ER Beta

I hope JellyDonut won't mind, but I thought I would re-post about this article and ER Beta here too.





Wow! Please read this article ladies and gentlemen. Including patient's with triple negative disease.



There are two estrogen receptors: estrogen receptor alpha and estrogen receptor beta. This has been known for about a decade. Currently, in the US, only ER alpha is widely tested for.



80% or more of ER+ breast cancers have estrogen receptor alpha receptors. The flip side of this, is that some percentage of breast cancers lack ER alpha, but have ER beta. It is currently not standard to test for ER beta, and some have questioned if this lack of testing limits effective therapy directed at the ER beta+ tumor. I've been meaning to bring this up, so here is an exciting reference to ER beta, including a Swedish finding that ER beta may be present in triple negative tumors:





" Estrogen receptor beta expression is associated with tamoxifen response in ERalpha-negative breast carcinoma." Citation: Clin Cancer Res. 2007 Apr 1;13(7):1987-94



Requests for reprints: Sofia K. Gruvberger-Saal, Institute for Cancer Genetics, Columbia University, 1130 Saint Nicholas Avenue, Irving Cancer Research Center, Suite 406, New York, NY 10032. Phone: 212-851-5263; Fax: 212-851-5267; E-mail: sg2414@columbia.edu.



Purpose: Endocrine therapies, such as tamoxifen, are commonly given to most patients with estrogen receptor (ER)–positive breast carcinoma but are not indicated for persons with ER-negative cancer. The factors responsible for response to tamoxifen in 5% to 10% of patients with ER-negative tumors are not clear. The aim of the present study was to elucidate the biology and prognostic role of the second ER, ERß, in patients treated with adjuvant tamoxifen.



Experimental Design: We investigated ERß by immunohistochemistry in 353 stage II primary breast tumors from patients treated with 2 years adjuvant tamoxifen, and generated gene expression profiles for a representative subset of 88 tumors.



Results: ERß was associated with increased survival (distant disease-free survival, P = 0.01; overall survival, P = 0.22), and in particular within ER-negative patients (P = 0.003; P = 0.04), but not in the ER-positive subgroup (P = 0.49; P = 0.88). Lack of ERß conferred early relapse (hazard ratio, 14; 95% confidence interval, 1.8-106; P = 0.01) within the ER-negative subgroup even after adjustment for other markers. ER was an independent marker only within the ERß-negative tumors (hazard ratio, 0.44; 95% confidence interval, 0.21-0.89; P = 0.02). An ERß gene expression profile was identified and was markedly different from the ER signature.



Conclusion: Expression of ERß is an independent marker for favorable prognosis after adjuvant tamoxifen treatment in ER-negative breast cancer patients and involves a gene expression program distinct from ER. These results may be highly clinically significant, because in the United States alone, 10,000 women are diagnosed annually with ER-negative/ERß-positive breast carcinoma and may benefit from adjuvant tamoxifen."



So, to me, and I could be off here, if you test ER negative using the current ER alpha test which is done alone, and for example, fall into the triple negative status (ER-/PR-/HER-), or ER-PR-HER+ double negative status, you may still be ER beta positive. Furthermore, this research on ER beta positive tumors is suggesting that an agonist or stimulant of the ER beta site may provide treatment to such a cancer. I'm not sure why this isn't getting more attention in America, but it seems to be gaining some momentum even in our literature (the citation above is a Columbia Univ, NYC researcher).



Back to the article Jelly Donut so wonderfully posted:



This famous Swedish hormone researcher is studying ER beta. It's a long article, and I'm not to sharp today, but it does offer an explanation of why women on aromatase inhibitors may suffer from such body pain: a shutting down of estrogen, which is needed to stimulate both ER alpha and ER beta. The researcher portrays ER beta as a protector against cognitive change, inflammation, etc. And the article mentions the NSAID class of drugs like ibuprofen or naproxen as agonists or stimulants for ER beta perhaps which may be why this aromatase inhibitor induced pain seems to respond to these drugs.



There are so many good points in this article but it is beyond me to go on...



I am wondering Jelly Donut if you would start a new thread in the hormone and perhaps triple negative called ER Beta, and then we all might contribute to discussion there.



Thank you for bringing this forth. 10,000 breast cancer patients who are ER alpha negative, and perhaps not checked for a positive ER Beta state is a lot of potentially treatable patients. Just now though, I see no reference to drug treatments for ER beta tumors, but they surely are being worked on.



Hope this helps some.

Tender

Twink,



I suspect this information might cause a stir similar to the CYP2D6 test and Tamoxifen. But whether one shakes or stirs, a true value to belonging to a discussion forum is information dissemination. Some may say cutting edge information, others may say confusing information.



Just of late I read of the estrogen receptor beta and how triple negative tumors and maybe 10% might test positive for ER beta if they were tested for it. As I understand it, currently only ER alpha is tested for in our ER marker status.



Androgen positive (AR+) or negative marker (AR-) is another tumor marker being looked into , just so you know. In fact Cliff Hudis, as Memorial Sloan Kettering has a clinical trial going for metastasis androgen positive patients, ER/PR negative patients:



A Phase II Study of Bicalutamide for the Treatment of Androgen Receptor-Positive, Estrogen and Progesterone Receptor-Negative Metastatic Breast Cancer[Protocol 07-022]



Full Title :

BICALUTAMIDE FOR THE TREATMENT OF ANDROGEN RECEPTOR POSITIVE((AR+), ESTROGEN RECEPTOR NEGATIVE, PROGESTERONE RECEPTOR NEGATIVE (ER-/PR-)METASTATIC BREAST CANCER PATIENTS: A PHASE II FEASIBILITY STUDY

Purpose :

Most breast cancers are sensitive to changes in the amount of estrogen in the body. Hormonal therapies that block estrogen can stop those types of cancer from growing. Some breast cancers do not respond to these hormonal treatments because they lack the receptors for estrogen and progesterone. Some of these estrogen and progesterone receptor-negative cancers do, however, contain a protein called the androgen receptor, and behave like estrogen-sensitive cancers.



Studies show that blocking the androgen receptor can slow the growth of breast cancer cells that contain this protein. Bicalutamide is a drug that works by blocking the androgen receptor. It is commonly used to treat prostate cancer, but has not been evaluated in patients with hormone receptor-negative, androgen receptor-positive breast cancer.



The purpose of this study is to assess the effectiveness of bicalutamide to treat metastatic breast cancer that contains the androgen receptor but not the receptors for estrogen and progesterone.





I give this to illustrate that hormone knowledge is ever evolving and certainly may lead to insight and help into what is called the triple negative state.



Do call your doctor, and perhaps even email the abstract above written by Sofia K. Gruvberger-Saal at Columbia University. I'll try and spend some time reading about estrogen receptor beta, which Jan-Åke Gustafsson's lab so diligently studying.



If just one woman or man benefits from evolving knowledge, our advocacy mission is achieved. If many do, well, that's an easy way to fall asleep at night when your head hits the pillow.



And our thanks, JellyDonut for your remarkable attention in bringing this news forward.

Tender