Commercially available test helps identify those for whom chemo will work vs not work

[Lani]

Test Helps Identify Patients with Breast Cancer Who Will Likely Benefit from Chemotherapy, and Those Who Won't [American Association for Cancer Research]
CHICAGO — A test that measures the amounts of two members of the same protein family - one of which appears to act as an oncogene, and the other as a tumor suppressor - helps identify patients with breast cancer who will likely benefit from chemotherapy and those who won't, according to researchers.

The test, known as OncoPlan™, is already commercially available, and studies have shown that it can predict the aggressiveness of the patient's tumor and the relative risk of disease recurrence following surgery in breast, colon and gastric cancers. Now, researchers in the U.S. and Canada have studied whether it also can help identify breast cancer patients who would benefit most from chemotherapy.

Results: were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

OncoPlan measures two forms of Shc protein, which are known to drive the formation of protein complexes involved in signal transduction pathways and have been found to be involved in many of the pathways important to development of aggressive cancer. These two forms have a "push pull" relationship with each other: tyrosine-phosphorylated (PY)-Shc helps drive these dangerous cell pathways, but p66 Shc, after initial stimulation, works to inhibit the very growth pathway the other Shc proteins promote.

"This may be one mechanism whereby normal cells prevent runaway growth," said the study's lead author, A. Raymond Frackelton, Jr., Ph.D., a Brown University associate professor, staff scientist at Roger Williams Medical Center and Vice President of Research at Catalyst Oncology, which is marketing OncoPlan. "Perhaps more importantly, aggressive cancer cells must endure oxidative stress—stress that in normal cells triggers p66 Shc to cause cellular suicide," he said. "Tumor cells, then, may have both growth and survival advantages if p66 Shc levels are low."

Chemotherapy-mediated killing of tumor cells, however, does not require p66 Shc, Frackelton said, suggesting that patients whose tumor cells have low p66 Shc might respond well to chemotherapy. To test this idea, the researchers looked at the Shc proteins in tumors from 2,380 women from British Columbia who were diagnosed with invasive breast cancer, 717 of whom received chemotherapy as part of their initial treatment.

They found that, indeed, patients who had low levels of p66 Shc and did not receive chemotherapy had very poor outcomes. If similar patients received chemotherapy, however, their chances of relapsing and dying from their disease were reduced by two-fold or more, said Frackelton. Conversely, women with high levels of p66 Shc had a much higher likelihood of surviving their disease, but appeared to derive no benefit from chemotherapy, he said.

Possible additional associations between PY-Shc and chemotherapy benefit has not yet been fully explored, Frackelton said. "But even at this point, the results are very exciting because, with further validation in clinical trials, OncoPlan, which is already being used to predict disease aggressiveness, will help to ensure that individual patients receive the most beneficial therapies," he said.

[suzan w]

Is this the same test as the OncotypeDX?

[AlaskaAngel]

Given that I am in "Lost Regiment of HER2s", (for whom research is minimal at best for our prognosis) when I do see my oncologist I am interested in having such a test done retrospectively. The only application I have seen mentioned for these tests is for the newly diagnosed. However, the idea that those of us who are stuck with hanging out and blindly hoping to stay NED due to lack of research for us fits me like a coffin. I hope my oncologist has the insight to be willing to provide me with a better solution that that. I hope other members of the "Lost Regiment of HER2s" will also seek better answers from their oncs. I would like to see more interest and discussion of this at the various cancer conferences, and sincerely thank Becky for her discussions about it.

AlaskaAngel

[Lani]

No. The oncodx test is meant to divide patients with early nonmetastatic(distal) breast cancer that is ER+ without lymph node metastasis into low, medium and high risk groups. A clinical trial is underway to see if chemotherapy can be avoided in the low risk group without endangering the patient with respect to distal metastasis, disease free survival and overall survival. It tests about 21 or 22 genes (via mRNA I believe), three of which are ER, PR and her2.

This test divides patients into high and low risk groups and ostensibly predicts chemotherapy benefit in patients who are ER+ or ER-, Lymph node+ or - . Thus it is applicable to more patients and seems to have been tested ALREADY regarding predicting recurrence after chemotherapy. Larger number of patients need to be tested in a clinical trial.

Hope this helps!

Good news--both tests can be done on paraffin-embedded tumor slices which are kept in the pathology department of the hospital where the surgery was performed. Multigene arrays and some other tests require fresh tissue, and thus cannot be performed retrospectively on paraffin sections.

[kristen]

Is this the AMAS test? Which is by Oncolabs. When I read it, I got the feeling that it is used as a tumor marker that is supposed to be more accurate then the CEA, etc. Here is the link, limited information, I tried to call the number listed and it was busy. I didn't read where it said BC specifically.


www.amascancertest.com


Has anyone used this test? Or heard of it before? Know anything about it from your onc? It would be great if this test really worked and you didn't have to decide between the CEA, CA 15-3 or CA 27-29. Thank you in advance if you have any comments or info on this.

[Lani]

no it is not the AMAS. For her2neu+ breast cancer, at least that which is metastatic, serum her2neu ECD will probably end up being the most accurate tumor marker, but other markers are more generally accepted to be tested and more widely available.

THis test is used in an entirely different way than tumor markers.

Tumor markers are measured to show to a greater or lesser accuracy if a tumor may be progressing.

This is a test to know ahead of time whether or not chemo is likely to be effective.

It still must be validated in larger numbers of patients. There is a website for the company. Put the name of the test into Google and it will get you there.

Oncologists usually don't like to order something until there have been large clinical trials validating its accuracy, as they don't plan to change their treatment protocols without good evidence to do so.

Hope this helped!

[sarah]

I bet insurance companies will be pushing for the test!

[Lani]

...in that for ONCE, the interest of the insurance company (saving money) AND the best interest of the patient (avoiding unnecessary toxic treatment) will converge!

[Cathya]

Lani;

When you refer to the serum her2neu ECD do you mean the Bayer Serum Her2 test? I'm confused about the ECD? Also, having already been through AC and Taxol I'm wondering if there are any genetic tests which should be done to help identify the best adjuvant treatment....and the best course of action should additional chemo be needed in the future? What test/tests would you have done?

Thanks,

Cathy