Stiles Program In Integrative Oncology - Cancer Alternatives - UCLA

Stiles Program in
Integrative Oncology
Herbal and Natural Products
for Cancer Prevention and
Therapy
Richard J. Pietras, PhD, MD
Jonsson Comprehensive Cancer
Center, UCLA

Herbs and Natural
Products in Cancer
• Cancer facts
• What is complementary therapy?
• Unproven and proven therapies
• Natural products in development and in
clinical trials for cancer treatment
• Herbal and natural approaches to cancer
prevention
• What you can do to stop cancer

CANCER, The 36 Years War
Jemal, A. et al. CA Cancer J Clin 2003
National Cancer Act
for “War on Cancer”
passed in 1971
Each day, 1,500 Americans die from cancer (559,650 /year)
About 40% men and 33% women at lifetime risk for cancer

The Bad News:
The Cancer Epidemic
- 10 million cancer cases, 6 million deaths / year worldwide
- 1,300,000 cases of cancer per year in US
The Good News:
- Currently, more than 10 million survivors of cancer
- US cancer death rates are falling by ~ 2.1% per year
- 40-60% of cancers may be avoided or prevented by :
a) personal changes in behavior (diet, lifestyle, habits)
b) environmental interventions
c) vaccines for papillomavirus,hepatitis B, H. pylori

Cancer Incidence in Men and Women

Annual Cancer Death Rates, 1930-2003
Since 1971, comprehensive research helped to raise 5-year survival for
breast, prostate and colon cancers, but lung cancer is only 15%
Jemal, A. et al. CA Cancer J Clin 2007;57:43-66; Morosini D. CURE 2007; 6: 80

normal cell
How do tumors form and
Heredity Endocrine
progress?
metastasis
Chemicals Nutrition Gene changes
Radiation Inflammation
Viruses
stem/progenitor cell
preneoplastic malignant
metastasis
INITIATION PROMOTION PROGRESSION

Cancer progression : early detection &
treatment is best chance for CURE
PROGRESSION
PROMOTION
INITIATION
DEATH
CURE CURE

Current Cancer Therapy
• Surgery
• Chemotherapy
• Radiation Therapy
• Biologic Therapy
• Complementary Therapy
• Preventive Therapy

History of Complementary
Medicine
Hippocrates
Father of
modern
western
medicine and
herbal
practitioner
460-370 BC

History of Complementary Medicine
Ancient Mesopotamia 3000 BC Sumerian Empire used plant
medicines for fever, stroke, lung and liver disease
Traditional Chinese Medicine 2900-2600 BC ‘Neiching’ and
yin-yang philosophy. Combines diet, >1800 herbs, and acupuncture
to enhance, restore health
Ayurvedic Medicine 800 BC- 1000 AD Indian healing system
with diet, herbs, exercise, meditation, massage, light
Greek Medicine 500 BC Hippocrates emphasized treating the
patient, not just the disease, with diet as main treatment and
herbs when diet alone not adequate
Aztec, Mayan, Inca and Native American Medicine in the
Americas. Medicinal herbs, minerals and natural products

Complementary
Medicines
WHO estimates that 80% of world
population relies on plant-based
medicines for primary healthcare
75% of all pharmaceuticals were
discovered by examining use of
plants in traditional medicine

Hope or Hype?
Alternative medicine is edging into the
mainstream, with Californians in the lead.
Debate rages about its effectiveness and
scientific oversight
ALTERNATIVE MEDICINE
The $22-Billion Experiment
Los Angeles Times (2005)

Complementary and Alternative Therapies
Complementary Medicine - complement traditional western,
evidence-based medicine :
• meditation to reduce stress
• acupuncture for relief of pain and nausea
Alternative Medicine – therapeutic approaches taken in place
of western medicine and often based on anecdotal reports,
uncontrolled trials or traditional use suggesting lack of harm
Integrative Medicine - combination of traditional western (or
allopathic) medicine & complementary medical approaches
Complementary and Alternative Medicine (CAM) - acronym
to describe study or use of complementary and alternative
approaches
American Cancer Society Guide to Complementary and Alternative Cancer Methods

Alternative Therapies
Disproven in Clinical Trials
Laetrile: cancer due to deficiency vitamin B17 (no such
vitamin); median survival 4.8 mo in advanced cancer pts
Livingston-Wheeler: cancer due to progenitor cryptocides
bacteria (but bacteria does not exist)
DiBella Multitherapy: cancer asstd with growth hormone
Antineoplaston: NCI trial in glioblastoma, TTP 29 days and
all patients died before study closed
High-Dose Vitamin C: No change in colorectal cancer
survival

Proven Antitumor Therapies
Derived from Natural Sources
Podophyllum peltatum, P. hexandrum:
etoposide
Catharanthus roseus (Madagascar periwinkle):
vincristine
vinblastine
Taxus brevifolia (Pacific Yew tree):
taxol (paclitaxel)
taxotere (docetaxel)

Complementary Therapies with
Potential Benefit in Cancer Prevention
or Therapy: Ongoing Clinical Trials
Saw Palmetto: BPH, prostate cancer?
Lycopene: prostate cancer
Beta-Glucans: lymphoma,
activate complement
receptor-3 to promote antitumor immunity
Squalamine: non-small cell lung cancer, ovarian cancer
Scutelleria: prostate, breast, lung cancers
Green tea: breast cancer, prostate cancer, oral cancers

Proven Antitumor Therapies
Derived from Natural Sources
Of 92 antitumor drugs approved 1983-1994, 62 (67%) were
of natural origin: based on natural cmpd:
Actinomycin D Vincristine aminoglutethemide
Asparaginase Epirubicin cytosine arabinoside
Bleomycin Estramustine floxuridine
Daunomycin Etoposide fluorouracil
Doxorubicin Idarubicin goserelin acetate
Mithramycin Irinotecan methotrexate
Paclitaxel Megestrol mitoxantrone
Streptozocin Vinorelbine tamoxifen
Vinblastine Leuprolide faslodex

Trends in use of complementary medicine
• 42% Americans use some form of complementary therapy
• 629 million visits to alternative practitioners > primary care
visits
• 50-70% of breast cancer patients use some form of
complementary therapy
30% dietary therapy (megavitamins, supplements)
24% spiritual healing
21% herbal remedies
15% physical methods (acupuncture, massage)
10% psychological methods

Why Do People Use
Complementary Therapy?
• “Safer” and “more natural”
•“Holistic”
• “My complementary practitioner spends
more time and treats me as a whole
person”
• Symptom relief (pain, nausea)

The Communication Gap
• Don’t ask, don’t tell. Patients not talking to
physicians about their use of CAM.
• Only 54% of breast cancer patients seeing a
CAM practitioner told their MD (“The doctor
never asked”)
• 94% cancer patients discussed their biomedical
treatments with their CAM providers
Herb-Drug Interactions : On review by
pharmacologists, more than 12% of herbal
treatments could interfere with conventional
cancer therapies

Federal Drug Law
1906 Pure Food and Drug Act : truthful labeling (TR)
1938 Food, Drug and Cosmetic Act : safety testing
1962 Food, Drug and Cosmetic Act : prove drug efficacy;
stringent guidelines for testing (preclinical toxicity, efficacy,
controlled clinical trials)(JFK) - thalidomide and phocomelia
1994 Dietary Supplement Health and Education Act :
allows OTC sale of herbals and food supplements for
general health maintenance without FDA review; no proof
of safety or efficacy required; burden of safety placed on
FDA to remove products with compelling evidence of harm
2004 FDA bans dietary supplements with ephedra

New Federal Drug Laws
2007 FDA Amendments Act - new FDA post-market
surveillance (adverse effects, advertising) and
enforcement powers to regulate prescription
drugs, but specifically does not alter regulation
of supplements under DSHE Act or adverse
event reporting under prior federal law
2007 FDA sets new rules to regulate what’s in a
supplement (purity) and to report adverse
effects, but manufacturers still not required to
show product safety or efficacy, rules that are
strict requirements for prescription drugs

Dietary Supplements, Adverse
Events, and Efficacy
FDA overload: 4,000 unregulated products in 1994
when DSHEA passed, but more than 29,000 now
In 2001, FDA had 500 reports of adverse events due
to supplements; and 19,468 at poison-control centers
FDA, California Dept of Health and Japanese Health
Ministry find 10%-32% of Chinese herbal products
contain undeclared drugs or heavy metals (lead,
mercury or arsenic)
Randomized control trial evidence of clinical efficacy
exists for < 30 herbs

Herbal Therapies
• Herbal supplements not standardized for safety
or efficacy; purity standards not mandated til 2010
-“Standardized” ginseng has defined % ginsenosides, but
more than 30 ginsenosides may contribute to biologic
effect; different suppliers provide different amounts
• “Natural” not necessarily beneficial
-Drug effects (PC-SPES reduces PSA prostate CA but
decreases libido, breast enlarge, nausea, diarrhea,
thromboembolism)
-Unknown drug interactions

Potential Adulterants and
Contaminants in Herbal Preparations
Drugs warfarin, anti-inflammatory, corticosteroids,
benzodiazepines, sildenafil, diethylstilbestrol
Toxic metals lead, cadmium, mercury, arsenic
Pesticides chlorinated pesticide, organic phosphate, triazin
herbicide, fungicide, carbamate insecticides
Microbes Staphylococcus aureus, E. coli, salmonella,
shigella, Pseudomonas aeruginosa
Toxins aflatoxin, bacterial endotoxins
Botanicals digitalis, rauwolfia, belladonna alkaloids
Wood (2002) NEJM 347 : 2046

Specific risks of complementary
therapies in cancer patients
Tumor CAM Chemorx Concern
NHL echinacea Rituximab stimulates targeted B-cells
breast yam hormonal estrogenic effects
milk thistle Taxol reduces taxol metabolism
kava chemorx hepatotoxicity
prost cod liver oil antithrombotic
ovary laetrile contains cyanide
any milk thistle adriamycin reduces drug metabolism
NOTE: refer to Memorial Sloan-Kettering Cancer Center Integrative Medicine
website for listing of 60 other herbal/natural products with known health risks

Potential Systemic Adverse
Effects of Herbal Remedies
Cardiotoxicity leigongteng, mahuang, licorice root,
colchicine-rich herbs, cardioactiveglycoside-rich
herbs
Hepatotoxicity mahuang, kava rhizome, chaparral,
herbs rich in anthranoids, podophyllotoxin,
pyrrolizidine alkaloids
Renal toxicity chinese yew, impila root, jering fruit,
pennyroyal oil and certain essential
oils, star fruit
Neurotoxicity mahuang, kava rhizome, nux
vomica, aconite root tuber, star fruit

Buyer Beware:
Consumers Can’t Trust That
• Plant was accurately identified
• Potency will be the same bottle-to-
bottle
• Herb is pure (until 2010)
• Herb is safe (until 2010)
• Herb is effective

Advice for Patients Taking Herbs
• Purchase only products labeled with name and
part of herb, batch or lot #, expiration date, name
and address of manufacturer
• Choose manufacturer in business for a while or
herbal products of major pharmaceutical firms
• Use multiple herbs with caution
• Talk with your practitioner and pharmacist about
possible herb-drug interactions
• Stop herbs before elective surgeries
• Learn as much as you can

How to Find a
Quality Product
• Use information from independent
testing laboratories, such as
ConsumerLab.com
• Look for a “seal of approval”, such as
USP, NSF
• Look for products that have been
tested in clinical trials

Learn As Much As You Can
Many websites offer info on CAM, but select public sites that review
published work. Be wary of sites reporting only testimonial or anecdotal
evidence from former users or promote only a particular product
Authoritative public websites:
• M. D. Anderson Cancer Center (www.mdanderson.org/cimer)
• American Cancer Society (www.cancer.org)
• NCCAM ( http://nccam.nih.gov)
• NCI data query (www.cancer.gov/cancerinfo/PDQ/cancerdatabase)
• MSKCC (www.mskcc.org/about herbs)
• Stiles Program (www.canceralternatives.mednet.ucla.edu)
• UCLA Collaborative Centers for Integrative Medicine
• Medline, PubMed and NaturalStandard.com
Books: Evidence-Based Herbal Medicine by Rothblatt & Ziment
ACS Guide to Complementary and Alternative Cancer Methods
Mary Hardy, MD: Simms/Mann-UCLA Center for Integrative Oncology
Ka Kit Hui, MD: UCLA Center for East-West Medicine

How to assess CAM research findings
Replication: Do not change your lifestyle because of
one study. Wait for other studies to confirm.
Size of Effect: Look for doubling or halving of effect,
but also look at absolute risk (rare vs common risk)
Size of study: studies with 10,000 subjects more
reliable than those with 50
Randomized, controlled trials : generally more reliable
than observational studies
Statistical Significance and Consistent Findings:
trends not sufficient; more precise results better.

Recommendations for patients with cancer*
1. Discuss use of CAM with your doctor
2. Ask your doctor for guidance on CAM advantages/disadvantages
3. Check dietary supplements, esp. herbals, for side effects and interactions
with other drugs. If likely to interact with chemotherapy, do
not use concurrently during chemo or radiation, or before surgery
4. In patients who do not respond to or decline antitumor therapy, it
is recommended to use botanical agents in a clinical trial setting
5. Consider acupuncture for poorly-controlled chemo-induced
nausea, vomiting or pain and for neuropathy or xerostomia
6. If anxiety or pain, massage by oncology-trained massage therapist
may be part of a multimodality approach, but deep, intense manipulation
not advised near cancer lesions or distorted postop areas
7. In those with bleeding tendency, acupuncture or massage should
be done only by qualified practitioners and used cautiously
8. Consider mind-body methods as another approach to reduce
anxiety, mood disturbances, chronic pain
*Based on Cassileth et al. Chest, 2007

Lobby for New Regulatory
Safeguards in Federal DHSEA
1. Register with FDA address, contact names of those
manufacturing dietary supplements for sale in US
2. Show evidence of good manufacturing practices to
prevent adulteration, standardize products (2010)
3. Premarketing FDA approval to show that products
have no risk of injury with recommended use
4. Manufacturers report all adverse events (2010)
5. Labels to list all constituents and inform about on
adverse effects, including herb-drug interactions

Evidence-Based Research:
Approaches to Discovery of
New Therapies
• Surveys
• Observational cohort studies
• Case-Control Studies
• Laboratory/Pre-clinical Models
• Prospective Trials (phase I/II)
• Controlled randomized trials (Phase III)

Strategies for Botanical
Phase I/II
safety and
efficacy
studies
Randomized,
Controlled
Phase III Trials
Drug Discovery
Herbs or regimens
used historically for
specific indications
Laboratory
studies of herbal
extracts
HPLC or other
compound
isolation strategy
Modified from Tripathy (2004)

Use of scientific principles to develop
antitumor medicines from plants
• Estimated 287,000 higher terrestrial plants, with less
than 10% investigated for medical application
• Ethnobotanical data important for drug leads
• Rational target-based drug discovery for screening
using data from DNA microarrays, proteomics,
molecular signal transduction
• Evaluation of purity, safety, interactions
• Natural products as templates for new drug discovery

Natural Products in
Testing for Cancer
Prevention and Treatment
• Squalamine for lung and ovarian cancer
• Scutellaria for breast, prostate and lung
cancers
• Tanacetum parthenium to enhance antitumor
antibody therapy
• Natural foods in the diet to promote survival
in patients with cancers

Lung Cancer in US Women
A Contemporary Epidemic
Age-adjusted death rates for lung cancer and breast cancer among women,
US, 1930-1997 (Patel et al. JAMA 291 : 1763, 2004)

Lung Cancer Statistics
• 214,000 people will be diagnosed with lung
cancer in 2007
• Majority of lung cancers, 60%, diagnosed in
non-smokers (former- or never-smokers)
• 10-15% of lung cancers, about 25,000,
occur in never-smokers (e.g., Dana Reeves)
• Most of the never-smokers (2/3) are women

Therapy for Advanced Lung
Cancer
• Modest improvement in past 20 years
• Response rates to combination cytotoxic
chemotherapies about 20-25%
• Median survival 8-10 months
• Need for development of rationally designed
therapeutics, possibly targeting tumor
and tumor-associated cells
Schiller et al. 2007

As in the legend of William Tell,
it’s important to aim for the
right target…
estrogen
and growth
factor signaling
in lung tumors

Activated estrogen receptor-α is
present in NSCLC tumor specimens
N
Anti-phospho S167
S118
ER-alpha Serine phosphorylation
S167
Anti-phospho S118
A/B C D E F C
Estrogen receptor alpha: substrate for kinase signaling

Lung tumor microarray: aromatase and survival
Low Aromatase
High Aromatase
Survival probability in postmenopausal women with Stage
I/II NSCLC and tumor aromatase expression (P

Ongoing studies and trials of
biologic antitumor therapies in
lung cancer
• Antagonists of estrogen receptor
(fulvestrant)
• Inhibitors of aromatase, a protein
that synthesizes estrogen in tumors
(anastrazole, exemestane, grape
seed extract)

Another
critical target :
tumorassociated
angiogenesis
Avastin
Squalamine

SQUALAMINE
Blocks blood vessel
growth in tumors
Starves tumors
+
H N 3
+
N
H
2
+
N
H
2
C
H 3
H
H C 3
H3C OH
O
O
O
S O
CH 3
CH 3
• Natural steroid, now synthesized in laboratory
• Orphan drug designation by FDA

Squalamine blocks vascular
growth factor (VEGF)-induced
reorganization and growth of
tumor-associated endothelial cells
CON SQ VEGF VEGF + SQ
pFAK (Focal Adhesion Kinase) / F-actin (phalloidin)

Squalamine Blocks Growth of
Human Non-Small Cell Lung Tumor
Tumor Volume (cubic mm)
600
500
400
300
200
100
0
CONTROL
0 10 20 30 40 50 60 70
Treatment Days
SQUALAMINE
World Congress-Gynecologic Oncology, 2003

Phase I/IIA study of
squalamine in lung cancer
• Stage IIIB/IV chemo-naïve non-small cell lung cancer: squalamine (5day
CI) + paclitaxel (225 mg/m2) + carboplatin (AUC 6) Q 21 days
• 45 pts enrolled (18 phase I, 27 phase IIA)
• Little to no squalamine-related toxicity and no drug interactions
• 43 evaluable for response : 28% PR, 19% stable disease based on ITT
• Clinical benefit 47%
• Median survival = 10 months; 1-year survival = 40%
• 40% completed full 6-cycle regimen as planned
• More frequent dosing of squalamine showing improved RR in new
phase II trials underway

Antitumor Activity of Squalamine
CA-125 LEVEL
in Human Ovarian Cancer
4000
3000
2000
1000
0
0 50 100 150 200 250
Days after treatment
Phase II clinical trials in patients with advanced
platinum-refractory or-resistant malignancy
Proc. ASCO (2003)

Herbals from Traditional Chinese
Medicine (TCM) for Breast Cancer
• Centuries-long Tradition of Use and Experience
• Based on Written Texts and Documentation
• Some Conformity and Reproducibility in Practice
• Licensed Profession in Many States and in Wide
Use by Patients
• Of note, China has now launched a "Plan for
Modernization of Chinese Medicine". Natural
products from TCM will be investigated for
development of molecular target-guided therapies
and individualized treatments.

Preparation of Extracts from Chinese
Herbs for Preclinical Testing
More than 120 herbs
reported to have
breast selectivity in
TCM practice
Preparation of selected
herbal extracts (UCLA’s
CDSRB)
Campbell et al. (2002)

Herb Scutellaria blocks MAPK
activation by growth factors and
estrogen in breast cancer cells
CON GF GF/HE
Mitogen-activated Protein
kinase (MAPK)
Growth Factor (GF)
Scutellaria (HE)

Scutellaria Stops Breast Cancer Cell
Growth
100
Cell proliferation (% control)
90
80
70
60
50
40
30
20
10
MCF-7/HER-2
MCF-7 Parent
0
0 10 20 30 40 50 60 70 80 90 100
Herbal extract (mcg/ml)

Phase I clinical trial in patients with advanced
breast cancer to test Scutellaria barbata extract
Clinical trial recruited patients with advanced and heavily
pretreated breast cancer to evaluate BZL101, aqueous
extract from Scutellaria barbata
Rationale: BZL 101 induces apoptosis (cell death) in
human breast cancer cells in the laboratory
Results: BZL101 was found to be safe, with a favorable
toxicity profile (low-grade nausea, diarrhea, headache)
BZL101 showed evidence of clinical activity. Of 16
patients evaluable for response, 4 had stable disease >90
days (25%) and 3/16 had SD for >180 days (19%). Five
patients had tumor regression, but no CR or PR
Rugo H, Tripathy D et al. (2007). Breast Cancer Res Treat.

Sampling of Complementary Therapy Data
• Chen S et al. (2006) - Enrolling patients in a City of Hope Phase I trial to
assess efficacy of different concentrations of grape seed extract on
estrogen suppression in women at risk for breast cancer, as phytochemicals
(procyanidin B dimers) in grape seeds inhibit aromatase
• Seeram et al. (2006) - UCLA phase II clinical trial with pomegranate
extracts show reduced PSA in men after treatment for prostate cancer
• Neto (2007) - Evidence for protective effects of cranberries and blueberries
against cancer
• Sartippour et al. (2006) - Green tea extracts may enhance activity of
tamoxifen in ER+ breast cancer cells
• ASCO Meetings (2007) - Ginseng may reduce cancer fatigue; flaxseed
may slow growth prostate cancer
• ASCO Meetings (2007) - Modafinil, treatment for narcolepsy, may help
reduce symptoms of memory decline and fatigue after chemotherapy
• NCCAM Breast Cancer Trials (2007) - Pycnogenol for treatment of
lymphedema of the arm in breast cancer survivors
• See NCCAM and OCCAM websites for listings of ongoing clinical trials

Dietary influence on survival
after ovarian cancer
609 women with new diagnosis ovarian cancer
followed for 7 years after diagnosis and treatment
Those who ate most vegetables and vitamin E-rich
foods in year before diagnosis most likely to survive
5 years after diagnosis
Nutrients via supplements had less effect
Cruciferous vegetables (cabbage, cauliflower,
broccoli) had greatest benefit
Nagle et al. Int J Cancer 106 : 264, 2003

Vegetable Consumption Improves
Survival of Cancer Patients
High > 5.6
Med 3.9-5.6
Low < 3.9
Int. J. Cancer 106
: 264 (03)

Intensive lifestyle changes affect
progression of prostate cancer
Men with low-grade prostate cancer who chose not to have RT, surgery or
hormonal rx assigned to experimental (lifestyle changes) or control groups
RESULTS: No experimental pts, but 6 control pts required conventional
therapies due to increased PSA and/or disease progression on MRI.
PSA down 4%
in experimental;
up 6% in control
(p = 0.016).
Changes in PSA associate with degree of
change in diet & lifestyle (P=0.005)
Ornish D et al. (2005). J Urol. 174 : 1065

- Nutrition, lifestyle and colorectal cancer incidence: a
prospective investigation of 10,998 vegetarians and
non-vegetarians in the UK
In a cohort of 10,998 men and women, 95 incident cases of
colorectal cancer were recorded after 17 years. Risk increased in
association with smoking, alcohol, and white bread consumption,
and decreased with frequent consumption of fruit. The relative risk
in vegetarians compared with nonvegetarians was 0.85 (95% CI)
[see British Journal of Cancer, 2004]
-Western diet increases recurrence, mortality risk in
patients with colon cancer
In a prospective observational study of patients with stage III colon
cancer s/p adjuvant chemotherapy, patients were followed 5 years
and classified as prudent diet (high in fruits, vegetables, poultry,
fish) versus western diet (high in meat, fat, refined grain, desserts).
The western diet associated with higher risk for tumor recurrence
and reduced survival. [see Meyerhardt et al. JAMA, 2007]

The Cancer
Process
Influence of
food, nutrition,
obesity and
physical activity
on the cancer
process
(AICR/WCRF)

Body Fat linked to 6 types of cancers
AICR/WCRF recommendations to prevent cancer
Limit red meat and alcohol, avoid processed meats and maintain normal
range of body weight. Increased body fat, esp. in abdominal area, alters
hormones and growth factors that influence cancer development. Excess
fat linked to cancers of esophagus, pancreas, colon & rectum, kidney,
endometrium, and breast in postmenopausal women.
• Be physically active at least 30 min each day
• Avoid fast foods, sugary sodas, processed foods low in fiber/high in
fat, processed meats (hot dogs, bacon, ham)
• Eat more fruits and vegetables
• Limit red meat to 11-18 oz. per week; every additional 1.7 oz. per day
increases cancer risk by 15%
• Get necessary vitamins and minerals from nourishing foods rather
than dietary supplements
Report at www.dietandcancerreport.org
See, also: www.sciencereview.silentspring.org

US Dept. Agriculture data collected
from 1998-2002
- 28% Americans get only 2 servings of fruit per day
- 32% get 3 servings vegetables
- 90% do not get recommended daily intake of 5-a-Day
- 52% of overall vegetable consumption by Americans comes
from lettuce, potatoes, canned tomatoes – fast foods
- Studies of diet often contradictory due to bias of tainted
memory, diet effects early in life, genetic differences,
cooking variations (fat-soluble tomato lycopenes best enter
the bloodstream after cooking, while the water-soluble
glucosinolates in broccoli become anti-carcinogenic in the
body but are reduced by cooking

Check to see if you
are normal weight,
overweight, or
underweight?
BMI = wt (kg)/ht (m) 2
Person 1.7 m (~5’6”) tall
and 68 kg (~150 lb)
BMI = 23.5
Recent data suggest
increased waist-hip ratio
or waist circumference
may be better cancer
risk indicators (Larsson
et al. 2007)

Chemoprevention Initiatives
People eating 5 servings/day friuts & veggies have
1/2 risk of developing cancer of those who eat < 2
servings/ day
NCI identified 35 plant-based foods with cancerpreventive
activity : garlic, soybean, ginger, onion,
tumeric, tomatoe and cruciferous vegetables
NCI “Five-A-Day for Better Health” Program –
encourages eating fruits & veg 5 servings/day
European Prospective Investigation of Cancer &
Nutrition (EPIC) - enrolled 520,000 subjects to
identify dietary determinants of cancer

Micronutrients and
Phytochemicals
Antioxidant vitamins in dark, leafy green vegetables
and yellow/orange fruits and vegetables may reduce
cancer risk, especially the dietary ‘ACE’ vitamins
(caution : excessive amounts promote some cancer)
About 1,000 non-nutritive phytochemicals have
cancer-preventive activity, and more than 100
phytochemicals are in one serving of vegetables
More than 400 potential agents now under study,
and NCI sponsored more than 70 Phase I-III trials
last year

Recommendations
Maintain a HEALTHY BODY WEIGHT
DO NOT SMOKE
Obtain most your nutrients and phytochemicals from foods
rather than supplements
Eat in moderation from a variety of food groups, especially
fruits and vegetables (>5 per day)
Favor dishes with multi-plant based ingredients: salads,
soups; add leafy greens to sandwiches
Most food additives now come from China, the world’s major
supplier of food flavorings, preservatives and vitamins ($2.5
billion exports in 2006). Buy with caution as China has limited
oversight of manufacturing, and toxic pesticide residues may
remain in many products.

The Promise of New
Antitumor Products
Valuable plants and
natural products may be
lost before their medical
use can be discovered

Deforestation and the loss of species

Threatened Species in 2006
Group Number known Threatened
Mammal 4,842 1,130
Fish 28,100 750
Molluscs 70,000 967
Plants 287,655 6,774
Harvard biologist E. O. Wilson recently estimated
that scientists have discovered only about 10% of all
the species of life that currently exist on the earth

“Silent Spring” in the Los Angeles Basin
Agri-chemicals
Agri chemicals
Pesticides
Organophosphates
MTBE
PCBs Asbestos
Mercury
DDT
Dioxin
Chromium 6
SMOG

A Toxic Landscape
Dozens of toxic chemicals are found indoors in American homes
Study of 120 residential homes in Massachusetts showed 67
carcinogenic chemicals in nail polish, hair-spray, some detergents,
household cleaners, pesticides
DDT, banned in US 30 years ago, was found in dust of 65% of homes
Human exposure to DDT was assessed in blood collected from 1959-
1967 from 129 women who gave birth. Women in the top 1/3 of blood
DDT levels were 5-times as likely to get breast cancer as women with
the lowest DDT levels
In California, 36 million lbs of 7 different fumigants were used on farms
in 2005. Fumigants, with some suspected to be carcinogens, used on
grape, strawberry, almond, carrot, lettuce, potato crops
Environmental Science & Technol, 2003
Environmental Health Perspectives, 2007

216 common chemicals linked to breast cancer
People are exposed to many of the following inductrial solvents, dyes,
pesticides, gasoline and diesel exhaust, cosmetic ingredients, and
hormone-like agents :
1,4-dioxane (detergents, soaps)
1,3-butadiene (vehicle exhaust)
acrylamide (fried foods)
benzene (vehicle exhaust)
perfluorooctanoic acid (Teflon)
styrene (carpets, adhesives)
vinyl chloride (vinyl)
toluene diisocyanate (furnishings, bedding)
polychlorinated biphenyls , PCB’s (electrical transformers)
Atrazine (herbicide)
Bisphenol A (polycarbonate plastic in baby bottles, food packaging,
juice and ketchup bottles, dental sealants)(recycling symbol 7)
Cancer, 2007

Support Cancer Research :
It Saves Lives
National Cancer Institute budget proposed for 2008:
~$5.5 billion (0.2% of federal spending)
US Congress agreed to an increase of 2.67% above
2007 levels for the 2008 National Cancer Institute
budget, but the President issued a veto of the bill
because he objected to increased funding
California Cancer Research Program budget for 2008:
$ 0 (applications closed)

Health and cancer care for all?
• War on cancer may be undone by lack of adequate insurance for
Americans. Some are unemployed; others receive no benefits from
employers, can’t afford costly premiums or are uninsurable due to
existing conditions. In 2006, 47 million Americans were uninsured and
millions more are under-insured (American Cancer Society)
• Failings of our health system may contribute to cancer suffering and
death. In 2006, 1/3 of patients diagnosed with cancer were financially
distressed, and 100,000 went bankrupt due to cancer care expenses.
• Of women with breast cancer, proportion with advanced-stage cancer
at diagnosis was 8% for privately-insured and 18% for uninsured.
Those with no or limited insurance less likely to obtain preventive
services and seek timely medical care (Halpern et al. Cancer 2007)
• Patients who miss prescribed drug doses have increased risk of death
• In spite of major advances in cancer prevention and treatment, it is not
enough if people cannot get access to the care that they need to fight
cancer (see cancer.org)

Acknowledgements
• Stiles Fund JCCC/UCLA
Dr. Michael Tobias Diana Marquez
Jane Morrison Hsiao-Wang Chen
Cary Freeny
• California BCRP Rebecca Rausch
• National Cancer Institute David Heber
• National Lung Cancer Steve Dubinett
Partnership Judith Gasson
• DOD Ovarian Cancer Lonnie Zeltzer
Research Program Dennis Slamon

END of presentation