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[Sticky] NSAIDs Before Breast Cancer Surgery Can Dramatically Decrease Recurrence

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Meech
(@meech)
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https://youtu.be/H8zVrYEW8vE

 

This is is a talk given by Dr. Vikas Sukhatme at MIT.

 

Essentially, out of the 40,000 women who die of breast cancer in the US yearly, 30,000 of them are initially diagnosed at a locoregional stage (Stage I or II). He speaks about a pattern of early recurrence amongst women who receive surgery - indicating that the actual surgical operation might initiate or aid metastasis. Some NSAIDs he talks about seem to dramatically decrease the rate of recurrence - I believe he said by up to 70%.

Obviously some care has to be taken since NSAIDs can cause insufficient wound repair and bleeding so it would have to be monitored carefully.

The full talk is worth a watch.


   
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Alex
 Alex
(@snake)
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I'm a strong believer in NSAID's most importantly Aspirin and Diclofenac in combination with Metformin and maybe statins.

It is sad they have side effects. 🙁


   
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Daniel
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Dear Meech,

This is a great presentation you found, and may save a lot of lifes simply by sharing this link here. Just think about the impact of you doing this ... I will make sure the awareness is created. I will probably write a short post to highlight this important information.

So here is a summary of what is discussed during this presentation, for those who like to have that prior to watching the video:

Dr. Vikas P. Sukhatme, Professor of Medicine at Harvard Medical School and Chief Academic Officer at Beth Israel Deaconess Medical Center, presenting at December 8, 2015 at MIT in Cambridge, MA and a co-founder of a not-for-profit organization, GlobalCures:

- 200.00 women diagnosed with early breast cancer in US annually

- 40.000 annual deaths from breast cancer, 75% have been initially diagnosed with localized cancer (no macroscopically sign of disease in other places) and still had recurrence and passed away

- that means 15% of early detected breast cancers are passing away every year

- in other cancers the recurrence is even higher

- most recurrences occur one year after the surgical resection, suggesting that there is something related to the surgery moment that is fueling the high number of recurrences at one year

- an experiment: introducing 15 cancer cells into the portal vein of a rat à no tumor growth; at about 3 months they started to perform repeated surgery on the rat à at 5 months many tumors on the liver à tumor cells can survive for long time without multiply à can be take out of dormant cells by repeated wounding even if wounding is done at a totally different location

- surgery wakes up dormant cells following the inflammation triggered by surgery

- using NSAIDs we can block the inflammatory response – what if we give them prior to the surgery? – the key is to give them prior to the surgery to block inflammatory response

- giving a NSAID, Ketorolac IV prior to the surgery leads to a strongly reduced recurrence rate https://www.ncbi.nlm.nih.gov/pubmed/22622810

- this has also been observed in lung cancer and it is expected to be relevant in all the cancers

- the rule: Anti-inflammatory medication administered prior to surgery may cure more early stage cancers

- the Professor from MIT is asking: “Why are cancer patients slated for surgery not receiving ketorolac routinely? If you would go today to the hospital for tumor surgery and you would ask your surgeon for ketorolac he/she will probably say NO. 99% of the time the answer will be NO even at major hospitals.” He argues this should be standard of care! They would not give because there is a risk of bleeding or inability of the body to heal as rapidly. But that risk has to be weight with the risk of recurrence which is something not considered by most surgeons as they are not aware of the benefits.

- the reason why some (lucky) patients received NSAIDs prior to surgery was to reduce the use of morphine, i.e. serendipity

- actually this knowledge can be used not only for the early cancers but also for advanced cancers: i.e. countering the wound healing response might improve outcomes in patients with advanced cancers

- untreated cancer resembles a wound: cancer cells develop so fast beyond the access to nutrients and as a result part of the tumors die – cell death in turn triggers a wound healing response

- every treatment for cancer makes the situation even worse! Those cells that are not killed by the treatment will get a second life. BUT if you treat at the same time with NSAIDs such as Ibuprofen, the outcome can be very much changed to positive

Conclusion: Cancer is a wound and antiinflammatory medication will likely reduce the chance for recurrence, will work great with chemo to inhibit potential regrowth of the tumor, and/or will slow down the evolution of existing tumors.

There is a clinical trial going on in Belgium, supported by the Anticancer Fund, to test this concept.

Great!

 


   
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Daniel
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You don't have to use huge dose of NSAIDs to achive that purpose Alex, i.e. the anti inflammatory. Just the normal dose!


   
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Meech
(@meech)
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Topic starter  

Thanks Daniel. I hope somebody in need reads your summary or views the talk.

 

Alex: like Daniel said, even a small dose of 80mg/day of Aspirin can be sufficient as an anti-cancer agent. 


   
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Alex
 Alex
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My mother is now experiencing lot's of pain in more than one place.

This has been going on for a few days now but today it got worse.

In the recent past, getting an aspirin always muted the pain, likely due to slowing down of metabolism.

I am talking about 750mg of aspirin + 500/750mg metformin.

Today it only made pain worse.....  🙁

Coffee enemas always made her feel better in regards to pain, today it only made it worse.

Not knowing what to think this is, i write here. We are hoping it's necrosis. DCA?


   
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Daniel
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I am sorry to hear that Alex...

If I would be you, now that you have the freedom on this forum, I would create a specific post on that so that you can have a clean discussion on your experience. You can fit it under the topic "Lung Cancer" or "Various discussions".


   
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Alex
 Alex
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I wonder if you had a similar experience in the past where pain was an indicator of good with DCA or even other treatments.

Do you think it's likely to have met with healing at last or am i hoping for too much at this time?

What's your opinion about the pain based on your past experience, despite aspirin, metformin - who in the past have "muted" pain down to nothing on our side.


   
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Meech
(@meech)
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Topic starter  

Hi Alex,

Cancer pain can be caused by "mass effect", where the tumour starts to compress normal structures that surround it. I'm not sure that an NSAID would settle this type of pain as it isn't inflammatory. Usually cancer patients get treated with opiates for pain, as they don't tend to kill pain in the same way. Personally when I was prescribed opiates, it just made me less aware of the pain I was feeling, and didn't necessarily 'kill' it. Moreso dulled it.

 

It could be that the tumour has gotten large and is compressing normal tissue.

 

Daniel is right though, you should make a thread in the lung forum with details, and maybe we can work through trying to help out better there. Otherwise this thread's purpose may get cluttered with unrelated matters, and you probably won't receive the best advice in an off-topic thread.


   
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wonderwoman
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Thank u! This was very interesting as i am prepping for surgery in March! 


   
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wonderwoman
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Hi Guys, question:

So im finishing my rounds of chemo, should be done first week of march, so after that my surgery is planned lets say 3/4 weeks after that. I wanted to start my detox/fast / cleanse approach after chemo but im also wondering how would i incorporate any of the above to that?  Should i rather focus on the NSAIDS before surgery rather than my detox? 


   
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Daniel
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Hi,

I think there may be time for both. Regarding the NSAIDS before surgery, it could be a good idea to contact  https://www.anticancerfund.org I think this Foundation is supporting clinical trials on this approach and they should be able to point you towards the places where NSAIDS are given before surgery. Or if you wish to do surgery in a specific place, they may be able to connect your surgeon with others who can explain what are the benefits when using NSAIDS. The point is that your surgeon has to agree with that, since giving NSAIDS prior to surgery may also come with some risks that he needs to manage (although not that high compared to the recurrence risks).

Kind regards,
Daniel


   
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wonderwoman
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Thanks Daniel, will look into that!


   
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ZdenekSipek
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May I ask how much diclofenac would you recommend a day during prevention and how much during active disease?

Would you combine it with aspirin?

What about Naproxen? And the dose a day?

http://cancerpreventionresearch.aacrjournals.org/content/7/2/236

 


   
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Daniel
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Dear Ollie,

1. very good advice - thank you

2. the fact that Ketorolac may inhibit mets via a different mechanism compared to Aspirin does not makes Aspirin less relevant when it comes to fighting mets and recurrence. There is a large amount of scientific evidence that Aspirin had good potential on this line. Here are some examples, https://www.ncbi.nlm.nih.gov/pubmed/29265902
https://www.ncbi.nlm.nih.gov/pubmed/25023355

Your in depth points are very relevant and add value to the discussions here. So please continue contributing so that we can learn together. 

Kind regards,
Daniel


   
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Daniel
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@ollie

More evidence suggesting that Ketorolac is the best one to eliminate micrometastases and reduce tumor recurrence when given prior to the surgery https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597207/

If the inhibition of Rho-GTPase is the main mechanism behind as said here https://www.ncbi.nlm.nih.gov/pubmed/26558612, combination with mevalonate pathway inhibitors such as discussed here https://www.cancertreatmentsresearch.com/cholesterol-lowering-statin-drugs-to-fight-cancer/ may further help.

Kind regards,
Daniel


   
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Lovley
(@seyhun)
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@daniel and @meech

I just watch the video which is applying my situation 100%. Thank you very much for sharing this video and information with us. Wow,  what a presentation you folks brought here and highlighted. 
I live in New Hampshire which is 45 minutes ride from Harvard Medical School. I will try to communicate with Dr Vikas P. Sukhatme once I have my own metromap completed. I am still working on it. Also, I am trying to educate myself so I will have tons of information (Guns) against cancer that is trying to kill me. I MUST learn to kill it, before it accomplishes its goal. I am very serious, I will win this battle everyone. I am trying to learn as much as I can in my power. I feel extremely lucky that I find you folks, I am here in this Forum be able to ask my questions. You folks are helping me to survive. Thank you very much Daniel, Thank you very much everyone else here. I appreciate any information that I find here. Starting from today, I will spend more time to read, comprehend all of the information on this forum. 

I also shared this video with my Oncologist (I feel I must educate these Dinosaur protocol doctors) to widen their vision. Thanks again

Lovely


   
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Lovley
(@seyhun)
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@daniel

Should take Aspirin (low dose 2 baby aspirin 160mg/day) with Ketoroloc? They are both blood thinners. If yes, what is right mg dosages of each? How how should we handle daily Aspirin intake with Ketoroloc?

Thanks again

Lovely


   
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Lovley
(@seyhun)
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Hello Daniel,

Is there any specific inflammation drugs that you can recommend during chemo, radiotherapy, after surgery to keep my body clean from any inflammation?

(I understand that due to bleeding risk, inflammation drugs shouldn't be taken 2 weeks prior, and 1 week post surgery).

Thank you

Lovely


   
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asafsh
(@asafsh)
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@daniel

 

Hi Daniel

what do you think of compensation of ketorolac or any other drugs that may inhibit (unwanted) blood clothing by using natural extract of stinging nettle. Latter facilitates blood clothing and also carries anti-cancer properties.

btw, stinging nettle tea is used here as anti-lung cancer folk medicine in combination with another plant. 

 


   
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asafsh
(@asafsh)
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@snake

Hi Alex

Sorry to hear about that. From my limited experience i had with my relative who experienced high intracranial pain, it was eliminated by combination of 3 drugs (2 of them only pain killing). 

Those drugs if given separately won't eliminate the pain, but in combination it did the work. 

Not all oncology physicians have a knowledge in pain treatment and prescription was given by oncology pain physician.

imho, it is worth to find one and ask him to manage a pain. 

 


   
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Daniel
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Posted by: @seyhun

Hello Daniel,

Is there any specific inflammation drugs that you can recommend during chemo, radiotherapy, after surgery to keep my body clean from any inflammation?

(I understand that due to bleeding risk, inflammation drugs shouldn't be taken 2 weeks prior, and 1 week post surgery).

Thank you

Lovely

@seyhun

HI Lovely,

We have anti-inflammatory drugs and supplements.

Examples of anti-inflammatory drugs: Aspirin, Celecoxib, Ketorolac, etc. 

Example of anti-inflammatory supplements: Quercetin, Curcumin, Sulforaphane, Vitamin C, etc., but one of the best is Olive Leaf Extract.

In addition, to reduce the chance for adhesion of the circulating tumor cells, Cimetidine could help. But only one week after the surgery.

2DG metronomic will also help here but since is intravenous, it's not so easy to access/use.

I hope this answers your question.

Kind regards,

Daniel

 

 


   
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Daniel
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@asafsh

Hi Asafsh,

Thanks you. Very interesting! I will check that! I did not know it.

Kind regards,

Daniel

 

 


   
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asafsh
(@asafsh)
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@daniel

Dear Daniel, you are welcome. I just do continuous search and try to connect pieces of information together without much understanding of their values. Glad if this finding will be helpful. 

Kind Regards

Asaf

 


   
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asafsh
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Daniel
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Posted by: @asafsh

Perioperative therapies - enhancing the impact of cancer surgery with repurposed drugs

Thank you! I haven't seen this one before!

It includes: Ketorolac, Depot Progesterone, Atrial Natriuretic Peptide, Cimetidine, Aspirin, Arginine, Calcitriol, Propranolol, IL2. 


   
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dumbcritic
(@dumbcritic)
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I'm not sure if this has been posted before (I haven't got my glasses on), but will again just in case https://clincancerres.aacrjournals.org/content/early/2017/06/26/1078-0432.CCR-17-0152


   
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Yudaitheska
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@dumbcriticthe the previous post mentioned about the use of nsaids talked about using ketorolac before surgery... There was also a YouTube video.. I can't find it, but it is somewhere in here.

Good article! 


   
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Daniel
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@dumbcritic Thanks. I don't think we had this here before.


   
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medline
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Spreading Cancer (Or Just Waking It Up)

If you look at any collection of "common myths about cancer", you will probably find reassurances about the idea that having cancer surgery might cause the cancer to spread to other parts of the body. I remember coming across this one some years ago being surprised - I'd never heard that one myself, but it was apparently a pretty widespread fear. You could imagine a situation where tumor cells are mechanically detached and could spread, but that's actually less likely than it might seem, since not all of these cells can actually attach somewhere else and start growing again (although there are special situations where such disturbance, even to the level of taking a biopsy sample, is known to be risky).
What I didn't know enough about, though, is an effect seen in breast cancer treatment. After surgery, the risk of being diagnosed with metastatic breast cancer peaks about 12 to 18 months later. It's not a sure thing, fortunately, but it's definitely a real effect, and one that would certainly lead to people thinking that the surgery had (somehow) spread the cancer around. That's actually a pretty reasonable hypothesis, given the observations, so that particular "common myth" has something behind it. But how? The same effect is noted in patients who have undergone complete mastectomy, which doesn't disturb the tumor tissue itself much (or at all). Alternatively, were these actively growing tumors that had spread before the surgery and were just too small to detect? Some have argued for this explanation, and it's hard to disprove. There's yet another plausible mechanism: these tumor cells might have had already spread before the surgery, but were somehow not growing, and something happened to change that. What is it about surgery that would allow them to start growing?
This new paper has what may well be the answer. Studying the effects of surgery in mouse models of metastatic cancer, it appears that the post-surgical wound healing response is the culprit. There appears to be an ongoing T-cell response that is holding down these potential metastatic tumors, but it's disrupted by the inflammation response after surgery. Expressing GFP in murine mammary tumors and then injecting these into other (syngenic) mice caused a T-cell response to the GFP itself, and ultimately the tumors were rejected by the immune system. But surgically wounding these mice triggered an outgrowth of the tumors instead, probably through the actions of inflammatory monocytes (which differentiate into macrophages inside the tumor tissue).
What's even more interesting is that these effects can be abrogated simply by treating the mice with NSAIDs to damp down the inflammation response. To avoid interactions between the tumor cells and the anti-inflammatory drugs, the procedure was to do the surgical wounding (with and without NSAID treatment with meloxicam) several days before the tumor cells were even injected, with time enough to clear the system out:

Notably, treatment with meloxicam did not appear to impede wound healing in these mice. Seven days after surgical wounding (4 days after the cessation of either meloxicam or saline treatment), D2A1-GFP cells were orthotopically injected contralateral to the wound site. Meloxicam treatment had no effect on tumor growth in the absence of surgical wounding (Fig. 4G, left). In contrast, in wounded groups, tumors in meloxicam-treated mice were significantly smaller than tumors in wounded mice treated with saline (P < 0.05; Fig. 4G, right). Surprisingly, tumors in wounded, meloxicam-treated mice were even smaller than tumors in unwounded, untreated mice.

Interestingly, there had been a retrospective study of breast cancer patients that suggested that treatment with NSAIDs seemed to reduce the metastatic events, but no one was sure if that was a direct mechanistic effect on pre-existing tumors, or on their possible activation. These results, though, suggest that it really is an activation mechanism, and that patients should be treated with NSAIDs in just this way.

We undertook to model a clinical phenomenon that occurs at low frequency and arises only with delayed kinetics in patients. We therefore used hundreds of mice to ensure that we had sufficient statistical power to draw firm conclusions. In considering these conclusions, we do not wish to suggest that tumor resection surgery be avoided because of the potentially negative side effects suggested previously by clinical data and demonstrated here experimentally. Instead, we argue that coupling surgery with short-term anti-inflammatory treatments may substantially improve patient outcomes by mitigating the systemic consequences of surgical breast cancer resection. Of critical importance, perioperative treatment with the anti-inflammatory drug meloxicam potently inhibited the impact of wounding on tumor growth. Furthermore, our study suggests that the treatment of breast cancer patients with anti-inflammatory agents during and after surgical resection of primary tumors may yield substantial benefits by reducing the incidence of early metastatic relapse.

There seems to be no reason for this not to immediately move into clinical practice, and I hope that this paper gets widely noticed. NSAID therapy is cheap and well-tolerated, and the risk/benefit ratio would seem to be about as good as it can get. So in general, untangling the relationships of the immune system with cancer is continuing to provide results - both in turning the immune response up and (in this case) turning it down. That process is most definitely going to continue. . .

https://www.science.org/content/blog-post/spreading-cancer-just-waking-up


   
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