English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Introduction  The distribution of histopathological features of invasive breast tumors in  BRCA1  or  BRCA2  germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of  BRCA1  or  BRCA2  variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of  BRCA1 /2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of  BRCA1  and  BRCA2  mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling.    Methods  Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477  BRCA1  mutation carriers, 2,565  BRCA2  mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach.    Results  ER-positive phenotype negatively predicted  BRCA1  mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive  BRCA1  mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For  BRCA2 , ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of  BRCA1  mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive  BRCA2  mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)).    Conclusions  These results refine likelihood-ratio estimates for predicting  BRCA1  and  BRCA2  mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for  BRCA2  mutation carrier prediction. The estimates will improve  BRCA1  and  BRCA2  variant classification and inform patient mutation testing and clinical management.    Electronic supplementary material  The online version of this article (doi:10.1186/s13058-014-0474-y) contains supplementary material, which is available to authorized users.

breast cancer research

Refined histopathological predictors of BRCA1 and BRCA2mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia