Luminal A with high KI67

Can you be luminal A with a ki67 over 45%? Or 15% for that matter?

I fit the luminal A profile in everything except the Ki67. My results said "high"...but did not indicate the %. I kept forgetting to ask, and now 6 years out it is what it is so I don't think I want to know now. My oncotype score ended up being "low" at 14 and my doc and I agreed that tamoxifen would be my best weapon based on the score and because I was highly er/pr.

One interesting note. My biopsy pathology was originally grade 3 with a mitosis score of 3. My mastectomy tumor pathology went down to grade 2 with a mitosis score of 1. When I asked the MO about this.. he said that pathology readings can differ based on who is reading them. He put more weight in the results from the surgery readings and the oncotype test score since they seemed to cooraberate eachother. Though the time between my biopsy and surgery was 2 months. They took 4 core biopsy samples. I always wonder if stabbing the little 1.5cm tumor 4 times could somehow disrupt it's growth? I have no idea if I'm just grasping at straws here. Another question I'll try to remember to ask my MO at my yearly appt.

Hi cherrytree:

The standard immunohistochemical methods ("IHC") used by pathologists determine the level of the Ki-67 protein. Ki-67 protein determinations performed by IHC suffer from a number of deficiencies, including interobserver variability and lack of consistency across laboratories, as explained here:

Polley (2013): "An International Ki67 Reproducibility Study"

http://jnci.oxfordjournals.org/content/105/24/1897.full

(Free PDF available via link)

This 2015 paper reports a possible impact from prior biopsy: "Ki67 value significantly increased after CNB [core needle biopsy]."

Chen (2015): "Surgery time interval and molecular subtype may influence Ki67 change after core needle biopsy in breast cancer patients"

http://bmccancer.biomedcentral.com/articles/10.1186/s12885-015-1853-1

(Free PDF available at link)

"Intrinsic" or molecular subtypes (Luminal; HER2-like; Basal) were first defined by Perou (2000) using gene expression profiling ("GEP") methods that determine mRNA levels. mRNA is copied from or transcribed from DNA, and these mRNA levels reflect gene expression activity. Certain distinct patterns of gene expression in breast tumors were identified and used to define breast cancer subtypes. Later studies subdivided the "Luminal" subtype into Luminal A and B subtypes. Some gene expression profiling tests that measure multiple mRNAs can be used to assign subtype. However, these tests are costly and not available in all countries. IHC measurements of ER, PR, HER2, and Ki-67 proteins can be used as a surrogate to assign subtype (e.g., Luminal A or Luminal B status), but this approach appears to be somewhat less reliable than gene expression profiling methods. The articles above re Ki-67 illustrate some possible reasons for this.

The Oncotype and Prosigna tests are gene expression profiling tests that measure the levels of multiple mRNAs and provide a score based on multiple genes. The main output of the Oncotype test is the multigene Recurrence Score ("RS"), while the Prosigna test output is a Risk of Recurrence Score ("ROR"). Various validation studies have established correlations between the scores and recurrence risk. Thus, these scores provides "prognostic" information about recurrence risk that can aid decisions about chemotherapy. The Oncotype RS is also "predictive" of chemotherapy benefit in some cases.

- Neither OncotypeDX nor Prosigna provides a single gene readout for Ki-67 mRNA.

- Oncotype does not provide molecular subtype information as a test output.

- Please inquire with your Medical Oncologist whether Prosigna provides molecular subtype information as a test output, or whether it is more generally reflected in the ROR.

- MammaPrint / Blueprint does include molecular subtype information as a test output.

Although Oncotype is probably the most commonly used test in the US, the Prosigna test is included in the 2016 ASCO Biomarker guideline for node-negative patients:

"Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline" ***

Harris (2016): http://ascopubs.org/doi/full/10.1200/JCO.2015.65.2289

PDF: http://ascopubs.org/doi/pdf/10.1200/JCO.2015.65.2289

"If a patient has ER/PgR-positive, HER2-negative (node-negative) breast cancer, the clinician may use the PAM50 risk of recurrence (ROR) score (Prosigna Breast Cancer Prognostic Gene Signature Assay; NanoString Technologies, Seattle, WA), in conjunction with other clinicopathologic variables, to guide decisions on adjuvant systemic therapy. Type: evidence based. Evidence quality: high. Strength of recommendation: strong."

To my layperson's knowledge, there is no single correct approach to such testing, and selection of the appropriate test in the first instance is a question for an expert professional.

If you wish, you can ask your Medical Oncologist to explain why he selected the Prosigna test versus other such tests (e.g., Oncotype; MammaPrint/BluePrint), and what the advantages may be in his expert opinion. Your medical oncologist may have good reasons for selecting the Prosigna test in your particular case.

Best,

BarredOwl

***Although the 2016 ASCO guideline does not recommend the MammaPrint test, the guideline predates the recent publication of the MINDACT trial results. Thus, those interested in MammaPrint should consult their medical oncologist for up to date information regarding this test.