BRCA gene mutations mediate particularly high tnbc risk by defective estrogen signaling

Research output: Chapter in Book/Report/Conference proceedingChapter


Ubiquitously expressed protein products of BRCA1 and BRCA2 genes are implicated in processes fundamental to all cells, including DNA repair and recombination, checkpoint control of cell cycle, and transcription. BRCA gene mutations lead to disruption of BRCA proteins in mutation carrier cases and induce susceptibility to specific types of cancer. Among women with germline BRCA mutations near 50% of mammary malignancies are triple negative breast cancer (TNBC) presenting with a high grade histologically. Among women with breast cancer, TNBC was established in 57.1% of BRCA1-mutation positive and in 23.3% of BRCA2-mutation positive cases, whereas in only 13.8% of BRCA-proficient women. Although BRCA gene mutation carrier women usually exhibit clinical symptoms of defective estrogen receptor (ER) signaling; such as anovulatory infertility and early menopause, the serum estrogen levels of these patients are consequently elevated. In these cases, a compensatory feedback mechanism aims to break through the inherited or acquired ER resistance by increased estrogen synthesis so as to maintain the cellular estrogen surveillance. The higher the estrogen overproduction of BRCA-mutation positive cases, the higher the possibility of tumor-free survival. In conclusion, BRCA1 and BRCA2 gene mutations seem to increase the breast cancer risk, particularly that of TNBC, in case of insufficient compensation of defective ER signaling. Upregulation of these genes by means of elevated estrogen levels of high parity, artificial hormonal cycle created by oral contraceptives or a pregnancy mimicking high estrogen dose may decrease the excessive cancer risk of BRCA mutation positive women.

Original languageEnglish
Title of host publicationAdvances in Genetics Research
PublisherNova Science Publishers, Inc.
Number of pages16
ISBN (Print)9781634827409, 9781634827393
Publication statusPublished - Apr 1 2015


ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Suba, Z. (2015). BRCA gene mutations mediate particularly high tnbc risk by defective estrogen signaling. In Advances in Genetics Research (Vol. 14, pp. 137-152). Nova Science Publishers, Inc..