Topic: Bazedoxifene stops breast cancer resistant growth

May 18, 2015 05:50AM - edited May 18, 2015 06:00AM by Alpineartist

Well, I've finally been able to update on the question of whether estrogen receptor knockout affects er status of new lesions. This study on Tamoxifen suggests that long-term use of the drug in a small cohort showed a higher number of er-negative lesions in opposite breast. This article on the study quotes:

"The conclusion that there is an increase in ER-negative contralateral breast cancer was based on the results obtained on only 20 patients, 17 users of tamoxifen and three nonusers. The hazard ratio based on these numbers was 4.9 (95% CI = 1.4 to 17.4). The small number of events with a corresponding wide CI in a retrospective study does not provide clear evidence that the increased risk of ER-negative contralateral breast cancer is associated with tamoxifen use."

"No biologic data support the hypothesis that tamoxifen promotes ER-negative breast cancer. In fact, a comprehensive review of ER expression in breast cancer (12) concludes that ER expression is a stable phenotype. That is, there is no phenotypic drift, even in metastatic disease, after treatment with tamoxifen. However, there may be a decreased expression of the ER. It is known that breast cancer is heterogeneous and contains both ER-negative and ER-positive cells, which most likely have different origins, as has been recently suggested by gene-profiling studies of breast tumors (13). A more plausible scenario is that, when breast cancer is treated with tamoxifen, the ER-positive cells respond by decreasing proliferation and the ER-negative cells may continue to grow by selective pressure."

Footnote 12 above quotes:
"The concept that in breast cancers ER positivity drifts to ER negativity as a natural process of selection and increasing malignancy can no longer be supported. An alternative hypothesis is that ER is a stable phenotype in human breast cancer and ER positive-cells do not lose anti-oestrogen sensitivity by becoming ER negative."

Will provide more as it comes. Great week, all.

May 20, 2015 08:27AM wardells wrote:

Dear all,

I do not mean to barge in, but 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:

http://clincancerres.aacrjournals.org/cgi/content/abstract/1078-0432.CCR-15-0360.

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.

https://clinicaltrials.gov/ct2/show/NCT02448771?term=bazedoxifene&rank=1

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 08:51AM cp418 wrote:

Dr. Wardells - so glad to hear this update from you that Pfizer recognized treatment potential in Bazedoxifene. I truly hope their clinical trials show promising results to be fast tracked by the FDA. So many patients relapse with hormone resistance issues and are left with no other options. Thanks so much for posting here! All the research by the Duke team is so promising and gives us much needed encouragement. (Saw Duke in the news recently regarding pancreatic cancer research too!!) WOW!!