Aug 25, 2013 01:11PM LCC12345 wrote:
Petition urging Pfizer to move forward to assess the efficacy of Bazedoxifene in treating late stage ER positive breast cancers.
Please respect that this forum is for members with stage IV/metastatic breast cancer only. There is a separate forum for caregivers and friends: Caring for Someone with Stage 4 or Mets.
Metastatic breast cancer (MBC; also called stage IV) is breast cancer that has spread to other parts of the body, most commonly the bones, liver, brain, or lungs. Metastatic breast cancer can be treated but not cured. Metastatic disease is NOT hopeless. There are a wide variety of treatment options for metastatic breast cancer, and new medicines are being tested every day. More and more people are living life to the fullest while being treated for metastatic breast cancer.
Note: Please contact your doctor for any specific concerns about symptoms you are experiencing or your course of treatment.
Learn more about living with MBC.
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Last review date: November 22, 2020
Posted on: Jun 15, 2013 07:02PM - edited Jun 15, 2013 08:18PM by Moderators
I just saw an interview with somebody from Duke University on Fox news. He made it sound like this is the Holy Grail for estrogen positive women who've failed on Tamoxifin and Aromatase Inhibitors. I sure hope he's right! This has been approved in Europe and will most likely be approved here. He said it was right under their noses all along, and it's expected to work well on late stage breast cancer. This would be the next step after failure of the anti-hormonals instead of going on to chemo. It completely shuts down the estrogen receptors. Some of you may qualify for the trial.
Osteoporosis Drug Stops Growth of Breast Cancer Cells, Even in Resistant Tumors
About This Article
Published: June 15, 2013
Updated: June 15, 2013
By Duke Medicine News and Communications
DURHAM, N.C. -- A drug approved in Europe to treat osteoporosis has now been shown to stop the growth of breast cancer cells, even in cancers that have become resistant to current targeted therapies, according to a Duke Cancer Institute study.
The findings, presented June 15, 2013, at the annual Endocrine Society meeting in San Francisco, indicate that the drug bazedoxifene packs a powerful one-two punch that not only prevents estrogen from fueling breast cancer cell growth, but also flags the estrogen receptor for destruction.
"We found bazedoxifene binds to the estrogen receptor and interferes with its activity, but the surprising thing we then found was that it also degrades the receptor; it gets rid of it," said senior author Donald McDonnell, PhD, chair of Duke's Department of Pharmacology and Cancer Biology.
In animal and cell culture studies, the drug inhibited growth both in estrogen-dependent breast cancer cells and in cells that had developed resistance to the anti-estrogen tamoxifen and/or to the aromatase inhibitors, two of the most widely used types of drugs to prevent and treat estrogen-dependent breast cancer. Currently, if breast cancer cells develop resistance to these therapies, patients are usually treated with toxic chemotherapy agents that have significant side effects.
Bazedoxifene is a pill that, like tamoxifen, belongs to a class of drugs known as specific estrogen receptor modulators (SERMs). These drugs are distinguished by their ability to behave like estrogen in some tissues, while significantly blocking estrogen action in other tissues. But unlike tamoxifen, bazedoxifene has some of the properties of a newer group of drugs, known as selective estrogen receptor degraders, or SERDs, which can target the estrogen receptor for destruction.
"Because the drug is removing the estrogen receptor as a target by degradation, it is less likely the cancer cell can develop a resistance mechanism because you are removing the target," said lead author Suzanne Wardell, PhD, a research scientist working in McDonnell's lab.
Many investigators had assumed that once breast cancer cells developed resistance to tamoxifen, they would be resistant to all drugs that target the estrogen receptor, McDonnell explained.
"We discovered that the estrogen receptor is still a good target, even after it resistance to tamoxifen has developed," he said.
The investigators tested a variety of breast cancer cell types, including tamoxifen-sensitive cells that are resistant to the drug lapatinib, another targeted therapy that is used to treat patients with advanced breast cancer whose tumors contain the mutant HER2 gene. These cells had previously been shown to reactivate estrogen signaling in order to acquire drug resistance. In this cell type, bazedoxifene also potently inhibited cell growth.
Paradoxically, in bone tissue, bazedoxifene mimics the action of estrogen, helping protect it from destruction. Because bazedoxifene has already undergone safety and efficacy studies as a treatment for osteoporosis, it may be a viable near-term option for patients with advanced breast cancer whose tumors have become resistant to other treatment options, Wardell reported. In clinical trials, the most often reported side effect was hot flashes in the bazedoxifene treatment groups.
The study was funded by a research grant from Pfizer Pharmaceuticals, maker of bazedoxifene.
In addition to Wardell and McDonnell, Erik Nelson and Christina Chao of the Department of Pharmacology and Cancer Biology, Duke University School of Medicine, contributed to the research.
Edited by Mods to tidy up imported formattingLog in to post a reply
Posts 121 - 150 (152 total)
Aug 25, 2013 01:11PM LCC12345 wrote:
Petition urging Pfizer to move forward to assess the efficacy of Bazedoxifene in treating late stage ER positive breast cancers.
Aug 25, 2013 03:40PM Trish03 wrote:
I never clicked on this thread until this afternoon. I loved reading every post. Just signed the petition. Many thanks to all who contributed information. This is very promising.
Sep 7, 2013 08:13AM Linda-n3 wrote:
I asked my MO about BZA. I am currently on letrozole and Afinitor. I am having a holiday from the Afinitor until we figure out if that has caused some pneumonitis, so am on the letrozole only. Had been doing Zometa every other month, I just couldn't face it this month, so asked to wait until next month, so she suggested we do Xgeva instead (I am having BIG second thoughts about changing meds .... trade the devil you know for the devil you don't???). In any case, she said BZA would probably not work for me because she thinks my cancer cells no longer NEED estrogen to live, so altering the receptor won't give me that much benefit. Now I am very puzzled: if that is the case, WHY do letrozole????? This may be the wrong place to ask this question, but it seems that if BZA would work on bone AND estrogen receptors, I could use just ONE drug instead of several, and if it isn't likely to help, then why would the ones I am currently on help????
Sep 7, 2013 08:26AM SyrMom wrote:
I agree with you, Linda, and I want to at least give this medication a try as I just have a good feeling about it (not very scientific, I know).
I called the Pfizer phone numbers provided to us to let them know of my interest and desire to see this medication registered in the U.S. FYI, I got the run around until finally given another phone number to call. That phone number is: 800-438-1985; they took my name and address and that was about it. Hoping Pfizer gets enough pressure to reconsider.
I was switched from Zometa to Xgeva - Xgeva is very easy - one subq injection and you're on your way! No noticeable side effects.
Sep 7, 2013 08:36AM wardells wrote:
If your cancer cells no longer require estrogen, to quote your Dr, then the letrozole is not useful. Sometimes, however, the cells may not require estrogen, but may have found a different way to activate the estrogen receptor (this is actually pretty widely believed in the basic science field of breast cancer research, but we and the oncologists don't always agree...) This is actually why patients often go from letrozole to faslodex. BZA does the same as faslodex, but can be taken by mouth. So, if the cancer is still working through the estrogen receptor, then BZA would absolutely be useful, because it targets the receptor to the cells "garbage disposal" that chews up unwanted proteins. Thus, no estrogen receptor, and therefore no activity from the estrogen receptor. If the cancer is actually working independently of the estrogen receptor (which can happen, if cells reprogram their metabolism processes or gain HER2, etc), then neither letrozole nor BZA will help. And you are interpretting correctly. the BZA would work on both bone and cancer cells. And that is why we are still after Pfizer on this one.
Zometa is a bisphosphonate, while Xgeva is actually an antibody treatment, both are designed to do the same thing (block bone breakdown), but through different angles. both can have the same side effects, but they may be different for you. As my husband the nurse says, the last ingredient to any drug is "you". everyone responds a little bit differently, and it may be that the side effects will not be so bad for you on one drug, but worse on the other. The bottom line is that you do need to protect the bones if you are on letrozole.
Sep 7, 2013 01:51PM SyrMom wrote:
Would this mean, then, if you had progression on Faslodex (never worked at all as far as I'm concerned), then BZA would probably not work either? Initially, I had a good response to femara, for 18 months; progression and on to Faslodex, progression and now on Xeloda!
Sep 7, 2013 03:26PM wardells wrote:
Fasolodex is an interesting drug. It was really designed to be a research tool, and it has horrible bioavailability. that means that it is not well taken up by the body. despite the fact that we administer huge injections, we can really only reach about 30nM in the plasma, and when you consider that we use 10-100 nm in the dish in tissue culture, that tells you that it is barely making it (in some patients) to the point that it would be effective. that means that i am not convinced that patients that do not respond to faslodex are really resistant - their tumors may have just never received enough drug to feel it. BZA can be taken as a pill and is much better absorbed. So, the short answer is, no - i'm not convinced that if a patient doesn't respond to faslodex, they will not respond to BZA. If your mets still have PR expression, then ER is probably still active (since PR expression is controlled by ER), and that means it is worth targeting ER.
Sep 7, 2013 04:30PM BaseballFan wrote:
What if you have switched to ER+ PR- from ER/PR+?
Sep 7, 2013 05:36PM wardells wrote:
It is actually much less common to go from PR- to PR+ than in the reverse. It is much more common to lose PR expression, in part because the chosen therapy is supposed to block ER activity, and since ER controls PR expression, you would logically have less PR. And if tumors progress, it is more common for them to lose PR expression. One cause of a gain of PR status would be (I hate to say this) that the original diagnosis didn't pick up the PR - and that is as much likely to be from how the tumor was biopsied as from a mistake so please don't assume that. What does it mean? it could be a good sign. We regard PR as a marker of ER activity, and if PR is present then the chances of responding to an ER targeted therapy (be it tamoxifen or aromatase inhibitor) are better. If you are referring to your own status, then looking at your treatment history, I don't think that an incorrect PR status at the beginning would have changed the treatment choice.
Sep 7, 2013 06:27PM BaseballFan wrote:
I was originally ER+PR+ and now I'm ER+PR-. Maybe I didn't state my status correctly.
Sep 7, 2013 06:40PM Trish03 wrote:
SyrMom, scroll up to the first post on Aug. 25, and you'll see a link that will lead you to the petition.
Sep 8, 2013 08:30AM - edited Sep 8, 2013 08:31AM by BaseballFan
In 2011 I was participating in a clinical trial at Johns Hopkins. They biopsied some pleural effusions and told me the status had changed.
Sep 8, 2013 07:27PM SPAMgirl wrote:
Has anybody been on this drug? I'm asking my onc about it on Monday. I'm pretty sure she is going to say no.
Sep 9, 2013 08:35PM chanah wrote:
What, no like button?????
Sep 13, 2013 11:58AM Crone wrote:
Thank you Dr. Wardell for your BZA research and subsequent actions in bringing to a public forum knowledge regarding the potential extremely positive efficacy of using BZA in patients with Metastatic Breast Cancer. We take note of your review of several potential stumbling blocks in completing an adequate clinical trial in short order.
So, I, a MBC patient and my physician husband would like to suggest that a possible pathway to a trial would be to use for the treatment arm, those patients in Europe at various university centers and their affiliates who have MBC and osteoporosis and who are currently receiving or about to initiate BZA therapy. The control arm would be a similar group of patients in the United States who have MBC and are receiving similar therapeutic programs though without the BZA component.
We realize that funding a trial is an issue and we hear you when you review the potential reasons for hesitation on Pfizer's part. One suggestion would be that an interested third party might get involved such as Komen or other advocate groups Their financial input into such a project could change several things. First, it could help fast- track such a trial by virtue of its financial input: also it could also quickly change the ratio of research money allotted to MBC vs Early Stage Breast Cancer ( where many of the protocols have already been refined ); in addition it could enhance the reputation of such an advocate group.
Nov 8, 2013 06:05PM HLB wrote:
I just got an email from someone who was sending this petition around at work. Here it is:
Today I received via FedEx a letter from Pfizer - Vice President Corporate Affairs - Shreya Jani
This acknowledgement letter really lifted my spirit that they took notice of our BZA petition.
"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."
Nov 8, 2013 11:03PM Mompsych wrote:
nice to hear that response. I tried calling Pfizer and got the run around. They finally told me that I should go to the NIH trial sites to see if any research was being done.:(
Jul 29, 2014 01:34AM JohnSmith wrote:
I'd be curious to know more about this too!
I assume everyone here has discussed BZA with their oncologist.
The forum mods should change the topic to better reflect the subject. It really needs more attention, imo.
Jul 29, 2014 01:41AM exbrnxgrl wrote:
Don't assume anything! Except for your post and the one before it, this thread has been inactive for a year. I have never discussed BZA with my mo, but welcome any updates.
Jul 29, 2014 11:05AM wardells wrote:
Work is still continuing on building a case for the use of bazedoxifene for breast cancer treatment. The biggest road block is that all of the Pfizer's clinical trial data with this drug was accrued in clinical trials examining BZA in osteoporosis treatment, so not in a population at risk for breast cancer and/or breast cancer progression. That means that the stats currently aren't there to justify asking the FDA to approve bazedoxifene for breast cancer treatment. Therefore, in order to get a breast cancer indication for this drug, Pfizer would be back to square one and financing another big clinical trial to convince the FDA that it is worth approving. We are continuing to generate data to justify exactly that, and we are definitely going to continue our efforts.
Meanwhile, there is an ongoing trial evaluating a drug called ARN 810 (they will come up with a much more fancy name for it when it gets to the clinic), which works by a mechanism similar to BZA. It also is an oral treatment, as opposed to the injectable Faslodex/Fulvestrant. The initial trial results are not yet public; however, Genentech just purchased Seragon (inventor and trial sponsor of ARN 810) for a billion $, and since that drug is pretty much Seragon's only major asset, I'm going to guess that the data (confidentially viewed by Genentech prior to purchasing, of course) must look better than decent. If you think that this drug might benefit you, have a chat with your onc. Info:
This trial actually specifies that patients should be: locally recurrent disease not amenable to resection or radiation therapy with curative intent, or metastatic disease, both progressing after at least 6 months of hormonal therapy for ER+ breast cancer. (So, in essence, advanced stage III/stage IV, after tamoxifen or aromatase inhibitors and fulvestrant, limited to one round of chemo, I think.)
May 20, 2015 11:29AM wardells wrote:
I have exciting news. To introduce myself, I have been associated with the research conducted at Duke evaluating the potential of bazedoxifene in breast cancer treatment since the beginning, and it has been both amazing and humbling to see it evolve. 2 years ago, I started communicating with you courageous ladies on this site, mostly because I wanted to correct misinformation that was being spread after our initial results presented at Endo 2013 were well-publicized. I did not know then when I might ever be able to post the following:
I post this here only for information, not for self promotion. we have conducted follow-up studies, at Pfizer's request, on the potential usefulness of combining bazedoxifene with palbociclib, the venue in which Pfizer chose to develop bazedoxifene for breast cancer treatment. You might recognize palbociclib as being one of the drugs combined with letrozole in the Paloma trials that led to the FDA to fast-track palbociclib for breast cancer treatment. This research was a team effort combining resources here at Duke and also at Washington University in St. Louis. The results are really exciting. While both bazedoxifene and palbociclib alone were very effective in tumor models (studies done in animals) representing breast cancers resistant to tamoxifen or derived from patient tumors that had progressed during multiple endocrine therapies, the combination of these two drugs was really quite powerful. Based upon these results, Pfizer has opened a clinical trial of this combination therapy.
Obviously, there are inclusion/exclusion criteria. Among them are that patients will have progressed during one or more endocrine therapy (ie tamoxifen, faslodex or aromatase inhibitor), and that patients will not have previously taken either bazedoxifene or palbociclib alone.
One of the posters here asked whether the petition had done any good. Without the interest shown to Pfizer with all of your calls, letters, requests for compassionate use, and the petition, I really don't honestly know whether this drug would have gotten this far. You are a very passionate and powerful community, and I would really feel honored if some of the work that we have done can directly benefit any of you.
Best of luck to all.
May 20, 2015 11:36AM MusicLover wrote:
Although I am not a candidate this sounds amazing and I am so thankful that you have updated us with this information! I hope that this will help many, many women.