ASCO Adds MammaPrint to Adjuvant Treatment Decision Guidelines

Re: "The MammaPrint test is a genomic test that analyzes the activity of 70 genes in early-stage breast cancer and then calculates a recurrence score that indicates whether the cancer has a high risk or low risk of recurrence."

Actually, it is the OncotypeDX test (GenomicHealth) that provides a "Recurrence Score".

In contrast, the MammaPrint test (Agendia) produces a MammaPrint Index ("MPI") value (on a scale from -1.0 to +1.0), which is further classified (relative to the clinical classification threshold of zero) as either genomic "High Risk" or genomic "Low Risk".

See for example, the Agendia website (under the "Development" tab):

>> http://www.agendia.com/healthcare-professionals/breast-cancer/mammaprint/

>>QUOTE: "MammaPrint provides a numerical index with a range of -1 to +1, that is overlayed with a binary Low Risk / High Risk clinical classification system."

By the way, regarding the timing of the MammaPrint test, if recommended in connnection with adjuvant chemotherapy decisions, the MammaPrint test is typically performed after surgical treatment and lymph node biopsy are completed, when full information pertinent to (a) eligibility for the test, and (b) Clinical Risk Category ("Clinical High Risk" or "Clinical Low Risk" per specific MINDACT Trial criteria) are both available.

In my layperson's understanding, since MINDACT, in certain patients, it appears that the question of whether to order the test may be informed by "Clinical Risk Category" according to MINDACT Trial criteria. In addition, understanding the significance of the test results in light of MINDACT trial findings must take into account both Clincal Risk Category (per MINDACT Trial criteria) and Genomic Risk (the MammaPrint test result).

BarredOwl

Ok, BCO says this about the update:

• People diagnosed with hormone-receptor-positive, HER2-negative breast cancer with cancer in one to three lymph nodes and clinical characteristics that indicate a high risk of recurrence may use MammaPrint test results to make decisions about chemotherapy after surgery. Still, no matter the MammaPrint results, these people should be told that they are likely to benefit from chemotherapy, especially if the cancer is in more than one lymph node.

"However, such patients should be informed that a benefit from chemotherapy cannot be excluded, particularly in patients with greater than one involved lymph node."

It's not really the same thing...there is a big difference between someone being told they would likely benefit, and being told that the benefit could not be excluded. I'm nitpicking here, but I feel like BCO changed the wording, which I interpret differently when I read it. Yes, you have high clinical risk and at least one positive lymph node---therefore no one can guarantee that you won't have recurrence after skipping chemo--that is a very good thing for a doctor to explain to a patient. That's why the benefit can't be excluded (i.e., no one can see the future), but to say that they are likely to benefit is an extremely predictive statement that the ASCO doesn't make. Unless I am reading the ASCO statement (on the ASCO website) incorrectly.

Hi ChiSandy:

That very general information about risk that you supplied above does NOT appear to be what is meant in the context of the MammaPrint test, the related MINDACT trial publication or 2017 ASCO Guideline Update. In this instance, "Clinical Low Risk" and "Clinical High Risk" categorizations are specifically defined per clinical trial criteria. The ASCO Guideline Update uses specific wording: "with high clinical risk PER MINDACT categorization" or "with low clinical risk PER MINDACT categorization".

Regarding MINDACT clinical risk categorization, Cardoso et al. (links below) comment (bold and capitalization added):

>> "In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a MODIFIED version of Adjuvant! Online)."

So, they MODIFIED the program Adjuvant! Online to develop their own classification program. The paper further states:

>> "Details regarding clinical risk assessment according to the modified version of Adjuvant! Online are provided in Table S13 in the Supplementary Appendix."

Because I have not received the test and have not received any professional medical advice regarding this question, I strongly recommend that anyone interested in this test or who has received the test discuss the trial publication and Table S13 in the Supplementary Appendix with their Medical Oncologist and obtain accurate, case-specific professional medical advice regarding Clinical Risk category.

BarredOwl

___________________________

Cardoso (2016) (MINDACT TRIAL): "70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer"

Main Page: http://www.nejm.org/doi/full/10.1056/NEJMoa1602253

PDF version (Free): http://www.nejm.org/doi/pdf/10.1056/NEJMoa1602253

Supplementary Appendix (Free): http://www.nejm.org/doi/suppl/10.1056/NEJMoa1602253/suppl_file/nejmoa1602253_appendix.pdf

See also,

Hunter perspective (2016) (Free): http://www.nejm.org/doi/pdf/10.1056/NEJMp1608282

Hudis editorial (2016) (available for purchase): http://www.nejm.org/doi/pdf/10.1056/NEJMe1607947

The ASCO Biomarker Guideline Update was prompted by the publication of the MINDACT trial results in August of 2016 by Cardoso et al.

ASCO Guideline Update (2017): http://ascopubs.org/doi/full/10.1200/JCO.2017.74.0472