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Breast and other Hormonal Cancers and the Environment:the case for environmental oncology

Devra Davis, Ph.D., M.P.H.

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Fewer than 1 in 10 cases of breast cancer arises in women born with genetic defects

Fewer than 1 in 10 cases of breast cancer arises in women born with genetic defects

National Cancer InstituteNational Cancer Institute

Reasons why “environment” is a cause of cancer

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Reasons why “environment” is acause of cancerReasons why “environment” is acause of cancer� Cancer risk of adopted children mirrors

that of their adopted (NOT their biologic) parents

� Fewer than half of identical twins get the same cancer

� Workers have higher rates� Patterns remain explained

� Cancer risk of adopted children mirrors that of their adopted (NOT their biologic) parents

� Fewer than half of identical twins get the same cancer

� Workers have higher rates� Patterns remain explained

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Reasons why “environment” is acause of cancerReasons why “environment” is acause of cancer

� Migrants’ cancer risk changes to that oftheir new country

� The majority of cases have no known risk factors

� Women with higher residues of toxins in their blood have more aggressive disease

� Migrants’ cancer risk changes to that oftheir new country

� The majority of cases have no known risk factors

� Women with higher residues of toxins in their blood have more aggressive disease

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Unexplained patterns of breast cancer in women with BRCA 1 (M.C.King, 2003)

Unexplained patterns of breast cancer in women with BRCA 1 (M.C.King, 2003)

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Cumulative Risk of Breast Cancer in BRCA1 carriers born before or after 1940 (M. King, 2003)

Cumulative Risk of Breast Cancer in BRCA1 carriers born before or after 1940 (M. King, 2003)

0102030405060708090

30 40 50 60 70 80

<1940>1940

Cancer risk by age

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Change in U.S. Breast CancerIncidence 1975-79, 1990-94Change in U.S. Breast CancerIncidence 1975-79, 1990-94

500

400

300

200

100

040 50 60 70 80

Age (years)

Inci

denc

e pe

r 10

0,00

0

White 1990-941985-89

1980-84

1975-79

500

400

300

200

100

040 50 60 70 80

Age (years)

Black

1990-941985-89

1980-84

1975-79

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Risk factors are characteristics or experiences shared by those with the disease compared to those without it

Risk factors are characteristics or experiences shared by those with the disease compared to those without it

Risk Factors for Breast CancerRisk Factors for Breast Cancer

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FamilyHISTORYFamilyHISTORY

EARLYMENSESEARLYMENSES

LATEMENOPAUSE

LATEMENOPAUSE

RADIATIONRADIATION

LACK OFEXERCISE/obesity

LACK OFEXERCISE/obesity

Personal Risk Factors for Breast CancerPersonal Risk Factors for Breast Cancer

ALCOHOL

LATE OR NO PREGNANCY

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Higher Total Lifetime Exposure to

Unbound Hormones

�Is the Common Link Between

Most Known Risk Factors

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SolventsSolvents

PlasticsPlasticsMetalsMetals

Environmental Risks for Breast Cancer

Environmental Risks for Breast Cancer

PesticidesPesticides

Paints

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Figuring Out the Causes of CancerFiguring Out the Causes of Cancer� Means looking at all

evidence� Understanding limits of

study designs– Toxicology provides

controlled experiments– Human studies are

usually ‘natural’ experiments

� Means looking at all evidence

� Understanding limits of study designs– Toxicology provides

controlled experiments– Human studies are

usually ‘natural’ experiments

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Toxicology

Available Evidence for Understanding Causes of CancerAvailable Evidence for Understanding Causes of Cancer

Wildlife &Case Studies

HumanStudies

Human studies cannot always be conducted. Models and measurements of exposure along with toxicology & case studies fill knowledge gaps.

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Criteria for identifying causes of cancer Criteria for identifying causes of cancer

1. Strength of association

2. Consistency

3. Specificity

4. Temporality

5. Biologicalgradient

1. Strength of association

2. Consistency

3. Specificity

4. Temporality

5. Biologicalgradient

6. Biologicalplausibility

7. Coherence

8. Experiment

9. Analogy

6. Biologicalplausibility

7. Coherence

8. Experiment

9. Analogy

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Toxicologic Evidence on Causes of CancerToxicologic Evidence on Causes of Cancer

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Animal Carcinogens Cause Cancer in humans Animal Carcinogens Cause Cancer in humans

� Every compound known to cause cancer in humans

� Also causes it in animals, when adequately studied.

� Therefore any animal carcinogen should betreated as a human carcinogen*

� *IBM Think Magazine, 1983

� Every compound known to cause cancer in humans

� Also causes it in animals, when adequately studied.

� Therefore any animal carcinogen should betreated as a human carcinogen*

� *IBM Think Magazine, 1983

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Causes of Breast Cancer can be hormonal or geneticCauses of Breast Cancer can be hormonal or genetic

� Hormonal causes can distort hormones and influence breast cell growth

� Genetic causes can damage DNA – Diminish repair– Promote deranged growth

� Hormonal causes can distort hormones and influence breast cell growth

� Genetic causes can damage DNA – Diminish repair– Promote deranged growth

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Breast cancer biologyClavicle

RibsPectoralis (chest) muscle

Breast tissue:LobulesDucatConnective tissue

FATDuct openingNipple

Sebaceous gland

Inframammary fold

Dr. Susan Love’s Breast Book

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Cancer can arise through either/ or both hormonal/ genetic damageCancer can arise through either/ or both hormonal/ genetic damage

Hormones

Cancer

DNA

Bisphenol A

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Bisphenol A damages chromosomes*Bisphenol A damages chromosomes*

Normal

Damaged

*red=chromosomesCREDIT: P. A. HUNT ET AL., CURRENT BIOLOGY 13, 546 (2003)

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Bisphenol A distorts HormonesBisphenol A distorts Hormones

Bisphenol A Is Released from Used Polycarbonate Animal Cages into Water at Room TemperatureHowdeshell et al., Environmental Health Perspectives Volume 111, Number 9, July 2003

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Stages of tumor developmentStages of tumor development

do not depend on whether or not tumors first arose from hormones

or from genetic damage

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Some cancer-causing exposures in animal toxicology studiesSome cancer-causing exposures in animal toxicology studies� Benzene**� Formaldehyde� Isopropyl

alcohol/acetaldehyde� Freon� Epichlorohydrin/BPA� Toluene/xylene/acetone

(benzene contaminant)

� Benzene**� Formaldehyde� Isopropyl

alcohol/acetaldehyde� Freon� Epichlorohydrin/BPA� Toluene/xylene/acetone

(benzene contaminant)

� **mammarycarcinogen

� **mammarycarcinogen

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Some hormone distortingexposures from animal toxicology studies

Some hormone distortingexposures from animal toxicology studies� Bisphenol A (1936)

� Benzene**

� Isopropyl?alcohol/acetaldehyde

� Freon/nitromethane

stabilizer

� Bisphenol A (1936)

� Benzene**

� Isopropyl?alcohol/acetaldehyde

� Freon/nitromethane

stabilizer

� Mixed organic solvents?

� Mixed organic solvents?

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Unlocking breast cancer“Bad” estrogens

‘unbound’“Good” estrogens

‘bound’

AntioxidantsReductants

Less CellProliferation

EstrogenReceptors

Cancer

DNA

RepairDamage

26Source: Cunningham, Klopmanand Rosencranz, 1997.

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Human EvidenceHuman Evidence

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Epidemiologic Studies: Breast Cancer Risks from workplace studies

Epidemiologic Studies: Breast Cancer Risks from workplace studies

Chem.workers 15+yearsNo lagAll solvent workers*

1.84 (1.15-2.95)

1.59 (1.13-2.24)

1.3 (1.1-1.4)

8,767 cases & controls

Hansen, 1999

Danishworkers

DoctorsBenzeneworkers

14.7(5.9-30.3)

1.3 (1.1-1.8)

All Br CA cases in Shanghai 1980-84

Petralia,1998

Formaldehyde

Styrene

Org. solvents

1.19 (1.1-1.3)

1.19(.9-1.6)

1.10 (1.0-1.2)

29,397 cases white women

102,955controls

Cantor, 1995 24 U.S. states death records

1984-89

*aromatic solvents, BTX

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Epidemiologic Studies: Breast Cancer Risks from WorkplaceStudies

Epidemiologic Studies: Breast Cancer Risks from WorkplaceStudies

Freon

Isopropylalcohol

Solder flux

Lifetable/TG

309 (113-675)312 (125-643)

310(113-675)

14,457Utahns 9400men

3138 women retrospective

Spirtas,1991

methylenechloride and other organic solvents

SMR 204

Coiling/wire

1,044 women

826 men

Canadians

Shannon,1988

*xylene, toluene

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Acute effects of toxins imply chronic effectsAcute effects of toxins imply chronic effects

toluenefluorocarbons

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Acute effects of toxins imply chronic effectsAcute effects of toxins imply chronic effects

toluenemethanol

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Jobs with increased risk of breast cancerJobs with increased risk of breast cancer� Solvent workers � Chemists� Nurses/Dentistsand Physicians� Painters� Hair Dressers

� Solvent workers � Chemists� Nurses/Dentistsand Physicians� Painters� Hair Dressers

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Household exposures to breast carcinogens in the urban environment

Household exposures to breast carcinogens in the urban environment� Benzo-a-pyrene is

higher in house dust than soil

� Smaller particles are more toxic and tracked in preferentially

� Smaller particles have more surface area relative to their weight

� Benzo-a-pyrene ishigher in house dust than soil

� Smaller particles are more toxic and tracked in preferentially

� Smaller particles have more surface area relative to their weight

John Roberts, Master Home Environmentalist

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Studying Humans Is DifficultStudying Humans Is Difficult

� People seldom know what they have been exposed to, especially early in life

� Both good and bad xenoestrogens exist

� Studying current levels or recent residues in cancer patients can be misleading — diseasedevelopment affects storage of toxic compounds

� People seldom know what they have been exposed to, especially early in life

� Both good and bad xenoestrogens exist

� Studying current levels or recent residues in cancer patients can be misleading — diseasedevelopment affects storage of toxic compounds

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Problems of Power in EpiStudiesProblems of Power in EpiStudies

� Easier to find big risks in large populations than in smaller ones

� Harder to find differences between groups for common diseases like breast cancer

� The absence of evidence is not evidence of an absence of an effect

� Statistical significance is not the same as public health importance

� Easier to find big risks in large populations than in smaller ones

� Harder to find differences between groups for common diseases like breast cancer

� The absence of evidence is not evidence of an absence of an effect

� Statistical significance is not the same as public health importance

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Of 75,000 chemicals in widespread use only 1500 have been tested for carcinogenicity…..

Of 75,000 chemicals in widespread use only 1500 have been tested for carcinogenicity…..

National Academy of Sciences, 1983, 1999

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Woman about to smash a cathode ray tube from a computer monitor in order to remove the copper laden yoke at the end of the funnel. The glass is laden with lead but the biggest hazard from this is the inhalation of the highly toxic phosphor dust coating inside. The groundwater in Guiyu iscompletely contaminated to the point where fresh water is trucked in constantly for drinking purposes. Guiyu,China. December 2001. Copyright Basel Action Network.

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Man sweeping toner out of printer cartridge. Toners are made of carbonblack -- a class 2A probable carcinogen (IARC). The toner billows in hisface all day long without respiratory protection of any kind. Cartridges are later dumped by the river. Guiyu, China. December 2001. Copyright Basel Action Network.

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Migrant child from Hunan province sits atop one of countless piles of unrecyclable computer waste imported from around the world. Guiyu,China. December 2001. Copyright Basel Action Network.

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Just some of the many labels found on computers and monitors which indicated to investigators where each load of computersoriginated. Guiyu,China. December 2001.Copyright Basel Action Network.

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We must act on facts, and on the most accurate interpretation of them, using the best scientific information.

This does not mean we must wait for certainty

We must act on facts, and on the most accurate interpretation of them, using the best scientific information.

This does not mean we must wait for certainty

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San Francisco, Precautionary Principle Legislation, 2003San Francisco, Precautionary Principle Legislation, 2003

� Public has a right to know

� Government has a duty to assess publicly the full environmental and economic costs of alternative policies– Safe purchasing/shopping

– Assessing alternatives openly

– Evaluating policies and outcomes regularly based on developing science

� Public has a right to know

� Government has a duty to assess publicly the full environmental and economic costs of alternative policies– Safe purchasing/shopping

– Assessing alternatives openly

– Evaluating policies and outcomes regularly based on developing science

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Changing the Burden of ProofChanging the Burden of Proof� “We have become the

bodies of evidence” —Nancy Evans

� People should not be treated like laboratory rats

� How much proof do we need?

� “We have become the bodies of evidence” —Nancy Evans

� People should not be treated like laboratory rats

� How much proof do we need?

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Environment is one piece of the health puzzle that can best

be changed by social policy

Environment is one piece of the health puzzle that can best

be changed by social policy

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Time for GirlcottsTime for Girlcotts� Boycott means “NO”

� Girlcott means “YES”– Using purchasing

power to create markets for cleaner, greener, safer, and healthier products

� Boycott means “NO”

� Girlcott means “YES”– Using purchasing

power to create markets for cleaner, greener, safer, and healthier products

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whensmokeranlikewater.comcheforhealth.orgorcouncil.orgnottoopretty.orgnoharm.orghealthytomorrow.orgtoxicsaction.orgalaw.orgourstolenfuture.orgwatoxics.org