Single Hormone Receptor Positive -> ER+/PR-/HER2-
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Hello ladies,
Sorry to butt in on and hijack an ongoing discussion.
I've been diagnosed just a few days ago with ER+/PR-/HER2- IDC. YAY for rare types!
I was feeling pretty decent about it at first, especially with the HER2- bit, but then I noticed my ER+ percentage was relatively low (27%). So I'm a little more concerned about the aggression of the cancer now. I haven't met with my oncologist yet, so I'm pretty much blind as of right now.
I've read about some lower ER+ and PR- with HER2- cancers being treated as Triple Negative, which is not the most thrilling thing to think about. Does anyone here have any experience with that? I want to try to prepare and be as realistic as possible.
Thank you so much for all the incredible information on this forum. Not sure how I would have gotten through this last month without lurking around here
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Ciarratron, I was only 11-25% ER positive and (testing wasn't as precise when I was diagnosed) and grade 3 like you (with a bigger tumor). I am 13 1/2 years out and doing great (pausing to knock on wood). Do what is medically recommended and, in the end, you should be fine!
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ruthbru, thank you!
I'm really happy to see so many of you doing well now. It's certainly encouraging.
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Ciarratron - I have pretty similar stats to you except I am much older (57), had a positive lymph node and my ER was only 3% positive. MY MO considered anything above 0 as positive so I was not treated as triple negative. I went through surgery, very aggressive chemo, 35 radiation treatments and am now on Exemestane. So far so good at 3 years from final treatments.
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TomMorrow, I am PR-, and post-menopausal, and on Tamoxifen. I had pretty advanced osteopenia already and the bone loss with AIs was a huge concern. My onco was comfortable with doing tamoxifen for ten years.
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ciarratron - my oncologist says that he treats even 1% positive as hormone positive. He felt very strongly that you don’t treat it astriple negative unless you are truly triple negative. And really, why wouldn’t you want the safeguard of endocrine therapy?
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A new retrospective study and easy read that describes how estrogen blocking drugs significantly improve survival in those of us with ER+/PR- . Excerpts and link to abstract below. Would be happy to send you the pdf of entire paper.
Controversy exists regarding the efficacy of hormone blocking therapy for patients with ER+/PR− tumors. We identified 138,398 patients with invasive ER+/PR− tumors, 32,044 (23%) of whom did not receive hormone blocking therapy. Our analysis demonstrated that hormone blocking therapy administration was associated with increased overall survival for up to 10 years of follow up (HR: 0.58; 95% CI: 0.56–0.59, p < 0.001).
https://doi.org/10.1007/s12672-020-00387-1
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Thank you Murfy. I don't really understand what this means (HR: 0.58; 95% CI: 0.56–0.59, p < 0.001)
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Murfy, Something I read awhile ago mentioned that some ER+PR-Her2- cancers may not be as aggressive as others- are there different subsets of ER-positive, PR-negative cancer? It is often cited that these cancers are less endocrine dependent than PR-positive cancers because if ER were high it would be turning up PR expression, however I also read that cancers can have increased FGFR signaling, which can repress PR expression independently of the ER...
Also, I wonder if you are familiar with IntClust classification system and also wonder why it is not used in our genomics reports
https://genomebiology.biomedcentral.com/articles/1...
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"Our analysis demonstrated that hormone blocking therapy administration was associated with increased overall survival for up to 10 years of follow up (HR: 0.58; 95% CI: 0.56–0.59, p < 0.001)."
Lilly, those numbers mean that the group that took estrogen blocking drugs had a significant reduction in mortality vs. the group that didn't take estrogen blocking drugs. The treatment group had 58% of the mortality rate, or a 42% reduction in mortality (Hazard Ratio: 0.58).
The rest of the figures talk to the degree of certainty and the possible range of the results. For this finding, there is 95% confidence that any variation of the result falls between 0.56 and 0.59 (i.e. 56% - 59% of the control group's mortality rate, or a 41% - 44% lower mortality for the treatment group). The odds that this result could be random and not related to the difference in estrogen blocking drugs is 1 in 1000 (p <0.001).
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Thank you Murfy.
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Thank you so much Beese.
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Lilly, you're welcome!
And Murfy, thank you for the link to that research. What's really interesting is that my MO told me that endocrine therapy reduces the risk of mets by approx. 1/3rd. This is supported by the on-line models, PREDICT and CancerMath; if you input diagnostic/pathology stats and look at mortality rates with no treatment, and then add in endocrine therapy, the reduction in mortality in both of these models rounds to about 1/3 (or at least that's been the case whenever I've done this). Yet the study you linked found that the benefit of endocrine therapy for those who are ER+/PR-, is a 42% reduction in mets/mortality (at up to 10 years, which is the length of the study). That's really encouraging and certainly says that those who are PR- don't need to worry about lower efficacy rates from these meds.
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From my reading, there are subsets of ER+/PR- in that there are Grades 1-3 that show low (luminal A) to high (luminal
proliferation. The paper I linked did not include this data. I have emailed the author and asked him if tumor grade/proliferation/Nottingham score influences responsiveness to anti-hormone therapy/survival and will report back...if he does.Why PR- and in the presence of ER, indeed! Many with PR- are also HER2+ and it is thought that the ErbB2 mutant may directly suppress PR transcription. Other growth factor/receptor anomalies (ie, FGFR1) can directly affect PR synthesis and/or inactivate ER. I have the triple mutation in FGFR2 that renders the ER inactive and may, perhaps, render me triple neg. I wish I could get a FoundationOne report of my tumor to see what somatic mutations I might have!
I find the IntCluster data intriguing, as it further characterizes gene clusters/loci that may be driving the tumor. Perhaps naively, IntClust 1 vs 2 could explain Pr- (luminal A vs luminal
? Will be interesting to see if IntClust technology gathers steam within the oncology community. 0 -
Murfy, when I asked my MO if my case of cancer is more "dangerous" because PR <1%, he said maybe a bit but will be treated the same. Below is what pathology report did show after the biopsy:
ER: POSITIVE (90%, MODERATE)
PR: NEGATIVE (<1%, STRONG)
HER2: NEGATIVE (1+)
Invasive and in situ carcinoma are negative for E-cadherin and beta-catenin,
consistent with lobular origin.
P63/pancytokeratin stains aid in evaluation of the invasive carcinoma.I don't even know what the last paragraph means.
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Murfy- Oh, right, some significant fraction of the PR-negative cancers segregate into the IntClust1 group. It was recently shown that this particular subgroup have amplified the TRIM37 gene and therefore should respond to PLK4 kinase inhibitors.
https://www.sciencedaily.com/releases/2020/09/2009...
How would we know if we were part of the IntClust1 group, given that they do not include that kind of information on the genomics reports? I suppose if PLK4inhibitors move into clinical trials for breast cancer, the sponsor would include a blood test for that marker? I think PLK4 inhibitors are in trials now but just for triple negative cancers
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Yep, here it is- PLK4 inhibitor plus immunotherapy has just started a Phase 2 trial for TNBC
https://www.businesswire.com/news/home/20200812005...
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Trying to sort through all this information without a background in the hard sciences, with only moderate success. There are so may things you guys are talking about that I've not even heard of, and I've been a fairly involved patient with frequent searches on the NCBI site. I was struck by the abstract stating that one of the contradictions to hormone blocking therapy was "death." Yeah, when I'm dead I'll probably stop my tamoxifen, too.
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LilyisHere, I think your doc is right in that PR- does sometimes affect prognosis, especially if aggressive as determined by Grade/Oncotype score/tumor size. Most docs do treat the same as PR+.
Your tumor was determined to be ILC because it did not stain for E-cadherin/b-catenin, 2 cell membrane proteins. IDC does stain for these proteins. p63 and cytokeratin stains cell nucleus and cytoplasm, respectively, and allows pathologist to more clearly see entire cell for changes indicative of malignancy.
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Cure-ious, I think when TRIM37 is confirmed to be a reliable marker for treatment choices, perhaps then it will be included on a panel. Same goes for the IntClust concept. HOWEVER, Fulgent Labs would probably be very happy to sequence a blood sample or cheek swab for you! I found the following on their website:
"Sequence variants and/or copy number variants (deletions/duplications) within the TRIM37 gene will be detected with >99% sensitivity. Variants classified as unknown significance (VUS), likely pathogenic, or pathogenic will be reported."
So, I guess this would be a germ-line mutation vs circulating tumor DNA? I checked my Promethease report for TRIM37 and they included about every TRIM# EXCEPT 37 and all were normal. So, extrapolating....
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Wanderweg, I wondered what that meant too!! In Methodology section, they mentioned that the median time to initiation of hormone blocking therapy was 169 days. So, I'm guessing that with diagnosis, surgery, and chemo, some patients died before starting anti-hormone therapy, but that their data was included anyway.
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Murfy, Thanks, you are an incredible resource!! Of course, there is no point for me to get tested for TRIM37 without an available trial for a PLK4 inhibitor, and if/when they make one they will need their own biomarker diagnostic to go with it. TRIM37 is part of the 17q23 amplification that is diagnostic of IntClust1, and as you say, a subset (or maybe most?) of the PR-negative cancers are found in this group.I hope they follow up on this important clue, because it is so specific and action-able. Depends on whether somebody can make some money doing it, I suppose.
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Thank you Murfy. Just curiuus, are you taking any supplemnts or special diets to help with side effects of anti-homonal treatments?
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LillyisHere, it has been trial and error trying to find what works for the joint pain. The AI drug exacerbates old injuries and just makes me feel old(er). I have found no miracle supplement, but I have found that significantly reducing sugar helps. The other day I succumbed and ate a handful of candy corn and hours later I exhibited increased stiffness/pain in shoulders, fingers, hip joints. It's much better when I don't eat sugar. Exercise also helps. I do pop a glucosamine, calcium, and vit D every day and an over the counter anti-inflammatory every night. And, several times a day, I repeat the mantra 'just 2.5 more years, just 2.5 more years....'
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I read on these boards about taking a daily Claritin (non-D). When my wife first started Letrozole, she had pain and stiffness. But after taking Claritin everyday, she says most of this has gone away.
Ialso remember reading somewhere that it might be possible to have a test done to see whether your body can process/benefit from certain drugs. Has anyone done such a test with respect to Tamoxifen or an AI?
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Thank you Murfy. I don't eat or like sugar and I still get weird body pains. Now that I see an acupuncturist, he mentioned the connection of deprived estrogen with ligaments and it makes sense. What I thought was joint pains actually are the ligament inflammations. Yes, yoga and acupuncture helps.
TomOrrow, I heard about certain tests of the tumor tissue that can help figure out what meds work but I don't know much about it. I don't even want to think that the toxic AI I'm taking is not working
. Maybe someone else is familiar and can give us more info on this subject.0 -
My wife had an estrogen reading done on her last bloodwork and it was elevated. I was wondering if this test can determine if her body can't process Letrozole as intended.
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TomMorrow, I think what is important is that estrogen levels be reduced relative to pre- or post-menopausal levels, but you shouldn't expect to see a zero. There will also likely be fluctuations in levels from test to test. Are your wife's levels within the expected range but on the high side this time? There are medical conditions that might affect drug efficacy, but your doc would be aware of those conditions and would prescribe accordingly.
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LillyIsHere my MO told me to take turmeric for the joint pain from anastrozole. She said up to 3000mg is safe and that turmeric because of reducing inflammation helps with the joint pain. I've been taking it and I think it makes a difference. That and exercising. If I don't walk at least 20-30 minutes daily I feel it.
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Thank you mysticalcit. I have been taking turmeric since I was diagnosed last year. Together with other supplements and, I have been a yogi for several years
.What is interesting is that I have started acupuncture and the acupuncturist told me to be on a bland diet for 2-3 weeks and remove turmeric and other spices from my diet since they trigger nerves and make me feel the pain. I am in the second week and even though I miss turmeric since I developed a love for the tea, I have been feeling much better! I guess I was overdoing it. I can't wait to have it back in my diet. I also drink matcha tea and take fish oil, and glucosamine. My stomach is a mix supplements holder.
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