Luminal A vs. Luminal B stage 1 BC

Lisey

Hi everyone. New to the boards. I've just been reading up on how they are now starting to believe Luminal B should be treated completely differently than Luminal A BC, even though both are ER+ cancer. I currently have an ER+ at 98%, and a PR+ at 5%, (which is low)... if my Ki67 value comes back moderate, I'll fall into the Luminal B mode, which isn't as effective to treat with Tamoxifen and other ER based antigens. Can anyone enlighten me further?

Meow13

I think I must be luminal B my ER is 95% and PR less than 1%. I did 4 years of AI drugs and no chemo. Also I had 2 types ILC and IDC. I would definitely entertain other options like vaccine if available to prevent reoccurrence.

Anonymous

The last time I tried to find out conclusively the Luminal A Vs B question I didn't get anything definite. If anyone can point me in the right direction I'd appreciate it. I'm ER+ PR- HER2-.

MsPharoah

Hi, my understanding is that luminal b vs luminal a depends on the k167. Luminal a has low K1 and b has hi K1. Now the problem is that there are differences in the low/hi cut off. Some say <20 is low and some say <14. my er is very high and pr is considered negative. My onc acknowledges that this type of cancer is different from er/pr positive.

S

Anonymous

MsPharoah thanks. It's been a while since I looked at this and remember something about ki67. I'm not sure what the test for that entails or even if it's possible years out from dx. The luminalB thing was mentioned in the "How Many are doing 10 years on Aromatase Inhibitors" thread. SpecialK gave me a link but it doesn't conclusively speak about us with +--. It also gives one of the criteria for LuminalB's as being LN positive which I'm not. So.... still a grey area. For what they considered fell into each category, they used the phrase "tend to be" which doesn't make it definite.

Lisey

does anyone know if you have to be HER2+ to be Luminal B? In everything I'm reading it says ER+ and/or PR+/HER+. It's that and/or that is throwing me.

Anonymous

Lisey, yes that and/or effectively excludes Pr Neg unless I'm seeing things inside out 8-|. I know some years ago there was a couple of threads on this topic, or touched on it. I'd love to find out just what category us with + - - fall into.

MsPharoah

Musical, we +-- breast cancer patients are "weirdos". LOL. The only research I have found about us is related to how well we respond to tamoxifen. I have always assumed that I need to be more aggressive.

SpecialK

musical - I linked some info at the other thread where this is being discussed. It appears that the subtype identification came about with St. Gallens, and the info contained in the first link indicates that you can be luminal B with PR- and Her2- but with a high Ki67%. Check that first link and see the specifics about subtype in the immunohistochemistry section.

Here is how they spell it out:

In brief, breast cancers were classified into five subtypes as follows:

Luminal A (ER+, PgR+ or PgR-, HER2-, and low Ki-67 index)

Luminal B (HER2 -) (ER+, PgR+ or PgR-, HER2-, and high Ki-67 index)

Luminal B (HER2+) (ER+, PgR+ or PgR-, and HER2+)

HER2 (ER-, PgR-, and HER2+)

Basal-like (ER-, PgR-, and HER2-).

cajunqueen15

Hi ladies,

I'm stage 2 but luminal b by molecular subtype testing (blueprint). I was wondering if I was a very rare case of basal like HR+ cancer because my ki67 was so high (78%), but came back as high risk, luminal b. The testing is expensive if your insurance won't cover it, unfortunately. I'm taking arimidex, Prolia, and a year of everolimus on the e3 trial. I wanted to know, because luminal tends to mets to the bones and liver, basal like to the lungs and brain. I know my odds of mets are high and wanted to know where I'd be looking first as well whether to push a Dexa for the Prolia (I have borderline early stage osteopenia).

cajunqueen15

Meant to add..,ki67 is the % of cells actively dividing. a high number means an aggressive cancer more likely to respond to chemo. Luminal b is the red headed step-child of HR+ cancer with a prognosis comparible to triple neg. My ER was 99% and my MO said I may be on AIs for life, not just 10 years.

Wildflower2015

Hiw do you find out your ki67? I can't find any mention of it on my pathology report.

ChiSandy

Me neither, but I suspect with a low Oncotype Luminal A, it too was low.

Anonymous

MsPharoah, yes it sort of rings a bell that PR Neg was said to be worse than PR +. Im Stage 11 so I hope I haven't encroached on a St1 thread but this isn't exactly easy to understand.

Marie confusing is the word. SpecialK gave a couple of great links over on the other thread which I've just looked at. (Thanks SpecialK!) The first one had my head spinning but the second one has made things a bit clearer. *I think*

SpecialK here's the 5 Subcategories from your 2nd link. Could you help us out here as it seems to differ from your list above.

Luminal A – ER positive, HER2 negative, Ki-67 low, and PR high;


Luminal B (HER2 negative) – ER positive, HER2 negative, and either Ki-67 high or PR low;

Luminal B-like (HER2 positive) – ER positive, HER2 overexpressed or amplified, any Ki-67, and any PR;

HER2 positive – HER2 over-expressed or amplified, ER and PR absent;


and triple negative – ER and PR absent and HER2 negative.

Here's a few extras that might be interesting.

Quote:

The conclusion was made that when Ki-67 was found to be higher, patients also showed a higher involvement in their ALNs.

A higher Ki-67 index has been found to correlate significantly with young age, large tumors, positive lymph nodes, negative ER/PR, p53 overexpression, and positive HER2. A higher Ki-67 index has also been found to correlate with a poorer prognosis and early recurrence (<2 years). On the other hand, a lower Ki-67 index has correlated with a favorable prognosis and late recurrence (>10 years).

Unquote

NancyHB

SpecialK - thanks for sharing the different subtypes. We've been discussing this topic for years and the confusion continues to be challenging. There are several good threads if one searches for them where we've talked about the importance of understanding what Luminal B means - both the positive and negative aspects.

There are two subtypes of Luminal B. The first is Her2+, which is fairly straight-forward. It's the other subtype that causes more confusion: low to negative PR, and high Ki67. When my Oncotype test came back with a RS of 42, PR-, and my pathology showed Ki67 at 50%, my oncologist declared me Luminal B (my original pathology was ER+ 50% and PR+ <10%). She said those were clear-cut indicators of the subtype, but it's not always that easy to determine. It's generally accepted that a KI 67 over 20% is considered "high" but that's not enough to constitute Luminal B. "Progesterone receptor loss" - which can be identified as PR- or a low to very low PR score - is also required. My MO also explained that the higher the correlations (higher the Ki67 score/lower the PR loss) the more like Luminal B/less like Luminal A the cancer appears. It's the same with ER+ cancers: The higher the ER+, the more likely the cancer will respond to Tamoxifen and/or anti-hormonals. It's all about the biology (is that the right word? I haven't had enough coffee yet, sorry) of the cancer, and how it will respond to treatment.

There are plenty of scholarly articles about what those cutoffs are, my favorite article being this one (be forwarned - this, and a lot of other articles on Lumial B, use the words "worse prognosis" and "worse outcome" frequently - read this with a grain of salt):

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430090/

I recently had a local recurrence (and my ER hormone receptor changed, I'm now TN). My MO says he doesn't believe that this recurrence had anything to do with my Luminal B status, but I don't know how I feel about that. Knowing whether I was Luminal A or B helped inform my treatment plan, but it's not something I dwell on or worry about. It's just another piece of the BC dx puzzle for me.

SpecialK

musical not sure why the discrepancy on Luminal A in the two articles - I cut and pasted from the first link, didn't retype. It looks like Ki67% and high PR (although what classifies high - I believe the article measured PR positivity at anything over 1%, and I have seen high Ki67% in differing cutoffs too) are what is different from the other list. Otherwise the rest of the list looks consistent.

Also when comparing your individual receptors to these lists it is important to remember that tumors are not homogenous. The measurement you receive on your pathology report is , to some degree, subjective - it is showing that particular area of the tumor that was tested. Testing for receptor status generally involves looking at a slide and identifying 100 cells - out of those 100, the number with staining receptors is counted. So, if you had 50 with ER receptors on those 100 cells and 27 with PR receptors, you would be 50% ER+ and 27% PR +. If you looked at a slide from another section of the tumor those numbers could certainly change.

Anonymous

specialK thanks! and LOL thanks for translating it into English. WOW that throws another light on it about the slides. Lots of variables. I would suppose that they've ascertained how consistent a tumor might be throughout? I'd hope so. That might be a whole new study in its own right.

Lisey someone on the Hormonal thread has suggested a dedicated place for discussing this and I agreed. Ive put a request down the bottom of BCO to see what the Mods say. Not sure what they'll do but they may want to include this thread - again, not sure. It sure is an interesting discussion.

Moondust

My young and inexperienced MO refuses to believe I am Luminal B. In fact even though my Ki67 was stated on the pathology report, she refused to consider it at all. It is 30%. My ER is 80% and PR 40%. On the Oncotype results, the PR came back in what they consider the negative range and my score is 26. I had to fight with my MO to get chemo. That's why I'm having it 5 months after surgery, and after radiation. She sent me for a 2nd opinion before she would give me chemo. In her words, "chemo will not benefit you". Uh, that's not what the doc at UCSF said. He agreed with me that I should be doing chemo (I started it June 8). I will be switching MOs at the conclusion of chemo, because the one I have is not only in the dark about the newest BC stuff, she is also unwilling to learn.

NancyHB, it does not surprise me that your recurrence was TN. If you were ER+ 50%, that means half the original tumor cells did not have an ER receptor. And 90% of your original tumor cells did not a PR receptor. One of the cells that didn't have either receptor started a new cancer. To my mind, nothing mysterious about it.

Lisey

Wow... so much information, thank you ladies. It seems not many other forums even understand this luminal stuff at all. I'm reading that they are basically trying to pin everything on the Ki67 score to determine Luminal A / B. I found a graph that shows that if you have a low Ki67 score and low PR+, you can still be Luminal A, but the minute your Ki67 goes above 20, and your PR+ is less than 40% that puts you in the B category.

The thing that doesn't make sense to me is this. I am 98% ER+. 5% PR+. If my Ki67 score is high, that means tamoxifen will not be as effective on me. But why wouldn't it since so much of my tumor is ER+?

Everyone is always saying, "Oh good, you got the best kind of BC...!" But apparently not with the low PR+ score... It's about as bad as Triple Negative when it comes to outcomes. Should I be pushing to not be on tamoxifen and instead get my ovaries out? I'm Younger, 41, and completely premenopausal.

cp418

Lisey - this is an older article but it mentions a better benefit with an AI. I would research this more in regards to taking an AI over Tamoxifen for this hormonal subgroup.

http://jco.ascopubs.org/content/23/4/931.full

Lisey

CP, that is an incredibly helpful study you posted I will be bringing it up to my oncologist in two weeks and see what they say about it thank you again

Meow13

I never got a ki67 score.

cp418

Lisey - this article more recent.

http://dl.kums.ac.ir/bitstream/Hannan/142826/1/201...(2).pdf

Anonymous

Meow, I didn't either, but apparently high scores are much more likely to be synonymous with affected LNs. I'm no closer to figuring out where I am except maybe I'm one of those that's fallen through the cracks as us + - - 's tend to feel.

CP418 just read your first link. Interesting. Here's a couple of points to note.

QUOTE:
In this study, approximately 30% of patients were biochemically ER+/PR− and responded poorly to tamoxifen;

while ER+/PR− tumors might receive initial treatment with an aromatase inhibitor because of their relative resistance to tamoxifen.
UNQUOTE

It's my understanding and I was told this, that AIs are only effective post meno. I had Tamox. 2 years. I had a blood test to make sure I post Meno before starting on the AI. It would be interesting to know what they mean by "responded poorly" I suppose that would mean reoccurrence?

QuinnCat

MarieB - "This topic confuses me! My ki67 was 15% but my tumor was grade 3. That seems conflicting?"

While I see 20% being thrown around here as high, I've seen anything over 12% as high.

windingshores

I was ER+ PR+ Her 2-, grade 3, ki67% was 20 with cutoff, I think, at 19. LVI but not lymph node involvement. However, my Oncotype score was 8.

I talked with Genomic Health, the company that does Oncotype Dx, and they said that ki67% is only one of the markers they use for proliferation. They also said that 30% of grade 3's have low Oncotype scores.

I drove myself crazy with this Luminal A and B thing while deciding for or against chemo. I got 4 opinions (one lab had me Her2+ so I also had that retested). My oncologist said I am Luminal A but her lab didn't do ki67%, another one did.

I chose not to do chemo with that low Oncotype and am on Femara. I guess I'll let you all know!

cp418

kayb - "Those of us who post here are an inquisitive bunch and we're always trying to read the tea leaves of the latest study to determine our risk. I think we spend more time at it than most clinical oncologists."

Totally agree with what you wrote and your last statement is so TRUE!!

gerrib

Yes I agree with you kayb. I think my onc thinks I'm mad when I start talking about these things. Don't know whether she sees a broader pic or is not up to date. Feel as though concerns about my pleomorphic ILC Er 30% + Pr neg (HER neg) ki67 20% have never been addressed. No oncotype here in Australia. Discouraged from having chemo so didn't push it. I feel pretty sure I will get mets in the next few years due to my unsual tumour but I have given up trying to get my concerns raised.

Hopeful82014

Kayb - your last 2 paragraphs nailed it.

Meow13

gerrib, I had 2 tumors also but on left side only. I always wonder about having both kinds ilc and idc and what happened.

KNardo88

It is very important to ask your questions and get them answered! Even if it takes a couple times to get it all straight. Your MO should never think you are mad for asking questions :-)

To provide another example of a Luminal B case:

My pathology from my original biopsy at the clinic where I received my diagnosis reported 30-40% ER+, PR-, and HER2-. The ki67 was 80-90! Talk about a panic attack...

However, I quickly went for a second opinion from one of the top 5 cancer centers in the U.S., and their pathology on that same original biopsy reported 20% ER+, PR-, HER2-.....and they do not even test for ki67. It was explained to me that the results for ki67 are somewhat unreliable. Seeing here that quite a few of you did not have ki67 reported on your pathology reports shows that there must be many other institutions that also do not use it for that reason, and maybe others. Could be another question worth asking!

Obviously, my MO and BS at my place of treatment (I went with the second opinion) are aware of the high score that the original biopsy pathology reported, and I've brought it up several times as an area of concern for me. I was explained a couple factors, maybe these may help:

- again, ki67 is not dependably reproducible, so one area of the tumor could report high, another area low, etc.

- a number of other factors going on internally can affect ki67, such as if something had been in the process of healing. I, for example, had been in to my original clinic prior to the core needle biopsy where they attempted to do a fine needle aspiration on it first. Not that this was the definitive explanation for my high score, but something to consider as a contributing factor.

Prior to surgery, I had absolutely clear scans, and when surgery came around I had absolutely clear nodes and the resulting final pathology confirmed that and also showed LVI was absent, and the tumor was less than a centimeter, clear margins, the whole happy sha bang... Except it was grade 3, I'm 27 years old and BRCA 1+ and despite all the other good pathology results, is in fact suggestive of Luminal B subtype.

However, I've never once been told that I was considered "high risk", though. In fact, I'm repeatedly told that I'm actually low risk... And I've brought this subject up several times now. I am being treated with chemotherapy, to bring my already supposedly low risk down even lower. 4 AC, one every three weeks, and then I will go on Tamoxifen for the next 10 years. None of my doctors have felt concerned about Tamoxifen being used in my case, and I've asked if it isn't as effective in Luminal B cases and was told that there are no data that support that Tamoxifen would be less effective on a case like mine.

Bottom line, It's important to ask all the questions and get all the clear, informed, credible facts from the people who know your specific case, and know what is relevant to YOU. That's your doctors :-)

Best wishes everyone