Single Hormone Receptor Positive -> ER+/PR-/HER2-
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Thank you Anna-33. I am concerned that the medication can block Progesterone.
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This 2019 article (link attached) may explain WHY I have such a high oncotype score, high Ki-67, and grade 3 tumor (all hallmarks of being triple negative), despite having very high ER levels. I had already discovered that I have 3 mutations in my FGFR2 gene, all 3 of which predispose to breast cancer. According to this new article, these mutations render ER useless (at the nuclear level). As PR depends on the presence of functioning ER, this could also explain why I am PR-. So am I essentially triple negative?
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Also feeling a little alone and concerned, my original report was DCIS and now it's also IDC 30% ER+ PR- and HER-2 sill pending, they have sent my pathology off for Oncotype genetic testing. Anyone eslse have Oncotype testing done with similar dx?
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TJF, I just responded to your another post.
My oncotype showed 27% ER+, 10% PR+, HER2 was negative. My Oncotype score was 39. I did the chemo. The positive side is that that it responded very well to chemo. From what I understand the PR- (or very low in my case) tends to have a higher Oncotype score but there are many factors involved. Hopefully, you will get your results back quickly so you can make informed decisions. Waiting is so hard. Praying for the best possible outcome for you.0 -
Yup. My diagnosis last year was IDC (with just a few DCIS cells), ER+(95%), PR-(0%), HR2-. I had the Oncotype testing done and it was invaluable in providing an aid in making the chemo/no chemo decision. As it happened, the TailoRx study of intermediate-Oncotype-scores of 11-25 had JUST some out. My Oncotype was 24 (at the very top of the Intermediate range studied). I could either have chemo or not; I had a lot to weigh and my Medical Oncologist helped a great deal in laying out what I should be considering, without telling me what to do. Risks vs benefits plus the very positive benefit of the AI I was going to be on (as opposed to the Tamoxifen which is assumed in the Oncotype data). Ultimately, I did NOT do chemo. (I would have had barely a 3% benefit with chemo + AI. Anyway, that's my story - EVERYONE IS DIFFERENT. Read up on how to read the Oncotype report you'll get. Read up on the TailoRx 2018 study (it's really an update on the 2015) - Here's one link to a somewhat simplified piece - http://bit.ly/TailoRxResults. Keep us posted - and keep asking questions. You're definitely not alone here!
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mine was similar to yours Patsy but my score was 34. I didn't do chemo I did AI still no sign of cancer 8 years later.
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Hi All....Just wanted to send a little hope to some of you. I am over 11 years out with ILC ER + PR - HER2 -. My tumor was 2.2 cm 7 positive nodes, grade 1. Chemo AC and T..25 rads, and 10 years of arimidex. I worry often about a recurrence but want all of you to know that if you can enjoy each day. I wish I hadn’t worried all these 11 years and had enjoyed/treasured them. I have no guarantee about tomorrow but know making memories and enjoying the time God gave me is what life should be about
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Could someone please explain why we might be considered triple negative as we are er + so how can that be? I am 100% er.
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Hi All...I am 13 years out with PILC, oncotype 9 and living life to the fullest. Technically, I'm Stage 4 because of skin mets but the Ibrance and Femara is keeping me alive and well. Good luck ladies and remember to enjoy everyday:)
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wintersocks, are you speaking about Murfy's post from Sep 4?
so, I think the explanation is that as we get better at analyzing breast cancers, we're finding out that the categories of ER, PR and HER are very broad and that within those categories, there are many subtypes of cancer. (OncotypeDX is an example of a test that goes much further than just looking at hormone expression and looking at actual genetic markers of the tumor to see what is making it replicate and succeed.)
What the article Murfy is posting suggests is that in some cases, someone who is ER+ but also has a bunch of genetic variations in their cancer, the estrogen receptors are not really working the way traditional ER+ cells do, and their cancer cells function more as triple negative.0 -
Wintersocks, some really good news is statistically being 7 years out from er+ pr- you are in good numbers to never see it again. Almost all recurrences hapoen in the first 5 years for both triple negative and er + pr-. Not to say it can't come back but it dies not look probable.
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Hi Mot
Yes I did it read it here and it sounds like Murphy's post I was thinking of. I see - that having the 'rogue+' er + could make the cancer be more like triple neg? I wonder if we know if ours is that sort? I don't think we have the oncotype dx test here in the UK., perhaps that's the only way to know? Thanks for the explanation - it helps in understanding the more unusual dx we have,
Meow
wow! that's heartening to hear, however my onc when I saw him last about 2 years ago said I would remain at 'significant risk of dying from your disease' and added that when Femera is stopped the cancer (this type) usually returns. I am wondering because it was a large tumour. Sometimes it's so difficult to know what to think.
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There is benefit in doing AI vs tamoxifen for er+ pr- cancers. Although second study was not encouraging as the ATAC trial.
https://bmccancer.biomedcentral.com/articles/10.11...
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wintersocks, I think the discovery that ER receptor status isn’t the whole story, making some of us look more like TNBC, is all the more reason for opting for chemo. Chemo is just a given in TN cancers. To my way of thinking, between chemo and the tamoxifen, I’m doing all I can and I try not to fret needlessly about stats at this point
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Meow, the study you linked compares the characteristics and prognosis of ER+/PR- to ER+/PR+ and other ER/PR subtypes, but specifically notes that they did not look at the benefit of AIs vs. Tamoxifen.
"Furthermore, we did not stratify patients according to treatment with tamoxifen or aromatase inhibitors. Although the use of aromatase inhibitors instead of selective estrogen receptor modulators improved the outcome of ER + PR− patients in the ATAC trial, the BIG 1-98 trial did not demonstrate a significant benefit of letrozole over tamoxifen in ER + PR− tumors. In addition, at our center, most postmenopausal patients with HR+ tumors received aromatase inhibitor, excluding patients with contraindications or adverse effects."
While overall ER+/PR-/HER2- cancers appear to have a less favorable prognosis than ER+/PR+/HER2- cancers, it is interesting that they did not find this difference for ER+/PR-/HER2- cancers that have a low Ki-67 (below 14%).
Here is a link to the BIG 1-98 trial referenced in the quote above:
Prognostic and Predictive Value of Centrally Reviewed Expression of Estrogen and Progesterone Receptors in a Randomized Trial Comparing Letrozole and Tamoxifen Adjuvant Therapy for Postmenopausal Early Breast Cancer: BIG 1-98
The conclusions:
"Our study shows that the endocrine treatment effect on DFS of postmenopausal patients with breast cancer is primarily influenced by ER status. The role of PgR could be determined only in patients with ER-expressing tumors, since few with tumors not expressing ER entered the trial. Of these, a better outcome was seen among patients with PgR-positive (≥10%) tumors—a finding consistent with the report of Bardou et al.13 Patients treated with letrozole manifested better outcome than those treated with tamoxifen regardless of their PgR status, and there was no statistical evidence of heterogeneity in the treatment effect whether PgR was considered as a categorical variable or as a continuum in the STEPP analysis.
Using real-time polymerase chain reaction assessment of ER and PgR status, Baehner et al28 found that the level of PgR was prognostic in untreated patients but not predictive of tamoxifen benefit, a finding parallel with our observation that PgR expression level did not predict the additional value of letrozole on ER-expressing tumors.
Our data do not confirm the hypothesis that aromatase inhibitors may offer a particular advantage over tamoxifen in patients whose tumors express ER but not PgR raised by Dowsett et al16 based on local laboratory PgR assessment in the ATAC trial. Our results conform more closely with the findings of no effect of PgR on relative efficacy of aromatase inhibitor and tamoxifen in the IES9 and the lack of significant difference seen in the ARNO/ABCSG trials."
Overall, AIs perform somewhat better for all post-menopausal women, versus Tamoxifen. Although the ATAC trial suggested that Tamoxifen is less effective for those who are ER+/PR-, all subsequent trials, including the large BIG 1-98 study, have not found this difference and instead have found that the performance of AIs vs. Tamoxifen is similar for those who have ER+/PR+/HER2- cancers or ER+/PR-/HER2- cancers. Therefore, while it is preferable that post-menopausal women taken an AI, for those who are unable to tolerate an AI because of side effects or other health concerns, Tamoxifen is a good alternative, regardless of whether the cancer is PR+ or PR-.
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https://bmccancer.biomedcentral.com/articles/10.11...
This also talks about the prognosis for er+ pr- and I will let others read it for themselves. Prognosis may be improved for er+ pr- read it for yourself.
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Thanks so much for that thorough summary, Beesie! And as someone who already had worsening osteopenia, I went with Tamoxifen because I wasn't willing to have more bone loss (and am not willing to take a bisphosphonate). It's reassuring to read about tamoxifen being a decent alternative.
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Just to say that most studies I have read suggest that an AI has better outcomes than Tamoxifen for ILC disease. This is not to suggest that it does not work for ILC but in every study I have read, the consensus was better outcomes with AI. Please note I am referring to ILC in particular and not IDC.
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trinigirl, the AIs also have better results than Tamoxifen with IDC - the BIG 1-98 study that I linked above found that on average AIs were 18% more effective.
In other words, if on average Tamoxifen reduces metastatic risk by approximately 30% (give or take a percent or two), the AIs reduce risk by approximately 35% (again, give or take a percent or two).
I don't know if the difference would be greater for ILC or similar.
Specific to PR-, looking at HER2- cancers, all studies I've seen show that ER+/PR- cancers have a less favorable prognosis than ER+/PR+. This less favorable result is consistent whether the patient takes an AI or Tamoxifen, although to my previous point, both ER+/PR+ and ER+/PR- patients do somewhat better on AIs. From the study that Meow linked, the only situations under which PR- cancers have an equally favorable prognosis to PR+ cancers is when the cancer is HER2+ or when the Ki-67 is less than 14%.
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Agreed Beesie. I also understand this is Single Hormone receptor positive thread, but still felt it important to mention the ILC component when it comes Letrozole vs Tamox for those of us who are both ILC and Single Hormone receptor positive.
"Metzger Filho et al21 compared the relative efficacies of tamoxifen and letrozole for lobular and ductal carcinomas in the BIG 1-98 trial. This trial was among the first randomized controlled trials of aromatase inhibitor therapy in the adjuvant setting and now has relatively long follow-up (median 8.1 years). Comparing patients by histologic subtype, patients with ILC were far more likely to benefit from letrozole than tamoxifen, regardless of whether patients were luminal A or luminal B like. The 8-year disease-free survival estimate was 66% for tamoxifen compared with 82% for letrozole in the ILC subset (hazard ratio [HR] 0.48) and was 75% for tamoxifen and 82% for letrozole in the IDC subset (HR 0.80). The test for interaction was significantly positive (p = .006). These seem, on the face of it, to represent a clinically significant difference and are paralleled by overall survival differences (74% for tamoxifen compared with 89% for letrozole in the ILC subset [HR 0.40]; 84% for tamoxifen and 88% for letrozole in the IDC subset [HR 0.73])."
If, as suggested by the BIG 1-98 analysis, lobular carcinomas are relatively less sensitive to tamoxifen than ductal carcinomas, what molecular changes might underlie these findings? Sikora et al23 have recently evaluated the response of lobular carcinoma cell lines in vitro. Their work suggests that the ER drives a unique program of gene expression in lobular cancers when compared with ductal carcinomas. Indeed, tamoxifen appears to drive the growth of these cell lines, rather than inhibiting them, although this limited cell line work cannot be safely extrapolated to the clinic."
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Wow, that is quite a difference for AIs versus Tamoxifen for ILC - much greater than the difference for IDC. That is really important information for those who have ILC.
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Yes and I am amazed that the Drs/oncologists that I have dealt with are so unaware. I have literally educated both my BS and my ONC. I think there is an information booklet in ILC thread. I will check and ensure this info is part of it (I think it is).
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Thanks for this info and Beesie for breaking it all down. i understand that with a TNBC dx the risk drops significantly after 5 years of no recurrence. But if we are similar to TNBC our risk does not similarly drop. So I do not understand how the two can be compared as similar? I wonder what I am missing here ?!
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wintersocks what studies have you seen that show our risk does not drop? I only had seen this. . (https://wjso.biomedcentral.com/articles/10.1186/s12957-016-0988-0) which seems to indicate it is the ER+PR+HER- that tends to recur after 5 years. That concomitant PR-positive is more likely to have late recurrence. A few excerpts from the link:
"Previous studies reported that high-bulk disease, high proliferative index, and HER2-positive malignancies corresponded to recurrence earlier than 10 years, whereas progesterone receptor-positive (PR+) disease was associated with relapse later than 10 years.
Conclusions
ER+/PR+ and HER2− patients have higher risk of recurrence later than 5 years, especially in patients with high ER titer and low nuclear grade. Larger and node-positive tumors had higher risk of early recurrence.
A previous study showed that recurrence that occurred later than 10 years was associated with positive lymph node or PR+ disease [2].
Tumors larger than 2 cm, lymph node metastasis, and high nuclear grade were related with early recurrence. Estrogen receptor-positive, progesterone receptor-positive, and HER2− disease predicted late recurrence.
Given that coexpression of ER and PR were related to late recurrence compared with patients who had only ER or PR, our findings support greater benefit of extended letrozole treatment in patients who had ER+/PR+ tumors, as shown in subsequent analysis of MA17
Conclusions
Larger and node-positive tumors associate with greater chances of early recurrence. Factors that predict late recurrence are luminal tumors, especially with concomitant PR-positive status, high ER titer, small tumor, negative lymph node, low grade, and HER2− disease."
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Wintersocks, the article I posted earlier might have contributed to your confusion. I have a mutation (in FGFR2) that may result in the inability of my ER to function properly, in which case I could be TN. This would be a relatively rare occurrence in PR- individuals. Most with only PR- have functioning ER and when treated with AI/TAM have significantly improved outcomes, an advantage that those with TNBC do not have. I hope this helps...
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Thanks ladies.
Hmn interesting reading. Perhaps cos I had a large tumour I may be considered more at risk? My onc did not present me with a pretty picture last time I spoke with him. He told me I 'was at significant risk from dying from your disease' I am 100% er and negative for HER2 and PR too. It's just that I never know where to 'pitch' myself. I am just passed 7 years since dx now. I never know if I am nearer recurrence or further away from it!. Thanks for all your research I appreciate it.
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wintersocks
I am in the same boat. 100%er 0%pr. Large tumour, (unlike you I also have lots of nodes). I have all the hallmarks of early recurrence and late recurrence (lol), in fact the only positive that I have to hold on to, is that pr- means less likely to reoccur after 10 years, so I am taking it.
Therefore if and when I get to 10 years, I am going to consider myself cured. Why not?
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Hi Trinigirl
Yes, we are similar but I have IDC and you ILC. I guess that must make some difference somehow. That's good to hear it's less likely to return after 10 years if pr -, look for the positive in the (pr) negatives I say!
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ILC more potential for late reoccurrence than IDC. So to steal from you: that's why I said the PR negative is my only positive (for getting past 10 years). Lol. Gotta hold onto something.
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I found this article which relates to ILC ER+ PR-. https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182397&type=printable
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