Will we be changing the name of this site to GRB7 support soon?

[Lani]

Researchers Isolate Importance of Gene in Determining How Aggressive a Patient's Breast Cancer Will Be
[Oregon Health & Science University]
Oregon Health & Science University Knight Cancer Institute researchers found that the GRB7 gene drives an aggressive form of breast cancer and acts independently of the HER-2 gene, known to be a stimulator of breast cancer growth. Isolating the role of this gene could ultimately help fine-tune a patient's treatment and enable physicians to provide a more accurate prognosis.

The study, published online this month by Breast Cancer Research and Treatment, established that levels of GRB7, or growth factor receptor bound protein seven, are important on their own as a marker for aggressive breast cancer. Previously it was understood that patients whose breast cancer tumors tested positive for high levels of HER-2, the protein human epidermal growth factor receptor-2, tended to have a more aggressive form of the disease than patients whose tumors did not have elevated levels of this protein. However, OHSU Knight Cancer Institute researchers found that the protein driving this aggressive form of the disease is GRB7 rather than HER-2 on its own.

"Our work shows GRB7 protein levels are an important and independent factor in determining a prognosis for breast cancer," said OHSU Knight Cancer Institute member Shiuh-Wen Luoh, M.D., Ph.D., assistant professor of medicine in the Division of Hematology and Medical Oncology, medical oncology director for the Comprehensive Breast Cancer Clinic and senior author of the paper.

The findings could have implications for the types of therapies used. Luoh said a next step will be to determine if high levels of the GRB7 protein influence patient responses to anti-HER-2 therapies such as Herceptin or Tykerb.

The research into GRB7's role is advancing the OHSU Knight Cancer Institute's mission to provide cancer patients with personalized treatments that target the specific characteristics of their disease.

"Our work was only made possible with the availability of a breast tumor repository that OHSU and the Knight Cancer Institute began collecting about 20 years ago," said Ed Keenan, Ph.D., who served as co-investigator on the study. Keenan, former associate dean of medical education for OHSU's School of Medicine, is a professor in the Department of Physiology and Pharmacology and the Department of Surgery. He also serves as president of The Foundation for Medical Excellence.

Other researchers who worked on the paper, titled "GRB7 protein over-expression and clinical outcome in breast cancer," were Betsy Ramsey, B.S., research associate, OHSU Knight Cancer Institute and Department of Physiology and Pharmacology; Tao Bai, B.S., research associate, Division of Hematology and Medical Oncology; Amy E. Hanlon Newell, Ph.D., senior research associate, Department of Molecular and Medical Genetics; Megan Troxell, M.D, Ph.D., associate professor, Department of Pathology; Byung S. Park, Ph.D., research assistant professor, Division of Biostatistics, Department of Public Health and Preventive Medicine; and Susan B. Olson, Ph.D., FACMG, professor, Department of Molecular and Medical Genetics and director of the Clinical & Research Cytogenetics Laboratories.

The study was funded by the Department of Veterans Affairs, Portland VA Research Foundation, OHSU Presidential Bridge Award and OHSU Foundation.

ABSTRACT: GRB7 protein over-expression and clinical outcome in breast cancer
[Breast Cancer Research and Treatment]
The growth factor receptor-bound protein-7 gene (GRB7) encodes a multi-domain signal transduction molecule. The purpose of this study was to examine the clinical significance of GRB7 protein expression in human breast cancer. Western blotting analysis of protein extracts from 563 annotated frozen breast tumors was performed. Expression status of GRB7 and HER-2 was correlated with clinical covariates and outcomes. Cox proportional hazards were used to identify factors associated with breast cancer-free interval. The median follow-up was 71 months. P values <0.05 were considered statistically significant (two-sided). A discrepancy between HER-2 and GRB7 protein over-expression was observed. GRB7 protein over-expression was associated with negative estrogen and progesterone receptor status, higher tumor grade, larger primary tumor size, (more) axillary lymph node involvement, higher clinical stage, and shortened breast cancer-free interval. HER-2 protein over-expression was associated only with higher tumor grade. Multi-variate analysis revealed that GRB7 protein over-expression was an independent adverse prognostic factor for breast cancer-free interval (hazard ratio 1.69, 95% confidence interval 1.07-2.67; P = 0.024). The same was true of the subset of patients who did not receive any adjuvant systemic therapy (hazard ratio 1.68, 95% confidence interval 1.16-2.31; P = 0.0055). Using FISH analysis, 32/32 (100%; 95% CI 89-100%) tumors which over-expressed both HER-2 and GRB7 proteins and 1/35 (3%; 95% CI 0-15%) tumors with HER-2 but no GRB7 protein over-expression with Western blotting analysis demonstrated HER-2 gene amplification. GRB7 protein over-expression is an independent adverse prognostic factor in human breast cancer.

[Barbara2]

Thank you, Lani; important discovery! It's these baby steps that will bring bring about what we all are waiting for. We're getting there...

[Sandra in GA]

I have always believed that knowledge is power. Hopefully this new information will give more power to our treatments! Thank you Lani for sharing this!

[mmoons]

Wonder how we can get tested for this protein?

[Lani]

GRB7 is one of the 21 genes included in the OncoDx test, but getting OncoDx to divulge more than the recurrence score has been extremely difficult in the past. I think an exception may have been made for ER and PR--perhaps pressure can be put on them to divulge GRB7 results as well!
How about trying to get together a form letter for oncologists for those who have been oncoDx tested in the past? If they would be willing to sign and send it in, perhaps Genomic Health will send out the GRB7 test results on those patients (Easier than them having to go through their high risk patients, decide which were her2+ and send them their GRB7 results.
I am sure one paper ona limited number of patients is not enough to motivate them to give out GRB7 results--most times their actions are based on consensus of oncologists based on large clinical trials. But I can't see them refusing to give out GRB7 results to oncologists if they were requested. The oncologists can interpret the importance of the result based on their take of the reliability and applicability of this article. Opinions?

[1rarebird]

This kind of research can possibly lead to future therapies that will help treat and possibly defeat Her2 positive cancers. But in the meantime, I am unclear how knowing whether we have this gene expression or not would change the treatment regimens currently used. Seems like they found the GRB7 gene is present when Her2 is over expressed. We can now find out if we have the Her2 over expression and start treatments based on that information. What would be different if we also knew the GRB7 status? Would this possibly open up the use of anti-Her2 drugs for Her2 negative cases? I'm apparently missing something here---

bird

[Rich66]

"getting OncoDx to divulge more than the recurrence score has been extremely difficult in the past. I think an exception may have been made for ER and PR--perhaps pressure can be put on them to divulge GRB7 results as well!"

Hmmm...kinda disturbing What difference does it make to them? Ah...must be their secret recurrence recipe.

I wonder if GRB7 is related to response to Herceptin or Tykerb.

[Jackie07]

I am excited about the new findings. Herceptin has been a God-send for treating Her2 positive breast cancer. But not everyone respond to it 100 %. So then we got Tykerb,...

The more 'gene' information they find out, the more 'targeted' therapy will be available. Eventually there might be a very complicated 'cocktail' system developed and really tailor to each individual.

I'm looking forward to the day when my gene information can be inputed to the computer and then it will list the chemo drugs I need to use for 'my' [breast] cancer.

[Lani]

GRB7 is on the same amplicon (segment of DNA) close by her2, but they are not always amplified together. It is similar to TOP2A (which if I recall is quite a bit further away down the amplicon from her2 than GRB7 is) Some her2 amplified patients also have TOP2A amplified, some do not and it influences whether/how effective and necessary anthracyclines are for these patients (Dr. Slamon has had lots to say about this)

There has been talk from time to time that GRB7 is the culprit and not her2, but that her2 amplification was what was noticed in the breast cancers with worse prognosis. Perhaps by making a monoclonal antibody to her2 we have merely found a target which tend to occur together with GRB7 (the possible culprit)--but not always--and that it is the ADCC immune reaction that the herceptin brings about that improves the prognosis of the breast cancer patients rather than the inactivation of her2, her3 etc.

Glad they keep looking at things with open eyes, rather than assuming what has been "considered dogma" in the past is ultimate truth. It may or may not turn out that GRB7 is the culprit and her2 the standerby, but every bit of research brings us a bit closer to the truth and a cure.

[Lori R]

Hi gang,
I question whether too much information "in the end" proves to be useful. I've come to the conclusion for me....bring it on, the more random details about my cancer the better.

As I face my 3rd round of chemo, anything that would help me select the next step or possibly help me understand why Herceptin didn't do the trick would help me feel more empowered.

Currently frustrated wtih the feeling that my Drs. at taking a swing at the pinata hoping to win the prize.

I would like to know as many details as possible.

[Rich66]

Lori,
Are you able to pursue chemosensitivity testing?

[Lori R]

Rich,
I would really like to pursue any available "personalized" testing. I went through some threads and didn't find one that focused on ER/PR- / HER2+.

If you have any leads, I'd love to pursue.

Current thought is Navelbine, following another cryo treatment.

[Rich66]

It would require either a needle or larger biopsy, depending on which test. Put some info here