Hello

The evidences showing the direct inhibitory effect of BRCA1 on ER suggested BRCA1 is a major antagonistic factor of E-ER signaling pathway. Since ER is an important transcriptional factor, the inhibitory effect of BRCA1 on ER is expected to have much profound impact on the ER directed transcriptional programs.

Involvement of both BRCA1 and E-ER in regulating cell metabolism pathways .Specifically, the BRCA1 function in prohibiting fatty acid synthesis by inhibiting ACC further strengthens its tumor repressor function by serving as the “caretaker” for the synthesis of the most important cell structural component, the membrane system, because fatty acids are the major substance to build up all the membrane.

Reference : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046883/

Good Luck 

https://www.ncbi.nlm.nih.gov/pubmed/12400015

Thank you very much for your help Saleh. Indeed, it could explain why there is a significant difference about ER receptor between BRCA1 mutated and BRCA2 mutated cancer.

The 15th breast cancer conferece on breast cancer held in St Gallen!

https://webcast.oncoletter.ch/

10 sessions... a lot of everything you wish to know and ... now you can actually know!

My best regards

Thank you very much Ricardo, effectively, one conference helped me a lot, not on this particular question, but still helpful.

Romain:

Excellent question!  I will take up here briefly your challenge as to the intersection of ER and BRCA2 mutational status, and offer one line of plausible explanatory power, and the evidence supporting it:

The seminal link comes from the pioneer preclinical work of Jeffrey Holt's team at the University of Colorado Denver which has shown that estradiol (E2) activates BRCA2 function to increase DNA repair responses in ER+ breast cancer cells, and the fact that E2 regulates BRCA2 explains and drives the association of BRCA2 hereditary cancers and ER-positivity (ER+), given that E2 is required for BRCA2 function in breast cells. The critical insight here is that BRCA2 mutations engender hormone-related malignancies secondary to the fact that normal BRCA2 function is itself hormone regulated [Malone 2009].

We have cross-confirmation of this in the clinical setting in Jayeon Kim and Kutluk Oktay's demonstration [Kim & Oktay 2013] of an association between high basal serum E2 levels and BRCA2 mutations in 96 premenopausal women with breast cancer, suggesting that increased serum E2 production plays an important role in the pathogenesis of BRCA2-mutated breast cancer, and that women with BRCA2 mutation had significantly higher E2 levels compared both to those with BRCA1 mutations, as well as  to women without BRCA mutations, which strongly suggests that  higher serum E2 level are associated with the development of breast cancer in BRCA2 mutation carriers, and help account for the widely acknowledged early-onset breast cancer in BRCA2 mutation carriers.

Given these facts, these interactions have been rightly dubbed by Zsuzsanna Suba of the National Institute of Oncology in Hungrary as the "Triangular partnership among estrogens, ERs, and BRCA genes" [Suba 2015]. 

REFERENCES

[Kim & Oktay 2013] Kim J, Oktay K. Baseline E2 Levels Are Higher in BRCA2 Mutation Carriers: A Potential Target for Prevention? Cancer causes & control : CCC 2013; 24(3):421-426.

[Malone 2009] Malone JL, Nelson AC, Lieberman R, Anderson S, Holt JT. Oestrogen-mediated phosphorylation and stabilization of BRCA2 protein in breast. J Pathol. 2009 Feb; 217(3):380-8.

[Suba 2015] Suba Z. DNA stabilization by the upregulation of estrogen signaling in BRCA gene mutation carriers. Drug Des Devel Ther 2015; 9:2663-75.

THank you very much Constantine for this very complete reply. I'm going to read these papers to understand correctly the relation between BRCA2 and ER receptor.