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Topic: Did anybody else see this?

Forum: Stage IV/Metastatic Breast Cancer ONLY —

A place for those managing the ups & downs of a Stage IV/metastatic breast cancer diagnosis. Please respect that this forum is for Stage IV members only. There is a separate forum For Family and Caregivers of People with a STAGE IV Diagnosis.

Posted on: Jun 15, 2013 06:02PM - edited Jun 15, 2013 07:18PM by Moderators

sincitydealer wrote:

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

Article Details

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 formatting

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Jun 15, 2013 06:12PM sincitydealer wrote:

This sure sounds like very good news!

Peggy

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Jun 15, 2013 06:19PM steelrose wrote:

Wow, Peggy, it does sound promising! We inch closer and closer to unlocking the doors that will lead to a cure. If we could all just hold on long enough...

Thanks for this hopeful post. I think of you and your mother often!

xo
Rose.

Dx 1/22/2010, IDC, Stage IV, mets, ER+/PR+, HER2-
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Jun 15, 2013 06:21PM kayrnic wrote:

Wow! So encouraging! Tamoxifen is still working for me as far as I know, but I love hearing about new possible treatments for when it does fail! Thanks for sharing!

Kay ---bone mets Dx 11/14/2001, IDC, 2cm, Stage IIA, Grade 2, 0/9 nodes, ER+/PR+, HER2- Dx 3/9/2012, IDC, Stage IV, mets, ER+/PR+, HER2-
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Jun 15, 2013 06:27PM sincitydealer wrote:

The guy from Duke was really excited about this!  Especially since it destroys the estrogen receptors instead of just blocking them!Laughing  It may be too late for my Mom, but it's not too late for many of you.  There is hope!

Thanks for thinking about me, Rose!



Peggy

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Jun 15, 2013 07:01PM - edited Jun 15, 2013 07:09PM by pajim

From this is sounds like they haven't actually tested it in breast cancer patients.  Only cell lines.  I need to read more.  Assume they have tried it in osteoporotic patients in Europe.

Can't get it in the US to try off-label.  Too bad.  Maybe soon.

Edited to say that the FDA apparently rejected it for osteoporosis in the US due to side effects, most notably stoke and blood clots.  doesn't mean it wouldn't suit us.

Dx 4/20/2008, IDC, Right, 4cm, Stage IIIA, Grade 2, 1/15 nodes, ER+/PR+, HER2- Dx 2/1/2013, IDC, Stage IV, metastasized to bone, mets, ER+/PR+, HER2- Hormonal Therapy 2/26/2013 Femara (letrozole) Hormonal Therapy 4/21/2013 Faslodex (fulvestrant) Targeted Therapy 2/24/2016 Ibrance (palbociclib) Chemotherapy 6/18/2017 Xeloda (capecitabine) Targeted Therapy 8/14/2018 Verzenio Chemotherapy 1/1/2019 Halaven (eribulin) Chemotherapy 12/29/2019 CMF
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Jun 15, 2013 07:10PM ibcmets wrote:

Peggy,  Wonderful news.  Thanks.

Terri

6/2009 stage IV diagnosis w bone mets ,Xgeva , 2015 brain mets, liver metastasis
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Jun 15, 2013 08:54PM Anne45 wrote:

Peggy thank you for posting....made my day today!

Dx 7/29/2009, IDC, Stage IV, mets, ER+/PR+, HER2-
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Jun 16, 2013 02:25AM Heidihill wrote:

Thanks, Peggy! Love this news, and the messenger, too!

Dx 8/2007, IDC, Left, 2cm, Stage IV, metastasized to bone, Grade 2, 2/19 nodes, mets, ER+/PR+, HER2- (FISH) Hormonal Therapy 3/25/2015 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Jun 16, 2013 03:04AM chrissyb wrote:

Wow!  That sure is great news Peggy and thanks for posting it.  I wonder how long it will be before it becomes standard of care both in the USA and 
Australia.

I found my peace which gave me strength. 52 at dx. Dx 12/8/2003, IDC, 4cm, Stage IV, Grade 2, 0/12 nodes, mets, ER+/PR+, HER2-
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Jun 16, 2013 04:37AM Angelfalls wrote:

Sounds promising! Thank you for sharing!

Dx 3/2003, IDC, 6cm+, Stage IIIA, Grade 3, ER+/PR+, HER2- Surgery 3/31/2003 Lymph node removal: Right; Mastectomy: Right; Reconstruction (right): Latissimus dorsi flap Chemotherapy 4/29/2003 Cytoxan (cyclophosphamide), Ellence (epirubicin), Fluorouracil (5-fluorouracil, 5-FU, Adrucil), Taxotere (docetaxel) Radiation Therapy 11/14/2003 Hormonal Therapy 1/4/2004 Dx 9/15/2006, 5cm, Stage IV Radiation Therapy 10/31/2006 Surgery 1/30/2007 Prophylactic ovary removal Hormonal Therapy 2/27/2007 Arimidex (anastrozole) Dx 10/5/2011, Stage IV, mets Chemotherapy 1/4/2012 Xeloda (capecitabine) Chemotherapy 3/19/2012 Taxol (paclitaxel) Hormonal Therapy 10/23/2012 Aromasin (exemestane) Targeted Therapy 5/6/2013 Afinitor (everolimus) Hormonal Therapy 1/6/2014 Femara (letrozole) Chemotherapy 1/30/2014 Navelbine (vinorelbine)
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Jun 16, 2013 01:33PM teacher911 wrote:

It is so encouraging to read about some new treatment that sounds very promising.  I just started Tamoxifen and don't know if it is working or not, but it is reassuring to know that there are new drugs on the horizon.  Thanks for sharing

Dx 3/2008, DCIS, 1cm, Stage 0, Grade 2, 0/1 nodes, ER+/PR+, HER2- Dx 9/2012, IDC, 1cm, Stage IV, Grade 2, ER+/PR+, HER2- Chemotherapy 11/16/2012 AC + T (Taxol) Hormonal Therapy 3/15/2013 Femara (letrozole), Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Radiation Therapy 4/17/2013 3DCRT: Breast, Lymph nodes, Bone Targeted Therapy 11/26/2016 Ibrance (palbociclib)
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Jun 16, 2013 02:12PM sincitydealer wrote:

I saw another interview with two doctors about the drug this morning.  In both interviews they kept mentioning how much it was going to help late stage breast cancer patients!!!  They said the trials were going to start soon.  If it works as well as they think it will, it'll definitely be fast tracked with the FDA.  They said it might be around a year before it's approved for breast cancer treatment in the U.S., sooner in England.  Both of these docs were very excited!  If it's as good as they think, it'll most likely be headed your way, too, Chrissy!  This is so cool!

Peggy

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Jun 16, 2013 02:15PM sincitydealer wrote:

Thanks for the edit, Mods.  Sometimes I can be computer challenged.  LOL!!!

Peggy

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Jun 16, 2013 02:30PM RobinNY wrote:

Peggy, thanks for sharing!   Very exciting!

Robin

If what doesn't kill you...makes you stronger ~ I should be able to bench press a Buick. Courtesy of "Fight like a Girl" Dx 10/1999, ILC, 2cm, Stage IIB, Grade 2, 1/5 nodes, ER+/PR+, HER2- Hormonal Therapy 3/8/2010 Femara (letrozole) Dx 4/8/2010, ILC, Stage IV, Grade 2, ER+/PR-, HER2- Hormonal Therapy 7/12/2012 Faslodex (fulvestrant) Chemotherapy 10/1/2012 Xeloda (capecitabine) Chemotherapy 2/18/2013 Navelbine (vinorelbine) Chemotherapy 6/17/2013 Taxol (paclitaxel) Chemotherapy 8/18/2013 Doxil (doxorubicin)
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Jun 16, 2013 02:48PM Heidihill wrote:

According to the European Medicine Agency, Bazedoxifene inhibited oestrogen-induced breast cancer cell proliferation "virtually completely, markedly more than two other SERMs also tested in the study" (one of them was raloxifene).

Dx 8/2007, IDC, Left, 2cm, Stage IV, metastasized to bone, Grade 2, 2/19 nodes, mets, ER+/PR+, HER2- (FISH) Hormonal Therapy 3/25/2015 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Jun 16, 2013 03:02PM blainejennifer wrote:

You know how caged monkeys look pitiful, especially when they reach their little hands out of the cage and make food gestures? That's exactly what I'm doing now, says the lady who failed Tamoxifen and Arimidex.

Has anyone seen any trials? I haven't. Not current ones, with breast cancer in mind.

Jennifer

ER/PR+, HER2-, Grade 3. Stage 4, July 2012. Currently on Gemzar/Carboplatin Dx 5/2006, IDC, 4cm, Stage IIB, Grade 3, 4/12 nodes, ER+/PR+, HER2- Dx 3/2012, IDC, Stage IV, 4/12 nodes, ER+/PR+, HER2- Chemotherapy 6/28/2012 Taxol (paclitaxel) Hormonal Therapy 6/5/2013 Faslodex (fulvestrant) Chemotherapy 7/1/2014 Xeloda (capecitabine) Hormonal Therapy 8/14/2015 Femara (letrozole) Chemotherapy 1/31/2016 Halaven (eribulin) Chemotherapy 8/31/2016 CMF Chemotherapy 11/1/2016 Halaven (eribulin) Chemotherapy Carboplatin (Paraplatin), Gemzar (gemcitabine)
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Jun 16, 2013 03:10PM - edited Jun 16, 2013 03:11PM by Latte

Is there any reason why a dr can't prescribe this anyway to see if it works for your cancer (if you live in a country where it is approved) especially if you have osteoporosis?
Isn't it the same as prescribing metformin, which is only approved for diabetes, but some drs prescribe it for bc patients?

30 Dec 2012: It's back! Stage IV, bone mets to spine, hip, femur, rads, Zometa, Letrozole. May 2013: further spread to ribs, skull, iliac, plus suspicious spots in lung and liver. Clinical trial with taxol and carbo plus velaparib/placebo. Dx 5/3/2010, IDC, 2cm, Stage IIIC, 1/2 nodes, ER+/PR+, HER2- Chemotherapy 6/3/2010 AC + T (Taxol) Surgery 10/27/2010 Lumpectomy: Right; Lymph node removal: Right, Sentinel Radiation Therapy 12/11/2010 Breast, Lymph nodes Surgery 3/15/2011 Prophylactic ovary removal Hormonal Therapy 3/17/2011 Dx 12/30/2012, IDC, Stage IV, mets, ER+/PR-, HER2- Radiation Therapy 3/2/2013 Bone Hormonal Therapy 3/10/2013 Femara (letrozole) Chemotherapy 5/13/2013 Carboplatin (Paraplatin), Taxol (paclitaxel)
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Jun 16, 2013 04:45PM steelrose wrote:

This drug does sound wonderful. Hang tough, blainejennifer and all. It's time we busted these doors wide open!

Dx 1/22/2010, IDC, Stage IV, mets, ER+/PR+, HER2-
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Jun 16, 2013 05:44PM Capriness wrote:

Peggy, this is great news.  I haven't felt this hopeful in years. I don't know why, if we're stage IV anyway, we can't try this drug if we want.  We are consenting adults!  Why would it have to take a year for it to be approved in the US?  That's very frustrating.  I hope they hurry up.

Teri

Teri Dx 7/23/1996, DCIS, 2cm, Stage IIB, 4/9 nodes, ER+/PR+, HER2- Surgery 8/15/1996 Lumpectomy: Right; Lymph node removal: Right, Underarm/Axillary Chemotherapy 9/15/1996 AC Hormonal Therapy 11/26/1996 Surgery 2/15/1997 Mastectomy: Right; Prophylactic mastectomy: Left Surgery 5/15/1997 Reconstruction (left): Free TRAM flap, Nipple reconstruction; Reconstruction (right): Free TRAM flap, Nipple reconstruction Surgery 9/15/2005 Lymph node removal: Right, Underarm/Axillary Radiation Therapy 2/1/2006 Breast, Lymph nodes Chemotherapy 4/15/2006 Fluorouracil (5-fluorouracil, 5-FU, Adrucil), Taxotere (docetaxel) Hormonal Therapy 6/15/2006 Arimidex (anastrozole) Hormonal Therapy 6/15/2006 Aromasin (exemestane) Hormonal Therapy 8/15/2006 Femara (letrozole) Hormonal Therapy 9/15/2006 Hormonal Therapy 7/15/2009 Faslodex (fulvestrant) Dx 8/15/2009, DCIS, 6cm+, Stage IV, mets, ER+/PR+, HER2- Hormonal Therapy 1/15/2013 Aromasin (exemestane) Targeted Therapy 2/7/2013 Afinitor (everolimus)
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Jun 16, 2013 08:02PM sincitydealer wrote:

The Government and the FDA moves like a sloth.Undecided  I think the docs are going to push for this one, though.  Question your Oncs about it.  Take the article in for them to see.  These findings came out at an Endocrinology conference in San Francisco, not a Breast Cancer conference, but hopefully, your Oncs will be aware of it, and the trials that will be starting soon.  Some of you will probably qualify for the trial.   If you guys start pushing maybe it'll get done faster.  Compassionate use should certainly be a possibility!

Peggy 

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Jun 17, 2013 05:14AM Heidihill wrote:

In Europe, bazedoxifene is called Conbriza.

Dx 8/2007, IDC, Left, 2cm, Stage IV, metastasized to bone, Grade 2, 2/19 nodes, mets, ER+/PR+, HER2- (FISH) Hormonal Therapy 3/25/2015 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Jun 18, 2013 07:36PM BabyRuth wrote:

I saw this on Fox news over the weekend. It is such promising news. Really hoping they start a clinical trial soon.

Dx 12/29/2008, IDC, 2cm, Stage IIB, Grade 3, 0/14 nodes, ER+/PR+, HER2+ Targeted Therapy 1/9/2009 Herceptin (trastuzumab) Chemotherapy 3/18/2009 Carboplatin (Paraplatin), Taxotere (docetaxel) Dx 4/23/2012, IDC, Grade 2, ER+/PR+, HER2+ Dx 5/13/2013, IDC, 2/2 nodes, ER+/PR+, HER2+ Chemotherapy 9/11/2013 Taxol (paclitaxel) Dx 6/26/2015, IDC, 1cm, Stage IV, ER+/PR+, HER2+ (FISH) Chemotherapy 7/15/2015 Taxotere (docetaxel) Targeted Therapy 7/15/2015 Herceptin (trastuzumab) Targeted Therapy 7/15/2015 Perjeta (pertuzumab) Hormonal Therapy Faslodex (fulvestrant)
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Jun 19, 2013 01:48AM Skream wrote:

So exciting! Thanks!

      “Faith is the bird that feels the light and sings when the dawn is still dark.” Dx 1/9/2012, IDC, 6cm+, Stage IV, Grade 2, mets, ER+/PR+, HER2-
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Jun 19, 2013 08:45PM Capriness wrote:

I took the article to my doctor yesterday and he said there are similar drugs in the US that are approved for osteoporosis already as well as this one.  He said he will give me a bone scan and look for any little osteo problems so he can prescribe it to me.  I'm excited that I'll get to try it.  It sounded so great.

Teri

Teri Dx 7/23/1996, DCIS, 2cm, Stage IIB, 4/9 nodes, ER+/PR+, HER2- Surgery 8/15/1996 Lumpectomy: Right; Lymph node removal: Right, Underarm/Axillary Chemotherapy 9/15/1996 AC Hormonal Therapy 11/26/1996 Surgery 2/15/1997 Mastectomy: Right; Prophylactic mastectomy: Left Surgery 5/15/1997 Reconstruction (left): Free TRAM flap, Nipple reconstruction; Reconstruction (right): Free TRAM flap, Nipple reconstruction Surgery 9/15/2005 Lymph node removal: Right, Underarm/Axillary Radiation Therapy 2/1/2006 Breast, Lymph nodes Chemotherapy 4/15/2006 Fluorouracil (5-fluorouracil, 5-FU, Adrucil), Taxotere (docetaxel) Hormonal Therapy 6/15/2006 Arimidex (anastrozole) Hormonal Therapy 6/15/2006 Aromasin (exemestane) Hormonal Therapy 8/15/2006 Femara (letrozole) Hormonal Therapy 9/15/2006 Hormonal Therapy 7/15/2009 Faslodex (fulvestrant) Dx 8/15/2009, DCIS, 6cm+, Stage IV, mets, ER+/PR+, HER2- Hormonal Therapy 1/15/2013 Aromasin (exemestane) Targeted Therapy 2/7/2013 Afinitor (everolimus)
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Jun 20, 2013 09:35AM wardells wrote:

Hello All,

First I want to say that I have ultimate respect for your community and that you are the reason I come to work every day.  Secondly, I will very much respect the purpose of your forum, and won't post here again without invitation.

Finally, I am first author on the study that was discussed in the news segment.  I have scanned through all of your comments and questions, and I have a few answers and comments myself.

1) Bazedoxifene (BZA for simplicity) is a selective estrogen receptor modulator (SERM) just like tamoxifen is.  However, a next generation SERM that removes the uterine stimulatory effect of this drug class.  Think of it as a WAY better raloxifene.  Better in that it is a) more potent, b) does NOT cause hot flash, c) far more effective antagonist of estrogen receptor in the breast.  Thus, while raloxifene is effective as a breast cancer preventative only, BZA has the potential to target ER action in breast cancer.  Capriness above, be sure that your Dr understands that raloxifene won't cut ice here and it needs to be BZA.

2) BZA works similarly to Faslodex, but is much more patient friendly (oral), and we expect it will be more effective, because it is much more readily taken up by the body.  I have to emphasize that we have great data in animal studies using predictive models, but BZA has yet to be evaluated FOR BREAST CANCER TREATMENT in humans.  However, in the studies that tested BZA for use in osteoporosis treatment, the Drs did observe decreased incidence (again, like raloxifene).  If you want to go down this road, please understand that distinction - that is the one that will give your Dr pause about prescribing it.

3) BZA is approved for the treatment of post-menopausal osteoporosis in Europe.  For reasons I won't go into here, 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.  That being said, if there is medical justification, the drug might be obtained from Pfizer through compassionate use.  You can address that with your Dr.

Again, keep the faith, and while it may not seem like it, we are working hard every day.  Even better things are coming.

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Jun 20, 2013 01:47PM BaseballFan wrote:

Wardells,
Thank you so much for taking time to read this thread and join the boards. Your last comment, "even better things are coming", give us the "hope to cope" that comes with stage IV. If you have time, we'd love to hear more about the things to come!

Bobbi Dx 3/14/2009, 6cm+, Stage IV, 11/14 nodes, mets, ER+/PR-, HER2- Surgery 7/22/2009 Lumpectomy: Left; Lymph node removal: Left, Sentinel Surgery 9/30/2009 Lumpectomy: Right Chemotherapy 8/31/2010 Xeloda (capecitabine) Chemotherapy 2/12/2012 Xeloda (capecitabine) Chemotherapy 12/11/2012 Taxol (paclitaxel) Targeted Therapy 1/25/2013 Afinitor (everolimus) Chemotherapy 9/30/2013 Carboplatin (Paraplatin), Gemzar (gemcitabine)
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Jun 20, 2013 05:47PM pajim wrote:

Dr. Wardell,  indeed, thank you for taking the time to read and respond.

Would you be willing to tell us a little about why you chose to study this drug as opposed to a different SERM? As it isn't approved in the US. . .  Are there other second generation SERMs coming along the pipeline which could be expected to have the same effects?

Dx 4/20/2008, IDC, Right, 4cm, Stage IIIA, Grade 2, 1/15 nodes, ER+/PR+, HER2- Dx 2/1/2013, IDC, Stage IV, metastasized to bone, mets, ER+/PR+, HER2- Hormonal Therapy 2/26/2013 Femara (letrozole) Hormonal Therapy 4/21/2013 Faslodex (fulvestrant) Targeted Therapy 2/24/2016 Ibrance (palbociclib) Chemotherapy 6/18/2017 Xeloda (capecitabine) Targeted Therapy 8/14/2018 Verzenio Chemotherapy 1/1/2019 Halaven (eribulin) Chemotherapy 12/29/2019 CMF
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Jun 20, 2013 09:14PM - edited Jun 20, 2013 10:00PM by sincitydealer

Wardells, thank you so much for responding to this thread.  The women/men here really need the hope you and your colleagues can provide.  I think most of them would want you to continue to post here with more information, updates, and words of encouragement.

Peggy 

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Jun 21, 2013 07:37AM YamaMama wrote:

I'm following this thread with great interest. My bone mets look very similar on my past 3 scans, but they are causing more symptoms, with back/leg pain particularly bad at night. I would like to think if they are not better on the scans they are at least no worse. But having dealt with met for 4 years, pain has always been an indicator for me.

I'm currently on aromasin and it's been discussed adding affinitor or changing meds at my last few visits.  So far we've decided to stay on the aromasin only.

I read another article about BZA and it stated it is "neutral on the breast and uterus and acts only on the estrogen receptors on the bone".  This same article also stated "Bisphosphonates should be used later on in the treatment in order to avoid atypical fracture and other long-term issues associated with the treatment."

So, based on those statements, here's my question: if started on BZA would the use of a bisphosphonate such as xgeva (I've been on one for a total of 4 years) cause bones more potential for fracture?  And would the bisphosphonate be stopped during use of BZA?  I'm trying to understand the relationship between bisphosphonates and the BZA.

I'm not familiar with Raloxifene, so I will have to read about it.

Here's the link for the article mentioned in my post:

http://www.pharma-share.com/pfizer-attempts-redefine-troubled-serm-market-ecceo-11

 Dr. Wardell, thank you for taking time to join this discussion. It means so much...to so many!

Dx 5/1/2009, IDC, Stage IV, Grade 3, mets, ER+/PR+, HER2-
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Jun 21, 2013 07:58AM wardells wrote:

Thank you, all, for the invitation to your community.  I do not take it lightly.  You have asked good questions, and the answers are interrelated.

To answer the second question first, bazedoxifene (BZA) is unique among SERMs in that it causes the cells to degrade the estrogen receptor, essentially by signaling the cell to put it through the cell's internal garbage disposal.  There are in fact improved estrogen receptor degraders (SERDs) coming along.  The original SERD was faslodex, which works amazingly well on cells in a dish, and reasonably well in cancer models when grown as tumors in mice.  However, the clinical response to faslodex is not nearly so robust and the route of administration (IM injection) leaves much to be desired.  We as a research community once thought that the limited clinical response to faslodex was because after tamoxifen or aromatase inhibitor resistance, targeting the estrogen receptor was no longer useful.  Further studies have shown that it is actually the chemical properties of faslodex that are limiting to its utility - this drug was never designed to be a drug, more like a research tool.  But it was so effective in vitro that we couldn't help but try it in vivo, in the absence of better drugs.  However, about 10 years ago our lab identified and developed another SERD that is just as effective in vitro, could be administered orally, worked great in animal models, and, when Dupont took it into a small investigator initiated trial, worked well even in patients who had progressed during therapies targeting estrogen receptor.  So well, in fact, that when BMS bought Dupont and assumed that a paint company knew nothing about healthcare and closed the trial, the patients' Drs sued to keep them on the trial.  BMS responded by destroying 4 million tablets.

Fast forward a decade, and we have the success and approval of enzolutamide (next gen androgen receptor inhibitor) for advanced prostate cancer.  This proved that there is still clinical benefit in targeting steroid receptors even after initial resistance, and then suddenly the drug companies are interested in making SERDs again.  Aragon (just bought by J&J) has been developing one that is loosely based on the drug that we had developed, and the Phase I trials for that started in February.  Novartis has a similar development program, which has produced a lead compound that will likely be entering tox studies soon.

Despite the progress, it's going to be a bit (1-2 years) before there is good trial data on these drugs, and probably a bit longer for the FDA to approve either/both.  So, we set out at the beginning of our study to take a step back and look at estrogen receptor targeting drugs that had already been developed (albiet for other purposes), had a clinical history, and could potentially provide an interim benefit while the SERDs work their way through the process.  That is how we ended up selecting the compounds that we originally did (BZA, lasofoxifene, and a couple of others) for screening in breast cancer models.  We were actually very pleasantly surprised to find that BZA had such a similar profile to faslodex in vitro, much more so than any of the other clinically relevant SERMs.  Since BZA is readily absorbed by the body and can be administered orally, we took that forward into in vivo models of resistant breast cancer, and ultimately generated the data that was released to the media.  When we started the process, BZA was being developed by Wyeth, which I think did intend to register the drug in the States for osteoporosis treatment.  Wyeth was then purchased by Pfizer, who elected not to, although the FDA has said they can if they so choose.  That is unfortunate in many aspects, as BZA is much improved from raloxifene (Evista) in that it doesn't cause hot flash - it would be nice to have such a therapy for osteoporosis, and we as a research community also think it would have benefit as a breast cancer prevention therapy, much as tamoxifen and raloxifene are given to high risk patients.  I would emphasize that their decision was based on sound reasoning from their perspective, and that NONE of that had to do with the potential usefulness of BZA.  If Pfizer chooses to change their plan, it will be because enough people asked them to.

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