Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2012
Differences in natural history between breast cancers in BRCA1 and BRCA2 mutation carriers and effects of MRI screening-MRISC, MARIBS, and Canadian studies combined.
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Heijnsdijk Eveline A M, Warner Ellen, Gilbert Fiona J, Tilanus-Linthorst Madeleine M A, Evans Gareth, Causer Petrina A, Eeles Rosalind A, Kaas Reinie, Draisma Gerrit, Ramsay Elizabeth A, Warren Ruth M L, Hill Kimberly A, Hoogerbrugge Nicoline, Wasser Martin N J M, Bergers Elisabeth, Oosterwijk Jan C, Hooning Maartje J, Rutgers Emiel J T, Klijn Jan G M, Plewes Don B, Leach Martin O, de Koning Harry J
Аннотация
BACKGROUND: It is recommended that BRCA1/2 mutation carriers undergo breast cancer screening using 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 analyzed. 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: BRCA1/2 mutation carriers (N = 1,275) participated in the studies and 124 cancers (99 invasive) were diagnosed. Cancers detected in BRCA2 mutation carriers were smaller [80% ductal carcinoma in situ (DCIS) or ≤10 mm vs. 49% for BRCA1, P < 0.001]. Below the age of 40, one (invasive) cancer of the 25 screen-detected cancers in BRCA1 mutation carriers was detected by mammography alone, compared with seven (three invasive) of 11 screen-detected cancers in BRCA2 (P < 0.0001). In the model, the preclinical period during which cancer is screen-detectable was 1 to 4 years for BRCA1 and 2 to 7 years for BRCA2. The model predicted breast cancer mortality reductions of 42% to 47% for mammography, 48% to 61% for MRI, and 50% to 62% for combined screening.
CONCLUSIONS: Our studies suggest substantial mortality benefits in using MRI to screen BRCA1/2 mutation carriers aged 25 to 60 years but show important clinical differences in natural history.
IMPACT: BRCA1 and BRCA2 mutation carriers may benefit from different screening protocols, for example, below the age of 40.
METHODS: Three studies of mutation carriers using annual MRI and mammography were analyzed. 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: BRCA1/2 mutation carriers (N = 1,275) participated in the studies and 124 cancers (99 invasive) were diagnosed. Cancers detected in BRCA2 mutation carriers were smaller [80% ductal carcinoma in situ (DCIS) or ≤10 mm vs. 49% for BRCA1, P < 0.001]. Below the age of 40, one (invasive) cancer of the 25 screen-detected cancers in BRCA1 mutation carriers was detected by mammography alone, compared with seven (three invasive) of 11 screen-detected cancers in BRCA2 (P < 0.0001). In the model, the preclinical period during which cancer is screen-detectable was 1 to 4 years for BRCA1 and 2 to 7 years for BRCA2. The model predicted breast cancer mortality reductions of 42% to 47% for mammography, 48% to 61% for MRI, and 50% to 62% for combined screening.
CONCLUSIONS: Our studies suggest substantial mortality benefits in using MRI to screen BRCA1/2 mutation carriers aged 25 to 60 years but show important clinical differences in natural history.
IMPACT: BRCA1 and BRCA2 mutation carriers may benefit from different screening protocols, for example, below the age of 40.