Topic: Bazedoxifene stops breast cancer resistant growth

Sep 2, 2013 06:47PM LCC12345 wrote:

http://petitions.moveon.org/sign/assess-the-efficacy-of?source=c.url&r_by=8507318

Bazedoxifene is approved for the treatment of post-menopausal osteoporosis in Europe.  However, Pfizer currently has no plans to either evaluate this drug in breast cancer treatment or to license it as an osteoporosis treatment in the USA.  If you have a vested interest in seeing that Bazedoxifene is evaluated for use in breast cancer, I encourage you to sign the petition urging Pfizer to move forward to assess the efficacy of Bazedoxifene in treating late stage ER positive breast cancers.

Aug 18, 2014 07:51PM mike3121 wrote:

From what I gather Pfizer has done nothing so far to have this drug BZA investigated. They offer Duavee a combination of BZA (

Bazedoxifene) and another drug, CEE. This Duavee drug increases estrogen! My Stage 4 wife is taking estrogen BLOCKERS. Maybe someone could explain.

Aug 18, 2014 10:43PM - edited Aug 23, 2014 01:44AM by mike3121

From what I gather Pfizer is just going to do nothing about BZA. Faslodex, a SERD (selective estrogen receptor degrader), is the only FDA approved one out their. BZA would be a pill whereas Faslodex is a once a month shot into the muscle (ouch) and doesn't work that well. No pharmaceutical is interested in SERD research. My wife is post-menopause so Tamoxifen won't do for her. What does she do when her aromsen doesn't work any more? I never wanted to believe those conspiracy nut types about "big pharma." Well this whole BZA business with Pfizers proves them right.

WIFE's Cancer:

Aug 19, 2014 08:25AM cp418 wrote:

My impressions are that there is WONDERFUL research done previously and now by some of our best universities and teaching hospitals.  The proof is in all the published journals and articles we read.   My speculation is these potential treatments will NOT go any further than the journals who published them - UNLESS some Pharma or Biotech companies shows interest to fund and pursue clinical trials.  They are in control IMO.  Obviously they decide what drug discovery pipeline they will invest in that will result in the largest pay off to their shareholders.  The bottom line here is big business in control and making a bleep load of money and it doesn't matter how it is made......

Aug 19, 2014 03:17PM cp418 wrote:

LtotheK - thanks to your help writing this petition - we actually got over 7,000 signatures if I recall !!!   I got confirmation of receipt by sending multiple certified mail copies to various higher ups to ensure it wasn't "misplaced".   You said it well - sex is the target market .....

Aug 20, 2014 11:04AM Alpineartist wrote:

My research on Bazedoxifene (BZA) shows that given alone, it has different effects on different tissues. In bone, it acts as an estrogen. In breast, it modulates and even destroys estrogen receptors (like Faslodex), even in cases of Tamoxifen resistance. It targets ER alpha, in particular, and sits on canniboid receptors like CB2, down-regulating mutant cell expression.

Paired with CEE, BZA apparently retains these properties. Thus, as above studies cite, CEE's benefits are retained in some tissues, with risks in others reduced/eliminated.  Promising as this sounds, it strikes me as more of a (less risky) HRT for some BC patients than a preventive agent per se. New studies of CEE/BZA with breast safety as sole end point are needed. In the meantime, I also would like to see BZA approved and would sign and help circulate a petition. 

My research on estrogen therapy for Tamoxifen resistance shows this: long-term estrogen deprivation causes estrogen receptors to lose ability to use estrogen (or feed ER+ mutant cells). Introducing estrogen to this environment causes apoptosis instead of proliferation. In science there are few true paradoxes. Whether estrogen proliferates or kills existing tumors has much to do with timing.I see no current studies on this either, and can only speculate that it's because demonstrating this end point sells no patent-able (profitable) substance. -Same old story. No one to pay for vetting a therapy which could benefit so many, but whose sales would benefit no one entity. Perhaps instead of a petition, we need to pool our pennies in a new paradigm: crowdsourcing. Here's one example.
Peace and health to all.

Aug 22, 2014 04:49PM Octobergirl wrote:

I am interested in finding a European clinic/endocrinologist who will prescribe BZA to patients with osteoporosis and history of breast cancer. My onc has said I may soon be taken off Femara (stage 3) because my osteoporosis has continued to worsen over the 4 yrs. I have taken it. My bones hurt like those of an elderly woman. I would go to Europe for a 2nd opinion and opportunity to try BZA.

Aug 28, 2014 06:22PM - edited Aug 28, 2014 07:12PM by Alpineartist

John, I haven't yet come across info on trials with that end point. If anyone has, I would love to see it also. Meantime, in vitro and in vivo animal studies with this end point are very promising. 
(edited to add):
Though estrogen has been villified by the WHI, if one looks more closely, it is the progestin used in the CEE/MPA arm that caused breast drama. The CEE only arm fared well breast-wise. Older (and in later studies) younger women alike. I reiterate: Conjugated equine estrogens administered alone showed reduced breast risk in these studies. In the SERC BZA/CEE, what little proliferative power CEE has on occult tumors is mitigated and unlike Tamox, eliminated, as target receptors are not only down-regulated but degraded entirely. A fair question: In light of these facts, is it even necessary to lobby or go across the pond for BZA mono?

Do we have the drug we're looking for in our hands at this moment? 

Aug 29, 2014 08:46AM Alpineartist wrote:

Heidi, BZA/CEE is now available on this side of the pond. -FDA approved in October last year and on doctors' shelves earlier in 2014.
And you are right, according to my study, about the missing receptors. Not only would it be of no help in making cancer worse, it could be the silver bullet in finishing it off.
As mentioned in the studies in previous posts (above), it appears that lost receptors are the very mechanism by which estrogen switches its action from proliferative (cancer feeder) to apoptotic (cancer killer). And BZA apparently even kills cancer cells that have become resistant to Tamoxifen and AIs. And remember, it not only shuts them off, it eliminates them, making the estrogen component in the drug itself less likely (or even unable) to stimulate cancer growth. Promising as all this sounds, I sympathize with your desire to see true trials before acting on this.

In the meantime, deep within a previously posted study, I found something most interesting, possibly the reason that CEE showed protective rather than proliferative in these studies. In vitro, CEE was absolutely unable to stimulate xenografts that Estradiol easily stimulated, even in very high doses.

CEE exerted no effects on tumor weight compared with CEE/BZA or vehicle. To potentially explain the lack of CEE stimulation, we postulated that the CEE dose was not sufficient to stimulate tumor growth and repeated the study using 10, 30, and 50 mg/kg CEE rather than 3 mg/kg. Neither the wild-type MCF-7 xenografts (Fig. 5D) nor the hypersensitive LTED (19) xenografts (Fig. 5E) grew in response to 10, 30, or 50 mg/kg CEE. To confirm absorption and deconjugation of these high doses of CEE, we measured uterine weight and found substantial stimulation over vehicle control levels (data not shown). These findings demonstrated an unexpected lack of the ability of CEE to stimulate xenograft growth, even at high doses.

Here, we have CEE not stimulating. Add BZA and certain components of cancerous changes are reduced to far below "normal." -Fascinating. Cancer reduction even in the presence of estrogen!
In the bioidentical camp, CEE has been criticized, mainly because it is derived from horse urine and its molecular makeup is not enough like that of human-made estrogen. But the more I read on this substance (a combination of many estrogens) the more it is confirmed that one should stay clear of camps, and trust only the studies. A cursory "google" will bring up other studies where CEE was much less proliferative to begin with than more human-like estrogen molecules such as E2. It appears the ideal partner in a drug such as this, where the need is to help menopausal-aged women with estrogen loss symptoms while at the same time not raising risk (or even lowering it) in uterine and breast tissues. Perhaps lowering it significantly.

In my opinion, we can watch this drug for trials with cautious optimism, and may be hearing very encouraging things about it. I'm setting a "Google alert" for BZA/CEE breast cancer trials."

Health and peace to all. Have a wonderful Holiday weekend,
Kay

Aug 30, 2014 02:29PM - edited Aug 30, 2014 02:32PM by cp418

Hi - for those who are following up on BZA from the petition we submitted last year. (petition now closed after our submission)  There has been no further contact/update with Pfizer.

https://community.breastcancer.org/forum/73/topic/808467?page=3#post_3771143

https://community.breastcancer.org/forum/73/topic/814241?page=1#post_3772683

Aug 31, 2014 02:03PM AlaskaAngel wrote:

Alpineartist,

Not to confuse the issue, but as a side question (thinking outside the box)...

Would that possibly mean also then that it could work for TN patients (if TN perhaps happens to be a form of estrogen-resistance)?

My apologies for interrupting if my question is off track.

A.A.

Sep 1, 2014 01:42PM AlaskaAngel wrote:

Thanks for feedback, alpineartist. One hesitation I have about it is related to your question. Would one succeed in controlling estrogen receptor bc only to find oneself dealing with ER- disease? I'm not trying to derail any efforts made thus far with so much dedication. I'm just thinking outside the box for anyone who might undersatnd it better than I do.

Oct 2, 2014 06:25PM mike3121 wrote:

See this link. It sounds like something similar to BZA which Pfizer doesn't want to do tests on. Maybe someone else will market a similar medicine.

http://medicalxpress.com/news/2014-10-osteoporosis...

Wife: Stage 4 at dx with mets to spine, Dec 2012. Taxol then A-C. Clean for now but painful neuropathy in hands and wrists.

Oct 2, 2014 11:56PM mike3121 wrote:

A petition was created last year some time and got quit a few participants. I don't have all the details about it though. Their is a separate thread about it. Maybe do a search on this site for the thread. The petition went no where with Pfizer, they ignored it. 

Mike, worried husband of Stage 4 BC wife.

Oct 6, 2014 11:31AM cp418 wrote:

This is the response we received from Pfizer posted in an earlier link.

From Pfizer - Vice President Corporate Affairs - Shreya Jani

"Thank you for taking the time to contact Pfizer. We share your interest and concern in ensuring that our investigational agend bazedoxifene reaches those patients who may benefit. As you may be aware, bazedoxifene is currently used for the treatment of hot flashes associated with menopause and the prevention of post-menopausal osteoporosis.

We are very interested in the results of Dr. McDonnell's per-clinical study of bazedoxifene in breast cancer cells and we are committed to understanding its mechanism of action. At the moment, Pfizer scientists are working closely with Dr. McDonnell and others to better understand the findings from this study and conduct appropriate preclinical experiments needed to help us make decisions on the next steps.  Pfizer is committed to the discovery, investigation and development of innovative treatment options to improve the outlook for cancer patients worldwide.

Again, thank you for reaching out to express your concern on behalf of patients with breast cancer.  I am happy to follow up as we learn more."

She would be your contact person to find out what they are currently doing with BZA.......