Bone Mets Thread
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To Piggy and all,
This has been such a useful push lately to try to understand the data suggesting what is best to do once the cancer becomes resistant to Ibrance-Femara, and/or Ibrance-Faslodex.
One common mechanism of resistance is to get mutation(s) in the estrogen receptor itself, which happens about one-third of the time, and not only does this make the cancer resistant, but it also ups its metastatic potential to other organs. And apparently ER mutations are not easily destroyed by Faslodex either, which I hadn't realized. However, they did a screen in cells with ER mutation (these cells can grow without any estrogen in the environment), to see what is driving their growth, and found that CDK7 is one of the drivers. CDK7 inhibitors used in combination with tamoxifen or with faslodex got good results in pre-clinical studies (cells and mice), and so worth following these drugs in clinical trials. There is one drug from Syros in Boston and a new one not yet in clinical trials in the UK. It would be good to know if CDK7 inhibitors also could work in other breast cancer subtypes, because originally there was a Cell paper that it works great in triple negative BC...
Here is some background:
Endocrine therapies, including tamoxifen and aromatase inhibitor drugs, can prevent recurrence of early breast cancer, and can slow the progression of metastatic disease. However, in about one-third of patients with metastatic ER-positive breast cancer, treatment with endocrine therapies leads to the emergence of tumor cells that grow even in the absence of estrogen hormone, resulting in treatment-resistant disease that is often incurable.
In studying the molecular causes of resistance to endocrine therapies, scientists found DNA mutations in the estrogen receptor gene in a substantial number of patients with ER-positive breast cancer. In 2013, Jeselsohn and colleagues reported finding ER mutations in the tumors of women with metastatic ER-positive breast cancer. The scientists then created laboratory models of breast cancer to investigate how the mutations (which they estimate occur in about a third of women with metastatic ER-positive breast cancer) cause treatment resistance. In these experiments they found that the mutations caused the tumors to be resistant to the drugs tamoxifen and fulvestrant (another estrogen-blocker) and estrogen deprivation.
In the new report, however, the Dana-Farber scientists revealed another previously unknown effect of three of the mutations in the ER gene. That is, the mutations not only cause resistance to estrogen blockade, but also turn on genes that drive the breast tumors to metastasize to other organs. This kind of unexpected additional action of a mutated gene is termed "neomorphic."
"That tells us that even though the drug therapies are selecting tumors that can grow without estrogen, the mutations also confer a metastatic advantage to the tumor," explains Brown.
The researchers then used the CRISPR-Cas9 gene editing tool to launch a search to identify which genes are essential in cells with the ER mutations. Among the essential genes they found, CDK7 was of particular interest because it was a potential drug target. In fact, Dana-Farber colleague Nathanael Gray, PhD, and his team had previously developed an experimental CDK7 inhibitor called THZ1. Tests in cell culture and in animal models with transplanted breast tumors showed that the combination of THZ1 and the endocrine blocker fulvestrant slowed growth of tumors more strongly than either agent alone.
"These results support the potential of this combination as a therapeutic strategy to overcome endocrine resistance caused by the ER mutants," say the authors of the report.
Jeselsohn said that clinical CDK7 inhibitors are being developed, and that "we hope to test these drugs and develop a clinical trial for patients with ER-positive metastatic breast cancer."
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Hi Cure-ious thanks for posting this info. Starting cycle 23 I/L tomorrow so good to know that there are other things coming along.
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I'm looking for advice and info. I just now posted a new thread asking about those who've had bone mets a long time what their experience has been with zometa.
I would also appreciate feedback from those of you here, regardless how long you've been dealing with bone mets.
I am 7 1/2 years out from stage iv diagnosis. My scan in March shows I am still stable.
The first couple years with mbc, I had zometa monthly. Since then, its been every 3 months. My onc finally agreed to cut the Zometa IV frequency to every 6. She seemed reluctant to do so, but I've been asking for the cut back quite some time now. I worry about long term side effects like kidney problems and jaw necrosis.
Can long term use also cause bone problems? I have a foot issue this year. The March scan showed a possible stress fracture in my right foot. It hurts, and I’ve been hobbling along. I've been babying it since then and it is not getting any better, so I have a podiatrist appt in a couple weeks. Could zometa be affecting the bone's ability to heal?
What other insights should I know about zometa and long term use? Many thanks.
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Divine- Zometa gave me a to of issues with bone loss in my jaw. I noticed one day my teeth were shifting and one tooth was loose. Cost me ten thousand of dental work. I was on it for a couple of years
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Iwrite and Z, Its so great that you got to meet and hike together! Your smiles are so beautiful!
Z, I am holding you close to my heart while you go through this difficult time! I am sending out hugs and prayers for you! I think that you would be surprised to know how much I rely on you for your kind support and sharing here! You are such a fount of information and you are such a special lady! You are a rock! I want you too know that even rocks sometimes need a little support and I am always here for you! Good luck with Mayo and know that I am thinking of you!
Claudia
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been on Zometa since May 2016. Jaw problems....can't open mouth all the way and sensitivity in teeth big time. Dentist says it's the zometa. On the net it says Zometa actually IS a type of chemo that's used for bone cancers, so of course we will have se's.
L
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Divine: I was diagnosed Stage IV with mets to bones, liver, and lungs in March of 2016 so I'm nowhere near as many years along as you are. I've been on Zometa since April 2016, with a few months break in 2017 but now receive it monthly. I guess I'm lucky because I can't say I've had any SEs of consequence. Yes, I have a loose molar on the left, bottom side but that was caused by prior bone loss from the missing molar in front of it (cracked, had a root canal, eventually lost it, had a bridge, now an implant!). The oral surgeon refused to pull it because I was on Zometa, as he stated that it may never heal up. It does cause some discomfort if I forget and chew way back there but all in all I'm managing it well. I don't have any other issues with teeth, do not have any others that are loose, nor do I have any trouble with my jaw. My MO explained Zometa to me this way: it helps repair the holes in the bones that the cancer causes and, as an added bonus, has anti-tumor properties. I'll keep going with Zometa until the SEs show up. When that happens, I'll discuss it with my MO. I wish you luck...keep going!
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lwrite is a lovely person and very kind.... trying to cover for my terrible deformities. That lady in that picture with her is a stranger we met on the trail. I am actually a cyborg ....
>Z<
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LOL!!!
Welcome to cyborg society. It’s a pretty exclusive club.
This was before coffee, right?
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No, Kathryn, that's after coffee. The before coffee picture ... I do not share.
>Z<
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oh Z, this too shall pass....may you receive great benefit from the TX...sending you a big hug
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Z, you still manage to be beautiful even in your cyborg incarnation. Wishing you best luck with your brain treatment and a speedy recovery.
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Z, you are rockin the cyborg look! I'm sending positive thoughts and prayers for you today!
Divine, I take nothing for the bones since I was taken off the Xgeva. I had a bone density test a few months ago and the results were good. Like Lita, I have issues with opening my mouth and sometimes chewing, but some of that is permanent damage from the tumor in my massiter muscle. I would not change what I did because I had so many bone mets I feel like my bones would really be weak had I not had two years on Xgeva.
Hugs and prayers,
Claudia
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Thanks, bigbhome, for your reply. How long have you been off the xgeva?
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Divine, I have been off for four years now. I am lucky in that most of my original mets show no uptake. Yes, I have had progression but mine is a slow growing cancer. Plus, so far, as soon as we change treatments, it seems to run and hide for awhile. It is very sensitive to the meds so far. I am hoping Xeloda will get me to Nead.
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oh goodness Z you are my hero! Good luck with this treatment! Keep us posted
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Divine - just wanted to chime in on Zometa. It is usually used for osteoporosis. I’ve been on it for bone mets for almost 4 years and have not had any issue. I started once a month for 6 months and now once every 3 months. I did make sure to get a ton of dental work done prior to taking it and so far so good.
Congrats on 7.5 years!
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Thanks, AnimalCrackers, for letting me know your experience with Zometa!
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Many healing prayers coming your way Z. Stay strong & positive.
crissy
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Hi all you amazing women, I find so much strength in reading your posts.
Just a short update, the last couple of weeks have also been tough, I was rehospitalised with muscle cramps in my leg with the recent hip/femur replacement. I had my EKG and Pet/CT scan last week. I had just arrived back home from the scan and they called me back 'you have pulmonary embolisms in both lungs', so back to the hospital and I was immediately put on LMWH. Today, I got the scan results from MO, (apart from the fractured ribs, which I apparently fractured when my leg fractured without warning, and the PEs (side effect from orthopedic surgery)) I have two small areas hip and C6 with slight and no uptake, respectively, that may be healing ? So the plan is now: start same Chemotherapy again, as my scar from the hip/femur replacement has healed and continue H/P, new scan in about 9 weeks.
Thanks for your wise words about scanxiety - one day at a time and yes we just get through it.....
The last months with biopsies, anMBC diagnose, fractured femur, PE....MO urged me to talk to a psychologist and work through this ordeal and my experiences. Done, I have an appointment for tomorrow, and in addition also focus on training my 'new leg' - doing one crutch now 😊.
Good luck to all, and may we all keep beating this awful disease and get on with living our lives.
Z, I admire you and hope that you are recovering well from your recent tx.
x Meja
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Hey Z. Since I don’t know what a cyborg is I’ll take your word for it. Thanks for showing us how this treatment goes and explaining so much.
I’m waiting for an MRI of my pelvis sacrum. Lots of pain with only a little walking.
I have a question about Xgeva. I only get it every 3 months but when I do the pain in back and pelvis seems much worse. Do you think this could be from xgeva or all in my mind? I think that’s one of my crazier traits. I always question if what I’m feeling is real. I’m working on that.
I have been going to a psychologist for a 2 years now. It’s been very helpful with cancer and my relationships. It was hard in the beginning but so worth it.
Meja Take care. You’ve been on a rough road. Sending gentle hugs and good thoughts to you
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I lurk more than I post as I am lucky not to be havingmany issues from my bone mets. However, I was measured today and I have lost about 1.5 inches since my bone mets were discovered. I'm worried that the Xgeva injections or maybe the tamoxifen or perhaps the bone mets cause this? It is no big deal as my dear husband used to be shorter than me and he is quite delighted to be a bit taller than me for the first time ever! Any ideas? Thank you in advance
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Divine-I've been on Zometa since June 2012. I had it monthly for 2 years,now every 3 months. I haven't noticed any se's until recently. I am not sure if it's the zometa, but I have been getting sharp pains, off and on in my right femur. I had zometa on Thurs, with my Taxotere. It's happened before too.I will have to ask my onc next Fri. Maybe it is the Zometa causing it. This is why I love these boards, learn something everday
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Lynne- I had the same pain when I was on zometa. Used to get a really sharp pain especially when I walked.
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Hi Vevs - its possible you have a compression fracture in your spine. That can cause you to lose some height. I have one and they keep measuring my height but I’m still 5’ 5”. Haven’t lost anything. The compression fracture doesn’t cause me pain, it just sounds scary.
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Hello everyone, I have been reading up but not posting much. You all have been such a great source of information. There are just things that even the oncology medical team can’t even tell me or confirm it happens but I’ll read it here. That or maybe I need to change my treatment center. I’m writing because I have had bone Mets for about 4 years now and been thru faslodex, letrozole, xeloda and navelbine with herceptin and zometa. I would say I was pretty stable and got better with navelbine which I started this year for a few months. Tumor markers went down and last scan in April showed tumors getting smaller some disappeared. but the last month I started feeling bone and nerve pain so dr sent me for an MRI. Well it now showed more tumors and compression fracture. Now I have to get kyphoplasty to fix the fracture pressing on the nerve and then radiation to couple or vertebrae. Has anyone gone through this? Wondering if kyphoplasty will really help and why radiation was only brought up now. I have been searching and I thought this would be the best place to get an answer. Thanks in advance to you ladies.0
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Vevs. I've lost over 2 inches b'cuz of multiple compression fractures in my spine.
Minnie, I have heard that kyphoplasty can help a great deal. Make sure you pick someone with a lot of experience. The spine is nothing to mess with.
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thank you Lita! Do any of your fractures cause pain? I don’t really feel much of the bone pain it’s the nerve pain that’s bad. Have you done kyphoplasty? The procedure seems simple enough but I don’t really like being put under general anesthesia. Considering I’ve had so many surgeries since diagnosis.0
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hi Minnie,
I had kaphoplasty on two collapsed vertebras and radiation done to the same area following the operation.
It took a while but my situation defenetly improved. I still can't stand up for long periods of time, before fatigue, pain and overall unease causes me to want to recline, but before those procedures I was too weak to take care of myself and in constant pain. I now use a 3 days fentanyl patch to take care of pains due to progression, as we all know, these TX are useless after a while. I also use a walker to support myself if I’m going out for long walks
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Minnie, I have a lot of back muscle pain, too. There's some degenerative arthritis going on as well as the bone mets, so I don't always know whaf is exactly causing pain.
Mo has a kypho person on deck in case I need the Sx in the future. According to scans, I'm not quite there yet.
L
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