Luminal A vs. Luminal B stage 1 BC
Comments
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Lisey - outside of the Mammaprint, why did your MO say you were luminal A? I guess your results have me questioning how my MO knew I was luminal B, though my oncoscore and Ki67 are double yours (39 and 60%), otherwise the same, but grade 3.
btw- yeah, no chemo!
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ThinkingPositive - while you're KI 67 is above the "high" cut-off value of 20%, your PR percentage is very high. Luminal B is defined as having negative or very low (usually 5% to maybe 10%) PR value. So it's quite possible and maybe even likely that you are Luminal A. The advantage of Luminal A is that it responds better to Tamoxifen and AIs (which you're taking).
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she called me and said luminal A... I have to wait for the reports to be sent to me from agendia. I'm assuming the mammoprint said low, and the blueprint said luminal A. I'm still in shock as to how the doc knew?. She did tell me weeks ago that ki value on healing tumor tissue (healing from the biopsy) is artificially high. And she felt my Pr from the biopsy wasn't homogenis with the rest of the tumor. I rebutted it could go the other way too. And she laughed and said she'd bet me on the mammoprint. As I mentioned earlier, her confidence made me want to trust her... but I had to know for sure. My low mitosis level on both biopsy and tumor were what she was sticking to.
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Ok, so my 3/3 on mitosis was key to luminal B?
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Lisey, that is double good news. Luminal A, and an oncologist who knows her stuff.
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so, what exactly defines Luminal B?
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Well.. From what I've read, the main difference is that Luminal B tends to have more aggressive cells and much lower PR+ (or PR-). It is ER+. It can have HER2, or not. The Ki-67 value has been used to determine aggressiveness, but like I mentioned, my doctor dismissed Ki, and said to focus on my Mitosis rate of 1. Luminal B is not treated as well with Tamoxifen, as the low PR tends to help the cell evolve to beat Tamox, but AIs do better for it. I am seriously thinking my PR+ must be higher than 5%, because that is just really low. Doc seemed to think it was higher than the biopsy found. It's just odd. Here's an overview of the options for Luminal B.
The thing is.. with my score of 30-35% Ki-67, and my low PR+, all the signs were pointing to B... BUT from what I've read (thanks to you ladies posting links), different labs cannot read ki-67 the same, so there is no standard and the same tissue can be read completely differently based on the lab. So perhaps they gave me a false high Ki?http://www.breastcancer.org/research-news/20121217-5
Here's another one on the differences and outcome differences:
http://jnci.oxfordjournals.org/content/101/10/736/F4.expansion.html
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Shetland Pony, Thank you! I really really want to see the actual reports. I had to scan in my driver's license and send a form to them. They say they fedex the results. I wonder if it will give a read on my true PR value... anxious and relieved to see the things in my hands rather than just the docs words. - and the fact they don't charge patients full price!!! I'm very happy with Agendia right now.
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I thought I knew mammalou, but not sure now. I though Lisey fit the parameters. Help!
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your er ishigher than mine... I think my er was 70 and pr 80... My ki 67 freaked me out.. My onco also said luminal A but I did not have the mammaprint
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QuinnCat, ME TOO! My doc insisted that the ki value wasn't to be trusted. Here is a study showing that Ki-value does well for grade 1 and grade 3 tumors but not for grade 2. In fact for grade 2 tumors the same specimens were label 30% or 5% depending on who was eyeballing it.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037379
Abstract
Adjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas.
Methods
Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or pre-defined areas of the tumors, comparing centrally immunostained slides with slides immunostained in the different laboratoires. To study intra-observer variability, the same tumors were re-examined 4 months later.
Results
The Kappa values for the first series of ten carcinomas of various degrees of differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56–0.72). However, we found very high inter-observer variabilities (Kappa 0.04–0.14) in the read-outs of the G2 carcinomas. It was not possible to explain the inconsistencies exclusively by any of the following factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv) the selection of the tumor area in which to count. Despite intensive confrontation of all participating pathologists with the problem, inter-observer agreement did not improve when the same slides were re-examined 4 months later (Kappa 0.01–0.04) and intra-observer agreement was likewise poor (Kappa 0.00–0.35).
Conclusion
Assessment of mid-range Ki-67-LI suffers from high inter- and intra-observer variability. Oncologists should be aware of this caveat when using Ki-67-LI as a basis for treatment decisions in moderately differentiated breast carcinomas.
MIB-1-LI results were all below 8% for G1 and above 30% for G3 carcinomas. However, interobserver variability was substantial for the G2 cases, values ranging between 5 and 30% for the same cases
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC416731...!po=34.3750
Addresses my question about how they determine type. I read it as Luminal B is ER+ Her2-, and either high KI67 or low PR.
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For more on the issues with Ki-67 determination and comparing values between labs:
Polley (2013), "An international Ki67 reproducibility Study":
http://jnci.oxfordjournals.org/content/105/24/1897.full.pdf
BarredOwl
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Barred, you know, I almost want to scratch out my ki-value since it's proven to be untrue. I am excited for the day when doctor's aren't having to eyeball things that we then make life/death decisions about. I knew there was a contradition in my statistics, And falling in the low gray area on the oncotype didn't help. I do think everyone should be told their subtyping during pathology as a standard procedure as Luminal B should be treated differently than Luminal A.
The only test left for me is my enzyme pathways test. I still have no symptoms from the Tamoxifen, so I'm interested to see if I'm a normal metabolizer... I should have that one Friday.
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I am frustrated that I will never know if I'm Luminal A or B. My doctors ignore ki67 even with mine at 40%. My MO said it is likely wrong. It's the only piece of my picture that would throw me into Luminal B. My understanding of Luminal B is that it is high KI67 or low PR as mammalou stated. I also read it could be ER + or ER -.
Does anyone know the validity of the enzyme pathways test Lisey mentioned? When I asked my MO about tests for metabolizing Tamoxifen I was told the validity is questionable. For this reason I'm on Aromasin but I really felt better on Tamoxifen and I'd switch back in a heartbeat if I knew it worked for me.
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Hi Warrior_Woman:
Here's a recent post of mine with some information about what clinical consensus guidelines from NCCN provide re CYP2D6 testing, with a link to a paper highlighting some of the major conflicting clinical studies in the area, and outstanding clinical validation questions:
https://community.breastcancer.org/forum/108/topics/844310?page=1#post_4760035
BarredOwl
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Warrior Woman, there are two areas to look at. 1 is that Luminal B does not do as well on Tamoxifen. Can you ask that your tumor sample be sent in? They can do testing years after it's collected. So even if you are a normal metabolizer of Tamox, it still means if you are Luminal B, an AI is better for treatment.
and 2 is that if you are Poor metabolizer (PM), and Luminal A then it still could be an issue for you. Keep in mind that even some PMs had low but still there endoxifen levels, so Tamox uses MULTIPLE pathways, the 2D6 pathway is just a primary one. The only way to know if Tamox is working for you, if you aren't having any symptoms, is to get your Endoxifen tested and not many labs test for it.
I figured there is a 75% chance I'm going to have to switch to an AI/OS within the year. Definitely if the mammoprint came back Luminal B (I figured 50% chance) and definitely if I test as a PM on the Kailos genetics test and have no symptoms on Tamox (I am currently symptomless 3 weeks in).
Here is a thread that discusses all the back and forth and rebuttals to rebuttals. It's defintiely has some merit, we just don't have work arounds yet or know enough to help change things.
https://community.breastcancer.org/forum/73/topics/798301?page=10
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Barred Owl and Lisey - Thank you both. As I'm postmenopausal, the AIs are certainly a better bet. I just hate the SEs. I've requested all sorts of retesting of my tumor but the response was No. I'm almost 3 years from Dx so they may assume I'm overthinking this. Even at the time of diagnosis when I asked if I was Luminal A or B my surgeon said, "You don't need to know that". It makes me nuts when what I read online is inconsistent with what my treatment providers tell me.
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Warrior, have you told them you are willing to pay out of pocket for the testing? Perhaps they feel they can say no because they think you are asking them to cover it. The Mammoprint/Blueprint will end up costing me $500... which is very much worth it 'to know' and not have this nagging doubt.
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Lisey - You're right. It really won't change Tx at this point but the "nagging doubt" is worth $500.
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Hi Warrior_Woman:
My current understanding is that the results of both the MammaPrint test and BluePrint tests are used to distinguish between Luminal A and Luminal B subtypes:
"BluePrint ["BP"] stratifies into three distinct molecular sub-groups: Luminal (BPLuminal), HER2 (BPHER2), and Basal (BPBasal).
MammaPrint substratifies BPLuminal into Luminal A (BPLuminalA for MammaPrint Low Risk) and Luminal B (BPLuminalB for MammaPrint High Risk)."
The cost of $500 is with assistance from Agendia, because insurance refused payment. It does not seem likely that Agendia will provide patient assistance for tests that will not influence treatment decisions. Your out-of-pocket cost seems more likely to be the list price of the tests (in the thousands of dollars).
BarredOwl
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These tests are designed to inform treatment decisions, as Barred Owl pointed out above. I think you said it best, Warrior Woman, when you said having the information would be nice for your peace of mind and so you know as much as possible about your particular cancer and, ultimately, to have a better idea of potential outcomes. At some point, though, we have to have faith that we've done all the treatment we can (or that we choose to do) given the information we have available at the moment. The more we worry about and second-guess our choices, the more power we give over to our cancer and its disruption in our lives.
Please, try not to let this stupid cancer take any more of your joy, peace, and life. It's hard, I know - I worried every day up until my recurrence was confirmed. Now that it's happened - I refuse to waste another moment of my valuable time wondering and worrying about what might happen next. Recurrence is often a crap shoot, and even being Luminal B and having a high Oncotype score, I never would have believed it could happen to me. And what else could I have done to prepare for it, to prevent it, to anticipate it turning my life upside down yet again? Pretty much nothing.
I carry this thought with me every day now, and try to fully embrance it: "Worry is a total waste of time. It doesn't change anything. All it does is steal your joy and keep you very busy doing nothing."
I wish you all some moments of peace with this awful disease.
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http://www.upmc.com/media/NewsReleases/2016/Pages/...
Sampling Method Used for New Breast Cancer Tests May Lead to Underestimate of Risk
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CP, I think the TAILORx study did show that RS below 11 is low risk period because they did exactly what this article is saying should happen. In fact, the second part of TAILORx is following those over 11 and will report their findings in a few years. So while I understand the heterogenius nature of a lot of tumors, the Science is still saying that RS score is pretty accurately predictive...
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Lisey thanks for sharing your story. My ki-67 was 25%, ER was 75% and PR was only 2%. But my oncotype was 15. I didn't have the mammaprint because I didn't know if I would trust the mammaprint or the oncotype. I wanted to start on Arimidex but I have osteoporosis. So I want to switch to it maybe next year or the year after when my bones improve. The hot flashes with tamoxifen are horrible!
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Lisey - Your graph is spot-on. MammaPrint/BluePrint showed I was NOT Luminal A, as originally believed. In addition, they told me because of the low PR Luminal B, AI not quite as effective.
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FarmerJo, isn't it just like a coin toss on our stats? They are nearly identical. I wonder how it is that Mammaprint gave me a low reoccurrence score (Luminal A) and you with equal stats got a high score (I'm assuming?) I see you are likewise Grade 2, do you mind if I ask what your mitosis number was?
On the AI, I've read it's equally effective for Luminal B.. but Tamoxifen is not. Did you mean Tamox? -
I was told my mo that my pr being less that 1% makes me higher risk equivalent to luminal b.
Thanks be given to God I've done well on AI drugs.
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Welp... I'm sticking to my plan, but found this small study showing that mammoprint/blueprint/targetprint Vs. Oncotype are really not working with eachother. what I did find fascinating is that Oncotype designated more of the tumors as low risk than Mammoprint did. 52 v 49. So here I am with an Intermediate Oncotype and mammaprint designates me low risk. But mammoprint pulled 18 Low Oncotypes up to "high risk". Really interested stuff..
http://meeting.ascopubs.org/cgi/content/abstract/33/15_suppl/11017
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Lisey, FYI, got my Prosigna test results today, and even with the Onco score of 20, the Prosigna placed me at high risk. MO said that is why the Onco results are so controversial for intermediates. I'm scheduled to start chemo next Monday.
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