Tamoxifen Resistance in Her2+ - what to do?

[wtfsanjo]

Hello ladies -

I am a frequent lurker, and generally spend my time over at Young Survival Coalition, but I'm having a Her2-specific problem, and thought you knowledgeable ladies could help.

I'm one of the few (the proud!) that has ER-/PR+/Her2+ pathology. My PR+ is only 10%, which puts me just above borderline hormone positive.

I have been taking tamoxifen for six months with no problems, but there is a lot of research indicating that tamoxifen has little to no benefit in Her2+ patients. My onc assured me that the herceptin interacts with the tamoxifen to mitigate that resistance, but I only have three doses of herceptin left. So, in about nine weeks I'm going to be taking a hormonal medication that is probably doing nothing.

Today I asked the onc "do you think doing ovarian suppression + arimidex is too aggressive?" and, unfortunately, she said "NO!" very emphatically. She said it might be a good idea due to my very young age and the aggressiveness of my tumor (have you ever even heard of someone with a Ki-67 at 85%?!?! - uggh!)

If I was highly ER+ or PR+ I would be all over OS + arimidex, but I just have a 10% PR+ receptor. The benefit from OS or any hormonal therapy is probably small, but we all know that 1% improved survival is as good as 100% improved survival if it keeps you alive.

So should I go ahead with the OS? I just came out of menopause - is it worth it to go back in? What would you do with such a small PR+ receptor?

PLEASE HELP!

katie

[Cathya]

Katie;

I think you could consider any family history of ovarian cancer along with the odds of your particular type of cancer spreading that way. I understand that lobular cancers tend to spread to the ovaries for instance. Along with the ER-/PR+ situation this is a consideration.... unfortunately and I'm so sorry given your age. I have this vague recollection of a discussion on this site of ER-/PR+ considerations and I'm sure you will hear from those ladies. I agree with you totally though that you must fight this disease very aggressively.....Lani has posts with some very interesting new trials going on that offer great hope for us all. Please keep posting and lurking. God bless.

Cathy

[Cathya]

Katie;

Just a thought.....you might consider using the Serum Her2 test on a regular basis. This might offer you some additional comfort regardless of what treatment you end up with. There's lots of information on the site about it. Here's Becky's explanation:

The Her2 Serum test measures the amount of "external domain" of the Her2 receptor in your blood. The external domain is the part that sticks out of the cancer cell on the outside - the part that Herceptin would latch onto. Theory is that the external domain is routinely shed. It ends up in the blood and can therefore be measured. So, if you have mets growing, the count would go up. However, what it is especially good for is if you have mets and are in treatment, you can get the test run and if the counts aren't going down, it is an indication the treatment is not working so it can cut down on scans just to see if the treatment is working.

If you search under Dr. Carney you will find lots of information. I know for instance that Gina uses it along with other tumor markers to moniter her metatastic disease. If the Serum Her2 is up she takes a loading dose of herceptin to stop any potential tumor build up. It has allowed her to use herceptin effectively for many years as her sole treatment. You are so young and have an aggressive, sneaky disease. It seems to me to offer you a way to monitor and potentially catch any spread very early on.

Cathy

[Becky]

Dear Katie

Did you get a second pathology opinion on your ER and PR status?

If not, you can choose 2 other labs to run this again for you and have 3 opinions on if you really are hormone positive or not. You may not be at all. Also, after that, let's say you are 10% PR, get other medical oncology opinions on being on Tamoxifen or doing something more aggressive. You are very young for an oophorectomy.

[wtfsanjo]

the pathology has been run twice, the second time by stanford university. both times it has come out as ER-/PR+(10%.) i suppose i could run it through UCSF - i will look into that. i know it's a really rare path profile.

and i'm not looking into get an ooph - i'm not BRCA positive and have no family history of ovarian or breast cancer - i would just do lupron shots with arimidex or femara for a few years. it just kind of feels REALLY aggressive to go back into menopause, even temporarily, for such a small receptor. but then again, i am super young, which bodes poorly for my prognosis, so i should probably just suck it up and deal with menopause again. argh - hot flashes!

i will look into getting second opinions on this, though. thanks.

katie

[Lani]

I have read that Ki67 can vary with the phase of the menstrual cycle and since you are so young, it is possible that that was an artificially elevated value ie, that if your surgery was done a few days later it might have been much lower.
Nice thought!

Don't really know what to say about the PR positivity--only what you have already commented on--that from my reading it is rare so probably not much is known about it (BIG HELP, THAT!)

If I find something helpful in the literature, I will pass it on.

[kcherub]

I didn't want to start a new thread on this, but I was wondering anyone out there can shed some light on the "younger women have more aggressive breast cancer" school of thought...

From the first time I read this, I wanted to know "why, and what makes it so?" From what I can find it is very vague, other than to say that we aren't looking for it as much (BSE and mammograms), therefore leading to a later diagnosis. I guess ER+ would play into it, as we have longer to have all that estrogen floating around. I kind of feel it isn't "fair" to put that tag on younger women. Hell, none of this is fair when it comes down to it.

One thing my oncologist said is that we "have longer to recur". I know that I am one of the youngers ones here, and that some of you may not have had reason to look into this. If you have, please send me a PM, as I am always looking to the root of what the standard literature says!

Take care and good night,

[wtfsanjo]

when cancer presents in young women it is not just generally later stage, but more aggressive in general. there are more grade 3, high proliferative, hormone negative, and Her2+ cancers in younger women. and even controlling for all of these variables, many studies show that the risk of death is higher for younger women even when they are matched against older women with the same diagnosis and stage.

there was actually an incredibly depressing study that came out last year showing that the risk of death of dying from your cancer increases by 5% for every year under 40 you are.

as for why this is, there really is no consensus in medical science. it sucks and is extra scary, but there are also lots of women who have breast cancer in their 20s and 30s - even some with many lymph nodes - who make it long enough to get breast cancer again when they're 80. and if i make it long enough to get cancer at 80, i'll be pretty freaking happy.

krista - are you on YSC?

katie

[Lani]

her2 breast cancer recurs earlier, spreads more extensively and has a shorter survival time (in the days before herceptin) and is more often resistant to various chemos and hormonal therapies than breast cancer as a whole.

At a lecture I attended yesterday by Joel Gray, who got this year's Brinker award at SABCS he highlighted what he called luminal/amplified (50% of which are her2+ER+) and basal which included ER-s as the two worst subtypes which skew all the rest of the breast cancer statistics when you examine breast cancer as a whole.

Another thing to think about is whether these subtypes appear more often at earlier ages, skewing the statistics similarly. Just as blacks have a poorer prognosis--partly because of poorer access to early detection and care and partly because they are more likely to have triple negative breast cancer.

These old statistics based on all breast cancer thrown together need to be thrown out with the bathwater to allow in new meaningful statistics based on subtypes of breast cancer so that we may learn the best way to treat each individually instead of giving anthracyclines to 92% of breast cancer patients who, according to Dr. Slamon's talk at SABCS, will gain no benefit from them and only expose themselves to possible health probles from them in order to gain some benefit in the 8% of patients who will benefit. And only by separating out those 8% have they found that their benefit with anthracyclines is no greater than if they were given TCH alone. They 92% and 8% figures and the equivalency of treatment of those 8% were all from Dr. Slamon's talk at SABCS and couldn't have been generated without learning from biomarkers how to differentiate subtypes of breast cancer.

[kcherub]

Katie,

Hey! I do read over at YSC, and have posted there a few times, but I tend to get quicker, more researched answers over here. Plus, HER2+ is what (I believe) is my worry stone with BC, so I need to get all the info about it I can.

Thanks for replying. I get that younger women are more likely to "have" those variables, but aren't those variables just cruddy in general, no matter your age? Wouldn't that also make the variables the bad part, not just the age? Sorry--I do have a real thought here, but I swear I still have some chemo lurking in (my usually very intelligent) brain!

Like for me, I do have the HER2 bugger, but was grade 2, node negative, and ER+. With Herceptin around now, HER2+ is not the "done deal" people used to think of it as. The woman who owns the shop next to mine said that when she first went to a support group and told them she was HER2+, several women went, "Oh. I am sooo sorry." That had to make her feel good, eh?

As for the "matched against older women", and the 5% for every year you are under 40, the "why" is what I want to know. Are we talking 70-year old women whose life span is around 80, and therefore 10 years DFS might not happen due to just age? Sorry again--I am rambling.

I am basically to the point where I think there are two ways it could go--it is either going to come back or it isn't. People keep telling me that I have "such a positive attitude". Well, what else am I going to do?!? I refuse to "live like I am dying" in a negative sense.

Oh--love the picture! Cute do!

Talk to you soon!

[dhealey]

Katie, I was told when I diagnosised that my survival would be less because I was 5 years younger that my mother when she was diagnosised (she was 58, I was 52) my mother fought 8 years ( same type cancer, same stage a diagnosis, only difference I don't know if she was her2 positive as she died in 1997) I try not to go by what I am told. My treatment has been the same as her's only I have been given Herceptin. Since I finished treatment yesterday I am trying really hard not to dwell on how long till it recurrs and just focusing on the act of living. It is surprising to me the number of younger women getting breast cancer. It is almost like an epidemic. I am believe you will be here to dance at your son's wedding! He is a cutie

[kcherub]

Thanks, Debbie! I am guessing you were writing to me--since my son is in my picture!

I try to have the same thinking as you...I tell people that this has all been a pain in the behind! I think that I do better being resentful and irritated at the BC, rather than being terrified of it. Now, that's this week...


Thanks!

[dhealey]

Yes, Krista I was referring to you. If your like me I go week to week. Next week may be a different story, but heck, we are allowed to feel pissed off once in awhile after all we have been through. Your son looks like he is the light of your life. You are very blessed.

[SusanC]

Katie,
I share a similar pathology as you. ER-/PR+ (70%), KI67 -50%, and her2+. I decided yesterday to stop taking tamoxifen for a week or two just to see how I feel. I believe my joint pain, carpol tunnel and weight gain are from tamoxifen. Who knows if it is effective with her2 or progesterone??? Please let us know what you decide to do.
Susan C.

[Cathya]

Ladies;

I am of the belief that with Her2+ bc one must not ever just use herceptin for one year. Because it is not an option for most to continue with early stage, I am a firm believer in using the Serum Her2 test along with other tumor markers on a regular basis to monitor for potential spread. As you ladies are so very young with "borderline" hormone positive disease I think this test would work better for you than for someone like me who is hormone positive....that is I have hormones driving my disease along with the her2 so it can get a little complicated. These blood tests are available and offer us an action plan to monitor our disease. I just heard today about a saliva test for breast cancer. Who knows, perhaps this can be used for the same purpose. My point is only that with herceptin available now, should tumor markers and serum her2 indicate something is happening, you can take herceptin to put a halt to it prior to tumors actually developing. This is the theory in any case.

Cathy

[Amy G]

Katie,

I have the same pathology, her2+++, er-, pr+10%, and didn't know it was rare??!! I haven't heard of Ki-67--but will look into it.

My onc has me on tamoxifen, she says that new studies show that it can give a slight edge with even small amounts of hormone receptors. I'm going for the edge. Although from what I've been reading it probably isn't even working, my side effects are minimal. If your hot flashes were bad, according to this article it may mean it was working...

http://abcnews.go.com/Health/CancerP...=4009620&page=

Amy

[wtfsanjo]

So the CYP2DP test can tell us a lot about if tamoxifen would work for us were it not for the Her2+. The ostensible tamoxifen resistance in Her2+ still applies, even if the CYP2DP test indicates that we are good metabolizers of the drug. We can metabolize it well, but when it reaches the cancer cells, all the Her2 receptors block the tamoxifen from being able to impact the cell.

I wish none of this was even possibly true, because I really don't mind taking the tamoxifen - I feel like I could take it forever. But if i'm going to do hormone therapy, I want it to work, side effects or not.

ARGH! Cancer blows.

katie

[Janelle]

Katie,
I had a normal CYP2DP test result. I don't have terrible symptoms from tamox. Is there another test us Her2 and hormonal positive women should be taking to see if the tamox is working for us? My onc assures me tamox is beneficial despite the Her2 "cross talk" and should still be beneficial when I end herceptin treatments in March.....but I would like more info if you have it. Thank you.

Janelle

[TSund]

Hi would like to keep track of this thread. Ruth is older than most of you but was still pre-menopausal at dx. Currently on tamoxifen and herceptin. From what I've read I would be concerned about tamoxifen w/o the herceptin.

Wishing you all the very best.

TRS

[Joanne S]

RE: Tamoxifen Resistance in Her2+, ER- & PR+

Katie,

We had some similar dicussions about Tamoxifen and HER2, I don't think the answer is clear:
http://her2support.org/vbulletin/showthread.php?t=30103

Since HER2+, ER- & PR+ is more rare, I couldn't find anything specific for you, but I have linked some articles of interest:

Tamoxifen for Patients With Estrogen Receptor–Negative

Breast Cancer (2001)
http://jco.ascopubs.org/cgi/reprint/19/suppl_1/93s

What about Estrogen Receptor Negative Disease?
http://www.abreastinthewest.ca/news2.cfm?Num=61

Quantitative Measurement of Epidermal Growth Factor Receptor Is a Negative Predictive Factor for Tamoxifen Response in Hormone Receptor–Positive Premenopausal Breast Cancer
http://jco.ascopubs.org/cgi/content/abstract/25/21/3007

Compound Boosts Tamoxifen's Cancer-Fighting Power
http://www.medicineonline.com/news/1...ing-Power.html

Optimal Tumor Control in HER2-Positive Tumors Requires Complete Blockade
http://www.cancernetwork.com/tech-fo...leID=204805400

Early Results Suggest Small Benefit of Longer Tamoxifen Therapy
http://www.cancernetwork.com/tech-fo...leID=204805322

Tamoxifen does/doesn't work for HER2-positive?
http://www.breastcancer.org/news_res...uestion_17.jsp

Molecular Changes in Tamoxifen-Resistant Breast
Cancer: Relationship Between Estrogen Receptor,

HER-2, and p38 Mitogen-Activated Protein Kinase
http://jco.ascopubs.org/cgi/reprint/23/11/2469

I hope that some of this information will help you to weigh the benefits and risks to help you find the best decision for you.
Best wellness wishes to you!