|
02-21-2008, 03:30 PM
|
#1
|
Senior Member
Join Date: Aug 2006
Posts: 3,380
|
Another Study on Her2 and Tamox Resistance
http://cancerres.aacrjournals.org/cg...tract/68/3/826
Note the interesting conclusion:
"This study provides a rationale to combine HER inhibitors with tamoxifen in clinical studies, even in tumors that do not initially overexpress EGFR/HER2."
Hopeful
|
|
|
06-25-2008, 07:41 AM
|
#2
|
Senior Member
Join Date: May 2007
Location: DFW area (TX)
Posts: 431
|
Hopeful,
Have you come across any studies that talk about how long Herceptin continues to work with Tamoxifen after the "year" of Herceptin is up?
Or, in other words I guess, how long does Herceptin stay in the body and how long does it keep "working"? Our onc (who really does know her stuff) reassured me that the Tamoxifen Ruth is taking is fine because she had the year of Herceptin and the Herceptin will continue to "do its work". I hink she still plans on switching Ruth at some point, not sure when.
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.
|
|
|
06-25-2008, 08:02 AM
|
#3
|
Senior Member
Join Date: Sep 2005
Location: Stockton, NJ
Posts: 4,179
|
Dear Terri
A couple of things - Herceptin's half life is 25 days meaning in 25 days, half the dose is gone. In another 25 days, another half of what was left is gone (have 25% of the dose left). By six months, there is virtually nothing left (within 4 months just 1/32 of the last dose left).
Secondly, is Ruth really ER+ but PR neg (like me). I ask because I did alot of research and continue to do so on this pathology and it seems that for low/moderate ER+ and PR neg, tamoxifen does not work and can actually stimulate the cancer especially if a Her inhibitor is not present.
Faslodex is supposed to be the best thing but AIs are considered better than Tamoxifen due to no direct associations with cellular surfaces.
You should have a lengthy discussion about hormonals with your onc and a second opinion.
__________________
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"
|
|
|
06-25-2008, 08:05 AM
|
#4
|
Senior Member
Join Date: Sep 2005
Location: Stockton, NJ
Posts: 4,179
|
Secondly, reduction of body weight and more importantly, exercise, down regulates IGF (therefore there is less to bind to that receptor which is mentioned in this article)
__________________
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"
|
|
|
06-26-2008, 06:04 AM
|
#5
|
Senior Member
Join Date: May 2007
Location: DFW area (TX)
Posts: 431
|
Hi Becky,
Do you have full access to this article? Though I know it to be true, I don't see the reference to the exercise down-regulator in the link that Hopeful sent.
While I am truthfully very uncomfortable with the AI issue also, yes, I also have something stuck in my craw about tamoxifen. This onc has been REALLY good, (Dr. Joyce O'Shaugnnesy), she is incredibly well versed and up to date, knows "Dennie" Slamon on a first name basis, and is involved in much research herself. I am having trouble digesting the apparant discrepancy between what she is telling us ( that in essence two years of Tamoxifen is OK for someone that was pre-menopausal and had a year of Herceptin) and what has been stated here. I am at a loss.
Did ask about the PR factor, Dr. O. said it wouldn't change the treatment plan because of the pre-menopausal status pre dx. (obviously and wisely trying to avoid what you went through when you started having periods again) Asked about ooph she said she doesn't believe in messing about with extra surgery. Our GP backed that up. The onc obviously knows that Lupron is an alternative and in her eyes the partial tamoxifen is a better choice.
Did try to get Ruth to get the surgeon's office to retest the original path, Ruth got to some sort of dead end there, don't know if it was her own discomfort with pushing the issue, or what.
I do think the research is somewhat flawed on both sides, between AI studies not having long term results documented, not taking into account the non-metabolizer factor, the Herceptin w/w/o Tamoxifen, etc. we have no clear apples and oranges.
I am frustrated, trying not to stress out completely and trying really hard not to stress Ruth out. It's hard for me to push, as Ruth trusts Dr. O implicitly and that is an important thing. I trust her too, actually, but this one issue has been confusing.
It's a conundrum for me.
__________________
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.
Last edited by TSund; 06-26-2008 at 06:17 AM..
|
|
|
06-26-2008, 03:32 PM
|
#7
|
Senior Member
Join Date: May 2007
Location: DFW area (TX)
Posts: 431
|
slides
Thank-you to both of you. THese slides were highly interesting and yet baffling, he presents the evidence and then says at the end that PR status should not be used at this time to determine endocrine therapy.
I guess due to the conflicting data sets.
These studies seemed to say nothing about the Herceptin Factor; AI + Herceptin vs TAM + Herceptin, and I don't think presented data re: endocrine therapy in the years following 12 month Herceptin.
This is something I'd definitely bring to Ruth's DR at any rate; Thank-you!
__________________
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.
|
|
|
06-27-2008, 07:18 AM
|
#8
|
Senior Member
Join Date: Aug 2006
Posts: 3,380
|
Terri,
The above presentation was from the same conference, but not exactly the one I was looking for. Here is one much more germaine to your question, also by Ken Osborne: http://www.cancerconf.com/media/2008.../WEB/index.htm
The title is "Insights on Resistance to Hormonal Therapy"
Here is the abstract:
There are many potential mechanisms for de novo and acquired resistance to endocrine therapy. Absence of estrogen receptor (ER) in the tumor or loss of ER expression over time results in endocrine therapy resistance, although ER loss occurs in only about 20% of the patients treated with Tamoxifen. Loss of progesterone receptor expression, on the other hand, is common, and might be related to increased signaling from growth factor receptor pathways. Clinical and preclinical studies suggest that overactive growth factor receptor signaling, either due to de novo amplification of Her2 or to increasing levels of epidermal growth factor receptor and Her2 during endocrine therapy, is a potential reistance mechanism. Therapies targeting ER can be enhanced by simultaneous treatment with growth factor receptor inhibitors. In clinical breast cancer, Her2 amplification is known in some patients to confer resistance to Tamoxifen and estrogen deprivation therapies. In the recent TAnDEM trial, in patients with Her2+ positive tumors, the addition of trastuzumab to an aromatase inhibitor resulted in more frequent responses and longer time to progression (TTP) compated to an aromatase inhibitor alone. In a more recent trial in ER+ patients unselected by Her2 expression, gefitinib/tamoxifen yielded modestly superior clinical benefit rates and TTP compared to Tamoxifen alone. Clinical trials also suggest that 12%-35% of tumors will change from Her2- to Her2+ during endocrine therapy. Thus, there are preclinical and clinical data to support the idea that some patients might need a combination of ER and Her targeted therapy for optimal treatment. The key will be to identify this small group of subpatients a priori. (emphasis mine).
I am not a medical professional, and this is MHO, but if tamoxifen can upregulate some Her2- patients to the point they are Her2+, I really think all Her2+ patients should be very cautious about taking Tamoxifen without a corresponding Her2 downregulator.
Hopeful
|
|
|
06-27-2008, 11:09 AM
|
#9
|
Senior Member
Join Date: May 2007
Location: DFW area (TX)
Posts: 431
|
This was a very pertinent presentation. THANK-YOU fo taking the time to send.
So the question remains: is our onc (who has otherwise proved herself extremely solid in her facts and experience) crazy for saying Tamoxifen is OK for a year or two if 12 month Herceptin was given even if it goes past the Herceptin dosing? She says the Herceptin keeps working in the body, but as Becky pointed out above, half life is fairly short.
__________________
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.
Last edited by TSund; 06-27-2008 at 11:23 AM..
|
|
|
06-27-2008, 12:26 PM
|
#10
|
Senior Member
Join Date: Aug 2006
Posts: 3,380
|
Terri,
Truthfully, I don't know how many oncs are following this reasearch, or are even aware it exists; the test, to me, would be what they say when you show them the research. I would be very interested in hearing what Ruth's onc says, if you present the information to her. Please post the results of the meeting, if you can.
Best of luck to you and Ruth,
Hopeful
|
|
|
06-27-2008, 08:35 PM
|
#11
|
Senior Member
Join Date: May 2007
Location: DFW area (TX)
Posts: 431
|
Becky (or Hopeful) please tell me more about faslodex being the best thing...(and why did you not choose to go that route rather than the AI)
Trying to sort out what to do next, I'm in Colorado all July and Ruth's not slated for another onc appt until August. She ended Herceptin about a month ago. Tick, tick, tick. Ugh.
THANKS!
TRS
__________________
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.
|
|
|
06-28-2008, 07:54 AM
|
#12
|
Senior Member
Join Date: Aug 2006
Posts: 3,380
|
Terri,
Fasolodex (Fulvestrant) is used as a second-line treatment for those who fail on an initial AI. My onc did not suggest it, but would have considered my request if I asked for it. I am not thrilled with the method of action, i.e., degradation of the estrogen receptor, as I understand it would degrade the receptors of cells where we want them (i.e., genetalia) in addition to cells where we don't want them (i.e., breast cancer cells). What researchers are finding is that cells which become hypersensitive to estrogen through the estrogen withdrawl that occurs with AI's are capable of being killed by large doses of estrogen once they stop responding to the AI's. I don't see how that would work if your cells no longer had estrogen receptors.
Again, this is all just my personal opinion (and my personal reasons for my preference for an AI) and take on things. I am not a medical professional.
Hopeful
|
|
|
06-28-2008, 09:17 PM
|
#13
|
Senior Member
Join Date: May 2007
Location: DFW area (TX)
Posts: 431
|
I've only recently heard about the large doses of estrogen sometimes killing cancer. (a little before one of the slide shows you sent also mentioned it). Pretty wild stuff considering that estrogen is considered the "evil" so often.
__________________
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.
|
|
|
Posting Rules
|
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts
HTML code is On
|
|
|
All times are GMT -7. The time now is 10:37 PM.
|