Aromatase Inhibitor and weakly ER+

[DianneS]

Hi ladies,

It seems like I make one decision about drug regimen only to be faced with yet another. ARRGGHH!!!!

How many of you are weakly ER receptive (positive) yet are taking an AI? My onc recommended Arimidex for 5 YEARS.

The risks from reading about this on pubmed seems, to me, to outweigh the benefits.

Increase in head and neck cancers as well as lung cancers is reported with anastrozole (arimidex). A notable increase.

But mainly I'd like to know if any of you ladies are taking an AI such as Arimidex and are weakly ER +. This to me sounds like the AI would only 'get' a small portion of any estrogens floating around and in five years or so I'd be facing yet another type of cancer.
Did anyone decide NOT to take AI's? I'd like to hear your reasons pro and con,

Thank you,
Diannes
6 more Herceptins to go............then maybe 5 yrs of Arimidex. And I thought I was done! Blah.

[Rich66]

Are the issues you are concerned about the same with all the AIs? For example, Aromasin has a slightly different mechanism.

[DianneS]

PubMed talked about: third generation AI's, letrozole, anastrozole & exemestane. The side effects and safety issues are what this article is discussing. This study was done by the Mayo Clinic and submitted in Feb. 2007 so fairly recent.

What can you tell me about Aromasin?

And I would still like to hear from some women who are taking AI's.

[Becky]

Also - what % are you when you say weakly. I am PR neg like you but 50% ER+ so I am moderately.

It is hard to throw out ideas as I think high is 70%+, moderate is 30-70% (or something like this). So I guess you are 30% or less but 30% is different than 5%.

In the "old" days, less than 10% was considered negative but now less than 5% is considered negative.

Let us know and we can play devil's advocate with you and give you some ideas to throw around with your oncologist.

[Rich66]

I just know Exemestane/Aromasin inhibits Aromatase differently than the non-steroidal inhibitors. I wasn't aware of the secondary cancer issues with Arimidex. I guess you have to look at the numbers. If the chance is very low to begin with, a doubling sounds bad but still may be outweighed by much larger possible benefit regarding the primary cancer. If I were you, I would investigate continuation of Herceptin until more agents that are thought to address cancer stem cells (CSCs)are up to speed. Some feel CSCs are ER-, Her2 + regardless of the makeup of their offspring. In an interview with Dr. Wicha, a CSC researcher, as well as a recent study from St. Gallen, a combination HER2/Endocrine blockade might be a prudent choice until a more definitive framework evolves. Have you had the serum her2 test?

[sassy]

Could you provide a link to the Pubmed article?

[NanaKaren]

Dianne,
I am ER weakly 5% and my oncologist still advised me to take an AI. I had so much trouble with all three (bone, muscle pain, etc.) that we finally decided to try Tamoxifen. I have the least side effects with this one, but it still makes me nervous, as it is not as effective as the AI's. She reminded me, that Tamoxifen was the only drug we had for a long time. I vaguely remember earlier posts that some women quit taking the AI's because their quality of life was so terrible.
I think this disease has no rules and can be very sneaky, that we need to do all we can to keep it at bay. Karen

[Debbie L.]

Hi,

I've heard of many issues with AI's but not increased head/neck and lung cancers. Can you send us a link to what you read?

How positive was your ER? Did they provide a number value? Where was this ER done? If not at a Comprehensive Cancer Center:

http://cancercenters.cancer.gov/canc...ers/index.html ,

I'd suggest that you send (or have your lab send) your tissue blocks and slides for a second-opinion on ERPR.

My cancer was said to be weakly ER+ also, at my local facility. Two years later (after 2 years of useless arimidex), I sent the tissue blocks to Baylor and it was found to be totally ERPR negative.

Before delving into your other excellent questions (how effective is an AI for low ER levels?), I'd want to confirm the test itself.

Debbie Laxague

[Rich66]

Interview with Dr. Wicha:
http://jco.ascopubs.org/cgi/content/full/26/17/2795
"It is also likely that treatment of patients with CSC-targeted therapeutics will require new clinical end points for monitoring therapeutic efficacy. This is the case because one is targeting only a small fraction of cells within the tumor, not the bulk of the tumor. In addition, responses may take a much longer time than is typically seen with agents that are cytotoxic to the rapidly dividing cells that constitute the bulk of the tumor. Rational approaches might also include using cytotoxic chemotherapies to target the proliferating bulk of the tumor in addition to a CSC-directed therapy directed at eliminating this critical cell population. An important end point will likely involve assessing changes in the size of the CSC population in response to treatment. One way to do this might be by monitoring the burden of CSCs in the circulation. Of course patient survival remains the ultimate clinical end point, which will involve appropriate clinical trials."




From St. Gallen 2009

http://ex2.excerptamedica.com/ciw-09...tRowDetail=218

Combined ER and HER-targeted therapy in breast cancer treatment

Citation: THE BREAST, Volume 18, Supplement 1, March 2009, Page S8

K. Osborne1, R. Schiff1

1Breast Center, Baylor College of Medicine, Houston, USA

The estrogen receptor (ER) and HER signaling networks are complex, redundant, evolvable and robust pathways, each with several regulatory controls. Several levels of crosstalk between these two networks act as modulatory circuits that when altered can contribute to resistance to therapies targeting them. Nuclear ER when bound by estrogen increases the expression of ligands binding to HER receptors while at the same time reducing the expression of the receptors themselves. At the same time, the HER signaling pathway reduces expression of ER and progesterone receptor (PR) while it can activate ER functionally through phosphorylation of the receptor and its coactivators. Therefore, blockade of ER signaling by endocrine therapy can increase the cellular content of HER1 and HER2, while blockade of HER signaling can increase the expression of ER and PR. Non-nuclear ER can also activate the HER signaling pathway by several mechanisms at the level of the cell membrane. Although there are several potential mechanisms for resistance to ER and HER-targeted therapy, preclinical data from our group and others, as well as supporting data from recent clinical trials, indicate that upregulation at the HER signaling pathway can cause resistance to ER-targeted therapy and that upregulation of ER signaling can cause resistance to HER-targeted therapy.
These data suggest that optimal treatment in some patients using therapies targeting these two pathways might necessitate simultaneous blockade of both pathways. In preclinical models and, now, data from clinical trials, simultaneous use of endocrine therapy to target ER and therapy targeting the HER receptor network can overcome resistance to endocrine therapy and delay the time to tumor progression. Using a combination of HER inhibitors to completely block the HER pathway together with ER blockade is very potent therapy in preclinical xenograft models of ER+/HER2+ tumors and is able to eradicate tumors even after short term therapy. In ER+ tumors that express initially low levels of HER receptors, the addition of HER receptor blockade to endocrine therapy anticipating upregulation of HER receptors during endocrine therapy delays the emergence of resistance and prolongs time to progression. Combined HER-targeted therapy in this situation does not eradicate these xenograft tumors indicating that other survival pathways still function and that these tumors have not yet become “oncogene addicted” to the HER pathway. There is an urgent need to biopsy patients immediately before embarking on targeted therapy to profile the tumor and to select the optimal patient for this new approach.


C. Kent Osborne
Director, Breast Center at Baylor College of Medicine
Director, Baylor Cancer Center
Professor of Medicine and Cellular and Structural Biology
Phone: 713-798-1641
Fax: 713-798-1642
Email: kosborne@breastcenter.tmc.edu
Funding
Publications
Research


More discussion here:
http://her2support.org/vbulletin/showthread.php?t=38998

[harrie]

I have not heard of an increased risk of head, neck and lung cancer from Arimidex.

[SuThorn]

Dianne-

I am also mildly ER+ (only 10%) and PR -. However, my oncologist still felt strongly that I take an AI. So strongly that she recommended an Ooph in order for me to begin taking one. I am currently taking Aromasin and have been NED on it and Herceptin only for a year now.

Regards-

Suzanne

[Barbara2]

I also have not heard an increased risk of head, neck and lung cancer from Arimidex.

In 2002, I was weakly ER + (my report said +1 which was considered low). Later, after taking Arimidex for a couple of years, I asked to have the ER tested. The report showed I was 61% ER which surprised my onc because of the earlier report.

From the beginning, even when we thought the ER could be quite low, he felt it was still beneficial to take the AI. At the 5 year mark, he opted to continue the AI stating that some studies are looking at using the AI for ten years...again, feeling that the benefits were greater than the risks.

[DianneS]

Hi all,

I just found the article I was looking for about head/neck cancer with anastrozole. The article is www.pubmedcentral.nih.gov/articlerender.rcgi?artid=2001222. Look under "Other adverse events" on page 8 of 11.

The article says 'a sprprisingly higher incidence of head and neck cancer with anastrozole compared with tamoxifen (10/3092 vs 3/3094, respectively). Similarly, there was an excess of lung cancer (25/3092 vs 16/3094) and lung cancer deaths with anastrozole; however, further analyses are required to confirm these findings. Of note, a higher incidence of secondary cancer was NOT noted in the IES (72 events exemestane vs. 107 tamoxifen) or in the BIG-1-98 trial (69 letrozole vs 82 tamoxifen)."

This is concerning to me. My onc lied to me yesterday saying 'it does not cause head or neck cancer'. She is flying in the face of what PubMed is saying and I don't think THEY lie! I just called her back and left a message on her answering machine with the article # for her to cogitate.

I don't like being a guinea pig. I already feel like that enough what with Herceptin and wondering if the new 'in' trend of using TCH will work. Yes I am angry and afraid! I am danged if I do and danged if I don't, but from the sound of the pain that AI's cause I think I'd be better off without it.

I like to hike and walk a lot. It's one of my few joys left in life. If I'm hurting too much from AI I can't do that either. Gets down to quality of life.

How many of you are either ER- or a weak positive and just decided NOT to take Tamoxifen or AI's? How many NED years are you?

Thanks, ladies........
Diannes

[Debbie L.]

That link is invalid. Can you try again?

Your onc may not be lying, anymore than I am lying. I have never heard of increased incidence of head/neck nor lung cancer with AI use, and I pay attention. So my denial of this knowledge is not lying (and it could be the same for your onc). You'd think that if this concern were valid, there would be SOME discussion of it among breast oncologists.

I am eager to see this information. If you can't make the link work, try copy/pasting the article into the body of your message, please.

Did you consider another opinion for the pathology on your ERPR values, so you are sure that you are basing your decisions on accurate information?

Warm regards, and empathy for your disenchantment,

Debbie Laxague

[alicem]

Two weeks ago I lost my friend Liz to Breast Cancer.


She was the most vivacious person I had met in a long time. We met during my 2nd chemo infusion in February. Her story . . . She was diagnosed 6 years ago when she was 37, it was early stage. She was ER/PR+, but pre-menopausal, and her onc. prescribed Tamoxifen. She did not like the side effects from it, and because she thought her cancer had all been caught early, she decided to stop taking the Tamoxifen. Within 2 years, her cancer had recurred in her lungs and her bones. She fought valiently, but the cancer eventually won. I will NEVER forget how she second guessed herself with the "what might have been" if she had stayed on Tamoxifen.

I don't know how strongly ER+ she was, and this is Tamoxifen not an AI, and I know she was not Her2+++. In fact the last thing I ever heard from her as she got on the elevator to go contact MD Anderson were the words . . . "You are so lucky to be HER2, I wish I was, at least there is something you can do about your cancer."

I do not know about the head/neck/lung cancer thing. I do see that 10 instead of 3 out of 3094 got the other cancer. But I also interpret that as . . . 3084 out of 3094 did NOT get head/neck cancer. I don't know what the odds are of cancer recurring when you don't take your AI, but I suspect they are higher than getting either head or neck cancer.

I am so very sorry that you have this crappy disease. I am also sad that it interferes with your walking and your quality of life. But, you at least have your life. I just started taking my Arimedex, and am starting to experience the aches and pains associated with it. However, every time I think about not taking my medicine, I think of Liz, and down the hatch it goes. She might just have saved my life.