Mammaprint Results

Butterfly1234

I'm starting this thread because I see that so many women have taken the Oncotype test. My breast surgeon recommended the Mammaprint/Blueprint because there's no intermediate "gray" area, I'm new to all if this so I'm not endorsing or recommending any test. The reason for this post is to discuss our treatment options. My RO and MO were sure I wouldn't need chemo and I came back Luminal B high risk. I have a lot of questions to ask him before I decide on chemotherapy. My nodes are clear, stage 1, clean margins, 9mm tumor, high levels of estrogen/progesterone receptors, Ki/67 5-10%, HER-2 neg. prior to these test results my treatment plan is 3 weeks of radiation and hormone therapy. 66 and post menapause. I don't have a hard copy of my test results. The breast surgeon nurse told me I need chemo, rather matter of factly which really upset me. The only number I have from the test is -0.13. Negative -1.00 is at the highest. range for high risk. I've posted on several threads being new to the community and I am so thankful for the support and love

BarredOwl

Hi Butterfly1234:

Could you please clarify your diagnosis? You noted that your nodes were "clear", yet your profile currently shows "Stage IB", which requires a specific degree of lymph node involvement, specifically "pN1mi" (i.e., "Micrometastases (greater than 0.2 mm and/or more than 200 cells, but none greater than 2.0 mm") as shown in lines 3-4 of the Chart on page 1 of this summary of the AJCC Staging Manual (7th Edition):

AJCC Staging Summary (7th Edition): https://cancerstaging.org/references-tools/quickreferences/Documents/BreastMedium.pdf

A tumor that is 9 mm in size would be "T1b" in terms of size only:

T1 Tumor ≤ 20 mm in greatest dimension - includes any one of the following:

T1mi Tumor ≤ 1 mm in greatest dimension

T1a Tumor > 1 mm but ≤ 5 mm in greatest dimension

T1b Tumor > 5 mm but ≤ 10 mm in greatest dimension

T1c Tumor > 10 mm but ≤ 20 mm in greatest dimension

The "T" or size component (e.g., T1b) does not determine TNM stage, which also considers "N" and "M" status.

If a person is purely node-negative ("N0"), with a "T1"-size tumor (including any one of T1mi, T1a, T1b or T1c), and M0, then they would be:

pT1 N0 M0 or Stage IA.

With a T1b-sized tumor, this may be more specifically designated as: pT1b N0 M0 (also Stage IA).

Please confirm it with your team.

BarredOwl

BarredOwl

Hi Butterfly1234:

I did not receive the test, but can provide some general information about it for those who have received the MammaPrint and BluePrint tests.

Please be sure to request an explanation of your results, and to obtain copies of all documents provided by Agendia (test provider) for your review and records. It is essential to confirm the accuracy of the result, whether received verbally or transcribed into a medical record, against the original report bearing your name.

Based on information on the Agendia website as of this date, in the USA, the documentation should at least include:

http://www.agendia.com/healthcare-professionals/breast-cancer/test-results/

(a) MammaPrint (FFPE) Result

Depending on the MammaPrint result, either a "High Risk" or a "Low Risk" report will be received.

There is a field for "Additional Comments," so it is essential to obtain a copy of your personal report.

(b) BluePrint Result

Depending on the "molecular subtype" result according to BluePrint, you will receive one of the following three reports: a "Luminal-type" report, a "HER2-type" report, or a "Basal-type" report.

There is a field for "Additional Comments," so it is essential to obtain a copy of your personal report.

(c) Summary of Results

One of the following four reports will be received:

(i) Summary Page Low Risk Luminal-type A; or

(ii) Summary Page High Risk Luminal-type B; or

(iii) Summary Page High Risk HER2-type; or

(iv) Summary Page High Risk Basal-type

(d) Any additional documentation received

For example, other members here have received additional explanatory sheets regarding certain results from the MINDACT trial.

---

With a "High Risk" and "Luminal-type (B)" result, until you get copies of your own reports and materials, you may be interested in the sample documents available on-line:

See for example, this MammaPrint FFPE "High Risk" sample report (USA):

http://www.agendia.com/media/25Sep15_MP-High-Risk.pdf

See for example, this BluePrint "Luminal-type" sample report (USA):

http://www.agendia.com/media/24Feb15_BP-Luminal.pdf

See for example, this "Summary Page High Risk Luminal-type B" sample report (USA):

http://www.agendia.com/media/High-Risk-Luminal-62116.pdf

Patients should also keep in mind that the content of the Diagnostic reports (a, b), Summary of results (c), and other materials (d) are summary in nature. These materials present only a portion of the available data in top-line form. Selected data points from certain studies are presented, but important context is not provided (e.g., in some cases, available confidence intervals are not shown, the sizes of groups (n) are not shown, etcetera). Footnotes to various study publications are included. Medical oncologists should be familiar with these studies and associated caveats, and it is presumed that patients will receive these materials together with explanatory advice from a medical oncologist who has expert familiarity with the underlying scientific literature and other relevant studies, as well as the details of diagnosis and patient presentation.

Best,

BarredOwl

BarredOwl

General Information regarding the MINDACT trial of MammaPrint ("70-gene") test:

Results from the MINDACT trial with 5 years of follow-up were recently published (Cardoso (2016)). This is a highly detailed and technical publication, so I refer others to the original. The documents can be accessed here:

Cardoso (2016):

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

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

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

(Available for purchase)

The MINDACT trial design incorporated two risk classifications. It used a Clinical Risk Classification (using a MODIFIED version of Adjuvant! Online) to assign clinical risk as either "Clinical Low Risk" or "Clinical High Risk". It used a Genomic Risk Classification (using the MammaPrint test result) to assign genomic risk as "Genomic Low Risk" or "Genomic High Risk".

This yielded four different study groups (MP = MammaPrint)

(a) Clinical Low / Genomic MP Low

(b) Clinical High / Genomic MP Low ("discordant")

(c) Clinical Low / Genomic MP High ("discordant")

(d) Clinical High / Genomic MP High

The group that is Low Risk by both criteria (Group (a)) and the group that is High Risk by both criteria (Group (d)) are "concordant" (same: Low Low or High High).

The two groups that have different clinical and genomic risks (one Low and one High) are "discordant" (Groups (b) and (c)).

Part of the study looked at whether directing chemotherapy decisions on the basis of genomic risk or on the basis of clinical risk led to any difference in distant recurrences in the "discordant" groups. Given the complexity and limitations of the results for some groups, patients should (as always) obtain advice regarding the implications of the trial results for their decision-making from an expert medical oncologist.

Always confirm your understanding of any information from such a publication with your Medical Oncologist to ensure accurate understanding and correct application to your situation.

BarredOwl

BarredOwl

Hi Butterfly1234:

In your upcoming appointment with your Medical Oncologist, be sure to ask about your "Clinical risk classification" (according to the MINDACT criteria) and its related implications:

(1) Given your MammaPrint "High Risk" result and other pathologic features, according to MINDACT criteria, would you be considered:

Clinical Low Risk / Genomic (MammaPrint) High Risk?

OR

Clinical High Risk / Genomic (MammaPrint) High Risk?

(2) What did the MINDACT trial find about this group, including any caveats or limitations?

(3) What other information is available from the trial that speaks to your particular case (e.g., node-negative, hormone receptor-positive, HER2-negative disease)?

(4) How do the MINDACT trial results affect understanding of the possible benefit of chemotherapy in your case?

Some types of disease may be particularly responsive to endocrine therapy (e.g., high percentage of ER+ cells). Some types tend to respond better than others to chemotherapy. Some may benefit from both kinds of treatment.

The study groups in the MINDACT trial were relatively diverse. Therefore, in addition to the above:

(5) Please also ask whether your BluePrint subtype information (Luminal-type (B)) provides additional information that might further inform your decision-making about added chemotherapy. For example, what are the possible implications of your "Luminal-type (B) status-as-determined-by-BluePrint / MammaPrint" with respect to prognosis (distant recurrence risk), response to chemotherapy, and potential benefit of chemotherapy?

Given that the MINDACT trial results are still relatively new and clinical guidelines from ASCO and NCCN have not addressed Cardoso (2016), you may wish to inquire if there is a "tumor board" (a multidisciplinary panel) at your current institution that could consider your case. Optionally or in addition, you may wish to seek a second opinion from another medical oncologist at an independent institution. Many look for an NCI-designated Cancer Center (be sure to confirm in net-work). With a second opinion, you have the option to seek treatment with your current team or second opinion team.

https://www.cancer.gov/research/nci-role/cancer-centers/find

Best,

BarredOwl

Butterfly1234

Hi Barred Owl,

I just wrote a very lengthy reply which vaporized. So here I go again. Thank you so much for your advice and information. I am printing the information you provided and bringing it with me to my office visit. I feel like we are kindred spirits. I have explored the Agendia website and reviewed all of their summary reports. I also spoke with one of their Medical Consultants early on in my journey and before I had my MammaPrint test results.

I am definitely State 1A and will change that on my profile.

I will check out the links you sent above. I'm pretty sure that I am in the discordant group - low clinical risk/high MP genomic risk. That's the research I really have to look at. What I've read so far about Luminal B is somewhat contradicting. I've read that this subgroup doesn't respond well to hormone therapy. However, that's because the receptor levels are low but mine are very high. Also, when I look at my notes from the conversation I've had with the Medical Consultant I have two ? marks next to response to chemotherapy for Luminal B. I'm trying to figure this all out.

I'm on track right now for three weeks of radiation and hormone therapy. I'm hoping to avoid chemotherapy if I can do that responsibly. I truly worry about the stress on my body. I already have osteoporosis and since I'm post menopausal the medication I will be taking will affect this. My MO said that we would monitor this carefully. I've learned there's nothing easy about breast cancer. I have so many friends who are survivors that it gives me great hope.

I will learn more when I finally can see my entire report. I need to weigh the risk factors and benefits of chemotherapy. I know the Medical Director told me that these are group and not individual scores. The only score I have thus far, is 0.-013 for high risk. With 0 being the "division" between high and low, I'm wondering if that is also something else to factor into my decision?  

Thanks to you and all who are part of this thread. Blessings.  

BarredOwl

Hi Butterfly1234:

I am hoping you have a very productive discussion with your oncologist regarding these questions and risk/benefit. Be sure to take notes, and don't hesitate to review key points in your notes with your MO to confirm you accurately captured the information. In addition, some people have asked to record appointments on their phone.

I think what the Agendia person was getting at is that the recurrence risk information featured in the reports is based on the results of various clinical trials that evaluated outcomes in groups of patients. So in your case, the MammaPrint test provides certain recurrence risk information based on what was seen in trials that looked at outcomes in certain groups of patients with tumors that were classified as MammaPrint "High Risk". In other words, they are average recurrence risk estimates based on risks determined for a group.

Recurrence risks can be of different types (e.g., distant metastatic recurrence risk) and time-frame (e.g., 5-year, 10-year), and patients may have received different interventions (e.g., chemotherapy plus endocrine therapy; endocrine therapy alone). Be sure to note these key details.

How the MammaPrint test works:

The test is "binary" in the sense that the output is a classification as one of two possible outcomes: "High Risk" or "Low Risk." That classification is based on the computed MammaPrint Index ("MPI") number, which is a number between -1.0 and +1.0 that is generated from the patient's mRNA microarray data by a software program which uses an algorithm or "classifier". First, mRNA is extracted from a sample of the tumor. Then, the levels of mRNA produced by 70 different genes are determined using microarray technology. The computer program takes the mRNA expression data from 70 genes, determines a "sample expression profile" for the tumor and assesses its degree of similarity to a standard low risk expression profile. The standard or low risk "template" profile is a "mean expression profile of 44 tumors with a known good clinical outcome" (per a regulatory document). The degree of similarity of the sample profile to the standard low risk profile is expressed as an MPI value between -1.0 and +1.0, with +1.0 being the highest degree of correlation. After this correlation step, the calculated MPI value is used to classify one as either "high risk" or "low risk" (relative to the "clinical classification threshold" of zero), within the accuracy of the test.

Thus, the MPI value reflects the degree of "correlation" between the sample profile and the low risk standard or template profile. The output of the test is the final risk classification of high risk or low risk. Various clinical validation studies were performed to assess the "prognostic" ability of the test. They determined various types of average recurrence risk among a group of patients classified as "high risk" and among a groups of patients classified as "low risk". Thus, the average recurrence risks provided are based on risks determined for the high risk or low risk group as a whole.

Please confirm it with your Medical Oncologist, but to my knowledge, the clinical studies in the adjuvant setting did not assess or report risk by specific MPI value. So, I believe it is not known whether there are any differences in recurrence risk (or the size of such differences, if any, or the statistical significance of such differences, if any) based on specific MPI values within the same risk category (e.g., High risk, MPI -0.3 versus High risk MPI -0.9). Until such studies are done, we don't know whether or not it behaves as a continuous variable.

BarredOwl

Butterfly1234

Thank you again for all of this information. I read through all of the links you sent me and I'm preparing for my office visit. Tuesday will mark 30 days since my surgery so if chemo is required I have to get going sooner than later. My MO is suppose to call me tomorrow after reviewing test results. I will call in AM to make sure I can get in to see him ASAP. He knows my radiation simulation is scheduled for Thursday, fortunately both are in the same building, My head is spinning but I cope better when I am being proactive. Enjoy the rest of your Sunday. I admire how well informed you are and appreciate your guidance