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BRCA1 Mutation and Young Age Predict Fast Breast Cancer Growth in the Dutch, United Kingdom, and Canadian Magnetic Resonance Imaging Screening Trials

Authors' Affiliations: Departments of ¹ Surgery, ² Radiology, ³ Epidemiology and Biostatistics, and ⁴ Medical Oncology, Erasmus University Medical Centre, Rotterdam, the Netherlands; ⁵ Centre for Research on Women's Health; ⁶ Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada; ⁷ Department of Medical Imaging, Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, Surrey, United Kingdom; ⁸ Department of Radiology, Addenbrooke's Hospital, Cambridge, United Kingdom; and ⁹ Department of Radiology, University of Aberdeen, Scotland, United Kingdom

Requests for reprints: Madeleine M.A. Tilanus-Linthorst, Department of Surgery, Erasmus University Medical Centre, Groene Hilledijk 301, 3075 EA Rotterdam, the Netherlands. Phone: 31-10-4391-161; Fax: 31-10-4391-412; E-mail: m.tilanus-linthorst{at}erasmusmc.nl.

Purpose: Magnetic resonance imaging (MRI) screening enables early detection of breast cancers in women with an inherited predisposition. Interval cancers occurred in women with a BRCA1 mutation, possibly due to fast tumor growth. We investigated the effect of a BRCA1 or BRCA2 mutation and age on the growth rate of breast cancers, as this may influence the optimal screening frequency.

Experimental Design: We reviewed the invasive cancers from the United Kingdom, Dutch, and Canadian MRI screening trials for women at hereditary risk, measuring tumor size at diagnosis and on preceding MRI and/or mammography. We could assess tumor volume doubling time (DT) in 100 cancers.

Results: Tumor DT was estimated for 43 women with a BRCA1 mutation, 16 women with a BRCA2 mutation, and 41 women at high risk without an identified mutation. Growth rate slowed continuously with increasing age (P = 0.004). Growth was twice as fast in BRCA1 (P = 0.003) or BRCA2 (P = 0.03) patients as in high-risk patients of the same age. The mean DT for women with BRCA1/2 mutations diagnosed at ages 40, 41 to 50, and >50 years was 28, 68, and 81 days, respectively, and 83, 121, and 173 days, respectively, in the high-risk group. Pathologic tumor size decreased with increasing age (P = 0.001). Median size was 15 mm for patients ages 40 years compared with 9 mm in older patients (P = 0.003); tumors were largest in young women with BRCA1 mutations.

Conclusion: Tumors grow quickly in women with BRCA1 mutations and in young women. Age and risk group should be taken into account in screening protocols.