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

Madeleine M. A. Tilanus-Linthorst, Inge-Marie Obdeijin, Wim C. J. Hop, Petrina A. Causer, Martin O. Leach, Ellen Warner, Linda Pointon, Kimberley Hill, Jan G. M. Klijn, Ruth M. L. Warren, Fiona Jane Gilbert

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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.

Original languageEnglish
Pages (from-to)7357-7362
Number of pages6
JournalClinical Cancer Research
Publication statusPublished - 15 Dec 2007


  • high familial risk
  • mammographic density
  • prognostic-factors
  • natural-history
  • survival
  • carriers
  • women
  • surveillance
  • ultrasound
  • maribs

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