for those who are ER-: tamoxifen (derivative) may work on ER- breast cancer!

[Lani]

1: Cancer Sci. 2007 Dec 19 [Epub ahead of print]
Induction of mitochondria-involved apoptosis in estrogen receptor-negative cells by a novel tamoxifen derivative, ridaifen-B.

Nagahara Y, Shiina I, Nakata K, Sasaki A, Miyamoto T, Ikekita M.
Department of Biotechnology, College of Science and Engineering, Tokyo Denki University, Hatoyama, Hiki-gun, Saitama, 350-0394, Japan.
Tamoxifen is an antagonist of estrogen receptor, which is used widely as an estrogen receptor-positive breast cancer drug that blocks growth signals and provokes apoptosis. However, recent studies have revealed that tamoxifen induces apoptosis even in estrogen receptor-negative cells. In the present study, we synthesized several tamoxifen derivatives to augment the apoptosis-inducing effect of tamoxifen and evaluated the apoptosis-inducing pathway. The estrogen receptor-positive human leukemia cell line HL-60 and estrogen receptor-negative human leukemia cell line Jurkat were treated with tamoxifen and synthesized tamoxifen derivatives, and thereafter subjected to cell viability-detection assays. Tamoxifen derivatives, as well as the lead compound tamoxifen, decreased the cell viability despite the expression of estrogen receptor. Among all of the synthesized tamoxifen derivatives, ridaifen-B had more potent cancer cell-damaging activity than tamoxifen. Ridaifen-B fragmented Jurkat cell DNA and activated caspases, suggesting that the ridaifen-B-induced apoptosis pathway is estrogen receptor independent. Moreover, mitochondrial involvement during ridaifen-B-induced apoptosis was estimated. Ridaifen-B significantly reduced mitochondrial membrane potential, and overexpression of Bcl-2 inhibited ridaifen-B-induced apoptosis. These results suggest that the induction of apoptosis by ridaifen-B, a novel tamoxifen derivative, is dependent on mitochondrial perturbation without estrogen receptor involvement. (Cancer Sci 2008).
PMID: 18167132 [PubMed - as supplied by publisher]

[mts]

Thank you Lani for this post !

But what percent added benefit is there ? I was on Tamoxifen with only being 10% ER+ and PR- and my onc and I decided the side effects were not worth the miniscule added benefit (around 1% reduction in recurrence).
The derivative- Ridaifin-B seems to be a whole new drug since it works without estrogen receptor involvement. Seems like it would work for both negative and positive ER... I will certainly look into this at my next onc appt !

maria

[Lani]

again it is mice vs people and finding the right subgroup of breast cancer patients in whom any one treatment may work (hard if you test it on too many subtypes lumped together)

Some drugs are also found to cause ER- bc to subvert or transform to ER+ bc and then tamoxifen works.

The numbers you and your oncologist used were probably generated from Adjuvant online which does not even include her2, let alone other factors such as ki67

Not to say anything is wrong, it is just that there are new developments which might make treatment protocols change in the future.

When I post things like this, it is because I want those who are newly diagnosed or facing a possible change in treatment to have the information
or at least signs of hope.

I wish I could somehow make these things dissapear for those who tend to
look at new research (which hasn't been proven to be applicable, safe or effective yet) and try to look back on their own diagnosis and treatment decisions wondering if they should have been different.

Some people don't worry about it and just print things out just in case their condition changes someday. When I think the information may truly question a treatment many have had or list new information of a side effect of a drug many may have had I put a yellow yield sign on it.

The main thing is that knowledge of the disease is constantly changing, one can only make decisions based on the best information one has at the time,
and there are no right answers!

Hope this helped!

[Lolly]

Yes, Lani, it does help to have this information; as ER/PR- I took a printout to my onc about the possibility of some ER-'s mutating to +'s and my following biopsy was tested for ER/PR. Unfortunately, still negative, but as my onc said, "If we don't ask the questions we don't get the answers".
Thanks for keeping us informed, and I will still be keeping this possibility in the back of my mind as I do usually have a biopsy when there's progression to a new area.

<3 Lolly