1. Triple Negative Breast Cancer & Naturopathic Medicine
Jake Psenka, ND

2. PMID?
Some of the slides make reference to a PMID number. This number can be copied and pasted into the search bar at to see the research article being referenced.

3. The Principles of Naturopathic Medicine:
Identify and Treat the Cause of Disease
Do No Harm
Doctor As Teacher
Treat the Whole Person
The Power of Prevention

4. Triple Negative Breast Cancer (TNBC)
Estrogen Receptor Negative
Progesterone Receptor Negative
Human Epidermal Growth Factor Receptor (HER2) Negative
15% of Breast Cancers
Appear at an earlier age
High Histologic Grade
Define Cancer

5. Six TNBC Subtypes: 2 Basal Types Immunomodulatory Mesenchymal
Mesenchymal Stem-Like
Luminal Androgen Receptor
Each subtype has characteristics which may make it more or less susceptible to a particular type of therapy. Hopefully, as research progresses, it will become possible to use more patient-specific treatment strategies.
PI3K- phosphatidylinositol-3-kinase, a signaling pathway, plays a role in growth and survival in many mammalian cancers
P53- tumor suppressor gene, mutations occur in up to 82% of TNBC
BRCA1
MIB-1
IGF-1R: Insulin like growth factor receptor, a tyrosine kinase, binds IGF.
Ki67: a measure of cell proliferation, higher # ass. With axillary mets in TNBC
mTOR:

6. Current TNBC Treatment Strategies
Cytotoxic Therapy (Adriamycin/Cytoxan/Taxol)
Radiation
Surgery
Chemotherapy is considered a cytotoxic and systemic therapy aimed at destroying rapidly dividing cancer cells.
Radiation: kills by ionizing DNA molecule within a cancer cells and the production of free radicals (hydroxyl radicals).
At the present time these therapies have a low rate of success and new more efficacious treatments are needed.
Adriamycin (docorubicin)
Cytoxan (cyclophosphamide)
Taxol (Paclitaxel)

7. Problems Associated with Current TNBC Treatment Strategy
Toxicity
Immune Suppression
Fatigue & Malaise
Depression/Anxiety
Drug Resistance
Lack of Efficacy
Ultimately a lack of efficacy.
We need new therapies that provide better outcomes.

8. Naturopathic Treatment Strategies
As a way to support the patient:
Promoting health of patient- both mind & body
Minimizing treatment related side effects
As integrative therapy:
Anti-Cancer Therapy
Improving clinical outcomes
Preventing Re-occurrence
Not anti-conventional treatments. Prefer integrative approach.
Frequent Question: Can a person use CAM treatments with Conventional? Yes, as long as you use the right ones.
How many people changed their diet when they were diagnosed? Yes = using CAM

9. Food As Medicine
Dietary habits can play a role in both the development and progression of cancer. A healthy diet supports the body’s natural processes and functions.
Inhibiting Unintended Weight Loss
Promoting Healthy Elimination
Reducing Treatment Related Side Effects
Anti-inflammatory Action
Energy Balance/Fatigue Reduction
Improving Efficacy of Treatments
Unintentional weight loss- either via LOA from treatment, or as a consequence of tumor
Many tx’s are toxic- want them in and out, if elimination routes are inhibited (aka. Constipation) this can cause more toxicity issues, may also produce additional problems (impaction), additionally many drugs are nephrotoxic and maintaining good hydration keeps the kidneys safe. Tumor lysis syndrome and hydration
In addition to bowel and urinary issues, healthy diets can also provide the body with what it needs to process chemicals and remove them from the body(cyp450 system).
Some foods promote a decrease in the levels of inflammation present in the body: n-3: PGE2, fish oil: vitamin D3
Nutritionally deficient diets do not provide for sustained energy levels. Simple carbs = transient energy followed by a crash.
If a patient does not maintain good health through their therapies then an extended chemo break, or dose-reduction is often needed. This can decrease efficacy.

11. INSULIN-LIKE GROWTH FACTOR-1
Food As Medicine .
INSULIN-LIKE GROWTH FACTOR-1
These results show that IGFs stimulate cell proliferation and promote cell survival in triple-negative breast cancer cell lines and warrant investigation of the IGF signal transduction pathway as a therapeutic target for the treatment of triple-negative breast cancer. Neoplasia Jun;13(6):504-15
Randomized controlled trials indicated that the circulating IGF-I level was significantly higher in the milk intervention group. Int J Food Sci Nutr. 2009;60 Suppl 7: Epub 2009 Sep 9.
An unhealthy diet does not provide the same benefits, and instead can have significant negative impact
Here is an example of a specific dietary manipulation aimed at inhibiting cancer growth:
No dairy on TNBC diet?
IGF-1 binds to IGF-1R , a hormone is one of the most potent natural activators of the AKT signaling pathway, a stimulator of cell growth and proliferation, and a potent inhibitor of programmed cell death (apoptosis).
These data suggest that a plant-based diet is associated with lower circulating levels of total IGF-I. Cancer Epidemiol Biomarkers Prev Nov;11(11):

12. Food As Medicine
“In vivo, the efficacy of blueberry to inhibit triple-negative breast tumor growth was evaluated. Tumor weight and proliferation (Ki-67 expression) were decreased in blueberry-treated mice, where apoptosis (caspase-3 expression) was increased compared with controls.”
“In combination with standard treatments, supplementing the diet with (n-3) fatty acids may be a nontoxic means to improve cancer treatment outcomes and may slow or prevent recurrence of cancer.”
Lung metastasis of TNBC was reduced (16-70%) by all treatments, significantly in the flax seed oil group. The distant lymph node metastasis was significantly decreased (52%) only in the flax seed oil group. The total metastasis incidence was lowered (42%). Mouse study.
Ki67, a measure of proliferation, higher expressions of this associated with axillary mets.(PMID: )
PMID:
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13. SUGAR/CARBOHYDRATE/GLUCOSE = ENERGY
Food As Medicine
SUGAR/CARBOHYDRATE/GLUCOSE = ENERGY
Higher SUVmax and %Ki67 are associated with higher histologic grades.
Histologic grade is a measure of proliferation, Scarff-Bloom-Richardson system most common rage from 3-9.
Recall our definition of cancer.
Cell reproduction (mitosis) takes energy. GLUT-1 receptors more expressed in TNBC (PMID: ) GLUT1 trasporters are upreg. When a cell is hungry.
What are the effects of a high sugar/refined carbohydrate diet?
PMID:
Glucose receptors are upregulated in TNBC (PMID )
Higher sugar uptake by TNBC cells correlates with increased cancer cell proliferation (PMID: )

14. Exploiting Metabolism

15. Supplements for cancer?
Reasons for using supplements with conventional therapy:
Minimize treatment-related side effects
Promote a well functioning immune system
Synergize with conventional treatments
Are supplements safe with conventional care? Yes, if you take the right ones.
Natural does not mean safe.
How many capsules can a person eat in one day. Try to maximize effectiveness

16. L-Glutamine protects against doxorubicin (aka Adriamycin) heart damage
Side Effects
L-Glutamine protects against doxorubicin (aka Adriamycin) heart damage
Glutamine for taxane induced neurotoxicity.
Melatonin inhibits Cytoxan-induced leukopenia and anemia
Melatonin inhibits taxane-related neuropathy
DHA, an n-3 fatty acid, is currently in trials
Hormones
Glutamine: PMID: , PMID:
Melatonin: PMID: , PMID:
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17. Immune Enhancement
LifeStyle Factors
Exercise-
but don’t over exercise
Stress Reduction
yoga, meditation, guided imagery, reiki, acupuncture, religion.
Alcohol Elimination
Sugar Elimination
Supplements
Arabinogalactans
NK function
Melatonin
T-cell function
Thymic Proteins
Beta Glucans
NK cells

18. Synergize
Multidrug resistance (MDR):
Defined as the ability of a tumor cell to survive exposure to clinically achievable concentrations of structurally diverse chemotherapeutic drugs which act at different intracellular targets.

19. Propolis (caffeic acid)
Synergize
Propolis (caffeic acid)
Inhibits TNBC tumor growth, both in vitro and in vivo without much effect on normal mammary cells.
Decreased malignancy potential of TNBC stem cells.
VEGF/Angiogenesis
Stem cells implicated with chemoresistance, tumor recurrence, metastasis, and high patient mortality.
PMID:
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20. Inositol Hexaphosphate (IP6):
Synergize
Inositol Hexaphosphate (IP6):
decrease proliferation rates in TNBC cells
works synergistically with adriamycin (and Tamoxifen)
inhibits metastasis
activates natural killer cell function
Patient study finds those who took it with chemo had no cytopenia, lowered leukocyte, or platelet levels, increased QOL and better functional status.
PMID:
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IP6: P27kip1 tumor suppressor protein
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21. Curcumin (extract from tumeric)
Synergize
Curcumin (extract from tumeric)
Modulation of the BRCA1 Protein and induction of apoptosis in TNBC
Blocker of COX and LOX
Shown to decrease the MDR1 gene through the PI3k/AKT/NF kappa beta pathway
Arachidonate metabolites: cycloxygenase and lipoxygenase: anti-inflammatory
One study was published stating that found curcumin to antagonize the effects of CTX. Serious methodological errors and misrepresentations of scientific data were found in that study.
PMID:
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22. Synergize
Vitamin D3
Potentiates the anti-tumor activities of chemotherapy drugs cisplatin, carboplatin and doxorubicin; 5-fluorouracil, cytarabine, hydroxyurea, cytarabine and gemcitabine; paclitaxel and docetaxel.
Vitamin D3 enhances the effect of hydrogen peroxide in cancer cells.

23. Inhibits TNBC proliferation
Synergize
Indole-3-Carbinol
Inhibits TNBC proliferation
Down regulated PGP transmembrane efflux pumps by 80%.
Decrease TNBC cell motility
Sulphoraphane
Inhibits inflammatory cytokines and pro-angiogenic growth factors in TNBC
PMID:
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24. Resveratrol enhances mTOR inhibitor
Synergize
Resveratrol
Sensitizies tumor to chemotherapy drugs including vincristine*, adriamycin, paclitaxel*, doxorubicin, cisplatin, gefitinib, 5-fluorouracil, velcade, and gemcitabine.
Resveratrol enhances mTOR inhibitor
NFKB
PMID:
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25. Detoxification: Get Specific
Remission
Preventing recurrence: NCCN guidelines for breast cancer state “Evidence suggests that active lifestyle, achieving and maintaining an ideal body weight (20-25 BMI) may lead to optimal breast cancer outcomes.”
Detoxification: Get Specific
National Comprehensive Cancer Network
Coffee enemas/colonics- rectal burn

26. New Ideas
Metformin
Breast Cancer Res Treat Sep;123(2): Epub 2009 Nov 22.
Dietary energy availability affects primary and metastatic breast cancer and metformin efficacy.
Phoenix KN, Vumbaca F, Fox MM, Evans R, Claffey KP.

27. New Ideas

28. Circulating Tumor Cell Studies
New Ideas
Chemotherapy Sensitivity and Chemo-resistance Testing
Circulating Tumor Cell Studies

29. New Ideas
Prevention