Correlations between brca gene mutations and the high risk of tnbc as defined by the defect of estrogen signaling

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

BRCA1 and BRCA2 are classic deoxyribonucleic acid (DNA) stabilizing, tumor-suppressor genes that repair accidental breaks in double-stranded DNA. Disruption of BRCA proteins in mutation carriers can induce susceptibility to breast and ovarian cancers, while the so- called safeguard activities of BRCA genes do not appear to be cell-type specific. Among women with germline BRCA1 mutation near 50% of malignant breast tumors is a poorly differentiated triple negative breast cancer (TNBC). Among BRCA mutation negative breast cancer cases, TNBC was established in only 13.8% of patients. Strong correlation between BRCA gene mutations and the high risk of TNBC proposes certain mediators between germline mutations and the risk for poorly differentiated breast cancers. Evidences support that estrogen-induced activation of the normal BRCA1 gene may be important in protecting the breast against cancer initiation. BRCA gene mutation carrier women frequently exhibit the clinical symptoms of estrogen deficiency, such as anovulatory infertility and ovarian failure, in spite of their elevated estrogen levels. By contrast, in certain premenopausal cases with BRCA gene mutation, the defects of ER signaling are clinically disguised by reactively increased estrogen synthesis and/or other compensatory mechanisms. With ageing, however, the relatively higher but decreasing estradiol levels are not enough for the breakthrough of ER signal transduction defects and these women have a lifelong increased risk for breast cancer. In cases with BRCA gene mutation, increased aromatase activity, elevated estrogen levels and higher ligand-independent transcriptional activity of ERs are defensive endogenous mechanisms for the improvement of defective estrogen surveillance. In high risk women, the key for breast cancer prevention may be the restoration of triangular partnership among estrogens, estrogen receptors and DNA stabilizer BRCA genes.

Original languageEnglish
Title of host publicationTriple-Negative Breast Cancer
Subtitle of host publicationBiomarkers, Emerging Therapeutic Strategies and Clinical Challenges
PublisherNova Science Publishers, Inc.
Pages63-88
Number of pages26
ISBN (Electronic)9781536123906
ISBN (Print)9781536123722
Publication statusPublished - Jan 1 2017

Fingerprint

Estrogens
Genes
Breast Neoplasms
Defects
Mutation
Triple Negative Breast Neoplasms
Germ-Line Mutation
DNA
Tumors
BRCA1 Gene
Aromatase
Signal transduction
Tumor Suppressor Genes
Estrogen Receptors
Ovarian Neoplasms
Infertility
Estradiol
Signal Transduction
Restoration
Repair

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Suba, Z. (2017). Correlations between brca gene mutations and the high risk of tnbc as defined by the defect of estrogen signaling. In Triple-Negative Breast Cancer: Biomarkers, Emerging Therapeutic Strategies and Clinical Challenges (pp. 63-88). Nova Science Publishers, Inc..

Correlations between brca gene mutations and the high risk of tnbc as defined by the defect of estrogen signaling. / Suba, Z.

Triple-Negative Breast Cancer: Biomarkers, Emerging Therapeutic Strategies and Clinical Challenges. Nova Science Publishers, Inc., 2017. p. 63-88.

Research output: Chapter in Book/Report/Conference proceedingChapter

Suba, Z 2017, Correlations between brca gene mutations and the high risk of tnbc as defined by the defect of estrogen signaling. in Triple-Negative Breast Cancer: Biomarkers, Emerging Therapeutic Strategies and Clinical Challenges. Nova Science Publishers, Inc., pp. 63-88.
Suba Z. Correlations between brca gene mutations and the high risk of tnbc as defined by the defect of estrogen signaling. In Triple-Negative Breast Cancer: Biomarkers, Emerging Therapeutic Strategies and Clinical Challenges. Nova Science Publishers, Inc. 2017. p. 63-88
Suba, Z. / Correlations between brca gene mutations and the high risk of tnbc as defined by the defect of estrogen signaling. Triple-Negative Breast Cancer: Biomarkers, Emerging Therapeutic Strategies and Clinical Challenges. Nova Science Publishers, Inc., 2017. pp. 63-88
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