Luminal A vs. Luminal B stage 1 BC

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  • cajunqueen15
    cajunqueen15 Member Posts: 794
    edited June 2016

    Adding fuel to the fire - all basal like tumors are not triple neg (while all triple neg are basal like) I knew I didn't have luminal A as all 3 of my path reports showed ki67>70% from different surgeries (DCIS and IDC). But I did want to know if I was that rare case of HR+ basal like cancer. I'm going to have to go back and check my PR status. I want to say 30-40%.

    I'm pretty confident I will have an answer on mets soon, within 3 years. It is either all gone or spreading like wildfire. It is almost enough to make me request another PET...almost.

    ETA: PR in IDC 91%. PR in DCIS 34%

  • Moondust
    Moondust Member Posts: 510
    edited June 2016

    Sandy, thanks for bringing up the topic of treating with progesterone. Here is a link to a good article which explains the study recently published in Nature regarding the ER and PR receptors. I believe in this study they gave some of the mice actual progesterone. It has some very nice graphics explaining the relationship between the receptors and the hormones.

  • ChiSandy
    ChiSandy Member Posts: 12,133
    edited June 2016

    Thanks, Alice! The only thing that scares me, though, is the statement “Many tumors evolve to lose their progesterone receptors.” I’m hoping that the higher the initial % of PR, the longer that will take or the less likely it will happen.

  • farmerjo
    farmerjo Member Posts: 518
    edited June 2016

    ChiSandy -

    Sigh. I mentioned progesterone to MO yesterday, and she was aghast! "Oh my, that's an old treatment!"

    Interestingly, she said to stop the AI - it was of no benefit at the moment. Eighteen months of that s**t! For naught???

    I am still bewildered...the awesomeness of an Oncotype of 19 (yay!) and the "Danger, Danger, Will Robinson!" of the Mammaprint/BluePrint. On the same darn specimen.

  • QuinnCat
    QuinnCat Member Posts: 3,456
    edited June 2016

    farmerjo - AI of no benefit? How? What? Why?

  • Meow13
    Meow13 Member Posts: 4,859
    edited June 2016

    Really, no benefit for ER positive PR negative

  • ChiSandy
    ChiSandy Member Posts: 12,133
    edited June 2016

    Progesterone may have been administered long ago (heck, decades ago it was given to pregnant women in danger of miscarriage), but that was probably before hormone receptor status was fully understood, and I’d be willing to bet that it wasn’t administered concurrently with SERMS or AIs, nor did they yet know PR status was anywhere near as important as ER status. The concept of a truly “double-positive” Luminal A cancer is a relatively new one, and nuances in treating it are constantly evolving. So everything old is new again..... (That article, BTW, was dated May 2016. Hardly “old treatment”).

  • Lisey
    Lisey Member Posts: 1,053
    edited June 2016

    I am SO GLAD you all found that mouse study. I read it and it was what started this luminal B treatment differences going. I am wondeering fir any of you have found the article which discusses the mice called ' Cross talk between hormone receptors has unexpected effects" from the Univ. of Chicago medical center.. Here is the paper published just 6 days ago. https://www.sciencedaily.com/releases/2016/06/1606...
    A
    nd HERE is the full article... for your PHD's out there. http://advances.sciencemag.org/content/advances/2/6/e1501924.full.pdf

    In the June 24 issue of Science Advances, however, researchers radically upgrade the significance of the progesterone receptor. They show that when exposed to estrogens and progestins, these receptor proteins interact with different sets of binding sites in the cell's chromosomes, with the progesterone receptor dramatically altering how estrogen receptors interact with the cell's DNA.

    "In the last year or two, researchers have tuned into the extensive and previously unrecognized cross talk between the progesterone and estrogen receptors," Not only is the progesterone receptor an "essential modulator of estrogen-receptor-regulated genes," but it also significantly contributes to the "prognostic value of estrogen receptors in ER+/PR+ breast cancers.

    In the mouse study the best outcomes had both tamoxifen and CDB4124 (a progestin antagonist). But would I want that if my PR+ is so low? or is that for those with a high PR+ as well?

    I tend to agree that the cancer wants to remove PR+ from the equation and that is the first to go as it evolves to become TN. My ER+ was really high, hopefully the oncotype will give me more specifics. I doubt Kaiser will pay for another test of a mammoprint, but I'm willing to pay the cost if it would be very beneficially - at this point money is not a consideration to our family in my treatment.

    The thing I don't want is to have this OC, whom I've never met, dismiss this new research - since it's so new, and give me a standard ER+/PR+ treatment without understand my low PR+ level.

    I LOVE you ladies actually digging into this luminal B stuff. Not many people even know about it and the facebook women thought I was spouting fear based crap at them.

    PLEASE keep digging and if anyone finds ANYTHING post it so I can keep trying to fit these new puzzle pieces together.



  • Lisey
    Lisey Member Posts: 1,053
    edited June 2016

    Ok. Since I feel time is of the essense to really understand more of this. I sent an email to the author of the sciencedaily study at UofC. I have no idea if he'll respond, praying he will.. but here is the gist of what I wrote.
    __________________

    Your recent article on the importance of PR+ receptors in breast cancer got my interest as I was newly diagnosed with breast cancer at 40. My questions is in regards to the mice you used who had the standard ER+/PR+ cancer phenotype and the testing on them. My cancer is actually ER+(>98%) / PR+ (<5%) (low), and I'm wondering given the idea that Luminal B tumors which are low in PR+ have a poorer prognosis, if your addition of the PR Modulator – would have a worse effect on someone with Luminal B, or a more positive effect on someone with Luminal B?

    I understand we are talking in purely hypotheticals, since this trial was done on mice who were short lived. But trying to piece together the puzzle of the HR+ receptor, especially for those of us with low percentages, is really important to me personally. Most of us with low PR+ are treated just as though we had traditional Luminal A (high PR+) cancer and it simply doesn't feel like science is there yet… but I'm very grateful you are working on it.

    Any help understanding the correlation you've found, especially in regards to if the mice would have had low PR+ receptors, would be so appreciated.

  • QuinnCat
    QuinnCat Member Posts: 3,456
    edited June 2016

    Lisey - I applaud you! I will be anxious to hear if you get a reply as that would be my question after reading your attachment oh HR+.

    I remember somewhere during the period of my chemo (2012), I was digging and digging for information on Luminal B. Anything I could find and if I had a memory left, I could go on and on, but at one point I was so fearful of cancer returning I was investigating Metformin. Either the MO or Endocrinologist that my MO referred me to even Rx'd it for me (probably just to give me peace of mind), but ultimately I found one study that had an incidental finding that Metformin not useful in Luminal B. "Incidental" as study was not set up to determine that, so never filled the Rx. It does seem that Luminal B versus Luminal A is a rich area for research. Sadly, as patients, we are on the Applied end of the research train, so anything they are discovering now would still need to be studied studied studied, clinical trials, blah blah. Personally, my hope rests in Immunotherapy. Maybe Luminal would not even be a factor there.

  • mammalou
    mammalou Member Posts: 823
    edited June 2016

    Being a PR 0%, I'm finding this very interesting. I have heard all the same things from my MO as you that PR status doesn't matter, blah, blah, blah. I brought up the Tamoxifen resistence issue in 2011 and was told there really weren't good studies on it. I will be finishing 5 years on Tamoxifen in August and it's time to discuss doing the next 5 years on an AI. I'm thinking moving to the AI is better with the PR status. Is that your understanding?

  • QuinnCat
    QuinnCat Member Posts: 3,456
    edited June 2016

    Mammalou - I hope someone answers your question about Tamoxifen versus AIs and PR status, but taking AI, over Tamoxifen confers a 2% reduction in 10 year recurrence from what one's oncoscore gives (Oncotyping totally based on Tamoxifen).

    I wanted to ask you why you didn't get Taxol along with AC? We are in the same time frames and that seemed to be a typical regime at the time, AC, then Taxol.

  • MsPharoah
    MsPharoah Member Posts: 1,034
    edited June 2016

    This is an interesting thread. The oncotype gene panel includes PR as one of the factors that is considered in the calculation of the score, so not sure how/why an oncologist would deny that there is no adverse impact for a low or negative PR score. At my first MO consultation, I was advised that my ER+PR- status was not as favorable as ER+PR+. It just sucks having to make such decisions about treatment when one has ILC (many say that chemo is not effective on lobular)and PR- with an intermediate oncotype score. I would have liked to avoid chemo, but just didn't want to take the risk that my cancer was more of an m-f-er than first blush. Hopefully, more will be learned soon to guide treatment. Being told that a treatment has more risks than benefits is not comforting.
    MsP
  • mammalou
    mammalou Member Posts: 823
    edited June 2016

    Quinncat - the not getting Taxol has haunted me for years! I had spread to my dermal lymphatic system in my skin which is basically the hallmark of inflammatory breast cancer. My doctors treated me for IBC but my oncologist said there was a study that showed that Taxol was not effective on highly ER cancer. I wish I had gotten a 2nd opinion but at the time I was just overwhelmed. I e mailed with the John Hopkins Ask the expert a year later. She told me I should have had Taxol and at that point I should be happy with every month that goes by without a recurrence. Wow, that didn't make me feel good atall, but I am still doing well

  • QuinnCat
    QuinnCat Member Posts: 3,456
    edited June 2016

    Mammalou - I'm chuckling a bit as I wrote to that Johns Hopkins board too. I saw many questions where people would describe their Stage 1 pathology and the general response was "You will be fine, go live a long happy life. " I wrote my question with my pathology - Oncoscore 39, etc.etc., and the response I got was "Eat broccoli seeds" and generally not very encouraging. Lost all respect for JH. I would not trust whatever intern they have assigned to that detail.

    I was very sad I got Taxol as it was a difficult chemo for me, but worse, I have permanent neuropathy. If there was any chance it wouldn't have worked for me, I would have bailed!

    MarieB - maybe someone more update with the definition of Luminal B, but your Ki67 fits, but I do think PR has to be very low to absent, BUT, since you are giving percentages, which indicates IHC, I will say my IHC ER and my Oncotyping ER were totally different and one always hears that Oncotyping trumps (I hate this word now) IHC testing.

  • Lisey
    Lisey Member Posts: 1,053
    edited June 2016

    Ok, ladies.. need your brains for a bit... I got the oncotype scoring over the phone just now.

    Here's what it's saying: Score = 20, 13% Chance of reoccurance with hormone therapy alone. PR = 6.6, ER = 6.6, HER2 = 8.8 (yet nurse said HER2 is STILL negative).


    Help me understand the numbers. The IHC numbers were 98%ER, 5%PR, and 0 HER2

  • farmerlucy
    farmerlucy Member Posts: 3,985
    edited June 2016

    I posted this the hormonal therapy thread, but I think it is worth repeating. This is the best description of the Oncotypedx testing I've seen. (Forgive me if I posted here and missed it.)


    http://www.stjames.ie/GPsHealthcareProfessionals/C...

  • Lisey
    Lisey Member Posts: 1,053
    edited June 2016

    well they just called with my ki67 numbers as well. 30-35%. I suppose I'm in the chemo club. But with Luminal B, that may just be a blessing in disquise.

  • farmerjo
    farmerjo Member Posts: 518
    edited June 2016

    Marie -

    Your ER and PR are high, with HER-, so I'm pretty sure you're Luminal A.

    The way I understand it from MO, with high ER, and borderine PR (0-5%), AI takes care of the ER part of the cancer, can't help the PR part.

  • BarredOwl
    BarredOwl Member Posts: 2,433
    edited July 2016

    Hi Lisey:

    Please be sure to obtain a copy of your Oncotype report for your review and records.

    The Genomic Health website has a Sample Node-negative (N0) Report. Scroll down to Page 3 of 3, "Quantitative Single Gene Report" with ER, PR and HER2 sample results on the sample report here:

    Sample Report: http://breast-cancer.oncotypedx.com/en-US/Professional-Invasive/Ordering/ReadingTheReports/Node-NegativeReport.aspx

    In this node-negative sample report, the "cut-off" values for each individual single-gene score defining "negative" or "positive" are printed in the orange and green bars for each range and noted in the text below, and they are different for ER, PR and HER2. The range considered HER2 "equivocal" is in gray. In your case, the statuses appear to be in accord (ER+ PR+ HER2-):

    Your Oncotype Quantitative Single Gene Scores were: ER = 6.6, PR = 6.6, HER2 = 8.8

    Your IHC numbers were: 98%ER, 5%PR, and 0 HER2

    Based on the information from the sample Oncotype report:

    ER score of 6.6 (positive): ER score greater than or equal to 6.5 units is positive

    PR score of 6.6 (positive): PR score greater than or equal to 5.5 units is positive

    HER2 score of 8.8 (negative): HER2 score of less than 10.7 units is negative (the equivocal range is 10.7 to 11.4 units; and positive is greater than or equal to 11.5 units)

    Generally, one should look to the surgical pathology report for an understanding of ER, PR, and HER2 status.

    ER and PR as determined by IHC (immunohistochemistry) by the pathologist on surgical samples are typically used to determine ER and PR status for the purpose of endocrine therapy, because IHC is more sensitive than the RT-PCR method of Oncotype. I note that the standard pathology methods and the RT-PCR method of the Oncotype test are quite different, so the results cannot be directly compared***.

    Similarly, the single gene HER2 Oncotype score has only limited applicability. The single gene Oncotype DX HER2 score (by RT-PCR) may yield false-negatives for HER2 status, and should not be relied upon as a sole method of determining HER2 status.

    I am a layperson, so the above is for information only. Please obtain a copy of your Oncotype report, so you confirm the scores and the "positive" and "negative" statuses set forth in your report.

    BarredOwl


    ***Usually, the validated pathology methods ("IHC") used to measure Estrogen Receptor protein and Progesterone Receptor protein look at whole cells. Results are reported as percent positive cells in a field of view (i.e., some cells are stained by a "molecular tag" and are seen as "positive for staining," and some cells are not stained). The percentage of cells that do stain is reported.

    Oncotype uses a completely different method ("qRT-PCR") to measure ER and PR mRNA from ground-up cells. It gives a numerical score in "units", where particular unit values falling below a specified positive/negative cut-off of X units are considered "negative" by Oncotype (if the arrow/triangle falls in the orange range at left).

  • Warrior_Woman
    Warrior_Woman Member Posts: 1,274
    edited July 2016

    BarredOwl - Thank you for this post. It's the first time I've had this explained. I've known that ER/PR were tested differently by Genomic compared with the pathology labs. My 2 path reports showed me ER+/PR+/HER2- and ki67 40%. However, my Oncotype showed me as ER-. It made me insane. I don't know if I'm Luminal A or B and I'm not confident that my course of treatment is effective. Are you saying that hormonal treatment decisions should be based on the lab path reports and Oncotype should be used only for chemo decisions? Does anyone know? I used to feel like an oddity in the cancer world. I thought I would never survive because of so many peculiarities to my cancer. Now I'm starting to think that there are many of us who simply don't fall into a neat and clean box.

  • Lisey
    Lisey Member Posts: 1,053
    edited July 2016

    I love you guys helping me navigate this. I found the page that showed the scale on the ER / PR / HER numbers finally, thanks to a link above. It looks like I'm still ER+/PR+(but less so)/ and HER2-... from the oncotype. My Ki67 score is 35%... so ladies I'm off to get some type of chemo.. which along with this iron bra of TE's I'm wearing I'm sure will make for a lovely summer.... but this is all a side note. I wanted to share a response I got to the email I sent to the research team. SharonK and others, please read this is from the main researcher of the mouse study.l
    _____________________________________________________________

    Thanks for your email. You are obviously quite knowledgeable about your cancer and about our research. I wish I could tell you that I know whether the experimental CDB4124 drug would be effective in a PR-low, high ER+ tumor, but I don't. The T47D breast cancer cells we used have high PR levels and we don't have animal data yet for low PR/ER+ tumors, although we plan to carry out these studies. I do think it is appropriate to treat your cancer as luminal A until proven otherwise (please note that I am not a medical doctor). 98% ER+ is very high and a good sign, in my opinion. It is well known that even low ER+ cancers respond to endocrine therapies (e.g tamoxifen). Less is known about how to interpret the % of cells that are PR+. I hope you are being treated by someone who is well informed about the latest clinical data for your type of breast cancer.

    best regards,

  • Jojo0529
    Jojo0529 Member Posts: 193
    edited July 2016

    I think the high or positivity is more important than the ki 67... At least according to the most recent research image

  • Moondust
    Moondust Member Posts: 510
    edited July 2016

    Jojo, can you give a summary of the article for those of us who don't have access? I am very interested in what it says. Did you decide to have chemo because of your high Ki67%?

  • Jojo0529
    Jojo0529 Member Posts: 193
    edited July 2016

    hello moo dust, I could not copy the link... I am not sure why.. It can be found under a Google search... I decided on chemo because of my ki 67 , tumor size, and the tumor sat misdiagnosed as b9 for several years

  • Jojo0529
    Jojo0529 Member Posts: 193
    edited July 2016

    hi moon dust ... I chose chemo for my high ki67, and my tumor was misdiagnosed for several years.. For some reason the link will not copy.. It does come up in a Google search

  • cp418
    cp418 Member Posts: 7,079
    edited July 2016
  • cp418
    cp418 Member Posts: 7,079
    edited July 2016

    This article is interesting for Luminal B patients. http://www.thebreastonline.com/article/S0960-9776(13)00296-8/abstract?cc=y=




  • Jojo0529
    Jojo0529 Member Posts: 193
    edited July 2016
  • Lisey
    Lisey Member Posts: 1,053
    edited July 2016

    I found another article - from a secondary site that seems even more interesting for those of us that are mildly Luminal A - or even fully Luminal A (the Oncotype swears I'm luminal A).

    Here's the takeaway in the lower section.. but it's a really hefty read full of good stats regarding the ki67 scores. Basically if your ki-67 is higher than 13% and you are node neg. Luminal A, you should STILL consider chemo.
    ______________________________________________________

    A prognostic significance of the Ki-67 index in each subtype was investigated. The Ki-67 index significantly correlated with DFS only in luminal A type tumors, and a multivariate analysis revealed that the Ki-67 index was a significant factor in this type of tumor. Moreover, approximately 40% of luminal A type tumors had a higher Ki-67 index (≥20%) and showed the same DFS rate as luminal B type tumors. The luminal A type group should be treated more frequently with chemotherapy, as tumors with a higher Ki-67 index frequently respond better to chemotherapy (1416). Cheang et al (17) suggested that the most appropriate Ki-67 index cut-off point to distinguish luminal B from luminal A tumors was 13.25% in a similar manner using a gene expression profile. Hormone-sensitive breast cancers with higher Ki-67 levels (>13.25%) were assigned to the luminal B group and were associated with a worse prognosis compared to tumors with lower Ki-67 levels (<13.25%). There were 625 luminal A, 263 luminal B and 55 luminal/HER2+ tumors that were node-negative at the time of diagnosis, and these cases were not treated with systemic therapy. This method using Ki-67 may be suitable for the diagnosis and treatment in practical clinical settings.

    https://www.spandidos-publications.com/etm/1/5/747

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