more on how ER+her2+ breast cancer differs from ER-her2+ bc

[Lani]

This may explain why not all ER+her2+ patients need herceptin to do well...
I know Alaska Angel has been wondering about this for years

They need larger numbers to be sure, but it looks as if it is her2mRNA and not just her2 by IHC or FISH that predicts which patients with ER+her2+ breast cancer require herceptin to do well.

her2mRNA level does not seem to matter for ER-her2+ patients.

Research article
HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer
Carsten Denkert, Jens Huober, Sibylle Loibl, Judith Prinzler, Ralf Kronenwett, Silvia Darb-Esfahani, Jan C Brase, Christine Solbach, Keyur Mehta, Peter A Fasching, Bruno V Sinn, Knut Engels, Mattea Reinisch, Martin-Leo Hansmann, Hans Tesch, Gunter von Minckwitz and Michael Untch

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Breast Cancer Research 2013, 15:R11 doi:10.1186/bcr3384

Published: 7 February 2013
Abstract (provisional)
Introduction
Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial.

Methods
HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in-situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro.

Results
Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, p<0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, p<0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (p=0.004), but not in HER2-positive/ESR1-negative tumors.

Conclusions
Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group.

[Laurel]

Man, it is gonna be a real bummer, Lani, if we triple pos gals find out we did not need the chemo or the Herceptin. Dang.....

[linn65]

Lani, I don't even know what that means what your wrote. Can you explain it in layman's terms...

[Lani]

if these findings are confirmed in larger numbers of patients, it may turn out that there is a subgroup of her2+ER+ breast cancer patients who do not need herceptin. It will only be a subgroup, and only that if these findings are confirmed in larger studies

[linn65]

I am both and her2+++ and ER + what does that mean for me?

[Lani]

Again, IF and I mean IF the results of this study are proven in larger studies, they may someday be able to test whether you really needed herceptin or not.

In the meantime, if you got herceptin you should probably do well as there was even a chance that you would have done well without herceptin.

[linn65]

That will be interesting because the only reason I thought I was getting Herceptin is because of the HER2 and it supposed to save my life if it works. My doctor told me I got HER2 at the "right" time meaing we have targeted drugs for it.

[AlaskaAngel]

Thanks for that info, Lani. Given that I am one of those who never did trastuzumab but was HER2+++ with a tumor over 1 cm and who has not recurred, I wonder if it is only the trastuzumab that was not needed for me or whether the new info is also an indicator that chemo was/is not needed for those patients, because of the lack of research documenting the need for chemo to be given in addition to trastuzumab.

I DID do 1 3/4 years of tamoxifen (the last part at half dose), but have never needed an AI, either.

But I also have to add into my own situation the question as to whether the steroids given with chemo may have actually been a/and/or/the basis for my lack of recurrence, since they reduce inflammation and inflammation is a major aspect of cancer. In my case, in order for me to tolerate the chemotherapy, they had to double my dose of steroids given concurrently with the chemo. (At the same time, I have felt that steroids increased the postmenopausal weight gain that then increased my risk post-chemo!)

A.A.

[AlaskaAngel]

P.S.

I also believe that another aspect further confuses the question. I think that ovarian ablation, whether brought about by chemo or surgery or drugs like Lupron, is probably a key factor. So in regard to Laurel's question, even though I may not have needed chemo to achieve ovarian ablation, it may have been the chemo that provided ovarian ablation for me.

I wonder if the study showed any relationship to age range.

[Lani]

Alaska Angel --many breast cancers have steroid receptors which can actually be activated by the steroids given with the chemo

Many patients with asthma,rheumatoid arthritis, and other inflammatory diseases are on chronic steroids and have no smaller risk of breast cancer, so I doubt your theory on the steroid would hold for many. That does not mean it could not hold for a few

There are so many receptors/pathways/alternate pathways. I think it is hard to know in your case exactly why you did not recur-- without studying your individual tumor with expensive tests most of which we do not yet know how to interpret

[AlaskaAngel]

Hi Lani.

It is hard to know, considering all the variables. I still wonder whether I got as much cancer recurrence reduction out of receiving a doubled dose all the way through the final 4 out of 6 CAF treatments as one would get from the CAF itself. I wonder if that might actually be a significant variable among cancer patients that is being missed -- those who receive doubled doses vs those who don't, and the incidence of recurrence.

And if many breast cancers have steroid receptors which can actually be activated by the steroids given with the chemo, then that could help to explain why chemo works for some, but not all.

Thanks,

A.A.