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Old 03-11-2011, 08:12 AM   #1
Hopeful
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Study on the Effect of Fulvestrant in triple positive BC

The results showed that while the anti-hormonal suppressed ER, it simultaneously sensitized the cells to growth factor signaling.

http://breast-cancer-research.com/co...df/bcr2848.pdf

"Conclusions

These current findings demonstrate that targeting ER signalling with the pure antioestrogen fulvestrant can both suppress and induce gene and protein expression in ER-positive ErbB2-low and -overexpressing breast cancer cell lines. As expected fulvestrant was a potent growth inhibitor in all four of these ER-positive breast cancer cell lines through its ability to suppress proliferation-related genes such as cyclin D1. However, the simlutaneous induction of ErbB3 and ErbB4 also provided a mechanism for these cells, when in a HRG Beta 1-enriched environment, to promote re-expression of cyclin D1 and ultimately drive resistant cell growth. What is more fulvestrant treatment converted HRG Beta 1 from a ligand with both growth promoting and suppressive activity, depending on cell type, into one that consistently and potently promoted cell growth, regardless of ErbB2 status. Thus, although anti-hormones, such as fulvestrant, may have potent acute grwoth inhibitory activity in ER-positive breast cancer cells their ability to rapidly induce and sensitize cells to growth factors, such as heregulins, may serve to reduce and ultimately limit their inhibitory activity. Indeed, such a rapid induction of these proliferative genes may provide a mechanism of de novo endocrine resistance in situations where heregulin expression in the tumor microenvironment is high."

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Old 03-12-2011, 12:32 AM   #2
Trish
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Re: Study on the Effect of Fulvestrant in triple positive BC

Thanks Hopeful. I think I am getting nervous about taking an anti hormonal with Herceptin and Tykerb which was the next plan.
Trish
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5/2004 (R) 30mm bre gr3 infiltrating ductal ca 16/18nodes er (2+) pr (3+) HER2 (3+)
6/2004
6 cycles(FEC), Oct 40 rads, Tamoxifen
5/2006
oopherectomy, Arimedex
12/2006
liver mets largest 9cm
1/2007
Herceptin,
3/2007
Taxol + Herc
1/2008
Herc alone
4/2008
Multiple bone mets,Zometa
7/2008
Herc + Gemcitabine
8/2008
Herc+Navelbine/vinoralbine
10/2008
Herc+Carboplatin+Taxol
12/2008
Tykerb+Xeloda
2/2010
Herceptin + trial drug
5/2010
Herceptin+Tykerb
8/2010
Tykerb+Abraxane
9/2010
Abraxane
12/2010
Abraxane+Tyk+Herc
4/2011
Tyk+Herc+Femara
6/2011
Liver and bone mets prog.Abraxane continue Herceptin,Tykerb,Femara and Zometa
8/2011
Probable liver progression and increased neuropathy. Xeloda with Tyk+Herc. Zometa 6 weekly.
9/2011
Liver progression,TM +++. Cyclophosphamide and Methotrexate metro Herc Zometa
10/2011 liver mets prog.Herc, 3 Tykerb +2mg decodron daily,Zometa
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Old 03-13-2011, 12:54 AM   #3
michka
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Re: Study on the Effect of Fulvestrant in triple positive BC

I do not understand very well. Could someone explain? Does this mean Fluvestrant (and in the article they quote Tamoxifen) stops working for triple positives after some time or does it mean that taking these anti hormonals may make things worse? Michka
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08.2006 3 cm IDC Stage 2-3, HER2 3+ ER+90% PR 20%
FEC, Taxol+ Herceptin, Mastectomy, Radiation, Herceptin 1 year followed by Tykerb 1 year,Aromasin /Faslodex

12.2010 Mets to liver,Herceptin+Tykerb
03.2011 Liver resection ER+70% PR-
04.2011 Herceptin+Navelbine+750mg Tykerb
06.2011 Liver ned, Met to sternum. Added Zometa 09.2011 Cyberknife for sternum
11.2011 Pet clear. Stop Navelbine, continuing on Hercpetin+Tykerb+Aromasin
02.2012 Mets to lungs, nodes, liver
04.2012 TDM1, Ned in 07.2012
04.2015 Stop TDM1/Kadcyla, still Ned, liver problems
04.2016 Liver mets. Back on Kadcyla
08.2016 Kadcyla stopped working. mets to liver lungs bones
09.2016 Biopsy to liver. no more HER2, still ER+
09.2016 CMF Afinitor/Aromasin/ Xgeva.Met to eye muscle Cyberknife
01.2017 Gemzar/Carboplatin/ Ibrance/Faslodex then Taxotere
02.2017 30 micro mets to brain breathing getting worse and worse
04.2017 Liquid biopsy/CTC indicates HER2 again. Start Herceptin with Halaven
06.2017 all tumors shrunk 60% . more micro mets to brain (1mm mets) no symptoms
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Old 04-01-2011, 08:39 PM   #4
chrislmelb
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Re: Study on the Effect of Fulvestrant in triple positive BC

Fulvestrant is not an AI so there are still options
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Christine

DX Sept 03 age 40 Stage 2B Grade 3 mastectomy (after 2 prior breast conserving surgeries)
"at least" 2.3 cm 3/12 nodes ER+/PR+ Her2+++
8 FEC. Tamoxifen then Arimidex. Ovaries out.
"late" Herceptin for 2 years (18months after chemo) on HERA trial. finished Herceptin Nov 2007.
Multiple bone mets May 2012 and now liver August 2012.
Abraxne, Herceptin and Zometa.
June 2013 Tykerb, Xeloda and Xgeva
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