Was this the thread? (i believe I have posted many on the topic, but this one seemed to fit what you were referring to???)
02-04-2013, 06:20 PM #7
IrvineFriend
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Join Date: Jan 2013
Location: Irvine, CA (Southern CA)
Posts: 219
Re: must read article --should her2+ breast cancer be divided into ER+ vs ER- subtype
Now I'm more confused by my pathology report (just when it was making sense). I was told I have two different cancers and will be treated for both.
02-04-2013, 07:23 PM #8
caya
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Location: Thornhill, Ontario Canada
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Re: must read article --should her2+ breast cancer be divided into ER+ vs ER- subtype
Yikes - major +++ here - but going on 7 years out. I figure I gave it my all - mastectomy, chemo, Herceptin, Tamoxifen, Femara - and Reclast for my osteoporosis and the double whammy of (hopefully) protecting me from a recurrence. Trying to watch my diet, exercise more and fully intending to drop the weight I gained from the anti-hormonals, now that I finished my 5 year sentence. Also switched all my makeup, body lotions, soaps etc. to Paraben free. Buying organic meat, yes it's expensive, but worth it, IMHO. As of Jan. 1, 2013 I am totally off all refined sugars - I have more energy, really don't crave it. Eat fruit for natural sugar, whole grain, lots of veggies, olive oil, etc. Trying hard...
all the best
caya
Last edited by caya; 02-04-2013 at 07:27 PM..
02-05-2013, 08:11 AM #9
sarah
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Location: france
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Re: must read article --should her2+ breast cancer be divided into ER+ vs ER- subtype
Thanks Lani for posting this very interesting article and of course upsetting to those of us who are ER+. I hope that oncologists will be aware of this and I also wonder what is suggested to lessen the probability of recurrence - they have said to stay on Tamoxifen longer than 5 years and again will people run into protocol problems??? Just when you think it's safe to go in the water again!!
02-05-2013, 10:18 AM #10
Cathya
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Join Date: Sep 2005
Location: Ontario, Canada
Posts: 594
Re: must read article --should her2+ breast cancer be divided into ER+ vs ER- subtype
Hi; two thing come to mind on reading this article....well three actually. Firstly I think that some form of bone treatment like actonel might help reduce our bone risk. Secondly, Lani recommendation for a bone biopsy is sounding very worthwhile. And thirdly, in the latest John Hopkins issue of Artemis there is a report of a study which identifies a DNA marker which apparently predicts cancer recurrence risk. Here's the link.
http://www.hopkinsbreastcenter.org/a...201302/21.html
I'm going to see if they are expanding this study.
Thanks Lani.
Cathy
02-05-2013, 10:29 AM #11
bejuce
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Join Date: May 2009
Posts: 489
Re: must read article --should her2+ breast cancer be divided into ER+ vs ER- subtype
I agree with Karen. I just read the article and it seemed to confirm what I had heard before: ER+ tends to recur more to the bones, ER- tends to recur more to soft tissues, ER+ can recur several years out and ER- tends to recur within 3-5 years.
I think what is clear is that breast cancer is a highly heterogeneous disease with many different genetic characteristics that vary from person to person. Even those of us who are ER+/HER-2+ have different percentages of ER+ that may influence the tumor biology.
What is great about this article is that the medical community is moving towards a greater degree of individualized approaches based on each tumor genetic characteristics. I can't wait to see the day when treatment becomes highly personalized for each one, the day we'll be able to detect cancer from a simple blood test, and the day we'll be able to characterize the genetic signature of each tumor and do a pattern matching to available drugs to determine which ones will be most effective. Some of my wishes seem very close to be granted, others may take many years (but I sure hope they are granted fast!)
02-05-2013, 10:45 AM #12
NEDenise
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Location: Philly Suburbs
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Re: must read article --should her2+ breast cancer be divided into ER+ vs ER- subtype
And, please God...
Could all of Bejuce's wishes come true before anymore of our sisters die.
Please.
02-05-2013, 02:47 PM #13
Hopeful
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Join Date: Aug 2006
Posts: 3,163
Re: must read article --should her2+ breast cancer be divided into ER+ vs ER- subtype
Here is a link to a paper by the same lead author which discusses patterns of recurrence in Her2+ patients based on hormone status:
http://breast-cancer-research.com/content/14/5/R129
Hopeful
02-06-2013, 04:27 AM #14
Ellie F
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Join Date: Feb 2009
Posts: 1,505
Re: must read article --should her2+ breast cancer be divided into ER+ vs ER- subtype
Hi everyone
Just want to restate what my onc ALWAYS says to me 'each breast cancer is individual in its make up and equally every immune system is individual in its response'
We just don't yet know why some apparently small tumours recur and some huge ones don't! I find it incredibly frustrating that the research is so slow and at present often all we have is generality.
There is an emerging body of thought that seems to suggest the 'cure' will come from tackling the underlying mechanisms of cancer rather than trying to find a cure for the two hundred or so different solid cancers.
Ellie
02-06-2013, 10:21 AM #15
karen z
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Re: must read article --should her2+ breast cancer be divided into ER+ vs ER- subtype
Ellie,
Your onc seems wise!
02-06-2013, 12:39 PM #16
Ellie F
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Join Date: Feb 2009
Posts: 1,505
Re: must read article --should her2+ breast cancer be divided into ER+ vs ER- subtype
Thanks Karen I think he is and very passionate about research!
02-07-2013, 07:53 AM #17
Hopeful
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Join Date: Aug 2006
Posts: 3,163
Re: must read article --should her2+ breast cancer be divided into ER+ vs ER- subtype
This must be a VERY popular topic for research right now - here is another paper than is analyzing response to Herceptin. The study was twofold, looking for response to Herceptin based on a protien (mRNA) for Her2+ and a subset analysis based on ER positivity:
HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer
http://breast-cancer-research.com/co...df/bcr3384.pdf
Of interest, beginning at page 10:
Our investigation shows that in hormone receptor-positive tumors the response to neoadjuvant treatment with trastuzumab plus anthracyline-taxane chemotherapy is driven by the degree of HER2 mRNA expression. This phenomenon could not be observed in the hormone receptor negative subset. Interestingly, Soon Paik’s group has described a similar finding in the adjuvant setting. While their full paper is not published yet, a summary of their results has been included in the recent St. Gallen recommendations: "An interesting STEPP analysis from the adjuvant trastuzumab NSABP B-31 trial examined the degree of HER2 mRNA expression and corresponding trastuzumab benefit separately for patients with estrogen receptor-positive and estrogen receptor-negative disease. The striking finding was that among patients with estrogen receptor-positive disease, trastuzumab benefit in terms of 8-year disease-free survival was entirely confined to those with the higher levels of HER2 mRNA expression."
Similar to these findings in the adjuvant setting, there is a considerable difference in our neoadjuvant study between ESR1pos/HER2pos and ESR1neg/HER2pos tumors. For ESR1neg/HER2pos tumors the amount of HER2 mRNA is not further relevant for response once a tumor is in the HER2-positive group. mRNA levels of HER2 have a dichotomous distribution and HER2can be used as a categorical parameter in this group.
For ESR1pos/HER2pos tumors the situation is different: HER2 mRNA has a more continuous distribution and the response to neoadjuvant trastuzumab/chemotherapy rises continuously with the amount of HER2 mRNA within the HER2-positive tumor group. This suggests that those luminal tumors with a higher activity of the HER2 pathway (measured as increased mRNA levels) are more dependent on this pathway and thus more responsive to trastuzumab targeted therapy. This finding is supported by the STEPP analysis and we observe the same effect with the classical approach of logistic regression, which also shows a significant effect of HER2 mRNA levels (measured as a continuous variable) on pCR only in the ESR1pos/HER2pos group. The traditional method of HER2 SISH ratio or copy number was not able to provide a similar result by STEPP or logistic regression, similar to the finding in the adjuvant HERA trial.
The relevance of a crosstalk between the estrogen receptor pathway and the HER2 pathway has been described in several in vitro cell culture and animal models, AIB-1 as well as PAX2 have been identified as relevant mediators of this crosstalk.The hypothesis derived from those investigations and our results would be that two important growth factor pathways significantly influence ESR1pos/HER2pos tumors and either HER2 or ER may be the driver of cell proliferation and survival. With sustained HER2 inhibition ER could function as a key escape or survival pathway, which may result in resistance to trastuzumab. However when HER2 mRNA expression is very high the primary driver of proliferation may still be the HER2 pathway even in the presence of the activated ER pathway. These findings are consistent with two neoadjuvant trials where a significantly lower pCR rates were observed in ERpos/HERpos tumors compared to ERneg/HER2pos disease. However in a recently reported neoadjuvant trial response rates to anti-HER2 treatment with lapatinib and trastuzumab (without chemotherapy) were fairly high (pCR 21%) when combined with endocrine treatment if hormone receptors were present. As in the adjuvant setting trastuzumab or lapatinib therapy (in contrast to the neoadjuvant approach) is usually combined with endocrine therapy in the HR-positive group, the combined inhibition of both pathways is already clinical practice. It would be interesting to further evaluate the contribution of the endocrine therapy to outcome in ESR1pos/Her2pos tumors.
Hopeful
Last edited by Hopeful; 02-07-2013 at 07:57 AM..
02-07-2013, 03:15 PM #18
CarolineC
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Join Date: Oct 2011
Posts: 97
Re: must read article --should her2+ breast cancer be divided into ER+ vs ER- subtype
Almost three years ago when I was to start Tamoxifen I had alot of questions-I had been reading about the cross-talk between the receptors,that Tamoxifen could possibly fuel the Her2 part back up, how some patients couldn't metabolize it, and I asked to be tested to see if I could metabolize it. I was told this was the protocol for pre-menopausal women and that the test was unproven. I started it with alot of reservations and hoped for the best.
After finishing my protocol in Nov of 2010 for early stage and dropping the Herceptin, I noticed within months some symptoms like dizziness, swelling on the mastectomy side, itching where the original tumour had been,my seatbelt would bother me, and my bra was feeling uncomfortable. I didn't have baseline TM's done as soon as the Herceptin was finished, but about 4 months later in March, when I believe things were stirring up. A few months later my CEA had doubled and I questioned my onc about it, who said he wasn't worried about it and that TM's are not diagnostic. I said I knew that they weren't diagnostic, but could be a helpful monitoring tool, and that "if you're not worried, I'm not worried". In April of that year I even saw a clinical trial doctor because I was interested in the Neratinib trial and he said I had a 10% chance of recurrence.
At the end of August my brother-in-law hugged me at a family function and it felt like I had been crushed and I was in alot of pain. An X-ray in Sept didn't show anything, but I kept persisting, especially after I talked to my onc's nurse at the larger centre where I also have been treated. She suggested a bone scan which my local onc wouldn't order because he thought I had costochondritis, an inflammation of the chest, but my gp ordered it. And it revealed a 3cm sternal lesion, and I was taken off Tamoxifen right away (that made me think someone somewhere knows something) and put on Letrozole. (when I had asked about my hormone levels a few months earlier and whether I was post-menopausal the local onc said that my numbers were still pre-menopausal) It was a farce, a comedy of errors, a nightmare, I felt like there were clowns to the left of me and jokers to the right and when I saw the larger centre onc (because I underwent rads AGAIN) I said I was mad that I was another statistic of recurrence on Tamoxifen. My CEA at that time went up to 25 (normal 0-5) and the 15-3 was 40 (normal up to 30). NOW we were looking at the TM's.
After having rads, being on Letrozole for 3 months and 6 MORE chemo rounds this time of Docetaxel and Herceptin (complete with a 3 day hospital stay after the first round with all the time to myself as I was put on reverse isolation) my TM's were CEA 2 and 15-3 of 6. The oncs said not to have the anti-hormonal but to save it for later. Against my better judgment, again, I held off on the Letrozole until my CEA went up to 5 in Nov. Then it went to 6, and now 7. I had also been having headaches, pelvic cramps, and backaches, like I was either going fully into or coming out of menopause and my estrogen levels which had been below normal for two years, were registering a number, even though it was still low. These might not sound like high numbers but for me it can show something is up. I am hoping the Letrozole will take effect soon, but it's only been a few months, and the first time I was riding the wave of having been on Tamoxifen, which was probably effective when I was also having the Herceptin-each medicine was keeping its receptors in check.
I am also looking into something my naturopath said about my lacking an enzyme to help me metabolize hormones in a benign liver condition called Gilbert's Syndrome, which I was diagnosed with in my mid 20's-the doctors initially thought I had hepatitis. I found an abstract on a study done last year -and thank you so much Lani for sending me the full article!- and found that researchers are hypothesizing on whether Gilbert's Syndrome is a new risk factor for breast cancer because patients lack an enzyme that helps to metabolize 4OH estrogen.....then I found, after searching and just googling "Tamoxifen and Gilbert's Syndrome" in a liver cancer book, that patients should use extra caution when having Tamoxifen therapy.....
I am trying to be a patient patient but it is hard, and I am having a hard time trusting doctors' opinions, although some of my medical team does listen. I so envy those of you who have a team who works with and looks out for you! I also don't want to freak anyone out, if I haven't already. Be informed, listen to your body. Possibly have yourself tested by the company that rhondalea has suggested.
I know the research will start to show that ER+, Her2+ patients should be on a dual blockade of medicine so they can each do their job effectively, or that ovarian suppression by oophrectomy or chemicals will also be effective. I know someone who was diagnosed with Stage IV liver mets from the beginning. She was put on Tamoxifen and Herceptin (she also takes supplements) and 5 years later they cannot find the mets. Based on these studies I don't understand how it went to her liver because she was ER+- maybe she had less of a positivity for ER and I had 90%, alot, and it did go to my bones. I believe the positivity will have a factor as well.
Anyway, thanks for reading my take on this situation. I only hope to help anyone else who may be having the same dilemma, and maybe those people won't have to go through the nightmare that I (and my family) have been going through.
02-07-2013, 04:35 PM #19
europa
Senior Member
Join Date: Jan 2012
Posts: 201
Re: must read article --should her2+ breast cancer be divided into ER+ vs ER- subtype
Thank you for this article. I have been wondering if I should even be on Tamoxifen since I only had 10% ER+ in my tumor. My Onc keeps telling me that it can prevent a recurrence but from what I keep reading it sounds like it can give HER2+ cells fuel. I'm 38 and ma pre menopausal. How does one test to see if they are metabolizing Tamoxifen or not?
02-07-2013, 06:08 PM #20
CarolineC
Senior Member
Join Date: Oct 2011
Posts: 97
Re: must read article --should her2+ breast cancer be divided into ER+ vs ER- subtype
Europa,
Rhondalea posted on Feb 1 about a test to see if you're a poor, intermediate, or extensive metabolizer and had information on a website-maybe she can add more info. Discuss with your onc the results, if any, on the Suppression of Ovarion Function Trial (SOFT) and if he/she is open to the test for CYP2D6. That is the test I asked to have, but was told it isn't proven, however it is now in a clinical trial at the BC Cancer Agency.
Before you get too far into the Tamoxifen treatment, since you have just finished Herceptin, ask to have your hormone levels checked as a baseline, and have them checked every 3 months. I think Becky suggested that in one of her posts. See if your onc is also open to you having your TM's checked.
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