"High Risk" Mammaprint Luminal Bs- what was your 'score'?

butterfly, did you get the oncotype as well?

MammaPrint may have a "binary" output (High Risk vs Low Risk), but as a result of the design of the MINDACT trial and certain findings pertaining to "discordant" groups, I have wondered whether a view that the test is more black and white than Oncotype is still entirely accurate.

BarredOwl

Hi Butterfly1234:

That is an interesting comment re "the high risk continuum", which was the original question in this thread. Please discuss it with your Medical Oncologist.

As noted above and in your other thread, I am unaware of any published validation study in the adjuvant setting that has assessed or reported on differences in distant recurrence risk based on MammaPrint Index values falling within the same risk category. If you are were provided with a reference that demonstrates such differences, please share the link.

I note that prognostic information derived from a biomarker test should not not be heavily based on the same data set used to develop the test or its clinical classifier, but should be based upon the performance of the test in an independent data set to the extent possible. See item (4) of the table below, taken from a 2016 ASCO biomarker guideline which included a discussion of the reliability of the evidence supporting such tests, and in which "[t]he panel followed the proposals made by Simon et al [9] for determining whether a biomarker test has clinical utility":

ASCO Biomarker Guideline 2016:http://ascopubs.org/doi/full/10.1200/JCO.2015.65.2289

Note: This guideline was issued prior to publication of the MINDACT results, and may not reflect current clinical practice, particularly in node-negative, hormone receptor-positive, HER2-negative invasive breast cancer.

In other words:

Febbo (2011): "NCCN Task Force Report: Evaluating the Clinical Utility of Tumor Markers in Oncology"

http://www.jnccn.org/content/9/Suppl_5/S-1.long

"For larger datasets, identifying a priori a "discovery" or "training" subset of samples and a "validation" or "test" subset of samples is common practice. The assay's characteristics are tested and refined in the discovery subset and, when the assay parameters are fixed, applied to the validation subset. Although this minimizes bias and overfitting within the dataset, a concern remains that characteristics specific to the dataset being used may result in validation that does not generalize to other sample or patient populations. Thus, independent validation sets are required for the most rigorous clinical validation of an assay."

Use of data from the "training" set (used to discover or establish the test) to prove the prognostic or predictive capabilities of a biomarker test is not very sound. Proper clinical validation is the basis for reasonable reliance in clinical decision-making, and ordinarily should be based on testing performance in an independent validation set, followed by a peer-reviewed scientific publication.

In the absence of adequate clinical validation, such differences would be a reasoned hypothesis. It would also have been a reasoned hypothesis to expect a different, more definitive result for the Clin Low-Genomic (MP) High group in the MINDACT trial, but this is not what was observed.

BarredOwl

[Edit: Added last paragraph]

BarredOwl,

Thank you for all your very useful information and links. I have read most of them, especially the NEMJ article on the MammaPrint. I am in the ''low clinical risk/high genomic risk'' category. From what I read in the NEMJ, if I understand it correctly, it says:

"Among patients at low clinical risk and high genomic risk, those who underwent randomization on the basis of genomic risk (and therefore received chemotherapy) had a 5-year rate of survival without distant metastasis of 95.8% (95% CI, 92.9 to 97.6), as compared with a rate of 95.0% (95% CI, 91.8 to 97.0%) among those who underwent randomization on the basis of clinical risk (and therefore received no chemotherapy) (adjusted hazard ratio for distant metastasis or death with chemotherapy vs. no chemotherapy, 1.17; 95% CI, 0.59 to 2.28; P = 0.66) (Fig. 2B). This finding does not show any advantage of directing therapy on the basis of genomic risk among patients at low clinical risk but high genomic risk, since these patients had no benefit from the use of adjuvant chemotherapy. In addition, among patients in the discordant risk groups, there was no significant difference between the chemotherapy group and the no chemotherapy group with respect to disease-free survival (Fig. 2C and 2D) and overall survival (Fig. 2E and 2F). Sensitivity analyses in the perprotocol population are provided in Table 2. Data regarding intervals without distant metastasis are shown in Figure S6 in the Supplementary Appendix."

In the final discussion, it also states, : "Some 50% of the study patients were defined as being at low clinical risk. In this group, we did not find any meaningful difference in the 5-year rate of survival without distant metastasis between patients at high genomic risk who received chemotherapy and those who did not receive chemotherapy. On the basis of these data, the results for the 70-gene signature do not provide evidence for making recommendations regarding chemotherapy for patients at low clinical risk. In clinical practice, genomic testing is best used in combination with clinical–pathological factors, since the gene signature has an added and independent prognostic value."

So am I correct in concluding that in my situation, chemo would not be helpful? I am low clinical risk. ER+, HER2-, tumor under 2CM, Negative nodes, bilateral mastectomy, June 2017. Also negative on all the genes tested in the Myriad 'MY RISK' genetic testing. My oncotype result was 21. (Very low in the intermediate category). Based on my oncotype results and my low clinical risk, my medical oncologist had originally recommended only Aromitase inhibitor. (I am post menopausal). However, after receiving the results of the MammaPrint, showing "high risk", and Luminal B, he is now recommending chemo. Going for 2nd opinion next week. Any opinions or feedback would be greatly appreciated.

Thank you BarredOwl. I went for 2nd opinion, and this oncologist also feels I should do chemo. They feel because of the Luminal B, that I would benefit from chemo, even though I am clinically low risk. (although the 2nd onco feels that my 1.9 cm tumor is another reason to do the chemo. And she added that the Luminal B may not respond as well as expected to the Arimidex. I have read all the articles, (referenced above), including NEJM, Journal of clinical oncology), and tons of other research, and they all point to not needing chemo. I am so confused because both oncos recommend chemo. My mammaprint score was in the high risk category, 0.090, (which was pretty close to the 0.0), but not sure that makes a difference. And I am clinically low risk, according to MINDACT study, and Adjuvant.

If I don't do chemo, I don't want to kick myself down the road if I get distant metastasis (which is why the oncos recommended chemo), but I also do not want to put myself thru unnecessary chemo and toxicity. And the thought of hair loss when the chemo may not even be necessary, really sends me into a depression. They said they would give me a very "mild chemo", (if there is any such thing!) CMF is what I would get, every two weeks, 8 treatments total, with a booster shot the day after each treatment. They claim hair loss wouldn't be "that great", (compared to some other regiments), but there would still be thinning, and suggested the Penquin cold cap. Wish I knew more about CMF.

And I really wish I knew what to do. I have two oncos recommending chemo, but my gut is telling me it may not be needed. I have done so much research, my head is spinning. I haven't slept in weeks. I don't know what to do :-(

luvtocraft, I had a 21 onco-score also. I was offered the mammaprint, but didn't do it. My half-sister did CMF many years ago. She fared well through it all. She lost some hair, but it wasn't really noticeable. She is doing well 15 yrs later! It's a hard and personal decision. My MO left it up to me, but leaned towards chemo. I finally just followed my gut. Mentally, I needed to do all that I could, while I could, to keep from having a recurrence. Of course, we all know, there is still no guarantee, but it eased my mind. My hair loss was not near as "difficult" as I had imagined...surprised myself. If you start chemo and feel you cannot tolerate it, you don't have to continue. I am not advocating that, but ultimately, it is YOUR decision... I had my MO reduce my last dose, bc I was having a (minor) allergic reaction that I didn't like. I have no long term SE's as far as I know and I tolerated chemo very well. There is probably another thread that pertains to CMF. It looks like you are getting all of the information you can to make the right decision! Good luck with whatever you decide:).

Hi LuvToCraft:

You have received some good perspectives above.

I have no answers for you. The MINDACT publication is on point in noting: "Ultimately, the decision to receive or forgo chemotherapy (or any other treatment) lies with each patient who is properly informed about the potential side effects and the potential benefits of such treatment. For the same risk–benefit scenario, different patients may make different decisions."

I did not face a similar decision, but I found it exhausting and challenging to consider the option of tamoxifen under my relatively unusual circumstances (isolated tumor cells on the DCIS side of unknown ER, PR or HER2 status) in which I was advised it would be equally reasonable for me to accept or decline it.

Here are some additional observations. Please confirm all information with your team if it influences your thinking.

I checked the Agendia website and see that they have revised the web site and some report content in light of the results of the MINDACT Trial. I noticed that the materials appear to treat Clinical High Risk / MammaPrint Low Risk (n = 1550 patients) and Clinical Low Risk / MammaPrint High Risk (n = 592 patients) somewhat differently. This likely reflects the quality and amount of the data for these groups. For example, the Clinical High Risk/ MammaPrint Low Risk group was the subject of the primary analysis, which met its objective, whereas the Clinical Low Risk/ MammaPrint High Risk group was not the subject of the primary analysis, and was a much smaller group of patients.

For example, by my layperson reading, on this page, MINDACT results are featured for every group EXCEPT for the group considered "Clinical Low Risk" / "Genomic (MP) High Risk":

Agendia Feature: Go to to www.agendia.com, and under the menu for "Health Care Professionals", click on "The MINDACT Trial" to access the feature entitled, "LEVEL 1A EVIDENCE. MAMMAPRINT® IS THE FIRST AND ONLY GENOMIC ASSAY TO ATTAIN LEVEL 1A CLINICAL UTILITY EVIDENCE FOR CHEMOTHERAPY BENEFIT IN EARLY-STAGE BREAST CANCER PATIENTS"

The gist is that a low risk genomic result may lead to a recommendation to forego chemotherapy.

____________________________________________________________________________

Did you receive a BluePrint test? BluePrint categorizes patients into three groups: Luminal-type; HER2-type; or Basal-type. The MammaPrint result is used to further subdivide the Luminal-type into two subgroups:

- BluePrint Luminal-type and MammaPrint Low Risk ==> Luminal-type (A)-like

- BluePrint Luminal-type and MammaPrint High Risk ==> Luminal-type (B)-like

In addition to your MammaPrint Result (High risk) and BluePrint test result (Luminal-type), you should have received "Summary Pages" for High Risk Luminal-type (B). If you do not have a copy of such a document, be sure to request copies of all test results and related documentation for your review and records.

Regarding potential chemotherapy benefit in light of MINDACT, please compare the Sample Summary Pages issued in the US for LOW RISK LUMINAL-TYPE (A) versus HIGH RISK LUMINAL-TYPE (B) regarding predicted benefit of treatment at 5-years based on Reference (2) (Cardoso):

(a) Low Risk Luminal-Type (A) Summary Pages:

http://www.agendia.com/media/June2017_LR-Luminal_A-Summary-Pages_FINAL.pdf

Note this section of the above document:

(b) High Risk Luminal-Type (B) Summary Pages:

http://www.agendia .com/media/June2017_HR-Luminal_B-Summary-Pages_FINAL.pdf

Note this section based on data from the ER+/HER2-/LN0 subset from the MINDACT trial and the comment regarding a potential chemotherapy benefit:

The DMFI (distant-metastasis free interval) value of 94.6% illustrated above with Chemotherapy plus Hormonal Therapy seems to be taken from the Supplementary Appendix of Cardoso (See the last line of Table S 9: Outcome by genomic risk when following genomic treatment strategy (G-low versus G-high), in the subgroup of HR+/HER2-/LN0 patients). In Table S9, the chemotherapy appears to have been ACT. Please see Table S9 and the legend to Table S9 for a discussion of the analysis and the assumptions. With statistical averages based on a group as a whole, there may be subgroup(s) who might benefit more or less.

Regarding clinical risk, the reference to "Clinical Low Risk" category per MINDACT criteria can be misleading in some ways. Multiparameter tests like Oncotype or MammaPrint are typically used to further inform decision-making in patients in whom chemotherapy is being considered because using standard clinical and pathologic criteria their distant recurrence risk would typically warrant consideration of or a recommendation for chemotherapy in addition to endocrine therapy.

Regarding "clinical risk", please also note that that High Risk Luminal-Type (B) Summary Pages include a "double-cross" footnote which indicates that certain patients categorized as "Clinical Low Risk" per MINDACT criteria would be deemed high risk clinically under some consensus guidelines:

The above observations may help explain in part the advice you received. Also, the advice received would not be based on the MammaPrint result alone, but a synthesis of all relevant information including those results in light of clinical and pathologic factors and Oncotype results as well.

If you still have concerns or questions, do not hesitate to arrange further consultation(s) with your Medical Oncologist(s) to specifically discuss any outside information that is of concern to you. (I highlighted copies of research papers and took them to my appointments.) If in doubt and/or if you would like further input, you may wish to inquire whether there is a multidisciplinary "Tumor Board" at your current treatment centers that would consider your case. Optionally or in addition, if you have time before timely initiation of treatment (please confirm it with your team), you may wish to seek a third opinion, which some people pursue. Many look for an NCI-designated cancer center (confirm in-network):

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

Although you may need to travel a bit, you can choose to seek treatment locally.

Please take some time this weekend to give yourself a break and rest. I send my best wishes for information gathering and decision-making.

BarredOwl

Barred Owl,

I did receive a BluePrint score of Luminal B, (+0.57 from a scale of -1 to +1) which I believe, in addition to the Mammaprint .090 score, is what put me in High Risk on the assay. i tried attaching the picture of my actual results, but when I tried to post, it said "you are not allowed to post links at this time. I have no idea why it wouldnt allow me to post those images.

<< From your post - BluePrint Luminal-type and MammaPrint High Risk ==> Luminal-type (B)-like >>

I understand what you are saying regarding the Low Clinical/High genomic risk that MINDACT hasn't really addressed. If you are low clinical/low geneomic, then no chemo. If you are high clinical/low genomic, also no chemo. And obviously high/clinical/high genomic would benefit from chemo simply based on the high clinical (now reinforced high genomic). This is why I am at such a gut-wrenching place in deciding whether to do the chemo, (CMF was recommended). If I had positive nodes, or a larger tumor, or other unfavorable aspects, then it would be a no brainer, I would do the chemo. But not being sure if any benefits would be derived from chemo, in my situation, I am at a loss. The only explanation given to me is that Luminal B, MAY be a little more aggressive. But from everything I know, and have read, chemo itself can be worse, can cause future cancers, can make cancer cells more resistant, can cause permanent cognitive issues, aside form all the side effects while going through treatment.

My summary page(exactly as you have shown in your post) showed DFMI of 94.6 benefit with Chemo AND hormone therapy. One of the drawbacks in this study, is that they did not test to see what benefits would be obtained with hormone therapy alone. Even the doctor at Agendia with whom I spoke, said that was a major problem. I am on the Arimidex, and have no way of knowing if it will be enough to limit my risk of mets. According the my RS of 21 on oncotype Dx, no chemo was recommended (only hormone therapy), by ANY oncologist. I wish I could just 'UNSEE" the mammaprint results and just rely on the Oncotype!!!

** Can you please explain a little further, what you mean by what you wrote:

<< Regarding "clinical risk", please also note that that High Risk Luminal-Type (B) Summary Pages include a "double-cross" footnote which indicates that certain patients categorized as "Clinical Low Risk" per MINDACT criteria would be deemed high risk clinically under some consensus guidelines:

C-low

Comprehensive Consensus Guidelines may differ and categorize a patient with these clinical factors as high risk.

The above observations may help explain in part the advice you received. Also, the advice received would not be based on the MammaPrint result alone, but a synthesis of all relevant information including those results in light of clinical and pathologic factors and Oncotype results as well. >>

** How do I find out if I fall into that category of being deemed clinically high risk?

-----------------------

As far as the oncotype, both oncos are now completely disregarding the Oncotype results, in favor of the MammaPrint, due to its results of high genomic risk. They are also discounting my positive prognostics of no lymph nodes, ER+, HER2-, tumor size 1.9cm, along with double mastectomy. I did show the oncologist all my printed material from the NEJM, and from Journal of clinical oncology, along with several other recommendations, as mentioned in my very first post:

"Among patients at low clinical risk and high genomic risk, those who underwent randomization on the basis of genomic risk (and therefore received chemotherapy) had a 5-year rate of survival without distant metastasis of 95.8% (95% CI, 92.9 to 97.6), as compared with a rate of 95.0% (95% CI, 91.8 to 97.0%) among those who underwent randomization on the basis of clinical risk (and therefore received no chemotherapy) (adjusted hazard ratio for distant metastasis or death with chemotherapy vs. no chemotherapy, 1.17; 95% CI, 0.59 to 2.28; P = 0.66) (Fig. 2B). This finding does not show any advantage of directing therapy on the basis of genomic risk among patients at low clinical risk but high genomic risk, since these patients had no benefit from the use of adjuvant chemotherapy. In addition, among patients in the discordant risk groups, there was no significant difference between the chemotherapy group and the no chemotherapy group with respect to disease-free survival (Fig. 2C and 2D) and overall survival (Fig. 2E and 2F). Sensitivity analyses in the perprotocol population are provided in Table 2. Data regarding intervals without distant metastasis are shown in Figure S6 in the Supplementary Appendix."

In the final discussion, it also states, : "Some 50% of the study patients were defined as being at low clinical risk. In this group, we did not find any meaningful difference in the 5-year rate of survival without distant metastasis between patients at high genomic risk who received chemotherapy and those who did not receive chemotherapy. On the basis of these data, the results for the 70-gene signature do not provide evidence for making recommendations regarding chemotherapy for patients at low clinical risk. In clinical practice, genomic testing is best used in combination with clinical–pathological factors, since the gene signature has an added and independent prognostic value."

----------------------------------------

I am exploring other less toxic options to prevent recurrence such as vitamin C infusions, PolyMVA infusions, chelation therapy, intermittent fasting, etc. Not sure if that may be a better approach in my situation. I am not going to feel comfortable whichever way I go. If I DON'T do chemo, I will always worry if I will regret that decision if it comes back as metastasis, but if I DO the chemo, what long lasting toxic effects will it have caused for my body, when it may not have even been warranted in my situation. (Plus, as we all know, and my onco pointed out, even WITH chemo, metastasis can still occur). Like I said, I wish I knew the right answer. :-(

On a side note, has anyone heard anything about the RGCC blood test out of Greece?

LuvToCraft, in one of your posts above you said, "I wish I knew more about CMF." I'm going to suggest that getting more detailed information from your doctors about chemo might help you with your decision. Find out the chances of each particular side effect and what could be done about it if it happened. Find out if you have any options for type of chemo, too. Talk about how your own personal health and family health history, and your lifestyle and activities, might play into the decision. Then instead of vague fears about chemo (understandable), you would have more information to be able to make a more educated decision.

It's a great thing for you to have BarredOwl here discussing the tests. BarredOwl, you rock.

Luv, because you are new. yOu have to post more to be allowed to post links and pics.

Hi LuvToCraft:

According to Sledge (2016), while invasive lobular breast carcinoma (ILC) is the second most prominent histologic form of breast cancer, it accounts for around 10%–15% of invasive breast tumors. One might expect a similar representation of ILC in the various validation studies for Oncotype and for MammaPrint. ILC tends to give low or intermediate Oncotype Recurrence Scores.

Re: "I guess bottom line is I have to try and find out what my % recurrence risk would be with hormone alone, but none of them were able to say."

Perhaps if you ask for any type of estimate or range, with all associated caveats and limitations, they might take a shot at it. Can the prognostic information from the Oncotype report be used, or do they feel it is an underestimate?

Re: "Everyone who achieves a high risk MP score is 29% high risk without ANY treatment, (as per pg 1 of MP results), and everyone has that same 94.6% DMFI at 5 years with chemo and hormone.

These two points are made in the Summary Pages:

These values were measured in different studies (one from a study predating MINDACT and one from a subset of MINDACT patients) in different patient populations and cannot be directly compared.

The 29% is a "10-year risk of Recurrence [if] Untreated." The term "Recurrence" is vague. Is it a distant recurrence estimate or any recurrence (loco-regional and/or distant)? Unfortunately, I could not find the data points (22% at 5 years; 29% at 10 years) in the cited reference (Reference (1), Buyse et al.). Perhaps Agendia has more information about this.

Not everyone has the same 94.6% DMFI at 5 years with chemotherapy ("CT") plus endocrine therapy ("ET"). The illustration shows that the 94.6% number was obtained from a group of patients who were all "ER positive, HER2 negative, Lymph Node negative patients (ER+/HER2-/LM0) from the MINDACT Trial."

Re: "Although I guess the potential benefit with chemo would be that 94.6%?"

That is a relatively nice statistic (good outcomes can be achieved in this group with ET + CT), but as you noted, it reflects the combined effect of ET + CT. Be careful not to confuse the observed percent DMFI (a single data point) with the potential benefit of chemotherapy, which would be determined (for example), from the difference between distant recurrence risk with ET alone versus risk with ET + CT. The benefit represents the amount of risk reduction attributable to CT.

I am sorry that I cannot be more helpful. While I have a basic grasp of the mechanics of the tests, the clinical research publications are hard for me to understand. I do not know how the various results are interpreted by experts and applied in practice, so I cannot provide you with any real guidance other than to suggest questions or areas of inquiry.

Given the less common diagnosis of ILC and your unanswered questions and concerns, if you have time and if feasible (in-network, etc.), you may wish to consider seeking a third opinion from an NCI-designated cancer center (see link in my prior post). If you choose to pursue a further opinion, then as part of the process, you may also wish to request an independent pathology review (actual slides sent overnight).

BarredOwl

Hi LuvToCraft:

Re: "I just noticed on my MammaPrint summary page, that it did have 2 dots on the graph for MY individual score of (minus) -.090. These correlated to a 5 yr risk of recurrence of approx 18%, and a ten year of approx 23%. So I guess what I can gather from this info is that the AVERAGE recurrence risk of 29% that is given for high risk, is for everyone within that (minus) -1.0 to 0.0 bracket. So since mine is -.090, the risk is somewhat lower, (not by much, but slightly), than someone e.g, in your above picture, with a .350 score, or even someone with a closer to 0.0 score."

Based on positioning of the dots, the 5-year and 10-year values do appear slightly different as compared with the sample report. The original topic of this thread related to whether different "high risk" MammaPrint Index ("MPI") values are associated with differences in risk. At the time, we found no evidence for it. Since then, I have seen a few publications indicating that an "ultralow risk" group can be identified. You should ask your MO whether that risk information (~18% and ~23%) is indeed personalized (and not just some weird printing glitch) and if he knows what evidence supports it (either internal Agendia information or a scientific publication).

__________

Re: "So my untreated risk in 5 years without ANY treatment would be approx 18%, and perhaps with hormone therapy can be half of that? I would opt out of chemo with those figures."

I don't know. Please confirm your understanding with your MO.

Be sure to inquire what type of "recurrence" estimate is it? Is it a measure of distant recurrence risk or any recurrence?

__________

Re: "And a side note is that I had read somewhere that the benefits of chemo only kick in for the first 5 years, (as per the blue bottom graph showing 94.6%, and then from 5 to 10 yrs, your risks are the same whether you had chemo or not?"

Please ask your MO how it works over time. In general, Cardoso stated: "We report 5-year median follow-up results. It is recognized that adjuvant chemotherapy exerts most of its beneficial effects early in the course of the disease (i.e., during the first 5 years), thus justifying our primary end point.24 Since the majority of tumors in our study population were considered to be "luminal," with a continuing risk of relapse beyond 5 years, we acknowledge that long-term follow-up and outcome data will be essential, and we are collecting those data. Hazards for events can have a complex time de- pendence, and Adjuvant! Online and the 70-gene signature were validated for 10-year outcomes; therefore, the planned 10-year follow-up analysis may be of interest."

__________

Re: "Have you heard anything about the Prosigna/PAM50 (NanoString Technologies Inc.) I am going to ask my MO if he can request that test. It would definitely help me in my decision. I now have the oncotype showing no chemo needed, the MammaPrint showing a benefit with chemo, so this would be a definite deciding factor."

I believe the test is included in the ASCO Biomarker Guideline and Update (Free pdfs under PDF tabs):

2017 ASCO Biomarker Update: http://ascopubs.org/doi/full/10.1200/JCO.2017.74.0472

See Table 1, Recommendation 1.10 re ER/PgR–positive, HER2-negative (node- negative) breast cancer.

2016 ASCO Biomarker Guideline: http://ascopubs.org/doi/full/10.1200/JCO.2015.65.2289

Please confirm it with your team, but it appears that the PAM50 risk of recurrence (ROR) score (Prosigna Breast Cancer Prognostic Gene Signature Assay; NanoString Technologies, Seattle, WA) is used "in conjunction with other clinicopathologic variables, to guide decisions on adjuvant systemic therapy."

Also subject to confirmation with your team, it appears that Prosigna test provides an "Intermediate" risk output in node-negative patients. Per the "Clinical interpretation of literature review" of the 2016 ASCO Biomarker Guideline: "The PAM50-ROR test assists with the decision about adjuvant therapy in patients with ER/PgR-positive, HER2-negative (node-negative) breast cancer.34-36 Chemotherapy should be considered for patients in the PAM50 high-risk group, but is not indicated for patients in the low-risk group. Future studies are needed to inform recommendations about adjuvant chemotherapy in patients with an intermediate PAM50-ROR."

Consistent with the above, Tables 7 and 8 of the Package Insert suggest that test outputs differ by Risk Category, and that the test yields "Low, Intermediate, High" outputs in the node-negative setting.

http://prosigna.com/wp-content/uploads/2016/09/LBL_C02223_06_Package-Insert-Prosigna-Assay-US.pdf

Patients should discuss with their medical oncologist the possible outcomes of any further testing and whether such further testing may or may not provide added clarity in their individual case.

__________

Re: "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603628/, entitled "Identifying patients at high risk of breast cancer recurrence: strategies to improve patient outcomes" and the quote: << Although there was a suggestion of benefit for chemotherapy added to endocrine therapy in high-risk patients, the level of evidence does not meet the threshold for determining clinical utility.>> (mammaprint)

This paper was published in October of 2015 and predates publication of the results of the MINDACT trial in August 2016.

There are a number of studies that show that different tests are not always concordant in individual patients. This is one possible reason why multiple tests may not necessarily clarify the situation for individual patients. The various tests have different designs, different outputs, and varying degrees of validated clinical significance in particular groups of patients, so such comparisons are not always straight-forward. For example, some commentary about one such study noted: "Oncotype DX was validated in patients treated with tamoxifen, while MammaPrint is intended to be used to gauge risk of recurrence for patients ahead of systemic treatment."

Unfortunately, none of these multiparameter tests has been shown to be a perfect predictor of individual outcome. They can help inform or refine predictions of recurrence risk and sometimes of potential chemotherapy benefit, further informing risk/benefit analyses, but the output is not always as clear a signal as patients would wish for.

__________

Re: "https://www.ncbi.nlm.nih.gov/pubmed/16720680/"

This is Paik (2006), one of the main validation trials of the Oncotype test. The results of this study (see Figures 3 and 4 of Paik (2006)) are reproduced in your node-negative Oncotype report (see graph and histogram in second section of the report regarding prediction of chemotherapy benefit).

From the experiences of others here who received the Oncotype test for invasive disease, clinicians tend to use the first graph from the node-negative Oncotype report to provide average 10-year distant recurrence risk after 5-years Tamoxifen associated with Recurrence Score (10 year distant recurrence risk, Tam Alone), probably because the first graph in the report re "Prognosis" is based on the results from a larger group of patients (668 patients) from the NSABP B-14 trial who were all assigned to receive Tamoxifen. The first graph of the node-negative report is based on Figure 4 of Paik (2004): http://www.nejm.org/doi/full/10.1056/NEJMoa041588#t=article

You can ask your MO if the Oncotype risk information from the first graph of your Oncotype report (with Tam Alone) is still a suitable estimate of your 10-year risk of distant recurrence with endocrine therapy alone, or does information from the MammaPrint and/or BluePrint test alter understanding of your distant recurrence risk with endocrine therapy alone? (AIs are comparable or slightly more effective than Tamoxifen.)

________

Re: "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089800/"

This article was published in 2008, before the 2013 publication of RASTER and well before the 2016 publication of MINDACT which included a large number of patients. Please ask your MO whether the observations in this early paper appear to be borne out in the older, post-menopausal patients in subsequent trials, such as RASTER or MINDACT.

BarredOwl

[Edited to add information re Oncotype]

Luv, I need to beg to differ with you on the idea that a oncotype of 21 is low risk. it is NOT. It is intermediate - which has not been determined to be low risk in validation yet. I was a 20, and that was NOT low risk. You got an intermediate risk on the oncotype and a high risk on the mammaprint. To me, they are agreeing with eachother, not discordant at all. I got a 20 on the oncotype and low risk on the mammaprint, and they were not discordant. Intermediate Oncotypes can go either or.