What causes AI or SERM failure?
Are the causes of hormone therapy failure due to mutations in the tumor dna or bypass mechanisms? Like if you’ve been on some therapy for a while but then develop a new primary, how is this possible when those receptors are suppressed (assuming the patient is compliant with dosing).
Also, has anyone had the Breast Cancer Index in addition to the oncotype or mamaprint tests? Did it alter treatment decisions? I don’t really understand what it tests but it doesn’t seem as specific as oncotype or mamaprint.
Lastly, has anyone’s oncologist offered or suggested testing to see if you have a difference in the way you metabolize these drugs, or checked to make sure you have therapeutic levels?
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waves2stars,
I am not certain, but I think the reason for hormone therapy failure is likely not fully understood. Additionally, there is no expectation going into it, whether tamoxifen or an AI, that it will work for everyone so it’s known that some progress in spite of anti-hormonal tx. When you talk about developing a new primary, I assume you mean a new primary bc. Again, though I can’t tell you why, it is known that these drugs do not prevent recurrence, whether local or metastatic, for everyone. Very few drugs work as they should 100% of the time for 100% of those who use them, even for those who are completely compliant, so although I can’t pinpoint what the “failure” is, there never was an expectation that they would work for everyone as demonstrated both by trials and reality. Even less complex meds such as aspirin don’t work as hoped all the time.
Can’t comment on BCI, etc. as I have never had those tests. Hopefully someone with a more specific knowledge of medication will be able to give you more concrete answers. Take care1 -
Hi @waves2stars, we're sure others will be by to weigh in with their thoughts and experiences, but exbrnxgrl offers some good insight. Breast cancer and its treatment is less than predictable (don't we all wish it was?!), so the best advice would be to discuss your concerns with your onc about the medication that will most benefit you. This podcast might be helpful in your conversations:
Additionally, it's possible a new primary breast cancer could NOT be hormone-receptor-positive, and therefore wouldn't react to the hormonal therapy one had been taking for the previous primary. So, "suppressing" that HR-negative cancer would not be possible on those medications.
Here's some information on the Breast Cancer Index Test that you might find helpful:
We hope this helps!
—The Mods
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Hi @waves2stars, The BCI test predicts whether an additional five years of estrogen therapy will reduce your risk of recurrence and what your risk of recurrence might be after five years of HT. It uses your original tumor sample. Some people find this helpful when deciding whether or not to continue an AI for a total of ten years but it can give discordant results. One possible answer is that there is not much benefit in continuing an AI and you have a high risk of recurrence.
There is pharmacogenetic testing that analyzes your saliva to see how well you respond to certain drugs and flags drugs that might cause dangerous side effects. My health insurance pushes this but I have never signed up for it since it could be used to limit what prescriptions they will cover.
Cancer cells can evolve to become AI resistant through many different pathways including DNA mutations, modification of microRNAs and changes in the tumor microenvironment. This is an ongoing field of research with cellular level discoveries constantly being made. Some of the current new therapies are a result of past research and hopefully more therapies will follow. It’s a matter of the survival of the fittest as far as the cancer cells are concerned. This article is pretty technical but if you just read the section headings you can see how many different causes of endocrine resistance are known. More have probably been discovered in the past couple of years.
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waves2stars,
One of the harder things for many of us to reconcile with respect to bc treatment is that there are many, many unpredictable outcomes and never any guarantees. It is frustrating and for as far as we’ve come with tx (I was dx’ed almost 13 years ago) there is more than enough room for improvement. The human body is complicated. Breast cancer is complicated. Add to that all the potential variations in terms of not only the disease itself but how individuals can react differently to the same tx and it’s not difficult to understand how a drug can work very well for some but not for others.
I am stage IV de novo. I had rads to my bone met and 12 years of one AI or the other. I have never had chemo and never had progression. Last November, my mo took me off all tx and I am, so far,fine. What caused this? No one knows, and I mean that quite literally. One of the difficult things I’ve had to accept with respect to bc is that there is still much to be learned and many mysteries to be unraveled. The complexity of bc should not be underestimated. Take care
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waves2stars,
I finished my 5 years of AIs in March of this year. My onc suggested the BCI test for me because of the science behind it. I had 3 positive nodes. I landed in the no benefit , high risk of recurrence category.
They actually give a number for recurrence instead of high or low. In my onc’s opinion, 14% is high (I agree with her). However, there’s no point in continuing HT if there’s no benefit. We looked at some clinical trials but I’m not a candidate for one (I took my AI for 5 days too long) 🙄I did listen to a podcast on here about a trial involving circulating tumor cells. Even contacted the oncologist on the podcast (she’s at Penn) and received a reply. However, the trial is too far way for me. There is a location closer to me if I want to pursue it.
The BCI is a great tool for oncs and patients in that it answers the question about extended HT. However, the answer you get (in my case) can leave you a little uncomfortable if you land in that dreaded category. It doesn’t change the follow up in my case. My onc says the “standard of care” is only scan if there’s a symptom or problem. I will go to yearly follow ups for blood work and exam.2 -
@waves2stars here is the podcast @dimples90 mentioned:
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@dimples90 Thanks for sharing info and your experience with BCI. I’m going to check out the podcast to learn more.
I hope monitoring cfDNA will soon be offered for people at high risk, like yourself. I’ve heard some oncologists at conferences say, “What are we going to do with that information, and does it change treatment decisions?” So there doesn’t seem to be an urgency to figure out how to utilize it. Glad you would be able to access that if you ever needed to.
Thanks again, and congrats on completing your five years!
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@exbrnxgrl So amazing the cancer responded completely to your treatment! Surely you’re a unicorn in bc bone Mets land, and hopefully someone has written you up in a case study!
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@maggie15 Thanks for the Frontiers In article! I have read a lot there for lung cancer but not breast. I just had great scans and a new and amazingly more effective lung treatment offered to me that opens up the opportunity for hopefully five years before progression, which makes me suddenly take a harder look at what I can do to get the best response/odds against breast cancer, too.
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Yes, it is amazing but… no one knows why. Did I respond completely to tx? We will never know. My treatment was very much outside of the mainstream in that I’ve never had chemo but to say that rads to the bone met and an AI for 10+ years is responsible for my good fortune is just a guess and my mo agrees. There really is no good explanation for my lack of progression. The human body can be very unpredictable.
I don’t think I have been written up.*For as much as my situation is rare , it is not totally unheard of but it is also not understood. Outlier is a very applicable term. We exist but no one knows why.
*I have been part of the Metastatic Breast Cancer Project since my dx.0 -
@waves2stars, It’s great that you have been offered a new more effective lung treatment. Unfortunately lung problems including my pulmonary fibrosis make one ineligible for most bc clinical trials including those treating dormant cancer cells and monitoring circulating tumor cells. Someday these treatments may become SOC and open to all.
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I personally found the podcast very exciting because this is almost the same information that Jane McLelland talks about in her book How to Starve Cancer. For years, she has spoken about blocking the pathways of cancer cells with a variety of existing drugs.
Certainly, she admits certain of those drugs work better on different types of cancers and she does speak some on that topic. But the challenge has been, which is addressed in this podcast, to find which cocktails work best for your type of cancer as well as finding those dormant cells. So many people have been left with trying to get those drugs and take all of them not knowing if they worked for their specific issue or not.
I took heed with a few of her suggestions from the book. I take baby aspirin, melatonin and green tea. I also wanted to try her suggestion of Metformin (for glucose and glutamine). But I believe Berberine is a substitute. Not sure. Most interesting from the podcast was her mention of Hydroclorquine. Jane mentions this too. I used to take that when my Lupus flared.
Her approach and knowledge seems to be coming to be top of mind, without the knowledge when she wrote it of how to find the cells and various other means of testing, so pretty much take everything. Which is hard to do and to find doctors who would prescribe all the drugs.
Nonetheless, I found the podcast to be enlightening and exciting. At least I feel as if I am possibly blocking pathways of dormant cells who think they want to awaken.
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