here we go again: How inexact ER status testing is!!!

[StephN]

I know of two cases among my friends here who have had new mets change from hormone positive to negative. Therefore stopping the AI they had been on for years. Both are HER2 positive and disease was progressing.

In one case it was new nodes in the neck and another case was bone. Each had biopsies to see why the old treatments were no longer working.

Also heard discussion at San Antonio that new mets can change hormone status, but don't recall about ER/PR neg can become positive for certain.
(You would think I would have remembered that one since I am hormone neg!) Maybe the talk did not cover that case.

[Lani]

Probably not all ER+her2+ breast cancers are alike--perhaps some have topoIIa amplified, some not, and many other differences. When they are all lumped together the average of them do better with herceptin and chemo than with chemo alone and when ER+ tumors (both her2+--about 10% of them--and her2negative tumors, the other 90% of them) are considered as a whole on AVERAGE they hardly respond to chemo. This is probably because subsets are not identified and the results are skewed.

Perhaps there are a group of her2+ER+ tumors that would do fine with herceptin and fulvestrant (more likely than with herceptin and an AI, according to Dr. Slamon) without chemo, but all we can say now, is that when all her2+ tumors ER+ or not were lumped together in the HERA, NO American combined, TCH (BCRG009) and Fin Her trials that upon analysis of all lumped together the % improvement in recurrence and survival did not differ between those who were ER+ vs ER- ON AVERAGE.

Noone is an average. Someday, hopefully, each tumor will be evaluated individually and treated differently.

To more fully respond to your question--It seems a subgroup of her2+ tumors respond particularly well to anthracyclines (perhaps the TOPO IIa amplified group) and another group respond particularly well to herceptin and taxanes (perhaps the cMyc group and perhaps all subgroups, but we don't know for sure yet). They have not yet dissected this out with respect to ER+ vs ER- from the talks I have heard/papers I have read.

And no, if only a needle biopsy and not an open or excisional biopsy or node biopsy were done, methylene blue would not have been used, from what I understand.

[TSund]

Lani,

You are about 1000% ahead of me as far as being well read up, but from what I understand about TOPO is that the latest info about Her2+ and TOPO flies in the face of what was thought previously. When Her2+ and Herceptin enters the equation, all of a sudden the anthrcycline is not necessary in chemo to achieve similar results (i.e the latest stats on TCH - San Antonio). The TOPO positive people do better in general, and that is true in HER2+ whether they do the AC+TH or TCH. I was given this answer when I asked our onc if the fact that Ruth was responding well to the TCH meant that she was TOPO negative as the other onc (not a bc specialist) had given us the hard core insistence that Ruth must have an anthracycline in case she was TOPO positive. I think I read something early on by Dr. Pegram (sp?) that indicates something similar.

[TSund]

...and I know this conflicts with the early indications of the Slamon trial. I think that the latest stats were different than the earlier ones.

Found what I read... and it was not Pegram, it was an interview with Dr. Burstein.


"DR BURSTEIN: The TOPO II issue, which has been discussed a lot since the BCIRG 006 data were presented in 2005, looks less relevant now with the 2006 data (Press 2005; Slamon 2006; [4.5, 4.6]).
The TOPO II gene is on human chromosome 17, not too far from the HER2/neu locus. In some cases of acquired HER2 gene amplification, you also have amplification of the TOPO II locus. TOPO II is a target of anthracyclines, and many people have suggested that TOPO II overexpression particularly identifies tumors that benefit from anthracyclines.
In the preliminary work from the BCIRG 006 trial that Dennis Slamon and Mike Press reported at the San Antonio meeting in 2005, they suggested that in TOPO II overexpressors, the anthracycline/ trastuzumab (ACTH) arm was superior to the nonanthracycline/trastuzumab (TCH) arm. For the majority of tumors in which the TOPO II is not amplified, however, TCH was more or less equivalent to ACTH (Press 2005). If in the aggregate they’re the same, it washes out the effects of the TOPO II test question. I believe if clinicians decide that they can use a nonanthracycline/
trastuzumab-based regimen, it doesn’t matter whether they perform the TOPO II testing.
In the 35 percent of cases in which the tumor was both HER2-positive and TOPO II-positive, the curves all track similarly, which is a puzzle (Slamon 2006)"

[Lani]

Tamoxifen may prevent both ER+ and ER- breast cancers and select for ER- carcinogenesis: an alternative hypothesis.
Breast Cancer Res. 2005;7(6):R1153-8. Epub 2005 Nov 21.
PMID: 16457695 [PubMed - indexed for MEDLINE]

[Gerri]

Lani,

Thank you once again for posting. I am still in the learning curve of reading abstracts/articles and just want to clarify the statement below taken from the conclusion of the article you posted.


"Tamoxifen is likely to remain an important chemopreventive agent, particularly in the premenopausal setting. Thus, this hypothesis may help us to consider other combinations of agents for prevention, such as combinations of tamoxifen with small molecule inhibitors that target the EGFR family or novel receptor tyrosine kinases. More importantly, it should encourage the design of prevention interventions in a setting where we can follow biomarkers and prospectively test the hypothesis presented in this paper."

To me this is verification that Tamoxifen is still a viable agent for those of us who are premenopausal HER2+ and ER+. Does this apply to those of us already diagnosed with bc or only as a preventative in the high risk population of possibly developing bc?


I am currently on Tamoxifen and was confused about whether it is appropriate for HER2+ bc. I am still premenopausal (age 53) and have been wondering whether I should push for suppresion of my ovaries so I can switch to an AI. My onc doesn't feel there is enough data to support this yet but has left the decision up to me. If my interpretation of the article is incorrect can you guide me to research that supports switching to an AI?


I really appreciate the time you take to help out those of us who are not as skilled in interpreting the results of the research out there. I am very interested in learning how to search for articles and how to to effectively interpret them. Any suggestions of how to hone those skills?


Thanks again,

[Lani]

sorry

more soon, I hope!