BRCA1 mutation and young age predict fast breast cancer growth in the Dutch, United Kingdom, and Canadian magnetic resonance imaging screening trials

Clin Cancer Res. 2007 Dec 15;13(24):7357-62. doi: 10.1158/1078-0432.CCR-07-0689.

Abstract

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 < or =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 < or =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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Canada
  • Cell Proliferation*
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2
  • Genetic Predisposition to Disease
  • Humans
  • Magnetic Resonance Imaging
  • Mass Screening*
  • Middle Aged
  • Mutation
  • Netherlands
  • United Kingdom