Recent path report shows Her2 & Er changes...

[Chelee]

As most of you know I had a large mass removed from right femur...and rod placed in femur to prevent fracture.

I just received path report and I am very surprised at the results. My orignal bc dx was stage IIIA, Her2/neu 3+++, Er & Pr weakly positive. (Only 15% Er & 5% Pr)

But now the biopsy sample from femur says Her2/Neu "Negative" (1+). Er positive ("moderate", 60%), & Pr "Negative" (0%). Why would there be such a big difference?

Chelee

[suzan w]

a new cancer??? not related to first?? just a guess. glad the surgery is behind you!! XO Suzan

[Becky]

Dear Chelee

I don't think this is a new cancer at all. Many things may have happened and some have been already discussed on the board.

Firstly, the cancer may have totally mutated but I don't think this is what really happens when there is a pathology change - especially when the patient has had previous chemo or other therapy.

I will explain this using your pathology.

Originally, you were highly Her2+ (confirmed by Dr. Slamon no less) and you were 5% ER+ (PR neg). Let's first focus on the hormone status.

What 5% ER+ really means is that when a pathologist first tested your tumor for hormone status they observed that only 5% of the cells of the entire tumor were ER+ and the remaining 95% of cells were ER neg. Since you were also highly Her2+ this means that (in general) 5% of the cells were ER+/Her2+ and 95% of the cells were just Her2+ (all this is generally speaking).

So you took your TCH chemo and the year of Herceptin. I am sure, as Dr. Slamon even said, that the Herceptin did a great job - especially on the ERneg/Her2+ cell line but it probably did not do the whole job on the ER+ line. Therefore, when you recurred, what was left was the cells that were ER+ and therefore, they proliferated and that tumor is now 60% ER+.

Now, thinking out loud again, you are barely Her2+. Is that TRULY correct? I am sure by this pathology report it is but remember, you began Herceptin treatment prior to this surgery so this is not a pathology of what was there prior to the Herceptin/Zometa treatment either. Perhaps the original mets were more Her2+ than this is showing (perhaps).

The main point - and I have said this repeatedly before, is that if one has bc mets to the bones, even if the original cancer was NOT ER+ or was weakly ER+, one must suspect that the bone mets are more highly ER+ as ER+ bc (if metted) likes the bones. That is why I advise biopsy if possible and if not possible, assume that the bone mets are ER+ and take an antihormonal (Tamoxifen, an AI or Faslodex) and try it for 3-6 months and see if it starts helping. If it doesn't, it doesn't.

You are in a quandry as you now might not be able to continue Herceptin although you should. You also have more ammo to start Faslodex immediately as you are now more hormone positive.

We must remember that our cancers are a mosaic and that our treatments may do well on some cell lines and not others. That is why I am a huge advocate that even if one is weakly hormone positive, you should take an antihormonal at least while on Herceptin therapy (wipe out 2-3 receptors at one time) and if high positive, continue on the antihormonal for the obligatory 5 years.

It is good that the cancer became more hormone positive. I think you need to continue with Herceptin even though you are only 1+ as this change may have occurred with your recent two Herceptin treatments.

Sorry this is sooooo long.

[Lani]

It is called selection and is the equivalent of evolution on a cellular scale

When you received treatment for your initial cancer it (hopefully) killed cells
susceptible to the treatment, but selected out those cells capable of changing their genetics / metabolic pathways to survive the onslaught.

As I understand it,it is much more common for ER+ tumors to increase their her2 pathway to survive antihormonals, but some tumors decrease their her2 (or select out those cells which don't have her2 amplified) to survive the onslaught of herceptin. Your original tumor was probably heterogeneous with areas with cells with different characteristics, some triple positive, some triple negative, some ER+PR+her2-, same ER+PR-her2- etc. What treatment you received influenced which subset was to win the "survival of the fittest contest"


In addition it is possible that you had preexisting micrometastases in your bone marrow at the time of diagnosis and treatment which were dormant and had characteristics much more commonly ascribed to cancer stem cells which then survived the treatment (which works on actively replicating cells)
who subsequently "awoke from their sleep" , started to multiply and differentiate

As I have previously described, tumors are like puppies who want to go out of the house and chase the squirrel...if you close the front door, they try to get out of the backdoor...as they get older and more experienced and grow taller(ie, after chemo, radiation and other treatments) they learn to jump on
top of the dresser and jump out of the window!

Dr. Stephanie Jeffreys at Stanford has a new way to examine Circulating tumor cells and has found CTCs in stage IV patients to be very heterogeneous with even triple negative CTCs in stage IV patients treated
with herceptin.

To look on the bright side, at least they were not triple negative, so there are still targets to attack!

Also, wait and see if they FISH test the biopsy as some IHC tests differ from FISH results. Maybe you should ask Dr. Slamon if you should ask the pathologists to see if they looked at several areas of the biopsy, as there may be some areas that are her2+ whereas others are her2-.Just a thought

Hope some of this helps!

[Rich66]

Chelee, The good news is that your original biopsy should allow you to continue Herceptin. The sliding scale between ER and Her2 is fairly established and suggests dual blockade. Sounds like the fact that it's bone mets explains the difference too. I wish we were all chasing puppies.

[Joan M]

Chelee,

I had the same result with my brain met. It was HER2-.

My onc said there's roughly a 15% chance that the met and primary don't match.

And Becky and Lani, thanks for the explanations.

Joan

[StephN]

This is another good thing from the surgery. Most patients are not able to get a bone met biopsy. So the treatment crap shoot continues.

Well, that path report is not a HIGHLY unusual development. I know of other people who had that happen - HER2 not at the original diagnosis, HER2 with mets to nodes and skin, then non-HER2 when a new node was biopsied.

It seems like a person can have BOTH kinds of tumors as mets. As the above posts indicate - heterogeneous cells at the outset and only the main ones were treated.

So, regarding your NODES. If you could get a biopsy of one of those a different path might show up.

Getting on Faslodex right away should not be a problem while you heal from the surgery. Ask them. Get that hormone door slammed shut.

[ElaineM]

I think it is quite possible for a reoccurance or a metastisis can result a different kind of pathology report than the original cancer did.
The cancer has been affected or changed by treatments, so it might not be exactly the same as it was in the beginning if it reoccures or travels to another part of the body.
Take care.

[bejuce]

Hi Chelee,

I'm sorry you're going through this. I don't have much to add to the above except to say that I too am cheering for you.

One suggestion I have is to perhaps get your original block of tissue from your original biopsy to have it retested for its hormonal status. I had read somewhere (most likely on this site) that false negatives of the ER/PR status can be common.

For example, I was originally diagnosed as weakly ER+ (5%) in February. After my surgery, I asked to have my ER/PR status rechecked. Since there was no tumor cells left in the breast itself, my doctor told me that they could only retest the original tissue block. So I requested that from the clinic where I was diagnosed, had Stanford retest it, and it came back as 30 % ER+ (2+). I had already started Tamoxifen after radiation, and now even more so, believe it's going to be an important part of my treatment plan.

So perhaps consider retesting your original biopsied tissue to make sure of its initial result. Then you can discuss with your doctor whether you're a good candidate for hormonal therapy.

All the best,

Marcia (bejuce)

[Rich66]

Pathology from multifocal tumors in the same breast can be different. I suspect differences can be found within the same tumor.

[flynny]

Becky thank you so much for that information. I really appreciate the full detail. I too am weakly positive and hope that by taking the tamoxifen it will still help me no matter what.

[Carolyns]

Chelee,

I don't know what to say about the hormonal status. I found Becky's comments to be very informative. And Lani's statement of :

"Maybe you should ask Dr. Slamon if you should ask the pathologists to see if they looked at several areas of the biopsy, as there may be some areas that are her2+ whereas others are her2-."

I was hysterical when a trial was going to use bone tissue as the benchmark for my entry. It was the only sample that showed weaker Her2 status. Ultimately when the trial did all of their tests on the sample the results came back different and Highly Her2 Positive like the rest of the samples. I can only imagine that the trial did as Lani said and looked at multiple areas.

I also read that Her2 testing (like all testing) can be off by about 30% (when it reads Negative). If someone knows for sure please correct me.

I am sorry that you must go through this. It is so tough.

Love, Hope, Peace, Carolyn

[Faith in Him]

My receptor status change at my recurrence also. Her2+ to her2-. I was in shock. I sent my breast tissue to UCSF four months ago and they are still sitting on it. I want it retested but since I have both medicare and kaiser, they are fighting over who will pay for this. Very frustrating to say the least.

I am sorry that things have been so complicated for you. I wish you a speedy recovery from your surgery and overall healing.

Tonya

[Chelee]

Becky, I love the way you explain things. Your post was very helpful, and very informative! I was curious if the herceptin I've been on could be the reason I'm showing that I'm only her2 (1+) now. So you answered that for me too.
I see my onc Monday morning & I will ask about the Faslodex. I did ask Dr. Slamon if I should be on it when I saw him...and he said no? (That surprised me?) Maybe because I was Er & Pr weakly positive? I wonder what he'd say now that I am showing to be 60% Er pos.

One thing I do know is they are not going to take away my herceptin...just let them try! I know herceptin works for me...my tumor markers dropped instantly after my first loading dose...so no quandry here Becky. lol

Lani, I also want to thank you for your feedback...it too was very helpful. Both you & Becky are so good at explaining things for us non-propeller heads...and it IS appreciated. I called my cancer center today to find out if they are going to run a FISH test on this biopsy? I told them I wanted that done. I know since I was out-of-network at City of Hope they wouldn't do it...but I do expect my place to send it out asap. I was told that would be done.

Thanks to all of you for the replies!

Chelee