as subtypes of her2+ breast cancer discovered, a particularly nasty one ID'd

[Lani]

this one has overexpressed her2 and LMW (low molecular weight) cyclin E

The bad news: It's 5 year survival is 14%--the good news is that the 5 year survival of those that are her2 overexpressed but LMW cyclin E -in this study was 89% Perhaps as we weed out the different subtypes with better and worse prognosis, the stats given will be more meaningful and everyone can get the best treatment for their subtype, no more and no less.

Oncogene. 2010 May 10. [Epub ahead of print]
A novel interaction between HER2/neu and cyclin E in breast cancer.
Mittendorf EA, Liu Y, Tucker SL, McKenzie T, Qiao N, Akli S, Biernacka A, Liu Y, Meijer L, Keyomarsi K, Hunt KK.

Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
Abstract
HER2/neu (HER2) and cyclin E are important prognostic indicators in breast cancer. As both are involved in cell cycle regulation we analyzed whether there was a direct interaction between the two. HER2 and cyclin E expression levels were determined in 395 breast cancer patients. Patients with HER2-overexpression and high levels of cyclin E had decreased 5-year disease-specific survival compared with low levels of cyclin E (14% versus 89%, P<0.0001). In vitro studies were performed in which HER2-mediated activity in HER2-overexpressing breast cancer cell lines was downregulated by transfection with HER2 small interfering RNA or treatment with trastuzumab. Cyclin E expression levels were determined by western blot analysis, and functional effects analyzed using kinase assays, MTT assays were used to assess cell viability as a marker of proliferation and fluorescence-activated cell sorting analysis was used to determine cell cycle profiles. Decreased HER2-mediated signaling resulted in decreased expression of cyclin E, particularly the low molecular weight (LMW) isoforms. Decreased HER2 and LMW cyclin E expression had functional consequences, including decreased cyclin E-associated kinase activity and decreased proliferation, because of increased apoptosis and an increased accumulation of cells in the G1 phase. In vivo studies performed in a HER2-overexpressing breast cancer xenograft model confirmed the effects of trastuzumab on cyclin E expression. Given the relationship between HER2 and cyclin E, in vitro clonogenic assays were performed to assess combination therapy targeting both proteins. Isobologram analysis showed a synergistic interaction between the two agents (trastuzumab targeting HER2 and roscovitine targeting cyclin E). Taken together, these studies show that HER2-mediated signaling effects LMW cyclin E expression, which in turn deregulates the cell cycle. LMW cyclin E has prognostic and predictive roles in HER2-overexpressing breast cancer, warranting further study of its potential as a therapeutic target.Oncogene advance online publication, 10 May 2010; doi:10.1038/onc.2010.151.

PMID: 20453888

[bejuce]

14% only? Wow! How do we know whether our tumors overexpress LMW cyclin E? I'm thinking now that with all your recent postings about HER-2+/ER+ interactions, I'd sure like it for my tumor to be tested for this and p95...

Has anyone here ever tried to contact a researcher directly to see if they could test your tumor? I have my pathology slides with me (my breasts reduced to a small Fedex box) and will meet up with a pathologist next week to look at them. I'd love to get more information out of them if I can...

Thanks Lani for all your postings!

Marcia

[StephN]

Thanks, Lani.

The difference in the low and high levels of cyclin E survival in these studies is huge in terms of patients' lives.

You are right in the subtype categories enlarging. The more we learn about the variations in Her2+ at the molecular level, the more fortunate I feel for my longevity!

March onward, dear researchers!

[Hopeful]

bejuce,

When you read complete research papers, the methods section is usually quite lengthy and detailed. In it, the reserarchers describe how they developed the test they used to measure certain attributes about the tumor, like Cyclin E or p95 for example. There are not standard tests for all of these things, so the methodology really needs to be considered as much as the results that were derived. I am no scientist and have no idea how much weight to give any of those descriptions; I can't tell if it was a good method, if there was a better or competing one, etc. But basically the answer to your question is that there isn't a place you can go that will know how to do the tests, because they could have been created by the researcher for a specific study, or they are tests that are only done by specialty labs that do work for researchers.

Hope I made sense there,

Hopeful

[hutchibk]

I just spoke today with the heads of pathology at the hospitals where I had my initial mastectomy and later surgery that yielded tumor, and made arrangements for my slides and paraffin to be held indefinitely at my discretion (beyond the minimum 10 years they typically store it)... so that I can either use it for further testing for myself or offer it for research testing. I just signed authorization 2 weeks ago for samples to be used in upcoming biomarker research...

[Rich66]

It's probably worth noting, as frustrating as it is, that good ole standard Her2 testing seems to stil have some kinks to work out. The cutting edge lab pathology work is probably quite a ways from applicable.

[Hopeful]

I just signed authorization 2 weeks ago for samples to be used in upcoming biomarker research...

Brenda,

That's great. Will the researchers share their findings with you about your particular tumor?

Hopeful

[hutchibk]

I don't know for sure, but I am close to the research nurse (she used to be my onc's nurse) and I plan to ask her...

[Barbara2]

Early on in my breast cancer, I had read frightening things about this "cyclin E" which made me quite nervous about the prospect of having high levels of that, too. I asked my onc if we could check for cyclin E and he said we could, but I was too afraid to do it, so let it go.