A Method of Treating Triple Negative Breast Cancer

This is a short post to share with you a method for treating triple negative breast cancer, and potentially other cancers, involving:

  • one or more checkpoint inhibitors in low dose
  • hyperthermia treatment
  • low dose chemotherapy
  • lnterleukin-2 (IL-2)
  • taurolidine [I discussed taurolidine in another post on this website (Ref.)]

As you probably know, at this point I still do not like the mainstream immunotheraphy due to its side effects and reduced effectiveness. This is why I am happy when I come across techniques that can reduce the side effects of imunotheraphies while increasing their effectiveness. 

The patent shared with you here, suggests a treatment strategy that may achieve just that, i.e. improved effectiveness while using lower doses of conventional therapies.

Nevertheless, I still prefer the treatment strategies that are build around the metabolic perspective, as I feel that angle is both more effective and controllable as compared to treatment strategies build around the immuno perspective, such as the one discussed here. 

Here you can read the patent: https://patents.google.com/patent/WO2017158570A1/en

The method patented here represents a typical treatment strategy that can be accessed at private clinics around the world. Often, German clinics are using low dose immunotherapy drugs in order to reduce the side effects. Sometimes, private clinics use even 6x or even 12x lower monthly dose compared to the one suggested by the drug supplier. Nivolomab as it was used here at 0.5 mg/kg each week, represents 2mg/kg/month, that is about 3x lower dose compared to the monthly recommended dose.

In their patent, the authors share one example of a triple negative cancer patient who benefited from such a treatment strategy. Here is the case report discussed in the patent:

“Example 2: Human Treatment Case Study

Patient Diagnosis and History before Study:

September of Year 1 : A fifty year old Caucasian female with histological diagnosis of triple negative breast cancer of the right breast 3 cm G3, CS axilla (histologically G3 with medullary shares, ER, PR and Her 2-new negative).

Disseminated lung metastasis.

Ki-67: 61% indicative of very high breast cancer cell division.

Additional evidence of ductal carcinoma in situ (DCIS) with focal vascular invasion; BRCA1 neg.

Before entering the study, the patient had been treated with numerous oncology and chemotherapy treatments including weekly neoadjuvant Taxol chemotherapy, lumpectomy with wide local excision, and adjuvant radiotherapy of the right chest wall. These treatments were ineffective and the patient developed metastatic dissemination and neutropenia, and was an end-stage (stage IV) patient.

Study Protocol:

Patient began the study having a Karnofsky score of 80%, mild neuropathy with distal emphasizes in all four extremities; and also suffered from severe pain during inspiration left lateral chest wall; for example, sneezing extremely painful, severe shortness of breath (SOS) on exertion, lack of appetite, insomnia, and exhaustion.

Diagnosis: Breast Cancer ICD10: C50.9

Lung Cancer ICD10: C78.6 Lymphadenopathy ICD10: R59.1

The patient underwent a four week Treatment Protocol as follows:

1.Weekly low-dose checkpoint inhibitor therapy with PD1/PDL-1 inhibition with nivolomab (0.5 mg/kg) and CTL-4 inhibition with ipilimumab (0.3 mg/kg) over three weeks.

2.Loco-regional hyperthermia with radiofrequency fields (13.56 MHz) using

Syncrotherm device 3 times per week over the thoracic region in combination with high dose vitamin C (0.5 g/kg) and alpha lipoic acid (600mg) over three weeks followed by:

1.Long duration (6-8 hours) fever range (about 42°C) whole body hyperthermia in combination low dose chemotherapy using cyclophosphamide 300 mg/m2 to down modulate TReg cells followed by:

2.Five days high-dose IL-2 (54 Mio I.U./m2 as decrescendo regime) therapy in combination with taurolidine (250 ml 2% Taurolidine, i.v.).

The inventors found that the combination of IL-2 and taurolidine was effective in inducing remission in the patient’s TNBC and metastases thereof, where the other treatments had failed.

The day after completing the multidisciplinary therapy, a chest x-ray demonstrated the far advanced bilateral pulmonary metastasis. The induction of a cytotoxic T-cell response following immunotherapy may take between 1 -2 months up to even 6 months. Thus, after 2 months the patient underwent a second chest x-ray which already demonstrated a 20% improvement in reduction of lung metastasis. A chest x- ray after a further 2 months demonstrated a remarkable partial remission. Further, the patient exhibited an excellent clinical condition with a Karnofsky score of 100% and absence of shortness of breath or any other cancer-related symptoms.

Both checkpoint inhibitor types (PD 1/PDL-1 and CTL-4 inhibition) were used to avoid autoimmunity following checkpoint inhibitor therapy. Specifically, nivolomab and ipilimumab were used in an off-label use in lower dosages and metronomically in higher (weekly) sequences.

Discussion

Low-dose cyclophosphamide or gemcitabine therapy can selectively deplete T regulatory cells (Treg). Chemotherapy drugs (and irradiation) may be combined to break immune tolerance and create a tumor microenvironment for successful immune based therapies. Mild, fever range (40-42°C) prolonged whole body hyperthermia reduces interstitial pressure in the tumor microenvironment. Additionally, hyperthermia improves immunogenicity of cancer cells and lymphocyte trafficking. High-dose IL-2 has been known to have severe side effects and, as a result, IL-2 has never gained widespread use. The main side effects of high dose IL-2 therapy are induced by vascular leak syndrome with weight gain, generalized oedema, hypotension and impaired renal function being the main features. Vascular leak syndrome (VLS) is a life-threatening toxicity induced during IL-2 treatment of cancer patients. The co-administration of taurolidine, taurultam, oxathiazin-like compounds, and combinations thereof diminishes these vascular-leak induced side effects.

In summary, the present disclosure describes the demonstrated safety and effectiveness of the combination of IL-2 and taurolidine in inducing remission in the patient’s TNBC and metastases thereof, where the other treatments had failed.”

Reference: Method of treating triple negative breast cancer, 2016, https://patents.google.com/patent/WO2017158570A1/en

Disclaimer:

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

Please read an extended version of the Disclaimer here: https://www.cancertreatmentsresearch.com/?page_id=1794

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17 thoughts on “A Method of Treating Triple Negative Breast Cancer

  1. Hi Daniel !
    Thanks for this article.
    I was diagnosed with stg 3B TNBC a bit more than a year ago. I went through the regular treatment : 6 rounds of neo-adjuvant chemo followed by operation ( lumpectomy ) and radiation. The response to chemo seemed great, according to post operation histology the tumor disappeared from lymph node and was only 2 mm in the removed breast tissue . Doctor was satisfied and I was told that if any cancer cells remained, they will be killed by radiotherapy .
    Only 3 months after the radiation I had my first checkup and it showed local re-occurence. I had a mastectomy this time and the tumor was more than 3 cm ( 6 months after it was invisible !) .
    I am BRCA negative + PDL1 not expressed a- so the doctor told me I cannot have any new drugs that are more targeted and they suggested plain chemo as adjuvant therapy.
    This time I said no to chemo, as the results of the previous one seemed rather short lasting.
    Anyway , to make a long story short : I do feel somewhat insecure with doing nothing after the surgery.
    Are therapies described here applicable to me ? Where can I get it , if yes ? Any idea how much it would cost ?

      1. Dear Daniel !

        I believe you must be extremely busy , but I wander if you could give me a hint where I could get these therapies and how much they would cost ?
        I found a clinic in Germany – Huffeland clinic which seems to apply some of these that you mention. I am not sure I could afford ( the price is more than 5000 eur a week).
        Do you have any suggestions ?

        Thanks in advance and thanks for your efforts
        Gabi

        1. And a note : I had a local reoccurence in October ( 3 months ago ) . CT in december showed no cancer . I refused a new chemo , and I would really very much like to stay cancer free.
          Would these therapies be suggested for prevention too ? What is your opinion ?

          1. Hi Gabi,

            Most of the therapies above can only be accessed via medical doctors, e.g. private clinics such as in Germany. Since there are many involved, I can imagine the cost will end up in the range of a few to several k’s euro/week. But since you are at a point when there is no tumor, if there is no other suggestion from your oncologist, I would probably go for a cocktail of drugs and supplements to reduce chance of recurrence. One such cocktail used for a long time by a lady with triple negative breast cancer is this one:

            Curcumin 1000mg 2 x day
            Quercetin 500 mg 2 x day
            Super Omega 3 inc eha/dha 1000mg 2 x day
            Vitamin D3 approx 3 per week 10,000 iu
            Artemix 200 mg 1 x day
            Ultra isoflavone 1500mg 2 x day
            Coriolus 1500mg 1 x day
            Super Artemesinin 200mg 1 x day
            Paw paw (just started) 1000 mg 2 x day
            Aspirin 75mg 1 x day
            Reishi spore and reishi powder 500mg and 1 tsp 2 x day
            Cimetidine 400mg 2 x day
            Metformin 500mg 2 x day
            Dipyridamole 200mg 2 x day
            Lyposomal vitamin C 1000mg 1 x day
            Naltrexone 3-4.5ml 1 x day

            Next to the above, I would also consider adding drugs and supplements from this strategy https://www.cancertreatmentsresearch.com/reduce-cholesterol-in-cancer-cells-to-fight-cancer/

            Note that there is already a good overlap between the list of drugs and supplements from above and those from the anti cholesterol strategy I described.

            Of course diet (low fat, no sugar, low carbs) and life style (e.g. yes moderate exercise, yes walking and exposure to sun, no stress) is very important to stay well.

            Kind regards,
            Daniel

          2. Hi Gabi.
            It’s been a year since your last post. I’d very much like to ask how you are doing with your treatment, as my dear wife is in a similar situation. I’d very much appreciate your kind response. Thanks.

  2. Yes, I thought so, just wanted to make sure.
    27 fold improvement in honokiol delivery? Sounds great!
    When you can take essentially safe natural chemicals and achieve such an increase it would seem best not to let it get away!

    The microneedles in your url seem about right, though probably best to double check with them.
    Remarkably from the article the correct microneedles should cause no pain!

    {D, I have been having trouble posting some of my longer articles. I just tried to post a long response to Macros, though the forum software seems to have rejected it. Anything that could be done about this?}

    Best Wishes, Jcancom

  3. Hi Daniel,

    I was diagnosed with TNBC (stage 1b) in Feb. 2019 and had a double mastectomy as treatment, I did not do the chemo the dr. recommended. I live in the USA (Georgia) and went to a local natural Dr. that offered the RGCC blood test. My results were (isolated 3.4 cells/7.5ml, SD+/-0.3cells). He told me that was good and low. But, It’s been 1 1/2 years since this test and I have not done any further treatment other than vD3 and liquid vitamin C, I don’t feel this is enough to keep it away. As of now I do not have any signs of recurrence and believe I am cancer free. But, I am concerned it will return due to it being TNBC and would like to do whatever it takes (with no side effects) to keep it away.
    I have some questions….

    -Do you feel I should have the RGCC test re-taken to see if my results have changed since it’s been 1 1/2 years?

    -Would you recommend that I consider the RGCC Dendritic Cell Vaccine to keep my TNBC from returning? The Dr. I went to that ran the RGCC test for me suggests it but I can’t find much info on it or it’s success rate. I have also read on these forum posts that you have mentioned some patients have seen their cancer get worse once they got the DC vaccine? Did I read that correct and has anyone had good results with this vaccine who has had stage 1b TNBC? (cost is not a problem as I know this vaccine is expensive…just looking for your honest opinion on this vaccine for my situation)?

    -Anything else you can suggest for me to keep this cancer from returning? ex…list of supplements and dosages that have been proven to work for others with TNBC/any other treatments I may not of heard of?

    Any help or suggestions on the above would be greatly appreciated. Thank you so much.
    Rebecca 🙂

    1. Dear Rebecca,

      I apologise for the delay of my response. Great to hear that you are doing well!

      Answering your questions:

      1. I don’t think it makes sense to do the RGCC test at his point
      2. I would not do the DC – indeed I know people who started progressing or recurrence after DC while before that being NED and on the other hand I do not now people seeing great results with DC other than melanoma – even in those cases anti-PD1/PDL1 was used. I cannot say that the recurrence was due to DC but if it would be for myself, I would not use it while NED
      3. Here are some examples of drugs and supplements that may be relevant for TNBC according to the scientific publications:

      – Metformin and Statin
      Metformin Targets Cholesterol Biosynthesis Pathway, GM1 Lipid Raft Stabilization, EGFR Signaling and Proliferation in Triple Negative Breast Cancers https://juniperpublishers.com/ctoij/pdf/CTOIJ.MS.ID.555765.pdf

      – Artesunate
      The anti-malarial drug artesunate causes cell cycle arrest and apoptosis of triple-negative https://www.ncbi.nlm.nih.gov/pubmed/30660598/

      – Boswellia serrata
      Plerixafor is a CXCR4 inhibitor that reduces the chance of mets to the brain. Acetyl-11-keto-b-boswellic acid (AKBA) from Boswellia serrata does that too. https://www.dovepress.com/cxcr4-in-breast-cancer-oncogenic-role-and-therapeutic-targeting-peer-reviewed-fulltext-article-DDDT Therefore using Boswellia serrata supplements with high AKBA may help reduce the chance of mets to the brain.

      – Doxycycline
      Doxycycline, an Inhibitor of Mitochondrial Biogenesis, Effectively Reduces Cancer Stem Cells (CSCs) in Early Breast Cancer Patients: A Clinical Pilot Study https://www.frontiersin.org/articles/10.3389/fonc.2018.00452/full

      – Metformin and Propranolol
      Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356849/ Taken together our results suggest that metformin plus propranolol combined treatment might be beneficial for triple negative breast cancer control, with no symptoms of toxicity.

      – Bicalutamide
      Complete Response of Metastatic Androgen Receptor–Positive Breast Cancer to Bicalutamide: Case Report and Review of the Literature http://ascopubs.org/doi/full/10.1200/jco.2013.49.8899

      – Estradiol
      Another form of estrogen receptor — called estrogen beta — is present in 25 percent of triple-negative tumors, as well as in over 30 percent of estrogen receptor-positive breast cancer tumors. Research showed that the estrogen receptor beta is a tumor suppressor, which correlates with better patient outcomes.
      “Remarkably,” claims Hawse, “we discovered that estradiol, which normally stimulates [the] growth of cancer cells in tumors that express estrogen receptor alpha, has the opposite effect in triple-negative breast cancer.” https://www.medicalnewstoday.com/articles/323281.php
      Here is the research paper demonstrating the anti-cancer effects of Estradiol: ERβ-mediated induction of cystatins results in suppression of TGFβ signaling and inhibition of triple-negative breast cancer metastasis. https://www.ncbi.nlm.nih.gov/pubmed/30257941
      Mayo researchers identify potential new treatment for subset of women with triple-negative breast cancer https://newsnetwork.mayoclinic.org/discussion/mayo-researchers-identify-potential-new-treatment-for-subset-of-women-with-triple-negative-breast-cancer/

      One option here could be to use Flaxseed extract that acts as a weak estrogen.

      – Clofazimine
      Towards the first targeted therapy for triple-negative breast cancer: Repositioning of clofazimine as a chemotherapy-compatible selective Wnt pathway inhibitor https://www.ncbi.nlm.nih.gov/pubmed/30771433 Wnt signaling is overactivated in triple-negative breast cancer (TNBC) and several other cancers, and its suppression emerges as an effective anticancer treatment. However, no drugs targeting the Wnt pathway exist on the market nor in advanced clinical trials. Here we provide a comprehensive body of preclinical evidence that an anti-leprotic drug clofazimine is effective against TNBC. Clofazimine specifically inhibits canonical Wnt signaling in a panel of TNBC cells in vitro. In several mouse xenograft models of TNBC, clofazimine efficiently suppresses tumor growth, correlating with in vivo inhibition of the Wnt pathway in the tumors. Clofazimine is well compatible with doxorubicin, exerting additive effects on tumor growth suppression, producing no adverse effects. Its excellent and well-characterized pharmacokinetics profile, lack of serious adverse effects at moderate (yet therapeutically effective) doses, its combinability with cytotoxic therapeutics, and the novel mechanistic mode of action make clofazimine a prime candidate for the repositioning clinical trials. Our work may bring forward the anti-Wnt targeted therapy, desperately needed for thousands of patients currently lacking targeted treatments.

      – Others:
      Mebendazole Potentiates Radiation Therapy in Triple-Negative Breast Cancer https://www.redjournal.org/article/S0360-3016(18)33688-5/pdf
      Auranofin – REPURPOSING AN EXISTING THERAPY FOR TRIPLE-NEGATIVE BREAST CANCER https://nbcf.org.au/research/our-research/search-our-research/improved-and-new-treatment/repurposing-an-existing-therapy-for-triple-negative-breast-cancer/
      Repurposing antiretroviral drugs (Efavirenz) for treating triple-negative breast cancer via LINE-1 regulation https://openresearch-repository.anu.edu.au/handle/1885/164936
      Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer https://www.nature.com/articles/nm.4055
      The antipsychotic agent trifluoperazine hydrochloride suppresses triple-negative breast cancer tumor growth and brain metastasis by inducing G0/G1 arrest and apoptosis https://www.nature.com/articles/s41419-018-1046-3

      I am not saying that all these drugs should be used in NED situation, but is good to be aware of them.

      I hope this helps and if you have any other question please let me know.

      Kind regards,
      Daniel

  4. Hi friends, just adding the following information:

    https://pubmed.ncbi.nlm.nih.gov/24364759/
    Whole blueberry powder — inhibits metastasis of triple negative breast cancer — in a xenograft mouse model through modulation of inflammatory cytokines
    23 Dec 2013

    Together, these results suggest that blueberries may inhibit TNBC and TNBC-related metastasis by reducing inflammation via specific cytokine-driven pathways and thus reduce tumor growth and metastasis.

    ——-‐——————————————————-

    https://foodforbreastcancer.com/foods/blueberries
    Blueberries are highly recommended for breast cancer

    Thanks.
    Kimster

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