Triple Negative Breast Cancer&

Naturopathic Medicine

Jake Psenka, ND

PMID?

Some of the slides make reference to a PMID number. This number can be copied and pasted

into the search bar at www.pubmed.gov to see the

research article being referenced.

The Principles of Naturopathic Medicine:

Identify and Treat the Cause of Disease

Do No HarmDoctor As TeacherTreat the Whole PersonThe Power of Prevention

Triple Negative Breast Cancer (TNBC)

Estrogen Receptor NegativeProgesterone Receptor NegativeHuman Epidermal Growth Factor Receptor (HER2) Negative

15% of Breast Cancers Appear at an earlier ageHigh Histologic Grade

Six TNBC Subtypes:2 Basal Types

ImmunomodulatoryMesenchymal

Mesenchymal Stem-LikeLuminal Androgen Receptor

Current TNBC Treatment Strategies

Cytotoxic Therapy (Adriamycin/Cytoxan/Taxol)RadiationSurgery

Problems Associated with Current TNBC Treatment Strategy

ToxicityImmune Suppression

Fatigue & MalaiseDepression/Anxiety

Drug ResistanceLack of Efficacy

Naturopathic Treatment Strategies

1. As a way to support the patient:Promoting health of patient- both

mind & bodyMinimizing treatment related side

effects

2. As integrative therapy:Anti-Cancer Therapy

Improving clinical outcomesPreventing Re-occurrence

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 LossPromoting Healthy Elimination

Reducing Treatment Related Side EffectsAnti-inflammatory Action

Energy Balance/Fatigue ReductionImproving Efficacy of Treatments

Food As Medicine

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 7:330-40. Epub 2009 Sep 9.

These data suggest that a plant-based diet is associated with lower circulating levels of total IGF-I. Cancer Epidemiol Biomarkers Prev. 2002 Nov;11(11):1441-8.

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. 2011 Jun;13(6):504-15

.

INSULIN-LIKE GROWTH FACTOR-1

Food As Medicine

“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.”

“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.”

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.

PMID: 21228363, 15849746

Food As Medicine

SUGAR/CARBOHYDRATE/GLUCOSE = ENERGY

Higher SUVmax and %Ki67 are associated with higher histologic grades.

Glucose receptors are upregulated in TNBC (PMID 21266827)

Higher sugar uptake by TNBC cells correlates with increased cancer cell proliferation (PMID: 20012701)

Exploiting Metabolism

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

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

PMID: 19889810, 14718801, 20035269, 20567633

Immune Enhancement

LifeStyle Factors

Exercise-but don’t over exercise

Stress Reductionyoga, meditation, guided

imagery, reiki, acupuncture, religion.

Alcohol Elimination

Sugar Elimination

Supplements

ArabinogalactansNK function

MelatoninT-cell function

Thymic ProteinsT-cell function

Beta GlucansNK cells

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.

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.

Synergize

PMID: 21570765

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: 12846414PMID: 15868430PMID: 14666664PMID: 20152024

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

PMID: 19809577

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.

Indole-3-Carbinol

Inhibits TNBC proliferation Down regulated PGP transmembrane efflux pumps by 80%.Decrease TNBC cell motility

Synergize

Sulphoraphane

Inhibits inflammatory cytokines and pro-angiogenic growth factors in TNBC

PMID:21767081PMID:19728765

Resveratrol

Sensitizies tumor to chemotherapy drugs including vincristine*, adriamycin, paclitaxel*, doxorubicin, cisplatin, gefitinib, 5-fluorouracil,

velcade, and gemcitabine.Resveratrol enhances mTOR inhibitor

Synergize

PMID: 21261654PMID: 21168265

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.”

Remission

Detoxification: Get Specific

MetforminBreast Cancer Res Treat. 2010 Sep;123(2):333-44. 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.

New Ideas

New Ideas

New Ideas

Chemotherapy Sensitivity and Chemo-resistance Testing

Circulating Tumor Cell Studies

New Ideas

Prevention