Recurrence for ER+/PR-/HER-2+ tumors

[bejuce]

Hi fellow HER-2ers,

Does anyone know about the recurrence behavior of ER+/PR-/HER-2+ tumors? In particular, does recurrence peak at 2 years post surgery/diagnosis or does it also peak at 6 years after Tamoxifen/AI treatment? And does the fact that PR is negative while ER is positive affect the tumor response to hormonal therapy? Are there any studies that have looked at this subtype and how does it compare to the triple-positive, the ER-/PR+/HER-2+ tumors or the ER-/PR-/HER-2+ ones?

I've read some papers that talk about the role of the PR receptor, but nothing yet on how it affects recurrence rates for the ER+/HER-2+ cases. It seems to be a rarer subtype, but I do know that there are several of us with it here.

Any ideas? Who is doing research on the PR receptor and its role around the country?

Thanks!!!

Marcia

[Hopeful]

The question of ER+/PR- Her2+ pathology has come up before on the board. Try using the search feature with those keywords.

As to research on progesterone receptor, the most recent paper I saw pertained to triple negative bc: http://breast-cancer-research.com/co...df/bcr2588.pdf

Hopeful

[Becky]

Dear Marcia

I am also ER+(50%) and PR neg and there are more of us on the board (Jean and Pink Girl too). There is not alot of data on this pathology especially if you are NOT Her 2 as well like we are. I will tell you what I have learned.

When bc loses the progesterone receptor but not the estrogen receptor, its a pretty good indicator that something else is positive. In our case, we at least know the devil is Her2. If you are not Her2, you are probably positive for another receptor that isn't tested for yet like Her1 (aka EGFR), Her3 or IgGR. At least with Her2, there are drugs for it, plenty of new ones coming out and tons of research.

At lower % of ER (50% or less) and a negative PR may indicate resistance to Tamoxifen or other therapies however, it isn't clear if one is resistant or if another pathway is taking over. For example, when Herceptin didn't exist, you (or I) would take Tamoxifen but that wasn't our "big devil", Her2 was our big devil and a recurrence would likely be that. There is not alot of information on these new times with the advent of adjuvant Herceptin therapy. We are the ones writing the books.

Another interesting study that Jean and I saw together was a researcher who looked at the molecular assay of bc that was ER+PR+, ER+PR-, and ER-PR-. He did not divide these out by Her2 status or any other receptor, just the hormone receptors. When he did the molecular "pictures" of these pathologies he found some interesting footprints. Most ER+PR+ cancers had the same picture as did ER-PR-. However, most ER+PR- cancers looked like one or the other. A small percentage did have their own unique picture and these were considered true ER+PR- but the % was very small. Therefore, your picture might look like ER-PR-, Jean's may look like ER+PR+ - I think you get it. The really AMAZING thing in the study was that some ER+PR+ picture looks like ER-PR- and vice versa which could lead one to think that women who are ER-PR- but recur and new pathology says its still hormone negative just MIGHT respond to Tamoxifen or an AI anyway because the molecular assay doesn't match the pathology.

Keep the faith Marcia! I am still here (almost 6 yrs) and Jean just celebrated 5 yrs and Pink Girl is almost 5 yrs too and so will you.

I will say though, its hard to find anything about the PR- as most studies concentrate just on ER and not what PR is doing in general.

I believe also, in general, that the recurrence rate would be more upfront and the ER+ 6/7 yr blip is due to reawakening of the slower growing ER+PR+ cancer after hormone therapy (5Yr) is complete. It makes alot of sense. One gets 5 yrs of Tamoxifen (and these stats are based on 5 yrs of Tamox, no AI, no 5 yrs Tamox followed by 5 yrs Femara) and it ends. By this time, you are really 5.5 yrs from surgery, maybe alittle longer. The blip is at 6/7. Higher ER/PR values might well benefit from longer hormonal therapy (as the 5 yr Tamoxifen followed by 5 yrs Femara proved to this group).

Unfortunately, only time will tell and its so difficult in the beginning but trust me, it gets better with time!

[Jackie07]

Marcia,

I'm also ER+ PR-. Even though the ER amount was very small (5%?), a doctor I consulted (my 2nd Sister-in-law's oncologist in Taiwan) had told me that either 5 years of Tamoxifen or 2 years of Tamoxifen + 3 years of Arimedix (or other aromatease inhibitor) is recommended.

One does need to watch for the side effect of osteoporosis as is evidenced by the cervical vertebrae degeneration I'm currently experiencing.

I think the recurrence rate has more to do with the types of surgery (lumpectomy vs mastectomy) than any other factor. My surgeon has quoted statistics by saying that lumpectomy + radiation = mastectomy. I personally never bought that...

In my case, there was tumor left-over from the lumpectomy and the recurrence was overlooked for 4 years. So I don't quite buy the 'peak' theory. I think it has more to do with how long it takes the doctors to realize their mistakes. (In my case, they never did find it. I had to be the one persuing it.)

In your case, I think because you'd had neo-adjuvant treatment and mastectomy plus further chemo/Herceptin you should have a good chance not to have any recurrence in the near future.

Just be vigilent, you will be fine.

"I think the recurrence rate has more to do with the types of surgery (lumpectomy vs mastectomy) than any other factor. My surgeon has quoted statistics by saying that lumpectomy + radiation = mastectomy. I personally never bought that..."

Actual science supporting lumpectomy + radiation = mastectomy IS true.


http://www.rsny.org/200_PDFs/GSL-A-N...ER-MASTECT.pdf

[Rich66]

FWIW, revently spoke with a researcher who seems to focus on ER BC issues who said PR+ "tends" to be viewed as a surrogate for responsiveness to endocrine therapy. Not sure how that figures into Her2/ER crosstalk.

I had mastectomy and radiation, do most people only have radiation if they have a lumpectomy?

[krisvell]

Marcia; Thank you for posting this. I have similar stats to you; even the neoadjuvant chemo. Becky's post is very informativie. Thanks to you, I know more. I just finished Herceptin (06/22) so now I move on and hope for the best. I am looking into BC Vaccine trials.

Wish I had done the Lapatinib trial that you did. My oncologist offered it to me but 1 year ago, I was so freaked out by the diagnosis, I wasn't thinking clearly. You've done everything possible and then some.

Kris....

[tricia keegan]

Unregistered, rads are a must with a lumpectomy.

However, more treatment depends on nodes positive, size of tumour etc.....I think all who are her2+ should have herceptin though regardless of node status.

[Jean]

Marcia,
The er+ pr- Her2+++ seems to be a special club!
I remember well that day Becky and I sat and listened to the research on our subtype. We were pretty excitied.

As Becky points out we are now the ones who will be demonstrating the new and improved stats. I really believe we will see an entire change of history with the Her2 bc....early stage women are now having herceptin and that has to impact...AI therapy has made a major contribution also. And the research continues.

I will share this here and then will post on a main thread.
Just saw my onc. here on the East coast. This dr. is rather conservative. When I saw Dr. Slamon in late 05
10 months after my dx. and he was a green light for TCH...the dr. here on the East coast (along with three others) he was reluctant on the TCH with my early stage. Now just yesterday his position is any women with a 3MM tumor must have herceptin. I still believe anyone should have or must have herceptin. I am just pointing out to you how treatment has changed in a short period of years.

You will hit the 5 yrs...and the 10yrs....I in my heart believe that we will begin to see the numbers change.

Sending you best wishes.
Jean

Thanks Tricia, my tumour was 2.75cm and I had one node postive......I had bilateral mastectomy follwed by epirubicin, radiotherapy then taxotere. I finished chemo Feb 06 and started Arimidex, I didn't start Herceptin til June 06. I have just passed my five year mark.................fingers crossed for the next five :-)

[bejuce]

Thank you so much for all your encouragement and support! I need to be here for my family for a long time to come and I'm trying to do everything I can to make this possible.

I worry about recurrence frequently, but I'm trying to live my life with gusto. I had a very large tumor and hopefully my immune system kept/will keep it from spreading.

As for the PR receptor, I heard from a doctor recently that PR negativity with ER+ tends to indicate an ER receptor that is truly malfunctioning. Not sure about this one, but I'll continue to research the issue.

Thanks,

Marcia

What the physician may mean is that the tumor is less responsive to ER deprivation, such as tamoxifen, than ER+/PR+ tumors, however, before Herceptin, etc., these tumors were treated in the same way. The PR- patients likely recurred more frequently but before the Her2 pathway was understood, the reason why these patients recurred more frequently was not known. It appears that ER+/PR- patients respond favorably to EGFR inhibition (such as Herceptin/Tykerb) and do much better now than in the past. I think that triple positive is still the most favorable but not sure by how much now that we have Herceptin. So, it's not nearly as bad as it was before, same with ER-/PR- who are Her2+. The main driver appears to be the Her2 receptors in the early tumors. There are other drivers in addition to Her2 in later stage disease but the drugs to treat them are coming and some are in clinical trials. If the funding remains, I think we are getting closer to at least controlling later stage disease. I am interested in other comments on this but this is my take on the ER+/PR-/Her2+ subtype. Thanks.

[tricia keegan]

Congrats unregistered!!!

I hope to celebrate my five years on July 8th so coming up right behind you

[CoolBreeze]

I have the same stats.

Nothing else to offer though.

[Jackie07]

Ann,

I gathered that your mammogram turned out fine? Love that 'Hot' picture!

[CoolBreeze]

Ah...a blog reader. Thank you!

No results from the mammogram yet but I suspect all is well and I'll get that letter telling me I'm done for the year and to go get a colonoscopy.

Which, I need to do, but one thing at a time.