Tamoxifen effectiveness in HER+?

[Joanne S]

To see question click on I have a question...From: kcherub I have a question...I have... (http://her2support.org/vbulletin/showthread.php?p=134383#post134383) Yesterday, 03:18 PM
http://her2support.org/vbulletin/showthread.php?p=134383#poststop

1)

My oncologist once told me that:
Tamoxifen used in Estrogen Receptor positive breast cancer patients, is not as effective in HER2 positive patients as it is in Her2 negative patients.

Can someone elaborate?

2)
My oncologist also told me that:
AIs, such as Arimidex, are more effective than Tamoxifen in HER2+ ER+ patients.

I searched to internet, but couldn't find anything at my level or that I could comprehend.

[Joanne S]

Oh I manged to see a current post from Lani that answers the second question for postmenopausal women:

In postmenopausal women with hormone receptor-positive early-stage breast cancer, the use of aromatase inhibitors (AIs) to suppress estrogen is associated with improved clinical outcomes compared with tamoxifen therapy.


Click reference >>>> http://her2support.org/vbulletin/images/statusicon/post_old.gif Lani reference (http://her2support.org/vbulletin/showthread.php?p=134355#post134355) Yesterday, 09:40 AM for Lani's post

or http://her2support.org/vbulletin/showthread.php?t=30082
in the second post titled 'Reference"


Thanks Lani!
Perhaps you have knowledge regarding the first question you could share with us?
Also can you answer kcherub's question as she is 35 and not post-menopausal yet.
Click: From: kcherub I have a question...I have... (http://her2support.org/vbulletin/showthread.php?p=134383#post134383) Yesterday, 03:18 PM

Thanks any information you can share is greatly appreciated.

[saleboat]

There was a recent discussion of the big adjuvent Herceptin trials on breastcancerupdate.com (Volume 6) ...the interview was with Dr. Edith Perez that covers some of this.
http://breastcancerupdate.com/bcu2007/4/perez.asp

If I"m not mistaken, I think she says in one of the interveiws that in terms of effectiveness, there is no difference between AI and Tamox in women who have received adjuvent Herceptin.

Interesting stuff.

Jen

[Joanne S]

Jen, This is so confusing for me. I clicked on the site: http://breastcancerupdate.com/bcu2007/4/perez.asp

http://breastcancerupdate.com/bcu2007/4/images/1_1.gif
I didn't understand the chart so I clicked on Abstract 48: which opened a new window: http://www.abstracts2view.com/sabcs0...u=SABCS06L_406 (http://www.abstracts2view.com/sabcs06/view.php?nu=SABCS06L_406)


[48] Relationship between quantitative ER and PgR expression and HER2 status with recurrence in the ATAC trial.
Dowsett M, Allred DC, on Behalf of the TransATAC Investigators.. Royal Marsden Hospital, London, United Kingdom; Baylor College of Medicine, Houston, TX

Purpose: To determine the relationship between quantitative estrogen receptor (ER) and progesterone receptor (PgR) expression and human epidermal growth factor receptor 2 (HER2) status with disease recurrence, in primary ER+ and/or PgR+ breast cancer patients treated with adjuvant anastrozole (A) or tamoxifen (T) in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial (ISRCTN18233230).

Background: The ATAC trial randomized 9366 patients to 5 years treatment with A or T or the combination. Following analysis of the results of the main ATAC trial at a median follow-up of 33 months, the combination arm was discontinued since it was no more effective than T alone. After a median follow-up of 68 months, it was found that A prolonged disease-free survival significantly compared with T in ER+ and/or PgR+ patients (hazard ratio 0.83; 95% confidence intervals 0.73, 0.94; p=0.005). ER, PgR and HER2 expression have each been reported to influence responses to aromatase inhibitors and T differentially.

Materials and Methods: Retrospective consent to tumor block collection and biomarker analysis was sought from patients with ER+ and/or PgR+ tumors in the A or T arms (total number eligible: 5880). Tissue sections were cut and tissue microarrays (TMAs) were constructed. Immunohistochemical stains for ER (Novocastra 6F11 on TMAs), PgR (Novocastra 312 on sections) and HER2 (DAKO HercepTest on sections) were performed. Scoring systems were ER: H-score; PgR: percentage of positive cells; HER2: staining classification on a scale of 0 to 3+ (positive status 3+ or 2+ if confirmed by FISH). Relationships between biomarker expression and recurrence will be assessed by proportional hazards analysis.

Results: 1792 blocks (30% of total eligible) have been collected and are being tested. All blocks collected by the end of September 2006 will be analyzed. A total of >2000 blocks is anticipated at that time. Acknowledgements: We are grateful to the many investigators and pathologists who have collaborated in this work. Financial support was provided by grants from AstraZeneca and Breakthrough Breast Cancer.
Sunday, December 17, 2006 11:15 AM
General Session 7 (9:00 AM-11:30 AM)

--------------------
Anastrozole and Arimidex are the same thing so I don't think I'm missing the boat???????
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[saleboat]

Found it! This link has a discussion of her2, hormonal therapy and the adjuvent use of Herceptin.


http://www.breastcancerupdate.com/download-audio/bcu/2007/4/BCU407_O'Regan/BCU407_O'Regan_14.mp3 (http://www.breastcancerupdate.com/download-audio/bcu/2007/4/BCU407_O%27Regan/BCU407_O%27Regan_14.mp3)

[Joanne S]

Jen,
Good work! Thanks so much for finding it!
Audio sure beats all the articles I've been reading. This was very, very interesting. I listened to it twice. How in the world did you find it?

If I'm not mistaken the first question was confusing because I though he asked about AC---AC was not mentioned in the doctor's response---so maybe I misunderstood. At the end of the doctor's response I'm wondering if she misspoke and exchanged Trastuzumab (herceptin) when she meant Tamoxifen?

It appears to me that there is nothing about BC diagnosis and treatment that is cut and dry. Per the dr, it is also unknown if quanity of HER2+ and quanity of ER+ and quanity PR+ variables may play a role in which treatment would provide a better clinical response. I think another variable they did not mention was the womens' age/menopausal status as part of the spectrum or variables. Also, I personally would not be a willing candidate for a trial that may only give me Herceptin without any AI or T--that might unnecessary put me at risk for recurrence. Maybe there's no difference between treatments using AI or T in HER+ breast cancers. And possibly all or some HER2+ BCs are resistent to hormone therapy regardless of Aromatase Inhibitor or Tamoxifen. Will we ever know? I'm just grateful that I have had a good clinical response so far. Do you still feel tamoxifen is right choice for you now---(I think so)----that's what is important---you!

Continued well wishes to you!

[saleboat]

The audio was a bit confusing if listened to out of context. They seem to switch subjects between the treatment of early-stage bc and those patients with mets.

My main take-away is that in the adjuvent trials of herceptin, there is no, as yet, clinical difference between those women who also take Tamox and those who take an AI. I can't explain it, although there is a lot of conjecture. It does make sense-- Her2 is a nasty cancer, and really drives the bus-- the er and pr may just be a passenger on the ride, if you know what I mean.

For me, I wasn't really second guessing the decision to take Tamox-- I've already tortured myself about it and concluded, with the help of three different very respected Oncs, that it was the right course of action. For my own layperson read of the situation, I always placed my chips on the Herceptin-- not confident that the hormonal stuff would do much for me. THE MAIN THING-- and this gets lost--- is that Tamox is the ONLY anti-hormonal that is proven to reduce the risk of a new breast cancer. (It may be that AIs do this also, but there isn't data that I know of) So, this fact, plus the fact that I really couldn't take an AI without serious anti-ovary action, (I fear the QOL and long-term health consequences), I remain a happy Tamoxifin pill popper-- and thankfully, I don't have any side-effects from it.

Hope this helps!!!

Jen

[Joanne S]

'Her2 is a nasty cancer, and really drives the bus-- the er and pr may just be a passenger on the ride, if you know what I mean.'

I know what you mean and I love the analogy. Thanks.


Best to you!

[Becky]

Actually, they are not just passengers. The other receptors, it being ER, PR, HER2, HER1, IGFR - whatever you have there, communicate with each other. Every receptor needs another type to "get it on with" (so to speak). This excitation sends signals into the nucleus of the cell via phosphorylation and initiates cell division. Herceptin (or Tamoxifen) stop the receptor to receptor excitation via bonding with that receptor.

The only receptor that will communicate with a "like" receptor is Her2 (that they know of at this time). Her2 will communicate with another Her2. That said, this is the reason if a woman is ER+ but PR neg (or vice versa), but not HER2+, doctors are certain that something else is going on too since the ER likes to communicate with something different than itself to get excited and grow.

So they are not there for the ride. Its that if you cover the ER, HER2 is still left there. If you covered Her2 with Herceptin and did nothing more, ER and PR will run the show together. And most of us probably have other minor moities hanging around too. Secondly, being ER/PR+ is a good thing regardless of Her2 status. Even being ER+ only is better than nothing because something can be done about it and the cancer tends to be slightly lower grade.

[Joanne S]

Thanks for trying to clarify. I get the drift. Huuuh--no wonder scientists and physicians too have the never ending monumental challenge of communicating, comprehending, and finding cures for cancer. Another bus, going somewhere else with a different size engine and hitting chuck holes, road blocks, and obstacles along the way ...

[caya]

Thanks Becky for clarifying all this for us. My onc. did tell me that being ER+/PR+ ( and highly for both) was good, and I knew the Tamox. was good for me, I never really totally understood the entire concept until you laid it out for me.

Your explanations on this issue and others are greatly appreciated by me Becky, and I am sure by many others here.

all the best
Caya