HER2 Support Group Forums - ER+, HER2+

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I remember there was a discussion about how tamoxifen could interfere with Herceptin. I wondered if the recurrence of PR+ER+Her+ breast cancer has anything to do with it. Because if one can not have Tamoxifen while on Herceptin, then the ER+ part of the cancer may well be flourishing while Herceptin is stopping the Her2+ part.

Both time of my treatment I did not start Tamoxifen until finishing the Herceptin treatment (whether voluntarily or involuntarily). And I am thinking that the reason why the triples may have more problems might be because the medicines (Herceptin and Tamoxifen) can not be used simultaneously.

I have to think Ms. Budin (suddenly just can't think of her first name - Andrea?) must be ER- because she'd had more than 9 years Herceptin.

hi Debbie and everyone--
When a recurrence happens, the pathology isn't necessarily the same as the pathology we receive at the initial diagnosis. My onc and I had quite an interesting discussion about this a couple months ago when we were discussing my decision to go off Herceptin.

For example, I was Her2+++ and ER-/PR- (I don't recall the percentages negative, but that doesn't matter for purposes of this discussion). But suppose that I was 80% negative for each. That means that there were around 20% non-negative ER and PR cells in that primary tumor. So if I ever have mets down the road, the pathology may not necessarily be ER/PR negative. It depends on what cells migrated and then eventually turned into mets--if some of the minority ER/PR+ cells "got away," then the mets could display that pathology. It's also possible that the Her2 status of the mets could be different than the primary tumor.

What I find even more interesting is that the new primary case I had this year was ER+/PR- and since it was stage zero they didn't test for Her2. So I have now had cells with two distinct pathologies.

Not sure if this helps the discussion...probably clouds the issue a bit. The odds are that if someone is really strong ER/PR either way, that it will be that much more likely that the mets will match the primary. And the time to mets varies quite a bit. But the bottom line is that we can guess at the odds all day long, but each case will be different because we can't predict on what side of the odds a specific individual will end up.

That's enough of the geeky stats chat tonight :-) I'll be interested to hear what y'all have to say about this concept...I haven't seen this discussed on this board before (although I will admit my absence has been obvious the past year or so--sorry about that!!)

Val

I am not quite sure I understand this, but I thought I would post it for everyone to see. It seems to me that pathway could change, cell nature could change, everything could change...

J Mol Endocrinol. 2008 Sep 3. [Epub ahead of print</SPAN>
Improvement of Sensitivity to Tamoxifen in ER-Positive and Herceptin-Resistant Breast Cancer Cells.
B Chen, Department of Surgical Research, Beckman Research Institute of City of Hope, Duarte, United States.

Her2 overexpression in ER-positive breast cancer cells such as BT474 (BT) cells has been found to confer resistance to tamoxifen, and suppression of Her2 improves the antiproliferative effects of tamoxifen. In this study, the responsiveness to tamoxifen in BT/HerR, Herceptin-resistant BT cell lines established through constant Herceptin exposure, was evaluated. Compared with BT cells, improvement of sensitivity to tamoxifen in BT/HerR was demonstrated by ER functional analysis and cell proliferation assay. Tamoxifen in the resistant cell line was found to inhibit E2-stimulating estrogen-responsive gene pS2 expression more effectively than in BT cells in real time PCR assay. Western analysis showed cross-phosphorylation between ER and downstream components of Her2 was attenuated in BT/HerR cells. ER redistribution from cytoplasm to nucleus could be found in these cells through immunofluorescence and confocal studies and importantly, chromatin immunoprecipitation (ChIP) studies demonstrated that tamoxifen induced occupancy of the pS2 promoter by ER and nuclear receptor corepressor NCoR instead of coactivator AIB1 in these cells. Finally, combination of tamoxifen and Herceptin was found to improve the sensitivity of BT/HerR cells to Herceptin. Our results suggest that the ER genomic pathway in the ER-positive and Herceptin-resistant breast cancer cells may be reactivated, allowing tamoxifen therapy to be effective again, and a combination of tamoxifen and Herceptin can be a potential therapeutic strategy for ER-positive and Herceptin-resistant human breast cancer.
PMID: 18768663 [PubMed - as supplied by publisher]

Tamoxifen itself is a big issue for Her2+ ER+ bc, in that it has been shown in some studies to be stimulatory for this type of breast cancer. Combining Herceptin with Tamoxifen seems to ameliorate this effect, however, the duration of Herceptin treatment is one year and the duration of tamoxifen treatment is 5 years. THAT, IMO, is an issue.

Hopeful

As you can see by my stats, I was ER+, Her2+, PR+. I was told that invasive lobular BC is rarely Her2+. Proving that BC is not predictable (my thoughts!). My onc. said that "at least for me, having a drug to address the ER+ was a good thing" and in further discussion she meant that ER- has no tool to fight it. And she intends to keep me on Arimidex for more than 5 years. This is a very interesting thread!!!

I just marked 8 years on October 4. Diagnosed at age 41 with Stage 1, Grade 3 IDC. ER+(90%), PR+(80%), Her2+++. I was treated with lumpectomy, 4 A/C, 35 RADS, 3 1/2 years of Tamoxifen, and 3 years of Arimidex after my hysterectomy and oophorectomy in 2004. NO Herceptin for Stage 1 back then and NO Taxol for node negative either. So far, NED.
Recurrence crosses my mind since from what I've heard, most recurrences are within 2 years after completing treatment and, technically, I just completed treatment 11 months ago.
I have had 2 episodes of severe visual disturbances in the last 3 months; of course, everyone knows what the first thing that crossed my mind was; but, my PCP thinks it may just be something called ocular migraine but just to be sure he did order a brain MRI scheduled this Wednesday.
I will watch this discussion with much interest.
Gloria

This is a very interesting discussion and although I can't add to it I just want to thank you ladies who have posted such great info. I'm highly triple positive, I read early on tamox may interfere with herceptin and so had an ooph and began arimidex. So far so good as far as recurrance is concerned, despite the side effects.!
Thanks for great info and a great thread

This is a great discussion because my tumor was ER+(5%), PR+(2%) and HER2+++. I am young (dx age 34 should have been 33, but we won't go there). I have seen a few of you with my similar dx's and I too worry about Tamoxifen/Herceptin. I feel like there are so many opinions and different options that we all have taken, but the end result is we were diagnosed with BC and we all just want some answers about reoccurrence. My onc (and the others on her team) say no scans needed, but I have a very difficult time with this. How can anyone possibly same I am NED if they don't do any scans and see what's in there? I saw what happened with my mother (passed away on 6/17/08 of leptomeningeal brain cancer) and I know I am different because I am "early stage", but it just blows my mind. The only test I am having is a mammo in January on my left breast. Can anyone answer when I am considered NED? Is it immediately after chemo or after my herceptin tx? I haven't started Tamoxifen yet, I have the prescription, but just haven't filled it yet. I am doing the mail order thing, but I just can't send it in. Why??? I know I need to, but I am completely slacking. Thanks for listening.

second path opinion?

Sarah, where did you have your pathology done? Those levels of ERPR are low enough that it's possible they are not accurate. If you have not already done so, I suggest that you get a second pathology opinion from a central lab that does lots of breast cancer - an NCI-designated Comprehensive Cancer Center would be best. I sent my tissue blocks and slides to Baylor after learning that they are known for their accuracy in testing ERPR. But I didn't do that until I was two years into Arimidex, alas. See signature.

A second opinion on pathology is easy to do. I picked up my blocks and slides at the lab and sent them off to Baylor, per the instructions on their website. They evaluate for ERPR with the Allred Score. You could also request that your surgeon or oncologist arrange this for you.

There are statistics on false-negative reports of ERPR in community labs that cite up to a 30% error rate. That's more worrisome of course, than false positive reports, as a treatment opportunity is missed. But false positives are not without issues, either - no one wants to take a medication with potential side effects and no benefit.

Debbie Laxague

And I thought I was the only person that had happened to! I even had my original biopsy redone at Vanderbilt in late 2004 when the pathology showed as being so rare (according to that asco site earlier, only .6% of all cancers) and it came back the same. I had it re-tested (original tumor, not core biopsy) at KU Med and it came back as negative on both, and they retested it twice. Three years of hormonal therapy for nothing.

Get retested :) .

Sorry, probably getting OT. My gut is that triple positives overall will have a slower time to recurrance than her2-/er&pr+, but faster than hormone positive only, but I don't have any data to back that up wtih.

Herceptin/ Positive and Negative Hormone

Dear Friends:

When one first get tested you might be Hormone Receptor Positive, when and if you have a recurrence-after 5, 10, 20 years; your hormone receptors might be Negative.

I was dx in 1994, no Her2 test was available, but we knew I was Hormone Receptor Positive. Almost 91/2 years later I had a recurrence, I now am E,P,HR Negative..

Yes, my cancer- all cancers mutate.

Try not to spend a lot of time thinking about your cancer, be grateful for the now, you all are cancer-free. Enjoy Life.

Your signature indicates that you are Her2+++. I understand that once you test Her2+, your status is unlikely to change. Is it possible I misunderstood your signature?.

Just wanted to help...

Change in status vs. error in assay

Good morning all. We're getting off on two separate tangents - just want to clarify.

I was asking Sarah if she'd had a second opinion on her original pathology. A second look by experienced experts at the same tissue from the primary surgery. That's what I had. It was not that the cancer changed, it was that the first pathology report was wrong.

On the second tangent - yes it's possible (though not typical) for cancer to have changed status when it recurs. Most often, if there are changes, it goes from positive to negative in ER and/or PR and from negative/normal to positive for HER2. There are reports of the other way round (for both) but they are really rare and some people think when that happens, or appears to happen, that it's lab error not true change in that direction.

Debbie Laxague

Hi Debbie,

I know I'm in a VERY low category. But it is true. I had my surgery done in Manchester, NH an incredible surgeon (Dr. Ned Dalton) performed it. The original path came back ER+5% and the PR was neg, HER2+++. My story is complicated a bit, so I'll try and keep it short. My mother in 2004 was dx ER/PR+, Her2+, but did everything in Manchester,NH. In April '07, she was dx with a brain tumor, had a crainiotomy, 2 tx of SRS, and then on 8/10/07, it had turned into Leptomeningeal cancer. After 14 days of WBR, she went home and then in October, it had gone to her spine. She was down between BWH/DFCI and a rehab from 10/23/07 until this past February '08. Her oncologist (who I never mentioned about my "bloody nipple discharge" that I experienced in Nov '07) couldn't believe that I had just been dx'd and my mother was ultimately dying of met breast to the brain. Anyhoo, after getting a 2nd opinion at the DFCI for my surgery, I chose to stick with Dr. Dalton (same person my mother went to) because it was the exact same opinion. Ok, so now I have my mastectomy, in recovery, get my path report, call my mom's onc (Dr. Nancy Lin) and I wasn't about to stay up here to do all my tx's, so I sent all my path slides, reports etc to her. She too was a little perplexed about my results, so she had her top 3 THREE doctors take a look at it. The results (shown below) are pretty accurate in my opinion. Especially because the ER didn't change and the PR did to +. So where the heck does that put me??? In a very low category (she said approximately 8-10% of the women are dx with this low of a ER/PR). Dr. Lin also thought maybe I wasn't HER2+ because of the ER/PR results. Life is just very bizzare and you just don't know where it will take you. I am very optimistic because of the tx I have had, however I'm just looking for some advice on the scans (I saw a previous thread talking about this same subject). We are not a statistic, each of us are INDIVIDUALS. I have a very strong opinion about that one. I certainly don't sit here every day and wonder "will I reoccur", but I do wonder why I can't just get some kind of baseline for "peace of mind". I think for me, I just got done chemo, so I'm in that limbo where do I belong, what happens from here etc, etc. I'm sure ALL of you can relate to my questions and curiosity. Thanks for your support and assistance with this one.

Back to Sarah's real question

First, my condolences on the loss of your mother. Always a hard thing but the timing must have made it especially hard for you, and for her, also.

As to when you are considered NED, for most after a primary diagnosis that is after surgery, unless margins were not clear, etc. NED doesn't say no cancer - it says no evidence of cancer. A subtle but important difference.

Different oncs and different women prefer different styles of follow-up after primary breast cancer. There have been studies done that show no benefit (to survival time nor to quality of life) to finding a metastatic recurrence with scans before symptoms herald that recurrence (and the difference between the two is a few month's time, on average). There are several reasons why this could be true. One is that recurrent disease either does or does not respond to treatment - more about the biology of the cancer than about the extent of the cancer. We know women on this list who have been near death from organ involvement and have had a dramatic response to chemo and gone on to live many quality years. We also know women with small mets that did not respond and that progressed relentlessely though perhaps not rapidly. But the whole "find it small/early" approach is in question both in primary and metastatic cancer, because it's probably more about the biology/response of the cancer and less about the size of the tumor or amount of recurrent disease. The national guidelines (NCCN and ASCO) do not recommend any follow up except a basic history and physical and other routine health mainteneance testing, after a diagnosis of primary breast cancer. Follow up, alas, does not prevent recurrence.

The argument to the above, and there are many experts who would counter with this argument, is that it might be possible to use a milder treatment, especially in the ER+ population, if the recurrence were found before it was widespread. Specifically, a hormonal treatment instead of chemo might be first line, and have less effect on QOL. The argument to that is that even if chemo is needed initially to beat back something symptomatic, then there's still the option to go to the "easier" hormonal treatment once there's response from the chemo. So some oncs and patients favor intensive follow up and some do not. Insurance usually still pays for intensive follow up, despite the guidelines, which is somewhat surprising and imho, subject to change at any moment.

Okay, up until now I think that was a fairly unbiased appraisal of the thinking about follow up after primary breast cancer. What follows is my opinion only.

The "toolbox paradigm" makes sense to me. Once breast cancer is metastatic, there are a certain (limited) number of tools in the toolbox. The goal is to use up the available tools as slowly as possible, and to use the smallest (most gentle) tools first and the big jackhammer tools if desired as a last resort. It is always hoped that more tools will come on the market as time progresses. But the number of tools available is limited both by how many are in the box and by how much hammering a body will tolerate. So there is a distinct advantage to gleaning as much time as possible between tool changes.

As for scans for peace of mind - well, they will tell you that there is no cancer seen, that day. But they do not come with a warranty. There could be cancer to be seen the very next week - who knows? No one. Alas. That is not much reassurance.

After a primary cancer diagnosis, we experience incredible uncertainty. We can try to erase that uncertainty with things like expensive PET scans to (falsely) reassure us, or we can find ways to live with that uncertainty. We can use that uncertainty, and the pain that it causes us, to force us to make decisions about how we want to live. We can choose to live for this moment, savoring this moment, while accepting that we have little control of the future. We can of course hope for continued health. But if we waste our time fretting about what might come, and in futile attempts to achieve some illusion of control over what might come, we are wasting precious moments right now. I'm going to add a quote by MaryAnn Romano at the bottom of this post about that.

And then there's the stewardship issue. Scans are expensive. Many many people in our country lack basic health care services. If we abuse the system by demanding expensive scans that have no evidence of benefit, we are being poor and selfish stewards of limited resources. The technology has outstripped our (society's) ability to pay for the technology, and we cannot continue on this course. Each provider and each patient should feel some responsibility to use resources wisely.

A few caveats. The way the no-scan follow up plan works is if everyone (patients and providers) know what to do when symptoms arise. The rule I've heard most commonly is that if a symptoms lasts two weeks, or if it is extremely severe for any length of time, the patient reports it and the provider's first action is to rule out mets. Some providers will first try to rule out garden variety things - for example, advising rest for back pain. It's the other way round. Symptoms = scans, and then if they are clear, move on to garden variety things.

Every time we have this discussion we seem to get a little muddled with the difference between follow up after primary breast cancer and follow up after a recurrence. There are still some oncs and patients who like the same approach (wait for symptoms) even after a recurrence (although most do brain surveilance for HER2+ cancer). But most keep closer track with both scans and markers (if they are accurate for an individual), once there has been a recurrence.

So once again, the answer is - no single answer. Different answers, depending upon each person. And the right answer for each person can only be decided by that person. Consider the information, and go with what feels right to you - in your heart or gut or wherever that knowing is. Listen to that "still small voice". You'll have to be very quiet to hear that voice. Tell your busy chattering mind to take a break, and just sit and wait for the knowing. It will be the right decision, for you.

Debbie Laxague
Quote, as mentioned above, snipped:
"Serious illness takes you to life’s horizon. Yet, here at the edge is the first step of the beginning of the healing journey. It opens all other healing pathways with the gift of present moment living. That is, the awareness that the now is, in reality, the only reality. You have a choice here as well. Use this moment in wishes or regrets for a time past before illness…or with dread and fear for your future. In either case, you will poison the present and miss your opportunity to live this one moment to its fullest." Mary Ann T. Romano

Hi Debbie,

Just wanted to say I love the quote you include in your signature. That sums it all up in my opinion.

That's all....Just wanted to say that.

Mary Jo

wow, Mary Jo, you made it thru to the end of that?

I was somewhat aghast to see how long my post was when it appeared. I should have just posted the quote (laughing ruefully). Here's the whole thing:

"“Just as disease was present before your awareness, so illness can persist beyond physical recovery. When you learn that you have a serious disease, you want it fixed. You seek treatment for cure – to rid your body of the disease. You also want something more…something not only impossible, but detrimental to healing. You want everything to go back the way it was before illness. You imagine that the way to wholeness is backward, rather than the forward journey you must make.

Serious illness takes you to life’s horizon. Yet, here at the edge is the first step of the beginning of the healing journey. It opens all other healing pathways with the gift of present moment living. That is, the awareness that the now is, in reality, the only reality. You have a choice here as well. Use this moment in wishes or regrets for a time past before illness…or with dread and fear for your future. In either case, you will poison the present and miss your opportunity to live this one moment to its fullest." Mary Ann T. Romano

Thank you Debbie for the information as well as your opinion. I know I will do the right thing if I need to or when the time is right.