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09-17-2009, 06:53 AM
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#1
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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neoadjuvant study shows AI treatment may upregulate her2
Br J Cancer. 2009 Sep 15. [Epub ahead of print]
Nuclear receptor co-activators and HER-2/neu are upregulated in breast cancer patients during neo-adjuvant treatment with aromatase inhibitors.
Flågeng MH, Haugan Moi LL, Dixon JM, Geisler J, Lien EA, Miller WR, Lønning PE, Mellgren G.
[1] Institute of Medicine, University of Bergen, N-5021 Bergen, Norway [2] The Hormone Laboratory, Haukeland University Hospital, N-5021 Bergen, Norway.
Background:Acquired resistance to endocrine therapy in breast cancer is poorly understood. Characterisation of the molecular response to aromatase inhibitors in breast cancer tissue may provide important information regarding development of oestrogen hypersensitivity.Methods:We examined the expression levels of nuclear receptor co-regulators, the orphan nuclear receptor liver receptor homologue-1 and HER-2/neu growth factor receptor using real-time RT-PCR before and after 13-16 weeks of primary medical treatment with the aromatase inhibitors anastrozole or letrozole.Results:mRNA expression of the steroid receptor co-activator 1 (SRC-1) and peroxisome-proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha) was correlated (P=0.002), and both co-activators increased during treatment in the patient group as a whole (P=0.008 and P=0.032, respectively), as well as in the subgroup of patients achieving an objective treatment response (P=0.002 and P=0.006). Although we recorded no significant change in SRC-3/amplified in breast cancer 1 level, the expression correlated positively to the change of SRC-1 (P=0.002). Notably, we recorded an increase in HER-2/neu levels during therapy in the total patient group (18 out of 26; P=0.016), but in particular among responders (15 out of 21; P=0.008).Conclusion:Our results show an upregulation of co-activator mRNA and HER-2/neu during treatment with aromatase inhibitors. These mechanisms may represent an early adaption of the breast cancer cells to oestrogen deprivation in vivo.British Journal of Cancer advance online publication, 15 September 2009; doi:10.1038/sj.bjc.6605324 www.bjcancer.com.
PMID: 19755984
since rate increased among responders, question is if they recurred.
Will check article further
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09-17-2009, 11:27 AM
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#2
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Senior Member
Join Date: Aug 2006
Posts: 3,380
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Re: neoadjuvant study shows AI treatment may upregulate her2
Tamoxifen has been shown to upregulate Her2 also: http://cancerres.aacrjournals.org/cg...tract/68/3/826
Both studies support the logic for simultaneously blocking both the ER and Her2 pathways.
Hopeful
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09-17-2009, 06:36 PM
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#3
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Senior Member
Join Date: May 2008
Location: Hershey, PA. Live The Sweet Life!
Posts: 2,005
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Re: neoadjuvant study shows AI treatment may upregulate her2
The most pertinent question for triple pos. is: should we take A.I.'s without Herceptin? We are to do 4 years without anything blocking the Her-2 while on an estrogen blocker.
__________________
Smile On!
Laurel
Dx'd w/multifocal DCIS/IDS 3/08
7mm invasive component
Partial mast. 5/08
Stage 1b, ER 80%, PR 90%, HER-2 6.9 on FISH
0/5 nodes
4 AC, 4 TH finished 9/08
Herceptin every 3 weeks. Finished 7/09
Tamoxifen 10/08. Switched to Femara 8/09
Bilat SPM w/reconstruction 10/08
Clinical Trial w/Clondronate 12/08
Stopped Clondronate--too hard on my gizzard!
Switched back to Tamoxifen due to tendon pain from Femara
15 Years NED
I think I just might hang around awhile....
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09-17-2009, 09:34 PM
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#4
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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Re: neoadjuvant study shows AI treatment may upregulate her2
update --looked at the original article
many pts were her 2 undetermined, some were her2-, one was her2+
why don't they just go back to the specimens and her2 test??? oh, well
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09-18-2009, 05:01 AM
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#5
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Senior Member
Join Date: Sep 2005
Location: Stockton, NJ
Posts: 4,179
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Re: neoadjuvant study shows AI treatment may upregulate her2
Or, maybe the point is that antihormonals can upregulate Her2 even if the original tumor was not Her2+
__________________
Kind regards
Becky
Found lump via BSE
Diagnosed 8/04 at age 45
1.9cm tumor, ER+PR-, Her2 3+(rt side)
2 micromets to sentinel node
Stage 2A
left 3mm DCIS - low grade ER+PR+Her2 neg
lumpectomies 9/7/04
4DD AC followed by 4 DD taxol
Used Leukine instead of Neulasta
35 rads on right side only
4/05 started Tamoxifen
Started Herceptin 4 months after last Taxol due to
trial results and 2005 ASCO meeting & recommendations
Oophorectomy 8/05
Started Arimidex 9/05
Finished Herceptin (16 months) 9/06
Arimidex Only
Prolia every 6 months for osteopenia
NED 18 years!
Said Christopher Robin to Pooh: "You must remember this: You're braver than you believe and stronger than you seem and smarter than you think"
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09-18-2009, 05:18 AM
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#6
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Senior Member
Join Date: Aug 2006
Posts: 3,380
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Re: neoadjuvant study shows AI treatment may upregulate her2
Becky,
That is definitely the message in the link I posted on tamoxifen resistance. The researchers conclude by suggesting anti-her2 therapy for anyone on a tamoxifen trial in the future.
Hopeful
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09-18-2009, 07:38 PM
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#7
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Senior Member
Join Date: Jan 2009
Location: Colorado Springs, CO
Posts: 430
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Re: neoadjuvant study shows AI treatment may upregulate her2
Could you please explain what the term "upregulate Her2" means?
Thanks!
__________________
9/15/08 (age 52) - Mammo: calcifications
9/22/08 - Biopsy: DCIS, grade 3. ER,PR status: Pos. in 75-90% of tumor cells.
10/01/08 - Ob/Gyn appt.: found complex, mostly cystic mass on right ovary - 11cmx12cmx 8cm
10/15/08 - Hysterectomy & Oophorectomy, Lumpectomy: Cyst on uterus, not ovary - all was benign. Breast - 5 of 6 bad margins. 2 Sentinel Lymph nodes removed, both negative. Stage 0, Tis, N0
12/11/08 - Mastectomy & DIEP reconstruction: Surprise! 2 cm Invasive DC, grade 2 found. One benign internal mammary lymph node. Stage 1, T1c, N0, all clean margins. ER+ (Proportion Score = 2/5, Intensity Score = 2/3) and PR+(Proportion Score = 3/5, Intensity Score = 2/3)
HER2 score = 3+
1/09/09 - Oncotype DX: Recurrence S/core of 60 !?!?! ER status is NEG!! PR staus is NEG! HER2 score = 12.2 (still positive, greater than 11.5 is positive).
1/20/09 - Started chemo: TCH
5/26/09 - FINISHED CHEMO!
1/05/10 - FINISHED HERCEPTIN!
1/22/10 - Port-a-catheter removed!
3/07/18 - Still NED
9/10/23 - Still NED
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09-19-2009, 09:43 PM
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#8
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Senior Member
Join Date: Feb 2006
Location: Southern, CA
Posts: 2,511
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Re: neoadjuvant study shows AI treatment may upregulate her2
Bumping this up for Alice.
Chelee
__________________
DX: 12-20-05 - Stage IIIA, Her2/Neu, 3+++,Er & Pr weakly positive, 5 of 16 pos nodes.
Rt. MRM on 1-3-06 -- No Rads due to compromised lungs.
Chemo started 2-7-06 -- TCH - - Finished 6-12-06
Finished yr of wkly herceptin 3-19-07
3-15-07 Lt side prophylactic simple mastectomy. -- Ooph 4-05-07
9-21-09 PET/CT "Recurrence" to Rt. axllia, Rt. femur, ilium. Possible Sacrum & liver? Now stage IV.
9-28-09 Loading dose of Herceptin & started Zometa
9-29-09 Power Port Placement
10-24-09 Mass 6.4 x 4.7 cm on Rt. femur head.
11-19-09 RT. Femur surgery - Rod placed
12-7-09 Navelbine added to Herceptin/Zometa.
3-23-10 Ten days of rads to RT femur. Completed.
4-05-10 Quit Navelbine--Herceptin/Zometa alone.
5-4-10 Appt. with Dr. Slamon to see what is next? Waiting on FISH results from femur biopsy.
Results to FISH was unsuccessful--this happens less then 2% of the time.
7-7-10 Recurrence to RT axilla again. Back to UCLA for options.
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09-21-2009, 06:39 AM
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#9
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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Re: neoadjuvant study shows AI treatment may upregulate her2
cancer cell growth/survival/effects have been found to be due to various pathways being either upregulated (encouraged, turned up in volume) or supressed. There are various feedback loops involved so turning one pathway up may turn another up as well, and yet another down. In other words, things are interrelated.
Cancer can escape blocking one pathway or route by substituting another route to allow it to grow, spread, etc.
In this study starving the her2+er+ tumor (and in some patients the her2-ER+ tumors) of estrogen by using an AI, just caused the cancer cell to increase its usage (upregulate ) of the alternate pathway, in this case the her2 pathway in order to continue to grow, thrive and spread.
This article brings into question whether alternative and/or additional drugs should be given to prevent this escape before it happens ie, faslodex instead of AIs (which may or may not work) or a HSP90 inhibitor which affects both her2 and ER from what I understand.
Hope this helps
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10-08-2009, 04:56 PM
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#10
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Senior Member
Join Date: May 2007
Location: DFW area (TX)
Posts: 431
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Re: neoadjuvant study shows AI treatment may upregulate her2
Lani,
Do you suggest faslodex because it has a different interaction; or has it been shown or theorized that it does not upregulate Her2?
Thanks
Terri
__________________
Terri, spouse of Ruth, Dallas/Ft. Worth area
Ruth dx 05/01/07 (age 50) Filipino
multifocal, several tumors .5 -2.5 cm, large area
Breast MRI showed 2 enlarged nodes, not palpable
100%ER+, 95%PR+, HER2+++
6x pre-surgery TCH chemo finished 9/15/7 Dramatic tumor shrinkage
1 year Herceptin till 6/08
MRM 10/11/07, SNB: 0/4 nodes + Path: tumors reduced to only a few "scattered cells"
now 50% ER+, PR- ???
Rads finished 1/16/08
Added Tamoxifen,
Finished Herceptin 05/08
NOW is the time to appreciate life to the fullest.
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10-08-2009, 09:19 PM
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#11
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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Re: neoadjuvant study shows AI treatment may upregulate her2
since there seems to be cross talk between the ER and the her 2 receptor using a drug which irreversibly degrades the ER might possibly be more effective than just starving the ER of its ligand (estrogen)
Having no ER to cross talk with the her2 receptor may be more effective at stopping growth than having a "starved" ER talk to the her2 receptor, upregulate its pathway and give the tumor an alternative pathway to escape the ligand starvation of the ER.
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10-08-2009, 11:04 PM
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#12
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Senior Member
Join Date: May 2006
Location: Haarlem, the Netherlands
Posts: 835
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Re: neoadjuvant study shows AI treatment may upregulate her2
Hmm. I'm going to have to decide whether or not to continue on an AI, after 5 years of arimidex. I was Her2 ++ initially. On the other hand, I'm almost 6 years out from diagnosis and doing well. So it probably didn't harm me too much. Oh well, questions, questions.
Jacqueline
__________________
Diagnosed age 44, January 2004, 0.7 cm IDC & DCIS. Stage 1, grade 3, ER/PR pos. HER2 pos. clear margins, no nodes. SNB. 35 rads. On Zoladex and Armidex since Dec. 2004. Stopped Zoladex/Arimidex sept 2009 Still taking mistletoe shots (CAM therapy) Doing fine.
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