Prediction of breast cancer risk based on flow-variant analysis of circulating peripheral blood B cells

Mahrukh M. Syeda, Kinnari Upadhyay, Johnny C. Loke, Alexander Pearlman, Susan D. Klugman, Yongzhao Shao, Harry Ostrer

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Purpose:Identifying women at high risk for breast cancer can trigger a personal program of annual mammograms and magnetic resonance imaging scans for early detection, prophylactic surgery, or chemoprevention to reduce the risk of cancer. Yet, current strategies to identify high-risk mutations based on sequencing panels of genes have significant false-positive and false-negative results, suggesting the need for alternative approaches.Methods:Flow-variant assays (FVAs) that assess the effects of mutations in the double-strand break (DSB) repair genetic pathway in lymphoblastoid cells in response to treatment with radiomimetic agents were assessed for sensitivity, specificity, and accuracy both alone and as part of a logistic regression classification score. In turn, these assays were validated in circulating B cells and applied to individuals with personal and/or family history of breast and/or ovarian cancer.Results:A three-FVA classification score based on logistic regression had 95% accuracy. Individuals from a breast cancer-positive cohort with affected family members had high-risk FVA classification scores.Conclusion:Application of a classification score based on multiple FVAs could represent an alternative to panel sequencing for identifying women at high risk for cancer.

Original languageEnglish (US)
Pages (from-to)1071-1077
Number of pages7
JournalGenetics in Medicine
Volume19
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Blood Cells
B-Lymphocytes
Breast Neoplasms
Logistic Models
Mutation
Chemoprevention
Ovarian Neoplasms
Neoplasms
Magnetic Resonance Imaging
Sensitivity and Specificity
Genes
Therapeutics

Keywords

  • breast cancer
  • functional genomics
  • genetic testing
  • high risk
  • panel sequencing

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Prediction of breast cancer risk based on flow-variant analysis of circulating peripheral blood B cells. / Syeda, Mahrukh M.; Upadhyay, Kinnari; Loke, Johnny C.; Pearlman, Alexander; Klugman, Susan D.; Shao, Yongzhao; Ostrer, Harry.

In: Genetics in Medicine, Vol. 19, No. 9, 01.09.2017, p. 1071-1077.

Research output: Contribution to journalArticle

Syeda, Mahrukh M. ; Upadhyay, Kinnari ; Loke, Johnny C. ; Pearlman, Alexander ; Klugman, Susan D. ; Shao, Yongzhao ; Ostrer, Harry. / Prediction of breast cancer risk based on flow-variant analysis of circulating peripheral blood B cells. In: Genetics in Medicine. 2017 ; Vol. 19, No. 9. pp. 1071-1077.
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