Breast

Multiple supplements and functional foods have strong direct or indirect evidence of improving breast cancer treatment results. Overall the mechanisms frequently revolve around increased anti-tumor immune response, reduced treatment resistance and inflammation as well as balancing levels of crucial minerals and vitamins.

Studies of national patient records in Scandinavia have reported positively on the use of antihistamines. Desloratadine, loratadine and ebastine are highlighted in these studies as improving breast cancer outcomes, partly by reducing histamine related resistance to treatment. Overall evidence favoring interventions with antihistamines continues to mount, not least for supporting immunotherapy.

Similarly low dose aspirin and vitamin D3 also have growing evidence from case records of reducing progression and recurrence risks. At least one report confirming vitamin D3 improves relative survival rates 20 to 50% even for post-diagnosis use. Cancer activity, associated inflammation and drugs all deplete key nutrients such as D3.

These types of studies on the Tiawan national patient database for advanced breast cancer show much improved outcomes with use of danshen. A well researched and readily available herbal supplement, widely used in in asia to protect and re-balance immune system activity. Equally well proven astragalus can also restore immune system health, according to recent data using the well known neutrophil-to-lymphocyte ratio. This measure of immune related inflammation occurs commonly with cancer and during treatment, studies report lowering NLR reduces progression risks significantly.

Also reported in large scale studies of patient data for breast cancer, coffee consumption has surprising ability to reduce progression risk, in this data for ER+ tamoxifen treated patients in particular. The study shows caffeine inhibiting both estrogen and insulin growth factor receptors. Green coffee extract is also interesting since it contains far higher amounts of the active ingredients beyond caffeine. And another example from case records, prescription statin users that are “responders” for blood cholesterol control gain significant risk reduction in breast cancer.

Also from dietary sources soy consumption e.g as tofu has been linked to lowered recurrence and progression especially in postmenopausal patient groups. In other studies, progression risks are reduced with statins in the 20% range or higher. Even beyond 50% by the simultaneous use of low dose aspirin and anti-diabetics such as metformin. Being a “responder” applies to many compounds here, aspirin for instance has stronger effects in patients with systemic inflammatory diseases.

Less well known are emerging trials of functional foods based on oats and eggs that increase anti-inflammatory responses able to counter fluid pressure in tumors. In most solid tumors this physical barrier drives not only growth and metastatic spread, but also drug resistance. Selenium is proposed has having similar activity at high enough levels- see below. Breast cancer often increases its iron availability to fuel growth, shown by levels of enzyme like protein called 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 prebiotic 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.

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 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.

High levels of heavy metals like 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 studies with use of citrus pectin, ideally with marine alginates from kelp. In kidney cancer, high dose selenium has been shown to allow oncology drugs to penetrate tumors much more effectively, and has ongoing clinical studies. Another mineral, iodine in its readily available solution form, has evidence of significantly improving outcomes. Both substantially lower risk levels for progression following surgery and chemotherapy and for reducing side effects especially for stage III.

Melatonin is being actively trialed to explore its quality of life benefits, and is reported at moderate to higher doses to slow progression for some patients. Melatonin might be a factor in the 40% or so increased response rates to immunotherapy, studied in other cancers, given in the morning vs afternoon, something to be aware of. Also new research, plant flavonoid luteolin has striking results in reducing androgen receptor activity in prostate cancer management, something also common in breast cancer. (see Supplements Library)

Lifestyle changes can impact recurrence and risk levels quite substantially. Both anti-inflammatory diets and structured exercise are increasingly reported to improve outcomes (see Lifestyle)

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

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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
Improves outcomes are comparable to those from adding a second oncology drug, but with lowered side effects
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...

Antihistamines have extensive analysis of case data supporting their use

National scale case analysis for anti-histamine use in breast cancer patients over multiple years
Across a thousand patients desloratadine is reported with a 33% reduced risk
In the published data, ebastine also showed strong benefit in postmenopausal patients

We found a consistently improved survival of desloratadine users (HR = 0.67) [Hazard Ratio], as well as of loratadine users (HR = 0.80), relative to nonusers, regardless of patient age, menopause, estrogen receptor status or stage of the tumor, or whether breast cancer-specific or overall survival was analyzed. The survival of users of other antihistamines varied relative to non-users…Based on their safety and current use within the patient population, together with our observations, we suggest the initiation of trials of desloratadine and loratadine as treatment of breast cancer

Coffee show surprising risk reducing effects from dietary survey data

Around half the recurrence risk is shown for early stage ER+ patients consuming coffee
Particularly for ER+ type, treated with tamoxifen, also linked with less advanced tumors at diagnosis
Parallel lab work here shows suppression of major cancer growth pathways by caffeine

Moderate (2–4 cups/day) to high (≥5 cups/day) coffee intake was associated with smaller invasive primary tumors and lower proportion of ER+ tumors , compared with patients with low consumption (≤1 cup/day). Moderate to high consumption was associated with lower risk for breast cancer events in tamoxifen-treated patients with ER+ tumors (adjusted HR, 0.51; 95% confidence interval, 0.26–0.97). Caffeine and caffeic acid suppressed the growth of ER+ and ER− cells. Caffeine significantly reduced ER and cyclin D1 abundance in ER+ cells.

Aspirin has a majority of analysis in its favor including all-cause mortality

Low frequency low dose aspirin reduced early stage recurrence around 60%, for both ER+ and ER-
Relative overall mortality risk similarly lowered over 40% for low frequency use due to lower progression
Most studies look at low dose regimes often around 75mg daily “baby aspirin” and every day use

We found that aspirin use after a breast cancer diagnosis was associated with a decreased risk of distant recurrence, breast cancer death, and death from any cause. This is all the more notable because the NHS did not find an association between aspirin use and breast cancer incidence. We speculate that the association was stronger with breast cancer death than with recurrence because recurrence is more likely to be misclassified than death. We found a modest association with duration of aspirin use. Aspirin may influence proximal rather than distal events in the cancer pathway….Abund...

Vitamin D3 and its immune system health benefits are key, higher doses being trialed

Large scale meta-analysis reports 6 to 14% increased relative survival with higher D3 levels
Crucially, higher benefits were seen for higher circulating levels so a “dose dependent” effect
Up to 40% relative risk reductions are seen for the highest band in patient data (see Analysis)

At or above a 23.3 nmol/L threshold, for a 10 nmol/L, 20 nmol/L, or 25 nmol/L increment in circulating 25-OH-D levels, the risk of breast cancer overall mortality decreased by 6%, 12%, and 14%, respectively. There was no significant nonlinearity in the relationship between overall survival and circulating 25-OH-D levels. Our findings suggest that there is a highly significant linear dose-response relationship between circulating 25-OH-D levels and overall survival in patients with breast cancer….adding vitamin D supplements to traditional breast cancer therapy would be expected to be ...

Red Yeast Rice or where possible a prescription statin have multiple beneficial actions

Halved relative risk level in “responders” who saw lowered cholesterol
Largest effects in ER+ tumor types, but also PR- and HER2+
All cause mortality 20% lower for post-diagnosis users

..the inverse association between statin use and BC mortality was partly mediated by underlying cholesterol level. The risk decrease by statin use was clear only when the serum cholesterol level decreased simultaneously..The risk reduction was robust in participants whose cholesterol level decreased after starting statins (HR, 0.49) but was non-significant if cholesterol level did not subsequently decrease (HR, 0.69). Reduced BC mortality among statin users was also observed in females with estrogen receptor–positive tumors (HR, 0.82). Overall mortality was lower among statin users vs non...

Iodine and here the I₂ solution form are in development for breast cancer

New research shows significant benefits of molecular I₂ form
Post treatment recurrence risk reduction of 78% by adding I₂
Significant side effects are also reduced in the supplement group

After surgery, all patients received FEC/TE + I₂ for 170 days. I₂ supplementation showed a significant attenuation of the side effects and an absence of tumor chemoresistance. The control, I₂, FEC/TE, and FEC/TE + I₂ groups exhibited response rates of 0, 33%, 73%, and 100%, respectively, and a pathologic complete response of 18%, and 36% in the last two groups. Five-year disease-free survival rate was significantly higher in patients treated with the I₂ supplement before and after surgery compared to those receiving the supplement o...

SOY ISOFLAVONE studies are in dietary tofu and soy milk finding overall benefits

Post treatment recurrence reduced 18 to 28% from dietary soy at 60mg daily
Similar effects for all cause mortality rates, particularly stage III/ IV
Stronger benefits in postmenopausal women, as high as 43% risk reduction

Soy isoflavone intake was associated with significantly reduced risk of breast cancer recurrence for the overall population, with moderate heterogeneity [certainty] (HR = 0.74). After stratifying by menopause and estrogen receptor status, the effect remained significant only for the postmenopausal (HR = 0.72) and estrogen receptor–positive (HR = 0.82)…Soy products were associated with a 52% risk reduction in recurrence , and combined protein and products were associated with a 25% risk reduction in breast cancer–specific mortality for estrogen receptor...

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

Moderate to high melatonin reported to extend late stage survival
Small numbers of breast cancer patients included in data
Effects are dose dependent, here 1g doses are trialed in late stages

..preliminary study with a very high dose of MLT, consisting of 1000 mg/once day in the evening, was carried out in untreatable cancer patients, who failed to respond to the conventional anticancer therapies, and for whom the only available treatment was the palliative therapy. The treatment was well tolerated, and a disease control was achieved in 54% patients. These preliminary results would justify further clinical studies to generate a new interpretation of cancer control, consisting of the pharmacological reproduction of the same mechanisms responsible for the natural resistance agains...

Astragalus actions include protecting and balancing immune responses

This meta-analysis is across several compounds but astragalus is prominent
Findings are around 1/3 improved response to chemo and twice the progression free rate
Astragalus reduces immune inflammatory responses with similar risk reduction

In the study, the pooled data has shown that CHM [chinese herbal medicine, 3/4 including astragalus- the most common] combined with chemotherapy significantly improved the tumor response and performance status of breast cancer patients. Also, we found that the combined therapy significantly decreases adverse events caused by chemotherapeutic interventions as compared with chemotherapy alone, including nausea and vomiting at toxicity grade of III-IV, WBC reduction at toxicity grade of III-IV, and platelet reduction at toxicity grade of I–IV or III-IV

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

This study reports around 40% reduced risk for patients with relatively higher selenium
In other cancers, early interventional trials with supplements show some benefit
Zinc/Selenium ratio is also implicated in cancer patient prognosis

Women with lower levels of serum selenium (Se) may have a worse survival in breast cancer than women with higher levels, despite no difference in incidence of the disease…Lower overall mortality was found among women in the highest [pre-diagnostic levels] Se quartile compared to the lowest using an adjusted Cox proportional hazards model, hazard ratio 0.63. Similar results were seen for breast cancer-specific mortality, 0.60. The results of our study support that Se is associated with a lower mortality in breast cancer, not related to established prognostic factors.

Oat and egg based functional foods are entering early stage clinical trials for BC

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

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

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

Ferritin (marker for iron level) reported to increase relative survival 3.4X
Nearly 6X increased relative survival rates in low ferritin+low inflammation group
Improved response to immunotherapy with lower pre-treatment ferritin

[HER2+] Patients with low serum ferritin or low CRP had a median survival approximately six times longer than patients with high serum ferritin or CRP. More importantly, patients with high levels of serum ferritin or CRP had a shorter progression-free survival indicating that that trastuzumab-containing therapy was not effective . Therefore, our data suggests that cancer-associated inflammation, as assessed by serum ferritin and CRP, is either 1) inducing resistance to cancer therapies …either directly through activation of molecular pathways or indirectly through affecting the struct...

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

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

Akkermansia is increasingly reported as improving immunotherapy results

Progression to bone metastasis is linked to low diversity and microbiome health
Lack of akkermansia and other strains linked with disease progression
Supplements are an option short term, functional foods 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 inflammation levels indicated 30 to 65% reduced risks
C-reactive protein at high level >10mg/dL indicates high risk
Anti-inflammatory diet and curcumin have significant actions in trials

Elevated plasma CRP measured before treatment in patients with early-stage breast cancer is an independent biomarker of increased risk of recurrence and early death. CRP measures before treatment might be used to individualize follow-up of patients with early-stage breast cancer. A doubling of the plasma CRP concentration was associated with increased risk of recurrence and shorter survival. Survival was shorter in patients with plasma CRP levels of 3 to 10 and >10 mg/L versus <3 mg/L, with multivariate adjusted HR

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GUIDE

Pathfinder Element	Risk Reduction Factor	Anti-Metastatic	Reduces Side Effects	Research Study
Danshen	>50%	Yes	Yes	Link
Low Dose Aspirin	>50%	Yes	Maybe	Link
Structured exercise	>50%	Probably	Yes	Link
Red Yeast Rice or statin	>50%	Probably	Maybe	Link
Iodine (with surgery/chemo)	>50%	Maybe	Yes	Link
Coffee	>50%	Maybe		Link
Astragalus	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
Soy Isoflavones	26 - 50%	Maybe		Link
Melatonin	Up to 25%	Maybe	Yes	Link
Propolis With Radiotherapy	Up to 25%		Yes	Link
Akkermansia / gut health	Indirect - High	Yes	Yes	Link
Lactoferrin	Indirect - High	Probably	Yes	Link
Oat and Egg functional foods	Indirect - Moderate	Probably	Yes	Link
Citrus Pectin	Indirect - High	Probably	Probably	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	Activity against bone metastatic sites	Anti-metastatic in general	Higher doses eg in clinical trials	Comments
>50%	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	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%	Low dose Aspirin	Reduce blood clotting improves vascular health, lowers metastatic activity	75mg	There is evidence for lower progression and recurrence risks and	Yes, research does report promotion of healthier bone growth (helpful)	Yes	No	Nattokinase + red yeast rice is a natural anti-clotting and anti-metastatic. See Nattokinase in Supplements Library
>50%	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"	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	Atorvastatin is probably the most researched prescription drug
>50% for sustaining good hemoglobin	Lactoferrin	Large benefit 2X or more for higher hemoglobin (which treatment depletes badly)	10ml lipsomal LF daily, ideally on empty stomach	The benefit of well functioning iron metabolism is very large, a 6X effect.	Balanced iron metabolism is reported to reduce bone related inflammation and metastatic spread	Low iron levels strongly linked to increased metastatic activity	1.5g lactoferrin twice daily 1.5 g for three 6-week cycles used in lung cancer	Note this has direct evidence with trastuzumab in HER2+. (see Supplements Library). During chemo in particular, higher doses may help keep levels about 120g/dL if possible
>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	Not specifically reported	Probably	No	New studies confirming this in other cancers
>50%	Coffee	Moderates estrogen and direct anti cancer activity	4x 8oz standard servings	Yes there are clear and consistent links.	Not specifically reported	Maybe	No but effects are reported to increase with amounts	Also worth considering green coffee extracts for high chlorogenic acid content
>50%	Iodine solution (with surgery)	Immune system activation	5mg liquid iodine during treatment window	The research so far is focused on combination with surgery	No current evidence	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	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%	Anti-inflammatory diet	Lowering inflammation is crucial	Continuous	Research evidence continues to grow for mainly vegetarian diet with higher fiber content	Likely helpful	Yes		Also read Lifestyle section for view on evidence in diets and eating patterns
26-50%	Vitamin D3	Essential immune system support and more	At least 250ug/ 10,000IU daily with meals	These effects are very clear when circulating levels of D3 are relatively higher	Higher levels are essential for healthy bone metabolism. Aromatase Inhibitors deplete D3 so this is crucial	Yes not least a 3X increase of bone mets due to deficient levels	Research is into higher doses in order to increase the proportion of "responders"	Maintain magnesium and zinc levels carefully too. All these are depleted by drugs and inflammation
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, 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 describes balanced selenium and zinc as a factor for bone metabolism	Yes and in particular spread to bones	"High" dose selenium showing impacts in kidney cancer. See Supplements library	Drugs, their side effects, and infammation can reduce selenium levels
26-50%	Soy Isoflavones	Moderates estrogen and direct anti cancer activity	40 to 60mg mainly diet	Good evidence from dietary surveys data	No evidence reported	Maybe	No the research indicates 40 to 60g	Dietary sources eg tofu and soy beans are recommended with Isoflavones in supplement form as a backup
Up to 25%	Propolis ( with radiotherapy)	Protective actions against radiation induced cell damage	Per supplier	The data available shows very beneficial support for radiotherapy	Not specifically reported	Maybe	Trials have used 400mg x3 daily doses
Indirect - High	Gut health including akkermansia	Indirect importance of gut bacteria is large	Supplier dose, moderate level	Crucially, metastatic spread to the bone is linked to lack of a diverse microbiota including low akkermansia.	Likely helpful	Yes	No, evidence is to apply moderation with supplements	Foundation here is high vegetable and high fiber diet
Up to 25%	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.	Not specifically reported	Maybe	100mg and even 1g have shown responses in late stage trials
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.	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	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	Pending clinical trial results, this seem likley yes	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	As in most cancers, high inflammation is a major risk for metastatic activity	Maybe	Follow supplier program	Combine with piperine or black pepper if not already included in a supplement
Others	Urolithin A							Has probable benefit in reducing activity at bone metastatic sites
Others	Alpha ketoglutarate							Also attracting a lot of attention for health bone metabolism

To give some perspective to the opportunities for investing in your own plan consider the comparison to adding more drugs to the first line drug. There are many treatment options for the various types of hormone driven breast cancers. In the most common first approach with eventual surgery is a hormone therapy such as letrozole (Femara). Often paired with a so called CDK4/6 inhibitor such as palbociclib (Ibrance). Illustrating the challenge, even these inhibitors have research reporting limited impacts on overall risks of progression. But they do extend progression free periods https://www.nejm.org/doi/full/10.1056/NEJMoa1607303 . Immunotherapy such as pembrolizumab (Keytruda) has so far struggled to make a meaningful impact when added to regular first line combinations: https://pmc.ncbi.nlm.nih.gov/articles/PMC8691850/

A significant number of patients are also recommended to go with chemotherapy. The example from the HOME page describes the lack of impact so far from palbociclib in the PENELOPE-B trial https://ascopubs.org/doi/10.1200/JCO.20.03639

Similar patterns are seen in pre-menopausal treatments where even the use of ovarian function suppression only really shows benefit for a small subgroup of patients that remained hormone positive after chemotherapy . In real world data monotherapy with either tamoxifen or maybe ovarian function suppressors like goserelin were better than combinations, for most patients https://ascopubs.org/doi/10.1200/JCO.21.02844

Your PATHFINDER brings together research that may help maximize the effects of endocrine, targeted drug and chemotherapy 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. Depending on which class of drugs you elect, 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 “Targeted Drugs” and “Chemotherapy” etc 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 exercise
The PLANS section may have information from what others are doing and have learned

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