRCA2 (p<0.0001). In the model, the pre-clinical period during which cancer is screen-detectable was 1-4 years for BRCA1 and 2-7 years for BRCA2. The model predicted breast cancer mortality reductions of 42-47% for mammography, 48-61% for MRI, and 50-62% for combined screening. Conclusions: Our studies suggest substantial mortality benefits in using MRI to screen BRCA1/2 mutation carriers aged 25-60, but show important clinical differences in natural history. Impact: BRCA1 and BRCA2 mutation carriers may benefit from different screening protocols, for example below age 40.
Cancer Epidemiology Biomarkers & Prevention , résumé, 2012