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Breast Cancer and Environmental Chemicals: Why is there Concern


Why is there a concern about environmental links to breast cancer risk? ... Breast cancer risk is higher in women who worked the 'grave yard' shift for many ... – PowerPoint PPT presentation

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Title: Breast Cancer and Environmental Chemicals: Why is there Concern

Breast Cancer and Environmental Chemicals Why
is there Concern?
  • Suzanne Snedeker, Ph.D.
  • Associate Director of Translational Research
  • Cornell University Sprecher Institute for
  • Comparative Cancer Research
  • Program on Breast Cancer and Environmental
    Factors (BCERF)
  • http//

Lesson Outline
  • Why is there a concern about environmental links
    to breast cancer risk?
  • Which chemicals in the workplace and home are
    associated with increased risks of breast cancer?
  • What do we know about pesticides and breast
    cancer risk?
  • What can we learn from animal cancer bioassays?
  • What is known about endocrine disrupting
  • What are the challenges do we face in evaluating
    linkages between environmental chemicals and
    cancer risk?

How does cancer occur?
Initiated cell
Invasive Tumor
Risks Related to Breast Cancer
Close Relative
Advancing Age
Age at First Birth
Early Menarche
Passive Smoke
Late Menopause
Lack of Exercise
Chemicals -Work -Home -Garden -Recreation
Ionizing Radiation
Hormone Replacement Therapy
Benign Breast Disease
Exposure to Hormones
Late Menopause
Some Chemicals -Work -Home -Garden
Lack of Exercise
Breast cancer rates worldwide
Environmental links to breast cancer
Scandinavian Twins Study
  • Contribution of inherited vs. environmental
    factors to breast cancer risk
  • Inherited factors, 27 of risk
  • Environmental factors, 73 of risk
  • Suggests environmental factors play a
  • major role in determining breast cancer risk
  • Ref Lichtenstein et al., N. Engl. J. Med.,
    34378-85, 2000

How are we exposed to environmental
  • Routes of exposure
  • Air we breath
  • Food we eat beverages we drink
  • Contact with our skin
  • Contact with eyes
  • Some chemicals cross the placenta
  • Some can appear in breast milk

Exposure to environmental chemicals
  • Each chemical is unique
  • Some can be stored in body fat
  • Others quickly eliminated
  • Some need to activated by the body
  • Others are quickly detoxified
  • Some pose no cancer risk
  • Some are potent carcinogens
  • Others may be hormone mimics and support breast
    tumor growth
  • Some may act as anti-cancer agents

Chemicals in the workplace problems with many
  • Few high quality cancer studies of women in the
  • Many studies very small
  • Follow-up time often too short
  • Records of actual exposures often lacking
  • Methods for estimating exposures often crude
  • Frequently have exposures to multiple chemicals

Chemicals in the workplace what do we know?
  • Some evidence of higher breast cancer risk
  • Acid mists
  • Benzene
  • Carbon tetrachloride
  • Ethylene Oxide
  • Formaldehyde
  • Lead oxide
  • Methylene chloride
  • Styrene

Refs Blair and Kazerouni, Cancer Causes
Control, 8473-490, 1997 Cantor et al., J.
Occup. Environ. Med., 37336-348, 1995 Goldberg
and Labreche, Occup. Environ. Med., 53145-156,
1996 Hansen, Am. J. Ind. Med., 3643-47,
1999 Norman et al., Int. J. Epidemiology,
24276-284, 1995 Spiritas et al., Br. J. Ind.
Med., 48515-530, 1991
Chemicals in the workplace -light at night
  • Light at night
  • May disrupt the synthesis of the hormone
  • Changes in melatonin may affect levels of
  • Breast cancer risk is higher in women who worked
    the grave yard shift for many years
  • Refs Steven and Rea, Cancer Causes Control,
    12279-287, 2001
  • Davis et al., JNCI, 9315571562, 2001
  • Hansen et al., Epidemiology, 1274-77, 2001
  • Schernhammer et al, JNCI, 931563-1568, 2001

Chemicals in the workplace what do we need to
  • Workers that need further evaluation
  • Chemical manufacturing workers
  • Pharmaceutical industry workers
  • Laboratory and biomedical workers
  • Cosmetologists and hairdressers
  • Printers and dye workers
  • Health care workers
  • Metal plate workers
  • Airline personnel

Chemicals in the home what are we exposed to?
  • Cape Cod Breast Study
  • Silent Spring Institute
  • Measured household exposures to 89 hormone-like
    and cancer-causing chemicals in air and dust
    samples of 120 Cape Cod homes
  • Chemicals identified included plasticizers,
    disinfectants, certain flame retardants,
    persistent organochlorine pesticides and
    contemporary (permethrin) pesticides
  • Exposure is one step in the risk assessment
  • Results will help prioritize chemicals that
    should be studied further
  • Refs Rudel et al., J. Air Waste Manage.
    Assoc. 51499-513, 2001
  • Rudel et al., Environ. Science and
    Technol., 374543-53, 2003

Pesticides and cancer risk exposure concerns
U.S. Conventional Pesticide Use historical
Ref Aspelin and Grub, Pesticide industry sales
and usage, 1996 and 1997 market estimates, Figure
10.b, US EPA, November 1999.
Pesticides and cancer risk why is there concern?
  • Higher cancer risk in male farmers
  • Lip
  • Skin
  • Stomach
  • Brain
  • Lymphoma
  • Prostate
  • Ref Blair and Zahm, Environ. Health Perspect.
    103 (Suppl 8)205-208, 1995

Pesticides and cancer risk cancer risks on the
  • Environmental exposures on the farm
  • Sunlight / UV radiation
  • Nitrates
  • Pesticides
  • Solvents
  • Fuel exhaust
  • Mycotoxins (toxins formed by mold on crops some
    are cancer-causing)

Pesticides and cancer risk cancer risks on the
  • Agricultural Health Study
  • Evaluating health effects of agricultural
    chemicals in a 10 year, prospective study
  • 55,300 men and 30,000 women
  • Cancer risks
  • Prostate cancer risk elevated 14 in male
    pesticide applicators
  • http//
  • Ref Alavanja et al., Am. J. Epidemiology, vol.
    157, pp. 800-814, 2003

Breast cancer risk of farm women
  • Few studies on cancer risks of farm women most
    studies on men
  • North Carolina Study
  • Overall, breast cancer rates lower in women
    living on or near farms
  • In farm women who applied pesticides, breast
    cancer risk 2X higher if protective clothing or
    gloves not worn
  • Reducing exposure reduces risk
  • Ref Duell et al., Epidemiology, 11523-531, 2000

Pesticides and breast cancer risk
-organochlorine (OC) pesticides
  • DDT and DDE
  • Early descriptive studies suggested a positive
    association between blood or adipose tissue DDE
    levels and breast cancer risk
  • Over 20 of the recent, well controlled,
    large-scale studies have not shown that levels of
    DDT or DDE predict breast cancer risk in North
    American or European white women

Pesticides and breast cancer risk DDT/DDE
possible explanations
  • Exposure Issues - Chemical form matters
  • Predominant exposure in western white women
  • Was not to estrogenic form that was sprayed
  • But to very weak estrogenic form (p,p-DDE) in
  • Heavily exposed populations less studied
  • Few studies of breast cancer risk in countries
    that currently use DDT (estrogenic form) for
    malaria control
  • Critical windows of exposure
  • Little information on whether exposure to DDT
    during early breast development affects breast
    cancer risk
  • Ref Snedeker, Environ. Health Perspect., 109
    (suppl 1) 3547, 2001

Chemicals and breast cancer risk laboratory
animal studies
  • Why use laboratory animal studies?
  • Human studies have the most weight when
    evaluating cancer risk
  • For most chemicals we have no information on
    human exposures and later cancer risk
  • Use controlled animal laboratory studies to
  • Identify the hazard
  • Estimate cancer risks to humans
  • National Toxicology Program Animal
    cancer bioassays
  • Of 509 chemicals tested, 42 (8) cause mammary
    (breast) tumors in laboratory animals

Chemicals and breast cancer risk National
Toxicology Program
  • Types of compounds that cause mammary (breast)
    tumors in laboratory animals
  • Organic solvents
  • Dyes and dye intermediates
  • Chemicals used in manufacture of rubber,
    neoprene, vinyl and polyurethane foams
  • Flame retardants
  • Food additive
  • Gasoline additives / lead scavengers
  • Metals use in microelectronics
  • Medical instrument sterilizing agent
  • Mycotoxin (toxin produced by a type of mold)
  • Pesticides and fumigants
  • Pharmaceuticals
  • Rocket fuel

Refs Dunnick et al., Carcinogenesis, 16173-170,
1995 Bennett and Davis, Environ. Mol. Mutagen.
39150-157, 2002
EnviroChem and Cancer Database
  • On-line Information on 42 chemicals that cause
    mammary gland tumors in laboratory animals in NTP
  • Searchable by chemical name, CAS , or major use
  • http//
  • Includes information on the chemicals
  • Major uses
  • Cancer classification
  • Whether the chemical is currently produced
  • If / when it was taken off the market
  • Use in manufacturing processes
  • Consumer products
  • Exposures of concern
  • Overview of workplace regulations and advisories
    by OSHA

Endocrine disrupting chemicals (Hormonally
Active Agents)
  • We know that many hormones and local growth
    factors play a role both in normal breast growth
    and in the cancer process
  • Hormones (chemical messengers)
  • Estrogen
  • Progesterone
  • Prolactin
  • Growth Hormone
  • Growth Factors (local chemical messengers)
  • Epidermal Growth Factor family
  • Insulin Growth Factor (IGFs)

Endocrine disrupting chemicals Whats the
  • What we know
  • Pharmaceuticals that act like estrogen or
    estrogen / progesterone (E P) can increase
    breast cancer risk
  • Diethylstilbestrol
  • Prescribed to 5 to10 million women
  • In mothers - moderate increase in BC risk
  • In daughters - data not in yet
  • E P post-menopausal hormone therapy
  • Risk increases with duration of use
  • Small risk (8 cases per 10,000), but widely
  • May increase risk of more aggressive tumors

http// http//
Endocrine disrupting chemicals -(hormonally
active agents)
  • Hormonally active agents
  • may affect breast cancer risk by
  • Affecting the delicate balance that controls cell
  • Supporting the growth of a hormone-dependent
    breast tumor
  • The Concern
  • Do low levels of environmental chemicals that act
    like hormones or disrupt hormone pathways affect
    breast cancer risk?

Endocrine Disrupting Chemicals Need to know more
  • Polybrominated diphenyl ethers (PBDEs)
  • Flame retardant
  • Used in plastics, textiles, carpets, furniture
  • Detected in marine life and human breast milk
  • Can stimulate breast tumors cells to grow in the
  • Plasticizers
  • Nonyl phenol, bisphenol A - estrogenic
  • Phthalates - some may cause premature breast
    development in children (studies from Puerto
  • Heavy Metals
  • Cadmium and arsenite - environmental estrogens
  • Pesticides

Endocrine disrupting chemicals How can we
screen chemicals?
  • 1996 Food Quality Protection Act
  • Mandates testing of ALL pesticide active
    ingredients for endocrine disrupting effects
  • EPA is currently validating screening tests and
    prioritizing chemicals to be screened
  • Ref. http//

Early exposures to chemicals can they affect
breast cancer risk?
  • Terminal end buds (TEBs)
  • Target for cancer-causing chemicals

Genes influence response to environmental
  • Gene-environmental interactions
  • Many chemicals need to be activated to become
    cancer-causing agents
  • Certain genes control important enzymes involved
    in activation pathways
  • Variations in these genes can affect the
    activation pathway
  • This affects the level of cancer-causing chemical

  • Complexity of the disease
  • Many risk factors involved
  • Complex biology of breast tumors
  • Takes long time for breast tumors to develop
  • Exposure issues
  • Difficult to measure low-level exposures to
    multiple chemicals from the distant past
  • Few chemicals have validated biomarkers
  • Levels of exposure to chemicals at critical
    periods of breast development (in utero through
    puberty) is lacking
  • Exposures to many chemicals in the home and
    workplace are not well characterized

BCERF on the web
  • http//
  • Fact Sheets and Tip Sheets
  • Critical Evaluations of chemicals
  • A Place For Women site
  • Newsletters and News You Can Use
  • Bibliographies on environmental factors
  • Cancer Maps
  • Endocrine Disrupting Chemical Information
  • Companion Animal Tumor Registry