once again, with feeling.... yet another study confirms ER+her2+ breast cancer as a

[Lani]

different "disease" than ER-her2+ breast cancer

It used the GeparQuatro data and examined whether pCRs after neoadjuvant chemo/herceptin therapy could be relied upon to predict outcome and whether
how well they predicted relied on their levels of her2 and ER (and the method used to determine her2 level)

Again, I have previously posted that even among her2+ER+ tumors there may be several subgroups, especially even a subgroup which may do well without herceptin

Well here we go:

http://breast-cancer-research.com/co...1/R11/abstract




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

* Corresponding author: Carsten Denkert carsten.denkert@charite.de

† Equal contributors
For all author emails, please log on.

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.

[Ellie F]

Thanks Lani
Everything I read and you post makes me believe that bc is many diseases under one label. I feel we have not yet fully understood all the subsets and wonder if we ever will!

Ellie

[linn65]

What's an increased PCR rate mean?

[karen z]

thanks for posting

[Lani]

PCR=pathological complete response which refers to the fact that when they biopsy where a tumor had been AFTER neoadjuvant (presurgery) chemotherapy, they cannot find any tumor left

[linn65]

Then I guess I was a minority in the study because I did not have PCR?

I know when he explained pre-adjuctive therapy the doctor told me some people have complete response (PCR). Or the tumor shrinks so much we can save your breast and do a lumpectomy.

This is all very fascinating, and figuring it all out as nothing to do with me thinking about reoccurance or anything else. If I could I would take a class at College on the whole subject and learn more.

[tricia keegan]

Thanks Lani!