Hormone BreastCancer

David T. Zava, PhD Founder, CEO, Chief Research Scientist ZRT Laboratory

Breast Cancer And

Estrogen Metabolism

E ER

XENOESTROGENS (eg, DDT)

POLLUTANTS

XENOBIOTICS (eg, PCBs)

ESTROGENS (E1, E2)

PROGESTERONE

PROLACTIN

SHBG

THYROID

MELATONIN

CORTISOL

17B-HSD TYPE II (E1→E2) E1-SULFATASE (E1-S04 →E1) AROMATASE (A →E1)

BREAST STROMA

IMMUNE CYTOKINES SYSTEM TH1 ↓ TH2 ↑

DHEA

ADRENAL GLAND

STRESS

Emotional Physical Surgical

OVARIAN DYSFUNCTION

HEAVY METALS

ZINC SMOKING

POOR DIET (refined carbohydrates)

INSULIN

OBESITY

INSULIN RESISTANCE

TESTOSTERONE

(AROMATASE) LH/FSH

POLYCYSTIC OVARIES

ERT HRT

HORMONAL RISK FACTORS FOR BREAST CANCER THE ESTROGEN MATRIX

Vitamin D3

Iodine (I2)

2-OH-E1(E2)

E2 E1-S04 E1

16-OH-E1 4-OH-E1(E2)

4-QUINONE-E1(E2) 2-QUINONE-E1(E2) PROTEIN BINDING

DNA ADDUCT FORMATION


NO FURTHER EFFECT

DNA REPAIR DNA DAMAGE MUTATION

CANCER

Sulfotransferase

Sulfatase

17 ß-HSD-Type II

17ß-HSD-Type I

E1 = ESTRONE

E2 =ESTRADIOL

E3 = ESTRIOL

E3

GST-GSH conjugation of 2- & 4-Quinone E1(E2)

COMT-Methylation of 2- & 4-OH –E1(E2)

INACTIVE ESTROGEN

METABOLITES

ESTROGEN METABOLISM AND BREAST CANCER RISK

Cyp-1A1

2-MeO-E1(E2)

4-MeO-E1(E2)

2-GS-E1(E2)

4-GS-E1(E2)

ESTROGENS

The Angel of Life

Or

The Angel of Death

2-OH-E1(E2)

E2 E1-S04 E1

16-OH-E1 4-OH-E1(E2)




NO FURTHER EFFECT


CANCER

Sulfotransferase

Sulfatase

17 ß-HSD-Type II

17ß-HSD-Type I

E1 = ESTRONE

E2 =ESTRADIOL

E3 = ESTRIOL

E3



INACTIVE ESTROGEN

METABOLITES


Cyp-1A1

2-MeO-E1(E2)

4-MeO-E1(E2)

2-GS-E1(E2)

4-GS-E1(E2)

Different types of body fluids commonly

used for testing hormones

Serum and Plasma (Venipuncture)

Urine (Liquid and Dry)

Saliva

Capillary Blood (Finger Stick Dried Blood Spots)

Dried Urine Test

Steroid Hormone Metabolite Testing by GC-MS/MS and LC-MS/MS

Potentially Harmful

Harmful

Safe Beneficial

Chinese-US (ZRT) Urine Steroid Hormone

Metabolite Breast Cancer Study

Eric Shi, PhD, MD, David Zava, PhD et.al. 37 Chinese premenopausal breast cancer patients-newly diagnosed, no Tx 42 Healthy age-matched controls Morning spot urine collections on filter paper-dried-shipped to ZRT at ambient temperature Steroids extracted from filter paper, SPE, enzyme hydrolyzed, liquid extracted, dried, derivatized, analyzed by GC-MS/MS.

Internal Research Results on Estrogen Metabolites and

Breast Cancer (to be published)

- 4-OH-Estrogens higher in breast cancer patients than controls - Selenium low in controls and breast cancer patients but statistically lower in patients

Potentially Harmful

Harmful

Safe Beneficial

2-OH-E1(E2)

E2 E1-S04 E1

16-OH-E1 4-OH-E1(E2)




NO FURTHER EFFECT


CANCER

Sulfotransferase

Sulfatase

17 ß-HSD-Type II

17ß-HSD-Type I

E1 = ESTRONE

E2 =ESTRADIOL

E3 = ESTRIOL

E3



INACTIVE ESTROGEN

METABOLITES


Cyp-1A1

2-MeO-E1(E2)

4-MeO-E1(E2)

2-GS-E1(E2)

4-GS-E1(E2)

2-OH-E1(E2)

E2 E1-S04 E1

16-OH-E1 4-OH-E1(E2)




NO FURTHER EFFECT


CANCER

Sulfotransferase

Sulfatase

17 ß-HSD-Type II

17ß-HSD-Type I

E1 = ESTRONE

E2 =ESTRADIOL

E3 = ESTRIOL

E3

GSH Transferase

COMT

INACTIVE ESTROGEN

METABOLITES


Cyp-1A1

2-MeO-E1(E2)

4-MeO-E1(E2)

2-GS-E1(E2)

4-GS-E1(E2)

STRESS-BREAST CANCER

and

Cortisol-Melatonin-Estrogen

E ER


POLLUTANTS


ESTROGENS (E1, E2)

PROGESTERONE

PROLACTIN

SHBG

THYROID

MELATONIN

CORTISOL

17B-HSD TYPE I (E1→E2) E1-SULFATASE (E1-S04 →E1) AROMATASE (A →E1)

BREAST STROMA


DHEA

ADRENAL GLAND

STRESS


OVARIAN DYSFUNCTION

CADMIUM

ZINC SMOKING


INSULIN

OBESITY

INSULIN RESISTANCE

TESTOSTERONE

(AROMATASE) LH/FSH

POLYCYSTIC OVARIES

ERT HRT


Vitamin D3

Iodine (I2)

Sephton SE, Sapolsky RM, Kraemer HC, Spiegel D. Diurnal Cortisol Rhythm as a Predictor of Breast Cancer Survival. JNCI 92: 994-1000, 2000.

Normal Profile: Cortisol high morning, low night Breast Cancer Profile: Flat Diurnal Cortisol, high at night

Normal

Cancer

Normal Healthy Adult: Cortisol and Melatonin

Circadian Rhythm

Typical Cancer Patient: Cortisol and Melatonin

Circadian Rhythm

E ER


POLLUTANTS


ESTROGENS (E1, E2)

PROGESTERONE

PROLACTIN

SHBG

THYROID

MELATONIN

CORTISOL

17B-HSD TYPE II (E1→E2) E1-SULFATASE (E1-S04 →E1) AROMATASE (A →E1)

BREAST STROMA


DHEA

ADRENAL GLAND

STRESS


OVARIAN DYSFUNCTION

HEAVY METALS

ZINC SMOKING


INSULIN

OBESITY

INSULIN RESISTANCE

TESTOSTERONE

(AROMATASE) LH/FSH

POLYCYSTIC OVARIES

ERT HRT


Vitamin D3

Iodine (I2)

TYPICAL URINARY HORMONE PROFILE IN BREAST CANCER PATIENTS

ESTRADIOL & ESTRONE

4-OH-E1 & 4-OH-E2 RATIO 4-MeO-E1/4-OH-E1

PREGNANEDIOL RATIO PREGNANE/PREGNENE

TESTOSTERONE & DHT EPI-TESTOSTERONE

DHEA DIURNAL CORTISOL (FLAT)

DIURNAL MELATONIN

TYPICAL SALIVARY AND BLOOD (DBS) HORMONE PROFILE IN BREAST CANCER

PATIENTS

ESTRADIOL & ESTRONE PROGESTERONE

RATIO PROGESTERONE/ESTRADIOL TESTOSTERONE

DHEA(S) DIURNAL CORTISOL (FLAT)

Simple life style changes to reduce risk of developing

breast cancer:

Eat right-lots of organic vegetables Avoid pollutants Exercise Get adequate sleep in a dark room If hormone deficient: take necessary

hormones to create balance Find ways to reduce stress(ors)

Hormone BreastCancer

Documents

Transcript of Hormone BreastCancer