Breast – TNBC

Multiple supplements and functional foods have strong direct or indirect evidence of improving TNBC treatment results. A few differ from hormone driven tumor types. Overall the mechanisms frequently include improving anti tumor immune response, reducing treatment resistance and balancing both inflammation and levels of crucial minerals and vitamins.

Much lower risks for progression in TNBC are reported in post-diagnosis statin users, particularly those under active surveillance for elevated blood cholesterol levels. Cholesterol “responders” have been identified as benefiting from statins in studies of other cancers. Where a prescription statin is unavailable, red yeast rice is the natural source of lovastatin while atorvastatin is perhaps the most researched otherwise. In this research, the effects were even greater at higher doses.

National scale patient records studies report vitamin D3 levels affect outcomes, where deficiencies are common in most cancers. Higher levels are linked with improved response to pre-surgery chemotherapy and reduced risk of disease progression. These findings indicate the potential importance of maintaining sufficient vitamin D3 levels during TNBC treatment, interventional trials are now starting up employing 50,000IU weekly dose for 20 weeks along with chemotherapy (oral form, cholecalciferol).

Patient data also shows that increased levels of circulating enterolactones, high in crushed flax seeds, significantly lowered all cause risks in ER negative patient groups. As much or more than in ER positive types, perhaps unexpectedly so. Equivalent research into low dose aspirin has varied findings, but the weight of evidence for use of anti-platelet compounds is positive, including for reducing metastatic activity. Diet related, lifestyle changes can impact recurrence and risk levels quite substantially. Both anti-inflammatory diets and structured exercise are increasingly reported to improve outcomes. Interestingly, TNBC outcomes were especially improved by a fasting mimicking diet during treatment in a larger multi-cancer trial, which is suggested to be due to increased immune system activity over time (see Lifestyle)

The so called Th1/Th2 immune system balance is strongly linked to the progression and to treatment resistance. Molecular iodine solutions are emerging in this area in breast cancer management and seen boosting Th1 anti tumor activity and helping suppress over active Th2 used in resistance. The has improved results in surgery plus chemotherapy especially in stage III, and may support increased response immunotherapy (see Supplement Library). For immunotherapy the presence of high sodium levels is now idenfied as a key marker for success in other cancers. Also in other cancers, AM treatment programs are substantially more effective that PM/evening sessions

Higher levels of anti-aging supplement alphaketoglutarate have also been linked to immunotherapy response levels in several cancer types. Some fascinating lab studies (mouse models) have shown dramatically increased success for radiotherapy in TNBC. This widely studied anti-aging supplement has increasing preclinical evidence for its use alongside oncology drugs. Also related to much improved immunotherapy outcomes, a branded beta glucan product showed remarkable effect in metastatic, relapsed, TNBC patients with pembrolizumab (Keytruda). These immune enhancing compounds have expanding numbers trials, and similar yeast derived beta glucans are commercially available.

Also common in TNBC especially african american women are low levels of melatonin receptors, leading to much increased risks of progression. Whilst specific trials are lacking, advanced stage patients including breast cancers have, in some cases, seen substantial benefits (see Supplements Library). Melatonin is now being studied at up to 1g per day with some fascinating results published. Less well known are the surprising effects of functional foods based on oats and eggs that stimulate anti-inflammatory responses able to counter fluid pressure in tumors, pressure that drives not only growth and metastatic spread, but also drug resistance

As it progresses, breast cancer often upregulates availablity of iron to fuel growth shown by levels of the protein ferritin. Low levels are linked with improved prognosis, whilst increasing levels are seen with metastasis, particularly to the liver. Conversely, iron deficiency is common and increases during therapy, linked with much higher progression risks. The pre-biotic milk protein lactoferrin binds iron in the gut and regulates iron balance, homeostasis, and has its own evidence for anti-cancer activity. The same study highlights the benefits of lowering systemic inflammation c-reactive protein (CRP), indicating the importance of anti-inflammatory supplements and functional food diets.

High serum levels of copper especially with insufficient selenium and zinc are linked with poor prognosis.The exact mechanism is still being clarified, but one possibility is cancer switches the metabolism to free up copper for its needs to grow and spread rapidly, and down regulates selenium. Heavy metal detoxification has been shown in patient case with use of citrus pectin, ideally with marine alginates. In kidney cancer, high dose selenium has been shown to allow oncology drugs to penetrate tumors much more effectively, and has ongoing clinical studies. Citrus pectin has its own distinct anti-cancer mechanism, inhibiting the galectin-3 protein signaling which is a factor in nearly 2/3 of TNBC tumors growth and spread.

Systemic inflammation is linked with increased risks for progression, especially in later stages. Both acute type inflammatory responses measured by C-reactive protein, and immune system related neutrophil-to-lymphocyte ratios. Maintaining relatively lower levels of both make a substantial difference. Commonly used astragalus root has evidence of improving immune system balance and NLR while curcumin and other other functional foods including garlic can help bring down CRP. Widely used herbal extract astragalus has detailed lab studies showing its improvement in oncology drug results, with supporting TNBC patient records on improved outcomes. Also related to immune system balance, there is new research reporting large effects in maximizing chemotherapy outcomes in patients with relatively higher selenium levels. Similar to studies in across all types of breast cancer patient data, but amplified in TNBC for yet unknown reasons.

In repurposed drug trials, the combination of etodolac and propranolol is showing promise (see Repurposed Drugs)

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Statins reduce risks in TNBC and red yeast rice is an alternative

Users of prescription lipophilic statins had substantially lower relative risk levels
This particular study showed higher doses result in 75% risk reductions
Indications that effects are much higher in statin “responders” for cholesterol

In conclusion, we found a statistically significant association between incident (lipophilic) statin therapy and improved OS [overall survival] and BCSS in women with non-metastatic TNBC. Our results extend previous work supporting the association between statin therapy and improved outcomes in patients with breast cancer and specifically add weight to the strong preclinical evidence for a benefit of statin therapy in patients with aggressive breast cancer subtypes. Statins are a safe, affordable, and low-risk intervention…. Our data suggest that statins may have a role as a therapy i...

Aspirin has a majority of research showing cancer and all-cause risk reduction

Recent multinational meta-analysis shows 24% reduced risk in breast cancer progression
Importantly, a tendency to lowered all cause mortality is also present in the data
Confirmational findings in other patient data include two thirds reductions in metastatic spread

This meta-analysis aimed to evaluate the impact of post-diagnostic aspirin use on survival outcomes in patients with breast cancer, specifically examining DFS, OS, and breast cancer-specific mortality. Based on an analysis of twenty studies involving 141,251 participants, our findings indicate that post-diagnostic aspirin use was not significantly associated with DFS or OS, despite a trend toward improved OS. However, a statistically significant reduction in breast cancer-specific mortality was observed among aspirin users. TSA further reinforced these findings, indicating that the cumulati...

Antihistamines have large scale analyses showing how they decrease risks

ER- patients saw measurable increased relative survival rates for postmenopausal women
Point data shows nearly 60% relatively lower risk for ebastine users starting before diagnosis
Desloratadine and ebastine show measurable benefit for post-diagnostic use too

Desloratadine in particular stands out as a candidate forcancer therapy based on our findings,,,That an improved survival is seen regardless of hormone receptor status, menopausal status, age, and probably tumors tage as well, may allow for desloratadine and loratadine to be given in a broad range of breast cancer cases. It is especially promising that there is an association with markedly improved survival of desloratadine and loratadine users with ER negative breast cancer, as some of the most challenging cases, with the most limited treatment options, are found in this subgroup

Enterolactones eg from crushed flax are reported to reduced risk especially in postmenopausal BC and TNBC

Higher levels of enterolactones increased relative survival rates over 40%
For all cause mortality the data shows relative risk reductions nearly 60%
Effects were seen to increase with dose, or serum concentrations

For prediagnostic intake of dietary lignans, there were nonsignificant risk reductions for both cancer-specific and all-cause mortality in postmenopausal women…risk reductions were found for prediagnostic and early postdiagnostic serum and/or plasma ENL [enterolactones] with breast cancer–specific (28%) and all-cause (31%) mortality for both time frames, particularly for postmenopausal women (34% and 35%, respectively). For all-cause mortality, there was a 59% reduction for node-negative disease. The greatest risk reduction for mortality outcomes was at the highest serum and/or plas...

Alpha ketoglutarate anti aging supplements are developing in cancer research including immunotherapy

Higher serum AKG levels in patients clearly associated to strong response to immunotherapy
Yet to be confirmed in patient trials but strong pre-clincial evidence is emerging
Additional lab studies show possibility AKG would increase effects of chemo

Our [animal model] study underscores the potential of pairing DMKG [alpha ketoglutarate] with radioimmunotherapy as an effective strategy for treating TNBC by promoting apoptosis, immunogenic death, and remodeling the tumor immune microenvironment. This combination therapy could offer a promising therapeutic avenue for TNBC patients unresponsive to conventional immunotherapy…When combined with anti-PD-L1 drugs (α-PD-L1), they significantly inhibited tumor growth without causing obvious side effects during treatment.

Beta glucans protect and balance immune system activity improving outcomes

44 relapsed metastatic TNBC patients with a branded yeast derived beta glucan.
Response rate to pembrolizumab doubled with the added vendor drug and trials continue
Relative risk reductions of 50% higher vs best in class results for immunotherapy alone

Confirmed response was also evident in patients with liver or visceral metastases, high LDH. 10 patients were originally ER/PR+, received hormonal therapy and progressed to TNBC. Of these, 5 are confirmed PR, 4 SD [stable disease] (3 still on therapy), 1 PD. No unexpected safety signals were observed…These are the first clinical data to suggest that PGG [patented yeast derived beta glucan] provides added clinical benefit for patients with previously treated mTNBC and support further development of PGG + P for metastatic TNBC

Vitamin D3 and its immune system health actions are key, higher doses being trialed in oncology

Meta-analysis across several trials and hundreds of patient data records
Response to pre-surgery chemotherapy reported as +22% in those with higher D3 levels
Relative increase in Disease Free Survival 35%, aligns with studies in multiple cancers

The results revealed a 22% reduction in the likelihood of non-response to NACT [chemotherapy] associated with adequate vitamin D3 levels (low/deficient VD vs. high/sufficient VD; OR: 0.78) and a 35% reduction in progression risk with sufficient baseline vitamin D3 levels (low/deficient VD vs. high/sufficient VD; HR: 0.65)…These findings highlight the significance of maintaining adequate vitamin D levels in BC treatment and encourage further studies to unravel the role of vitamin D3 on cancer biology.

Astragalus actions include protecting and balancing immune responses often with clear effects reported

Meta-analysis of many trials show chinese herbal extracts extend progression free times
With chemotherapy, most prominent is astragalus, readily available and well proven
Confirmation outside asia exists in Turkish lung cell oncology

In this investigation, we noticed that intake of ADD was conducive to improving TNBC prognosis after chemotherapy, which implied that components of ADD, such as astragaloside IV, might be effective in attenuating fallouts triggered by chemotherapy….TNBC patients receiving ADD [several herbal extracts, most prominently astragalus] adjuvant therapy after chemotherapy… were less likely to relapse than TNBC population not undergoing ADD treatment . In addition, GEM/ADM/OXA/DDP-resistance and glycolysis of MDA-MB-231/ADR cell line were debilitated after exposure to astragaloside IV [...

Iodine in its I2 solution are developing with use in breast cancer treatment

New research shows significant benefits I₂ solution form started before treatment
Post treatment recurrence risk reduction of 78% in the group with iodine I₂
Significant side effects are also reduced in the supplement group

We evaluated the effects of I2 during the initial and advanced stages of breast cancer with respect to toxicity, tumor response, survival at 5 years, and transcriptomic response. Our data indicate that supplementation with I2 improves the effectiveness of the treatment, decreasing side effects and increasing disease-free survival specially in advanced conditions (stage III). We also show that iodine supplementation induces tumor re-differentiation and the reactivation of antitumor immune responses.

Oat and egg based functional foods are entering early stage clinical trials including breast cancer

Metastatic spread is strongly linked to fluid pressure in the tumor microevironment
Early phase breast cancer has an ongoing phase III trial with these functional foods
Significant reductions in many side effects of oncology drugs, especially gastrointestinal

Many studies have demonstrated the associations between peritumoral LVD [lymphatic vessel density] and tumor grade, tumor stage, lymphatic invasion, LNM [lymph node metastasis}, and overall survival in breast cancer. Our study not only demonstrates a positive association between intratumoral LVD and LNM in breast cancer but also reveals that peritumoral LVD has a moderately stronger correlation with LNM than that of intratumoral LVD. These results suggest that peritumoral lymphatic vessels have a more important effect on metastatic dissemination in breast cancer

Melatonin trials have shown longer survival rates, even in late stages, and improved side effects

Low levels of melatonin MLT1 receptors double relative risk of progression
Almost 1/2 of african american and 12% of caucasian women effected
Researchers conclude these findings support a need for clincial trials with melatonin

In multivariable survival analysis of TNBC patients tumors negative for MT1 showed significantly shorter PFS (hazard ratio, HR = 1.909 and OS HR = 2.01) ..A strong inverse correlation was observed between circulating plasma melatonin concentration and the amounts of ER and PR in the [TNBC] primary tumor … Our findings of the apparently favorable aspects of MT1 receptor expression in patients with TNBC support these findings and suggest the possible utility of melatonin

Citrus Pectin removes heavy metals such as copper and has its own anti-cancer mechanisms

Low copper/ high zinc have more than 2X relative cancer survival over 10 years
All cause mortality for lowest copper/zinc v highest is 2.26X lower
Both zinc and selenium deficency are linked with the poor prognosis

We have previously published survival data on this group of breast cancer patients according to serum selenium level, and now we present data on the relationship between survival and zinc, copper and cooper/zinc ratio levels. In the present study, we observed that a low serum zinc level (≤762.7 μg/L) and high copper/zinc ratio (≥1.563) was associated with a decreased overall 10-year survival and breast cancer-specific survival. We observed a clear correlation between high copper/zinc ratio levels and overall survival…serum zinc level and copper/zinc ratio provide an independent p...

Lactoferrin increases iron balance and reduces anemia rates countering cancers use of iron

Low circulating iron levels shown to strongly decrease disease progress
Around a one third risk reduction comparing relatively low vs high iron levels
Other studies show high iron is linked to rates of metastasis in TNBC

Significant differences in DFS and OS were found between these two groups… high IronMLR score was a negatively independent predictor of poor survival for early-stage TNBC patients. Subsequently, prognostic models integrating the IronMLR score and two clinicopathological features (T stage and N stage) for DFS and OS were established and graphically depicted as nomograms. These prognostic nomograms presented good discriminative ability and satisfactory predictive agreement between observed clinical outcomes and the nomogram-predicted survival probability.

Akkermansia is increasingly reported as improving immunotherapy results

Progression to bone metastasis is linked to a poor low diversity microbiome
Lack of akkermansia and linked with disease progression as a specific bacteria
Supplements are an option short term, functional foods are the sustained strategy

The lack of Megamonas and Akkermansia in the BM [patients with bone metastasis] compared with those in the NC [controls] and BN [non metastatic patients] groups was considered related to bone metastasis. Additionally, based on the distinct gut microbiota profiles, we predicted that lipid transportation and metabolism, as well as folate biosynthesis, participate in breast cancer occurrence and that steroid hormone biosynthesis influences bone metastasis. Our study demonstrated that variations in gut microbiota are associated with breast cancer occurrence and bone metastasis,...

Curcumin has evidence for reducing levels of systemic inflammation used by cancers

Lower systemic inflammation measured by CRP, c-reactive protein, has large benefit
Much higher response rates to immunotherapy, 2.75X relatively lower risk
Progression free survival doubled, overall survival time more than tripled

The systemic IL-6/CRP inflammatory axis is an independent factor linked with poor outcomes of mTNBC patients treated with atezolizumab monotherapy and may play unique roles in affecting the anti-tumor activity in this hard to treat patient population…. only CRP was associated to reduced ORR [response rate]. Multivariate analyses considering the aforementioned clinical demographic variables showed that IL-6 (HR 2.00 ); and CRP (HR 2.74)…were associated with Overall Survival

Selenium is developing kidney and ovarian cancer, high doses pulsed with oncology drugs

Relatively higher selenium increased complete response from 39% to 59%
Indicates about half the overall progression risk and suggests a need for trials
Aligns with 37% reported in a large scale meta analysis for any breast cancer type

Patients with triple-negative breast cancer (TNBC) were treated with a range of combination chemotherapies….After treatment, each patient was classified as having pCR [complete response] or no pCR. Results: In the entire cohort, the pCR rate was 59.0% for women in the highest tertile of blood selenium (≥107.19 μg/L) compared to 39.0% for women in the lowest tertile (≤94.29 μg/L) (p = 0.003). Conclusions: A high selenium level is predictive of pCR in women treated for HER2-positive or triple-negative breast cancer. If confirmed, this observation may lead to a study investigating ...

Danshen evidence from patient records is compelling both in cancer and vascular health

Added to standard oncology treatments, patient records show long term progression risks are halved
The study uses additional reports to conclude the effects of danshen are beneficial in ER- types
Taken during treatment at 3g daily from diagnosis and for at least 90 days for most benefit

The patients were also categorized into two groups according to the duration of danshen use after their breast cancer diagnosis: those who had used danshen for >28 days and those who had used danshen for ≤28 days….the use of danshen for >28 days remained highly associated with decreased mortality (the adjusted HR [hazard ratio] of danshen users for >28 days was 0.55 [vs “low” users<28 days]) …Thus, these data demonstrate the protective effects of a higher dose or longer use of danshen for patients with breast cancer….These data suggested that dans...

Propolis has yet to fulfill a wider role in cancer but helpful here with radiotherapy

A small trial adding propolis to radiotherapy shows significant protective actions
Tendencies to increased disease free survival can be seen in the data
Few trials with propolis, radiotherapy seems a likely use in other cancers

The supplementation of propolis 10 days pre, during and 10 days after completing radiation therapy caused a significant down-regulation of RRM2 level [marker of DNA repair levels]..after 30 months only 16% of these patients became metastatic with longer median DFS [disease free survival] in comparison to patients received radiotherapy only …. Propolis is an effective iron chelator and disturbs the di-ferric iron center that stabilizes the tyrosyl free radical, critical for catalytic function of RRM2 small subunits

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GUIDE

Pathfinder Element	Risk Reduction Factor	Anti-Metastatic	Reduces Side Effects	Research Study
Danshen	>50%	Yes	Yes	Link
Red Yeast Rice or statin	>50%	Probably	Maybe	Link
Structured exercise	>50%	Probably	Yes	Link
Iodine (with surgery/chemo)	>50%	Maybe	Yes	Link
Fasting mimicking diet	>50%	Maybe	Probably	Link
Astragalus	26 - 50%	Yes	Yes	Link
Beta Glucans	26 - 50%	Yes	Yes	Link
Anti-inflammatory diet	26 - 50%	Yes	Probably	Link
Vitamin D3	26 - 50%	Yes	Maybe	Link
Antihistamines	26 - 50%	Probably	Probably	Link
Selenium	26 - 50%	Probably	Maybe	Link
Flax	26 - 50%	Maybe	Maybe	Link
Low Dose Aspirin	Up to 25%	Yes	Maybe	Link
Propolis With Radiotherapy	Up to 25%		Yes	Link
Akkermansia / gut health	Indirect - High	Yes	Yes	Link
Lactoferrin	Indirect - High	Probably	Yes	Link
Citrus Pectin	Indirect - High	Probably	Probably	Link
Melatonin	Indirect - High	Maybe	Yes	Link
Alpha ketogultarate	Indirect - High		Maybe	Link
Oat and Egg functional foods	Indirect - Moderate	Probably	Yes	Link
Curcumin	Indirect - Moderate	Maybe	Maybe	Link

Plan Item	Cancers	Background Details	Trial Doses Under Supervision	References
Antihistamines	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Gastric, Ovarian, Cervical, Pancreatic, Melanoma, Lymphoma, Esophageal, Bladder	Research indicates desloratadine for localized cancers or loratadine for metastatic. There are examples of ebastine or other alternatives in certain cases. Growing research evidence indicates improved oncology responses. Taken between meals. Low histamine before and during treatment is beneficial.	Active use in clinical trials is still in early phase, follow the dose recommendation for instance 5mg daily unless under medical supervision where higher 10mg doses are frequent
Aspirin	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Ovarian, Cervical, Endometrial, Pancreatic, Melanoma, Myeloma, Head and Neck, Bladder, Gallbladder, Non Melanoma Skin, Gastric	Use of low dose 75 or 81mg "baby" aspirin is reported to benefit many cancer types across an average study group, and even all cause mortality. There are some indications of specific "responders" for instance those with existing inflammatory conditions or certain gene expressions. With food.	In a colorectal cancer trial responders were tied to the expression of particular genes (PI3KA). Doses were 160mg	LINK
Astragalus	Breast, TNBC, Lung, Colorectal, Liver, Gastric, Cervical, Endometrial, Pancreatic, Prostate, Kidney, Ovarian, Glioblastoma, Non Hodgkin, Lymphoma, Leukemia, Myeloma, Head and Neck, Bladder, Gallbladder, Thyroid	A typical astraglaus membranaceus supplement may have 50mg of astragaloside IV the main active compound. Its possible with meals can reduce any stomach upset. Use of a standard dose to help immune system balance before treatment.	Here, Astragalus is added to standard oncology in lung cancer Doses are 2-3 tablets of 250mg AMe (Solgar, NJ, USA) minimum for 6 months in this example	LINK
Beta Glucans	TNBC, Lung, Liver, Gastric, Cervical, Pancreatic, Melanoma, Non Hodgkin, Lymphoma, Leukemia	There are many options for mushroom or yeast 1,3/1,6 glucan and branded products include California Gold Immune Defense/Wellmune, AHCC, Biogen/ Yestimun, ImmiFlex, IP6 and many more. A pharma grade product, odetiglucan, is continuing in trials. Take on an empty stomach. Use a standard dose to help balance the immune system before starting treatments.	AHCC is used at 3x1g per day over several months during treatment. Beta glucans are used at 1-2g per day and higher.	LINK
Danshen	Breast, Prostate, Lung, Colorectal, Liver, Leukemia, Myeloma, Bladder	The most common chinese herbal medicine in oncology, also known as red sage. Premium brands such as MCS may recommend 1g twice daily as an ongoing dose. Its possible with meals can reduce any stomach upset. Start a standard dose a couple of weeks before treatment to help balance the immune system.	3 x1g daily between meals , over at least 90 days ideally longer to get maximum benefits according to reported patient outcomes, though even shorter dose period reduced risk	LINK
Green Coffee Extract	Glioblastoma	Supplements vary in terms of their chlorogenic acid content, it can be up to 50%. Quality brand might specify this level under their recommended intake. High dose commercial brands may be over 1000mg total, take before meals.	Analysis across trials reports metabolic health benefits start are higher at >500mg or daily. High chlorogenic acid content supplements eg Svetol have been trialed safely for 12 weeks at 200mg x 5 daily dose. As always, be aware of possible drug interactions	LINK
Red Yeast Rice Or statin	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Gastric, Ovarian, Cervical, Endometrial, Melanoma, Leukemia, Myeloma, Head and Neck, Esophageal	Red yeast rice is equivalent to lovastatin. Doses are essentially on the products, and there are many premium brands with guaranteed level of monokolin k around 3mg. A common theme is findings is those with improved cholesterol are "responders". With meals. Start cholesterol and inflammation reducing statins early.	Trial data is often case studies with multiple statins where lovastatin has average effects. Often atorvastatin and sometimes simvastatin come out on top. Research ususally reports intermediate doses ( 10-20mg) are effective but there are examples indicating higher doses under supervision.	LINK
Turkey Tail	Lung, Colorectal, Kidney, Liver, Gastric	A typical premium supplement such as MCS recommend 700mg twice daily with food. Mushroom based glucans can help balance immune response so start them before your treatment.	Pharma grade turkey tail, e.g PSP/ PSK/ Krestin is typically used at 3x 1g daily during oncology, up to 36 months and more. Trials in breast cancer have also used 3,6 and 9g daily regimes in 6 week periods	LINK
Vitamin D3	Breast, TNBC, Prostate, Lung, Colorectal, Gastric, Ovarian, Pancreatic, Glioblastoma, Melanoma, Non Hodgkin, Lymphoma, Leukemia, Myeloma, Head and Neck, Esophageal, Bladder	High dose commercial formulae can be 10,000IU. Which might be achieved by as little as 10 to 20 minutes in sunshine. Vitamin K2 is advised with D3. Take with some food containing fat. Its important to ramp these up before oncology treatments, and sustain the higher levels over time. Add magnesium for best absorption and metabolism.	The VITAL trial used 2000IU and discussed the potential of higher doses to increase responders especially higher BMI/ body weight. Whilst in prostate cancer there are trials demonstrating at least 10,000IU is required to see activity reducing PSA levels	LINK
Melatonin	Breast, TNBC, Prostate, Lung, Kidney, Liver, Ovarian, Cervical, Endometrial, Pancreatic, Glioblastoma	Commonly used in 10 to 40mg daily range no reported side effects, typically an hour before sleep.	Moderate and high dose trials report no significant side effects even at 1000mg daily	LINK
Citrus Pectin	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Ovarian, Cervical, Endometrial, Pancreatic, Non Hodgkin, Leukemia, Myeloma, Head and Neck, Esophageal, Bladder, Gallbladder, Thyroid, Gastric	Trials use a recommended dose up to 5g x3 daily and no significant side effects. Taken 30 minutes before or 90 minutes after food. Ideally, start PectaClear or similar products at least 4 week before treatment to reduce heavy metals. But sustain zinc with supplementation	Even in children age 5 to 12 the daily regime 3 x 5g was safe and effective for heavy metal chelation	LINK
Soy Isoflavones	Breast, Prostate, TNBC	Often dietary sources, tofu and soy based and no evidence of side effects. Supplements generally with food.	In a clinical trial setting up to 900mg with no issues	LINK
Fermented Wheatgerm	Prostate, Colorectal, Melanoma	Trials are with Avemar brand products with no significant safety concerns reported	Typical dose regimes may be aroung 9g daily over longer time periods for instance 12 months	LINK
Iodine	Breast, TNBC	General usage around 1000mcg or 1mg generally with food	Successful pilot studies in breast cancer use 5mg molecular Iodine daily for the duration of therapy	LINK
Lactoferrin	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Gastric, Ovarian, Cervical, Endometrial, Pancreatic, Glioblastoma, Melanoma, Non Hodgkin, Lymphoma, Leukemia, Myeloma, Head and Neck, Bladder, Esophageal, Gallbladder, Thyroid	200mg typical use daily , eg 10ml liposomal formula ideally 30 minutes before meals or 2 hours after. No side effects of note. Start this immediately to achieve and maintain healthy iron absorption, avoid deficiencies and reduce cancer related ferritin levels.	During oncology doses of up to 3g to 9g daily, even higher, have been used with significant side effects	LINK
Selenium	Breast, Lung, Kidney, Ovarian, Cervical, Endometrial, Pancreatic, Melanoma, Head and Neck	Supplements are 200ug doses and similar amounts from about 3 brazil nuts. Start buildin gup your levels immediately and keep them high during oncology. Selenium toxicity is a consideration for high doses over time, so seek medical advice. Ideally taken with meals.	This trial used 2500 to 4000ug 2x daily for 14 days then once daily in kidney cancer with no dose limiting toxicity	LINK
Vitamin B3	Liver, Gastric, Glioblastoma, Non Hodgkin, Lymphoma, Leukemia, Non Melanoma Skin	Typically 500mg for nicotinamide (niacinamide) form of B3 taken ideally with meals	Do not differ from standard doses, here 500mg twice daily related to skin cancer	LINK
Akkermansia	Breast, TNBC, Prostate, Lung, Kidney, Liver, Ovarian, Cervical, Pancreatic, Non Hodgkin, Lymphoma, Leukemia, Myeloma, Head and Neck, Gastric	Commercial products may be at 10B CFU typically 30 minutes before or 2 hours after food. Ramp up levels with diet and moderate supplementation before treatments, especially immunotherapy.	Under development. Results in oncology indicate this is one of many helpful guy bacteria. careful consideration and particularly following use of antibiotics. Diversity is crucial.	LINK
Berberine	Kidney, Liver, Cervical, Pancreatic, Non Hodgkin, Leukemia, Myeloma, Head and Neck, Esophageal, Gallbladder, Thyroid, Non Melanoma Skin, Melanoma, Bladder	A natural anti-diabetic used frequently at 400mg daily and above, shortly before meals	In metabolic health trials frequentlu use up to 500mg at 3 times daily .	LINK
Curcumin	Colorectal, Liver, Non Hodgkin, Myeloma, Bladder, Gallbladder, Non Melanoma Skin, TNBC, Breast, Prostate, Lung, Kidney, Gastric, Ovarian, Cervical, Endometrial, Glioblastoma, Melanoma, Lymphoma, Leukemia, Head and Neck, Thyroid	Doses from 500mg to 2000mg frequently seen. Piperine fron black pepper improves absorption, highly bioavailable formulae are available. Ideally with a meal containing fat.	Higher doses in trials are frequently 2 of 4 g daily (+40 mg piperine) during oncology for instance here at 3 periods of 30 days	LINK
Quercetin	Glioblastoma, Myeloma	Can be found in a healty diet. Supplements often 500 or 1000mg and can be taken with tocotrienols for enhanced absorption, a form of vitamin E . Some evidence that Quercetin should be pulsed on/off.	Clincial trials have safely used up to 5g daily in adults, and 1 to 4g for rare forms of paediatric anemia	LINK
Urolithin A	Prostate, Lung, Colorectal, Kidney, Gastric, Glioblastoma, Melanoma, Myeloma, Gallbladder, Head and Neck	Typical commercial brands run at 500mg once or twice daily, with or without food, some brands suggest with meals	Trials eg in anti-aging science use the same dose range	LINK
Oat and Egg Functional Food	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Cervical, Pancreatic, Glioblastoma, Melanoma, Head and Neck, Gallbladder	Follow supplier guidance on dosage and use. https://shop.lantmannenfunctionalfoods.com/? Lowering tumor fluid pressure helps treatments work, start these before your treatment if possible. Use egg based salovum for short term "pulse" during therapy and oat products for sustained use over longer time periods	This trial in glioblastoma used 16g egg based Salovum four times daily. It discusses lowering that regime in follow on trials.	LINK
Coffee	Breast, Prostate, Colorectal, Liver, Non Melanoma Skin	Most dietary studies use standard 8oz servings as a guide. In many cases the findings are that benfits increase with intake. But in some cases such as prostate cancer there are important details in the PATHFINDER	No, but chlorogenic acid and, separately, green coffee extracts are used at 400mg and up to 2000mg
Flax	TNBC, Ovarian	Crushed flaxseed alone or in foods around 1/4 cup daily	Doses up to 50g daily in clinical trials for various diseases. Here a fairly typical 30g regime in inflammatory liver diseases	LINK
Propolis	Breast	Typical supplements range from 400 to 1000mg	Here 400mg x3 daily help recovery from radiotherapy	LINK
Walnuts	Prostate, Colorectal, Melanoma, Head and Neck	Dietary food item shown even at low useage to be helpful even at a few oz per week	Here, 2oz (56g) daily showed measurable activity in breast cancer	LINK
Mushroom	Prostate	Both dietary sources and many commercial supplements normally taken with food	In this example some patients saw responses between 8 and 14g daily of button mushroom extract	LINK
Zinc	Kidney, Ovarian, Cervical, Endometrial, Head and Neck, Non Melanoma Skin	Commercial supplements vary considerably . Moderate 20mg range generally advised	No
Intravenous HIgh Dose Vitamin C	Pancreatic, Glioblastoma	Commercial supplements vary. A moderate range around 20mg with food is generally accepted as safe.	Same as general guidance
Alpha Ketoglutarate	Melanoma, Kidney, TNBC, Non Hodgkin, Lymphoma	Typical usage is 1000mg daily with or without food, safety is good. Its especially important to ramp up and sustain your levels for maximum immunotherapy responses.	Larger doses of several grams have been safely used in various trials including here in bone disease at 6g daily	LINK
Horse Chestnut (Escin)	Thyroid	Common 300 to 600mg supplements contain 50 to 120mg of active compound, escin taken with food	Escin up to 150mg daily in vascular health. In oncology 0.6 mg/kg/day for 9 days, intravenous injection has been used, high absorption premium supplement would reacj this level	LINK

Impact	What	Why	Dose	Impact summary	Later stage treatment, targeted drugs	Activity against bone metastatic sites	Anti-metastatic in general	Higher doses eg in clinical trials	Other comments or sources
>50% for immunotherapy, 0-25% chemo	Lactoferrin	Healthy balanced iron metabolism. Reduce iron used by tumors via ferritin	10ml lipsomal LF daily, ideally on empty stomach	The benefit of well functioning iron metabolism can be large, from 2-3X or more	Evidence shows essential need for well balanced iron levels, even more so during chemo	Balanced iron metabolism is reported to reduce bone related inflammation and metastatic spread	Low iron levels strongly linked to increased metastatic activity	Only with chemo. 1.5g lactoferrin twice daily 1.5 g for three 6-week cycles used in lung cancer	Hemoglobin over 110g/dL is reported with 2X effect vs lower. 130 to 150g/dL would be good. Low ferritin levels reduce progression risk from 60% to over 2X. LF helps with both
>50%	Sodium during immunotherapy	Boosts and activates immune response, enables strong anti tumor activity	With diet around 6g-8g daily, need to be at 140-145mmol/l	Recently seen as crucial to immunotherapy response	Astonishing 9X higher response rate with enough sodium (kidney cancer)	Indirectly, well balanced levels are a benefit	Surprisingly, LOW sodium has growing evidence of increasing metastatic activity	This is not defined but up to 2/3 of patients during immunotherapy see low salt levels	High risk that immunotherapy causes deficiency after 4-6 weeks. Consider increasing dietary intake
>50% including with immunotherapy	Red yeast rice or statin	Anti-lipid and anti-inflammation. Possible combination with nattokinase	Per the supplier guidance. Use a premium brand	Multiple studies from patient records. Effects mainly for post-dagnostic use especially LDL "responders"	Statins improve immunotherapy results across most cancers, typically by 2X	Yes, direct evidence reports benefits extend to bone health and repair	Probably	There is evidence risk reductions up to 60% or so with higher doses under supervision	Useful to know if LDL dropped with statin use. Interesting synergies with nattokinase (Supplement Library)
>50% for immunotherapy, 25-50% chemo	Vitamin D3	Boosts and activates immune response, enables strong anti tumor activity	At least 10,000IU daily with meals	For all treatments the link to higher D3 is clear and in immunotherapy data in other cancers shows around 2X	Across many other cancer types higher D3 levels are reported to improve results yes	Higher levels are essential for healthy bone metabolism. Chemo depletes D3 so this is crucial	Yes	Research is into higher doses in order to increase the proportion of "responders"	Existing trials assessed 30ng/ml as sufficient. Other studies actively discuss supplementation to reach at least. 40ng/ml. Be sure to include magnesium and K2
>50%, lower with chemo	Zinc during immunotherapy	Essential for supporting immune response	Use high absorption formula 20 to 40mg	Newly reported as doubling response in other cancers, its likely to transfer to TNBC too	Maintaining Zinc is always important including with chemo	Perhaps	Maybe	Unclear but moderation is probably good	About twice the response rates with good zinc levels in other cancers
>50% with ICI, indirect-high overall	Alpha Ketoglutarate (Ca-AKG) during immunotherapy	Helps immunotherapy drugs overcome evasion	500mg x2 daily any time	Patients with high AKG levels have around 2X response rates	Evidence so for for PD-1 blockade for instance nivolumab and pembrolizumab	AKG has related evidence in anti aging science and is gaining in attention in researchers work	likely yes, there is lab evidence for this	YES Load up Ca-AKG before and during therapy	AKG may be lowered by metformin. This anti aging supplement has excellent safety
>50% with ICI, indirect-high overall	Gut health including akkermansia	Indirect importance of gut bacteria is crucial in immunotherapy	Supplier dose, moderate level	Crucially, metastatic spread to the bone is linked to lack of a diverse microbiota including low akkermansia.	Has become a recognized factor in immunotherapy success, with likely strong importance here too	Poor microbiome is indeed linked to progression of inflammatory responses in bone	Yes	No, evidence is to apply moderation with supplements and lead with diet	Foundation here is high vegetable and high fiber diet
>50%	Inosine with immunotherapy	Immune cell activation increases	500 to 1500mg	Specific to immunotherapy, large benefit but being explored with chemo	May help reverse resistance to chemo, there is an ongoing trial	Pre-clinical evidence shows potential activity in bone health mechanisms	Ongoing trial in TNBC may provide evidence yes	Not to date	Trial with chemo at 200mg x 3 per day. But this has high safety
>50% with chemo/ surgery	Danshen	Improves blood circulation, immune system balance and activity level, can often reduce side effects. Studies focus on chemotherapy	At least 500mg daily	Large scale evidence for risk reductions of a half. Especially postmenopausal patients	Danshen evidence is focused in chemo, like astragalus its evidence is growing elsewhere	Pending studies, narrative reports do indeed highlight danshens probable benefit	Yes	Prescribed doses of 3g per day are typical in first months	Reduces many usual drug side effects during treatment and has protective effects in vascular health
>50%	Structured exercise	Multiple proposed anti-cancer actions	At least 2.5 hours moderate intensity per week	Yes there are new publications supporting this effect	Probably, there is clear evidence pointing to benefit	Likely helpful	Probably	No	New studies confirming this in other cancers
>50%	Iodine solution (with surgery)	Immune system activation	5mg liquid iodine during treatment window	The research so far is focused on combination with surgery	So far this is related to surgery.	No current research	Maybe	Not reported	It remains to be seen if iodine solution is effective support in chemo or radiotherapy
25-50%	Astragalus	Natural immune system balance and activity, studies are in chemotherapy but also inflammatory marker NLR	At least 500mg daily (50mg astragalaside)	Yes and significant reductions in chemotherapy side effects too	Astragalus has good results in chemo and TKI targeted drugs	Pre-clinical evidence shows potential activity in bone health mechanisms	Yes	Prescribed doses of 3g per day are typical in first months	Based on evidence in lung cancer, excellent alternative when diagnosed as unsuitable for immunotherapy
26-50%	Beta Glucans	Balance and help regenerate immune system, and reduce side effects	1 or 2x 250mg California Gold Immune Defense with Wellmune	Yes with immunotherapy so far, less clear for chemo	Beta Glucans are now patented drugs, early trial shows 2X response in immunotherapy	No direct evidence in relation to bone inflammatory activity	Indirectly, lower NLR is linked to lower metastatic activity	Yes up to 3g or higher has been used in many trials of various beta glucans
26-50%	Anti-inflammatory diet	Lowering inflammation is crucial	Continuous	Research evidence continues to grow for mainly vegetarian diet with higher fiber content	Always a valid approach	Likely helpful	Yes		Also read Lifestyle section for view on evidence in diets and eating patterns
26-50%	Desloratadine	Help immune system function and side effects	1 or 2 x 5mg daily	Large scale analysis of patient records reports this effect	Yes including lung cancer and more	Yes, histamine is a recognised driver of bone inflammatory responses via so called Mast cells	Probably	No current evidence but generally safe	Loratadine is reported as effective in metastatic disease stage . see Supplements Library
26-50%	Selenium	Immune system support and more. Higher does may weaken tumor resistance	200 mcg with meals	Relatively high natural selenium level predicts much better outcome. And with supporting zinc and magnesium.	Research tends to show increasing effects at later stages	Research describes balanced selenium and zinc as a factor for bone metabolism	Probably	"High" dose selenium showing impacts in kidney cancer. See Supplements library	Drugs, their side effects, and infammation can reduce selenium levels
26-50%	Ground flax seed	Compounds in flax are reported to reduce cancer growth rates	At least 1oz 3 to 4 tablespoons daily	Large scale analysis of patient dietary records reports this effect	Highly compelling pre-clinical evidence is reported for likely support of immunotherapy	No specific research here	Maybe	Yes there are suggestions of a dose dependent benefit	Has strongly beneficial effects on microbiome
Up to 25%	Low dose Aspirin	Reduce blood clotting improves vascular health	75mg	There is evidence for lower progression and recurrence risks and	Yes the effects are also evident in advanced stage treatments	Yes, research does report promotion of healthier bone growth	Yes	No	Nattokinase+curcumin is a natural anti-clotting and anti-metastatic. See Nattokinase in Supplements Library
Up to 25%	Propolis ( with radiotherapy)	Protective actions against radiation induced cell damage	Per supplier	The data available shows very beneficial support for radiotherapy	Focused on radiotherapy	No evidence here	Maybe	Trials have used 400mg x3 daily doses
Indirect - High	Citrus Pectin / Pectaclear	Reduce copper and harmful metals, also help sugar metabolism and microbiome	Copper removal with Pectaclear at 2g x 2 daily on an empty stomach	Heavy metals strongly linked to poor prognosis. Possible anti-metastatic activity too.	Lower copper is clearly linked to better immunotherapy responses in other cancers	Cadmium and to a lesser degree copper are linked to dysfunctional bone metabolism	Probably	Follow supplier program	Exposure to tobacco may contribute to heavy metal build up in some patients, and reducing this is crucial for those who are at risk
Indirect - High	Melatonin	Boosts natural immune system activity	Often 10 to 20mg evenings	Higher doses are reported with striking effect in late stages. More is needed on continuous use.	No current evidence	No current research	Maybe	100mg and even 1g have shown responses in late stage trials
Indirect - High	Oat and Egg functional foods (especially with chemotherapy)	Helps treatment side effects and potentially weakens physical tumor resistance	Per supplier	Clinical trial ongoing primarily to reduce side effects. Especially chemo related and reducing metastatic activity	No current evidence	Pending outcomes of ongoing clinical trials.	Probably	No data	Ongoing phase III trial looking at reducing treatment side effects especially gastrointestinal....may reduce tumor resistance
Indirect - Moderate	Curcumin	Good supplement in anti-inflammatory diet	Per supplier. Get a high absorption formula	Has potential copper removal actions and more	No current evidence	Some limited evidence for improving bone health	Maybe	Follow supplier program
Other	AM Immunotherapy	Unclear why results are better before 4pm		Around 40% risk reduction shown for other cancers
	Magnesium		Use high absorption formula	Ongoing research with preliminary confirmation of key benefits to immunotherapy	Improved responses are all >50%
	Urolithin-A					Like AKG, has related evidence in anti aging science and is gaining in attention in research

Most TNBC treatment plans include chemotherapy. Around 40% of TNBC tumors might also be receptive to immunotherapy as an additional drug, such as pembrolizumab (Keytruda). Illustrating the challenges of adding new drugs, studies show report no actual reduction in overall risks for patients in the data https://www.nejm.org/doi/full/10.1056/NEJMoa1910549 . Though there is evidence of about a third of patients avoiding surgical procedures https://www.sciencedirect.com/science/article/abs/pii/S0748798325004391. However, adding drugs brings the risk of additional major side effects too https://www.clinicaloncologyonline.net/article/S0936-6555(24)00524-7/fulltext

The majority patients are not recommended as likely responders to immunotherapy. New approaches such as sacituzumab ovitecan (Trodelvy) treatment are emerging but seem to face the same challenges https://www.annalsofoncology.org/article/S0923-7534(21)02026-3/fulltext

Your PATHFINDER brings together research that may help maximize the effects of chemotherapy, immunotherapy or targeted drug treatments. The IMPACTS tab summarizes these and can lead to Many more Good days by helping these treatments work, reducing your risk for progression and by easing treatment side effects. If you do elect both chemotherapy and immunotherapy or targeted drugs, you can continue to look for way to increase the results and reduce possible toxicities.

Be sure to fully read and absorb the PATHFINDER and its Impacts summary
If you have metastatic sites take a look into the corresponding Pathfinder for those too, for inspiration.
Use the Supplement Library Index and filter on “Chemotherapy” and “Immunotherapy” for ideas.
The Foods Library can complement your plan, including anti-metastatic strategies and metabolic health
In the Lifestyle section gathers fascinating evidence for diets and excercise
The PLANS section may have information from what others are doing and have learned

Breast – TNBC

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