Mamma print ki67 score 30% Help is this gray area for Chemo

Hi Positive2strong:

Please let me know if there are any errors in the following info. To recap your information:

Age: 66

Stage IA: T1c N0 Mx

Size: 1.5 cm (Note: This is T1 in terms of size, specifically "T1c", where T1c Tumor > 10 mm (1.0 cm) but ≤ 20 mm (2.0 cm) in greatest dimension)

Lymph Node Status: 0/4, node-negative (N0)

Additional information from surgical pathology report:

Histology: Invasive ductal carcinoma (IDC) with mucinous features

ER+ PR- HER2-

Nottingham Grade 2/3

ki67 = 20% (revised per your subsequent message)

MammaPrint FFPE test result (from your MammaPrint report):

MammaPrint Index ("MPI") = - 0.592 (negative 0.592)

MammaPrint Risk Category: "High Risk"

BluePrint test result (from your BluePrint report):

Molecular subtype: "Luminal-type"

Combined MammaPrint / BluePrint results (from your Summary Page):

"High Risk Luminal-type (B)"

As explained in the sample BluePrint report on-line for Luminal-type subtype (please confirm on your report):

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

"Luminal-type breast cancers can be sub-stratified into "Luminal A" and "Luminal B" using the MammaPrint categorical result of "Low Risk" and "High Risk", respectively, in combination with the BluePrint Luminal molecular subtype."

In other words, the subtype of "Luminal-type" as determined by BluePrint can be further divided into two sub-categories (either Luminal-type (A) or Luminal-type (B)) based on the MammaPrint risk category:

- If the MammaPrint result is "Low Risk", then the result is Luminal-type (A).

- If the MammaPrint result is "High Risk", then the result is Luminal-type (B). <==== Your situation

Hope that helps with the basic results.

BarredOwl

As noted by mellee, "Luminal B" subtype can weigh in favor of chemotherapy in many patients. (However, it may not necessarily mandate chemotherapy in all cases.) Patients should explore this finding with their medical oncologists.

Regarding Luminal B intrinsic subtype, the scientific literature in this area is extensive, and patients should be cautious about making treatment decisions based on a single report (particularly an abstract which may be preliminary in nature). It is best to discuss such publications with one's medical oncologist, to ensure currency and applicability to the individual case.

Similar "molecular subtypes" were first described by Perou in 2000, using a different methodology. Over time, other methods (e.g., IHC) have been used or newly developed (e.g., BluePrint), which seek to recapitulate or mimic those subtypes. As a result, "Luminal A" and "Luminal B" subtype have been determined using different methods in different clinical studies. Different methods may not be fully concordant with each other (may not classify all patients the same way).

Positive2strong, please be sure to include on your question list for your MO and/or second opinion MO to explain the 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.

BarredOwl

Hi Positive2strong:

Here is some very general information. I am a layperson with no medical training, so if any of this is new to you, please confirm it with your treatment team.

Rationale for Systemic Treatments, such as Chemotherapy and Endocrine Therapy

Some patients are surprised to learn that even relatively small, Stage I, node-negative (N0) invasive tumors can pose some risk of incurable, distant (metastatic) recurrence. This is true regardless of whether local treatment is by mastectomy or lumpectomy plus radiation.

Surgery is a local treatment. There is still some risk that some tumor cells may have broken off and migrated to distant sites before surgery, laying the groundwork for "recurrent" metastatic disease. Such undetected micrometastatic disease may be present after surgery, yet it may not be evident on scans and presents no symptoms initially. Systemic treatments, such as endocrine therapy (e.g., tamoxifen or an aromatase inhibitor for hormone receptor-positive disease), chemotherapy, and HER2-targeted therapy (for HER2-positive disease) may be recommended to address this risk.

How Much Risk?

Based on various studies, clinical and pathological factors that can affect distant recurrence risk include various factors, such as histology (e.g., ductal, lobular), lymph node status, tumor size, ER, PR and HER2 status, and to some extent, grade and the presence of lymphovascular invasion.

Gene expression profiling ("GEP") tests such as Oncotype and MammaPrint are also used to provide "prognostic" information about distant recurrence risk. This recurrence risk information comes from studies of groups of patients that looked at how may patients in a particular "risk category" (e.g., MammaPrint "High Risk") suffered a distant recurrence within a specific time frame (e.g., 5 or 10 years) and how many did not. Statistical information about recurrence risk from such studies is featured in the reports. (Note: Oncotype reports also provide risk information according to Recurrence Score.) Test reports may include one or more different types of recurrence risk information in terms of risk type (e.g., distant or some other type), time-frame (e.g., 5-year, 10-year), or treatments received (e.g., no systemic treatment; endocrine therapy alone; endocrine therapy plus chemotherapy).

Medical oncologists consider the above types of information to gauge a patient's potential distant recurrence risk. Again, recurrence risk estimates are based on clinical studies that looked at the rates of distant (metastatic) recurrence in groups of patients with similar risk profiles (for example, with the same hormone receptor status; HER2 status; tumor size; nodal status; and/or "risk category" determined by MammaPrint or Oncotype).

Note: This type of recurrence risk information can give you an idea of the odds of a similarly situated person in the same risk category (e.g., MammaPrint High Risk), suffering distant metastatic disease in the next five or ten years, based on what was observed in groups. This is useful to inform treatment decisions, but cannot predict the exact outcome of a specific patient.

What is the Potential Effect of Treatment?

Some clinical trials looked at the effect of specific treatments on recurrence risk in groups of patients (e.g., in a group of patients receiving endocrine therapy for five years versus a group of patients receiving no endocrine therapy). This type of trial is the source of information about the potential risk reduction benefit of specific treatments.

Personalized Risk / Benefit Analysis:

The estimated distant recurrence risk, the potential risk reduction benefit of each proposed treatment, the potential for serious adverse side effects of treatment, patient age and co-morbidities, are all considerations in a personalized risk / benefit analysis. For example, the potential risk reduction benefit of chemotherapy is weighed against the incidence of serious adverse events of any proposed chemotherapy regimen, in light of age, personal and family medical history, and co-morbidities (which may affect risk of certain adverse events).

The personal risk tolerance of the patient is also a factor. Because of differences in risk tolerance, people with the exact same diagnosis and risk profile might make different decisions about treatment. For example, one person may wish to do everything possible, whereas another may not feel that the potential benefit outweighs the potential risks.

It can be very helpful to learn how others viewed their situation, the advice they received, and how they came to a decision. However, it is important to understand that the advice that patients receive is case-specific and therefore their decisions are colored by the specific features of their diagnosis and situation (e.g., co-morbidities) (which might differ from yours in material ways) and by their personal risk tolerance.

Because clinical judgment may be involved, a second opinion can be very helpful. It can also help you learn about these things and make a more informed decision, whatever you decide.

BarredOwl

For those interested in the recent MINDACT trial results, the following links are provided.

The Preview Content available for free on the New England Journal of Medicine (NEJM) website is not the complete publication, and it is not a comprehensive description of the study, the published results, or the limitations of certain findings.

The documents can be accessed here:

Cardoso (2016): http://www.nejm.org/doi/full/10.1056/NEJMoa1602253

(The complete article, including all Supplementary Materials, is available for purchase.)

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

(The complete article is available for purchase)

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

You can purchase a one-day pass to the NEJM, download and save complete pdf copies of the Cardoso paper and the Hudis editorial (plus any other articles of interest). Be sure to access and save down pdf copies of the Supplementary Appendix to Cardoso and a copy of the MINDACT Protocol. The Supplementary Appendix contains a large amount of additional data and information.

Patients should always consult their Medical Oncologist about any such publications, to ensure accurate understanding and proper application to their situation.

BarredOwl

UPDATE: Cardoso (2016) and all Supplementary Materials, including the Supplementary Appendix, are now available for FREE at the link above.

BarredOwl, the official Mammaprint results do not yet show the new MINDACT trial data, but my oncologist received a supplementary letter that she forwarded on to me that summarizes the results:

Unfortunately, there were no provided statistics of recurrence risk for MammaPrint High Risk with hormonal therapy alone, which would help Postive2Strong make her decision. But it is clear that as a whole, MammaPrint High Risk patients vastly reduce their risk of recurrence with both hormonal therapy plus chemo.

I will be getting a copy of the complete study soon (it's practically journal-length, I hear) and I will see if there is more info that might help.

Also remember that tamoxifen vs AI is also different as far as statistical recurrence rates.

Hi mellee:

Thank you for posting the Supplementary Letter. Patients with pending treatment decisions should also request copies of all explanatory materials received with their test results for their records.

Patients should also keep in mind that the content of the Diagnostic reports, the Summary of results, and Supplementary Letter are summary in nature. These materials present only a portion of the available data in an extremely 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.

I have read the Cardoso manuscript and commentary several times, and perused the voluminous Supplemental Appendix. I am not sure I fully understand. 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.

The MINDACT results are more complicated and nuanced than suggested by the Supplementary Letter. 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 two groups that are Low Risk by both criteria (Group (a)) or that are 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. The study had some limitations. For example, the study was not adequately powered to demonstrate the statistical significance of some differences between groups for all endpoints. My layperson impression (which may be wrong) is that advice regarding the potential benefit of chemotherapy might possibly be different for those considered Clinical Low / MP High than for those considered Clinical High / MP High. I do not know how clinicians are currently advising patients in this regard.

In light of this, above, I suggested three questions for a person with a MammaPrint "High Risk" score to help obtain expert consideration of the MINDACT results and case-specific application and explanation.

Please seek expert professional advice from your medical oncologist about your "Clinical risk classification" (according to the MINDACT criteria described in the Publication and Supplementary Appendix):

(1) Given your MammaPrint "High Risk" result, are you considered:

Clinical Low Risk / Genomic (MammaPrint) High Risk?

OR

Clinical High Risk / Genomic (MammaPrint) MP High Risk?

(2) What did the MINDACT results show about your group?

(3) Do the MINDACT results affect understanding of the possible benefit of chemotherapy in your case?

The study groups were relatively diverse. Thus, Luminal-type (B) status may further affect understanding of the possible benefit of chemotherapy.

A medical oncologist should be able to provide a reasonable estimate of distant recurrence risk with no systemic treatment. Based on that and the known relative risk reduction benefit of any recommended endocrine therapy (e.g., 45% for tamoxifen), they can provide an estimate of distant recurrence risk with endocrine therapy alone. In this regard, above I suggested patients should be sure to obtain advice regarding distant recurrence risk with:

. . . (c) endocrine therapy alone (e.g., tamoxifen or an aromatase inhibitor, as applicable).

BarredOwl

I am in a similar situation:

However, when they talk about reducing rates and it shows 10% reduction, I believe that is an relative reduction but the true absolute reduction is 2-3%. For me, I am having a hard time deciding if a 2-3% benefit outweighs the risk of chemo?? I am in the medical field and this gray zone is difficult.

Keep asking questions and look at a second opinion if you feel it might help you. The other thing I am looking at is if I chose not to proceed with chemo, what are the options for follow up. There are some new things on the horizon to help with testing in future but limited availability now. Look at ONCOBlot and Liquid biopsy. I am researching further and going to discuss with my MO at next appt. Good Luck.

Here is my story: I have been recently diagnosed with a perplexing case of breast cancer, I am stage 1A, Mucinous Colloid Cancer, invasive ductal cancer, that is Grade II, ER+/PR+, HER2 LOW (that's the real issues...some of the tumor was negative and some low + but not enough to call me HER2+), tumor was 1.7 cm in left breast only, and Oncotype Reoccurrence score 25 and Mammoprint High Risk (-0.132) with blueprint Luminal type B.

My HER2 testing on biopsy was equivocal. My HER2 testing on tumor was equivocal via ICH and FISH thus sent Hi Resolution HER 2 in which pathologist called it HER2 low (not enough to call me a HER+) so we sent Oncotype and it showed me again in the middle zone with score of 25, after much discussion we sent Mammoprint which shows barely in high risk zone.

I am starting radiation first and then trying to decide if I need chemo. With the Mammoprint coming back as high risk they want to add chemo but they aren't sure how to treat with me being Stage 1. They don't think I need the entire ACT tx, and don't know whether or not to treat me with Herceptin. Chemo may reduce absolute risk by 2% so I am not sure if the benefits of chemo will out weight the risks for only a 2% reduction rate as I am sitting at 11-12% reoccurrence rate now.

I am 52 and post menopausal. No family history.

positive, have you chosen to do chemo? What are the pills you are talking about?