I’ve been curious about this and wondering if anyone can explain. I want to better understand the role of the hormone therapy eg Faslodex when taken with targeted therapy such as Ibrance. Does it just reduce the amount of estrogen available to the cell and “lightens the load” on the targeted therapy? Or is there a more complex interaction between the two drugs?
Also, if the targeted therapy stops working well, is it always due to that therapy no longer working or could it be due to the hormone therapy not working?
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HelenWi
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two different actions entirely. Hormone blocker does just that - provides less fuel for hormone sensitive cancer cells to grow. Targeted therapy slows down the growth of cancer cells by interfering their cell division. They seem to work in synchrony. Both hormone blockers and cdk can stop working effectively due to genetic mutations that happen as the disease progresses rather than being borne with the mutation as with brca1 or 2.
Yes, that is it. I will repeat it in my words. ER+ cancer needs estrogen to grow. If you can block all estrogen, it "starves" the cancer cells, no food. It is systemic. Different meds use different mechanisms to block or eliminate estrogen. Targeted therapies go after the cancer cells and try to destroy them.
As I understand it, the estrogen blockers or inhibitors do the heavy lifting and the targeted meds (three of them are CDK4/6 inhibitors) add another type of attack. I don't know how they know which has stopped working. When I had progression on fulvestrant and Ibrance, my oncologist interpreted it as a failure of the fulvestrant. She stopped the Ibrance, too, but said it was because of a rash. I disagree with that -- I have had a rash on everything. It seems they stop them in pairs.
Ibrance/Faslodex didn’t do anything for me, so my oncologist switched me to Piqray/Faslodex. That was more effective, reduced my bone mets, though now some have small increases in SUV. We’re continuing with the same drug for now. Who knows if it’s Piqray alone that’s doing the trick, or combination with Faslodex. I find it frustrating not to be able to fully understand what’s going on. But having had mbc for just a year, I’ve learned to take stability as being ok, even if we don’t fully understand why.
Do you have the Pik3 mutation? That is usually the reason for switching to Piqray (which is considered more effective in combination with Faslodex). If you haven't had genetic testing recently, your oncologist might have switched you because Piqray has been found to work when someone develops resistance to CDK4/6 inhibitors (I didn't know that, just read it).
It is frustrating, what we do not understand and, even more, what our oncologists do not understand. It is unnerving when my oncologist says, "we don't know why it works," or "there are no studies that show this works; it is just anecdotal." That is the way it is. I am always asking for answers, and looking things up. It gives me a sense of control (a false sense) simply to understand. It gives me the illusion that understanding makes this crap shoot feel more predictable. The important thing, though, is getting a treatment that works for your cancer and your body. That seems to be extremely variable, almost idiosyncratic. That mystery is even more frustrating.
On remaining stable, everyone told me that was the goal when I started treatment. I didn't believe it. I wanted better than that, and have had periods when everything shrank and even disappeared. Stable is a letdown after that, but it certainly is better than progression
Tammy, I’m just like you! I really like to understand the science and am frequently formulating questions. Right when I was initially diagnosed with MBC, my onc had me tested for Pic3ca. It was negative but they reported an alternate mutation in the Pic3ca gene. So when Ibrance didn’t work, he opted to try Piqray. It was a good call.
Recently I had the Guardant 360 genomic test and they found I had an alteration in the her2 gene — not her2 positive though. So my next drug may be Enhertu. In the meantime, he’s trying to milk the Piqray as long as possible even though there is some metabolic activity. I’ve had three mets treated with radiation as well.
I listen to DanaFarber videos that are very informative. I’m considering getting a second opinion from them…
I plan to use Dana Farber for my next 2nd opinion, too! Just not sure of timing on that. The first time I got a second opinion it was from MSK because I live in NYC and could go in person, and if they had a trial for me, as my oncologist hoped, I could do it. I am in Massachusetts now, and stupidly did not think to set up a second opinion before I left NYC. (I was on the phone with docs nonstop, trying to get appointments; many of the staff at Columbia are incompetent, don't return calls, don't have the info, don't follow through...)
The reason I want to try Dana Farber next for 2nd opinion is that I keep developing resistance. I am going onto 4th treatment when I have been in treatment less than 5 years. My oncologist says there is mutation and that causes resistance. I have been tested and don't have any mutation that corresponds to a known treatment. I have one that they know nothing about. But have I had mutations four times that would explain the treatment failures? No answer. Onc just says "mutation." Dana Farber says there are many reasons for resistance, not just mutation. That is why they say one can go back on Ibrance after a vacation and it works again. I will have been off any CDK4/6 inhibitor for 7 weeks by the time I next see my oncologist. I think that is a vacation, but she refuses to consider it -- even though Ibrance and fulvestrant left me NEAD for two years.
Sounds like your oncologist is more open-minded and creative about treatment than mine. I brought in an article about resistance and what Dana Farber is doing. The two nurse practitioners were all over it, excited. The onc. wouldn't look at it, waved it away, "mutation."
I’m not sure my Ibrance and anastrozole stopped working, but my doctor said on my last visit if my ANC count goes lower than 100 he’s changing me to immotherapy. Not sure what that involves I’ll wait till he decides. But the cancer is stable.
ANC is the Absolute Neutrophil Count which is a measure of part of the immune system. Targeted therapies have a suppressing affect on the immune system. If the ANC gets too low, the targeted therapy dosage or frequency is often changed.
My Neutrophils went below 100 at .9 for 3 months then started going back up, now 2300! It’s a roller coaster. I really thought when they stayed at .9 a change in dosage of my Ibrance would be ordered, from 125 mgs to 100 but Onc wanted to wait.
My understanding is that the hormone therapy is the anti-estrogen that works in conjunction with the targeted therapy. I believe they work better together. I've been taking Ibrance and letrozole for two years and my disease is stable. Hope that helps.
It's my understanding that targeted therapies are never given alone and work in conjunction with a hormone blocking therapy. Until 6-7 years ago, hormone therapies (like fulvestrant) were the standard of care for ER+ HER2- breast cancer. That was before targeted therapies became available. Currently, most doctors recommend trying a targeted therapy along with a hormone therapy. I'm not sure you can tell which drug stopped working when there's a combination.
I'm a long timer, MBC since long before targeted therapy was developed. The anti-estrogen meds were and still are given alone and targeted meds are only given with one of the anti hormonals so the anti hormonal is the main med...it always annoys me when people say they are on "targeted" and "anti-hormonal" instead of the other way around. Maybe that's just me....
it has been 5 years since I started with faslodex and ibrance. I know that the combination will stop working eventually but, honestly, I try not to think about that. I have bone Mets only which appear to be healed. I feel good over all and have had weird side effects only. My eyelashes fell out but have since grown back. My hair is thinner and dryer than it was. That’s about it. I know I won’t transition ti Pikray as I don’t have the mutation. I think I’m rambling and have not answered your question
Fabulous that you’ve had 5 years! And I love hearing others’ experiences … it’s not rambling. (I’ve researched a bit and I think the two generally work independently but I’ve read some speculation that there may be some interaction.)
My hair is thinner and way sparser after 7 months on Piqray but hoping that improves at some point.
Yes, definitely live in the present. I’m going on a knitting retreat in Portugal with a friend in a month, looking forward to it.
I think I just found the answer to my initial question. It’s pretty technical but seems that endocrine therapy has a direct effect on CDK4-6.
“The effectiveness of CDK4/6 inhibitors can be increased by combining them with drugs that prevent the downstream estrogen-dependent stimulation of the cancer cell. Inhibition of the estrogen pathway—by endocrine therapy—results in downregulation of cyclin D1 and reduced complexation of CDK4 and CDK6 [30]. Therefore, the selective CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib are given in combination with endocrine therapy (aromatase inhibitors or fulvestrant) in the treatment of HR+, HER2− breast cancer [31,32,33].”
Yeah that is what I do, look up articles. Sometimes I understand, but often it is too technical for me, and I only get the conclusion. I don't trust that so much, because I find that the conclusion is more positive than the actual results. (I am a social scientist, and know that in my field, the conclusions sometime are inconsistent with the results.)
Yes, exactly. It seems that the information we find is either really high level with not enough explanation or just too technical. So I pour over the technical stuff trying to find useful answers.
Interestingly, I just found an article that says that HER2 mutations can cause treatment resistance in metastatic ER-positive breast cancer. That seems that it could apply to me, but the article was posted by DF in 2018, and so I'm wondering why this info isn't being used; I looked up the drug that reverses this resistance and it seems to be approved for Her2 cases, but not for the ER+ scenario. The doctor posting this has been in videos addressing resistance. That seems to be his area - he believes that if we can figure out how estrogen therapy becomes resistant - that will be the key to solving ER+ breast cancer. I think I'll ask my onc about this anyway. He definitely thinks outside the box. (He wants to try a radium injection called Xofigo on me; it's only approved for prostate cancer that has gone to the bone but he thinks that since I only have bone mets at this point, this will help shrink them.)
I try to set aside limited time for my "research" -- got to spend time living, but once in a while I go on a research binge. You are right, it definitely feels empowering which, who knows, might have a good effect on us.
Oh, I have to look at those videos on resistance -- but I prefer reading to writing, and I have already collected articles on resistance from DF, but also more technical ones from others that I do not understand. If I cannot get my oncologist to think about it, or explain why she refuses to ("it's not standard of care yet" is her explanation), I don't know if there is a point to my efforts. Right, get on with living, as I shall right now.
@HelenWiant, I agree that the studies are not easy to interpret and hard for patients to keep up on ....I think the recent(2022) drug approval Enhurtu for her2 low is hopeful . I have not heard of Nerlynx , mentioned in the Dana Farber 2018 article re acquired Her2 mutations . I looked it up on another BC discussion board and I see it is prescribed for early stage her2+ and a few stage 4 . My original stage 1 was her2negative as was my 2019 stage IV recurrence . Going forward if/when I have progression I'll want a new biopsy as we all should have with progression , if possible .
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