New Exposure Biomarkers as Tools for Breast Cancer Epidemiology, Biomonitoring, and Prevention: A Systematic Approach Based on Animal Evidence

Table 2. Priority chemicals for breast cancer–relevant epidemiology and biomonitoring.
Chemical Common exposure sources Biomarkers
Abbreviations: BaP, benzo[a]pyrene; LC-MS/MS, liquid chromatography–tandem mass spectrometry; PFOA, perfluorooctanoic acid; sPMA, S-phenylmercapturic acid; TDA, 2,4-toluene diamine; TDI, toluene diisocyanates; ttMA, trans, trans-muconic acid. For more information, including a list of chemicals in each group, see Supplemental Material, Table S1.
1,3-Butadiene Gasoline, vehicle exhaust, tobacco smoke, heating of some cooking oils DNA and hemoglobin adducts in blood, derived from epoxide metabolites; mercapturic acid metabolites in urine
Acrylamide Cooked food, tobacco smoke, water-treatment by-products, some consumer products Hemoglobin adducts of acrylamide and glycidamide in blood; urinary mercapturic acid metabolites of acrylamide and glycidamide
Aromatic amines I: TDA and TDIs Uncured or newly finished polyurethane foam, spray-in insulation, sealants and coatings, some breast implants

TDA and hemoglobin adducts in blood, TDA in urine

(Most studies have tested occupationally exposed populations, but many find TDA in “unexposed” controls)

Aromatic amines II: benzidine and aniline dyes, combustion products, other Hair and textile dyes; used in the production of paints, printing inks, liquid crystal displays, and inkjet and laser printers, and in the food industry Parent compound in blood or urine; DNA and hemoglobin adducts in blood or breast milk
Benzene Gasoline, vehicle exhaust, tobacco smoke, solvents DNA and protein adducts in blood and dried blood spots; urinary metabolites sPMA (specific to benzene) and ttMA (metabolite of benzene and the common food preservative sorbate)
Halogenated organic solvents (e.g., methylene chloride)

Dry cleaning, spot remover, glues, degreasers, paint strippers, aerosol propellants, contaminated drinking water

(Use is decreasing over time)

Parent compound in whole blood and urine

Infrequently detected in blood from general population but widespread occupational exposure has been documented; parent compounds have been detected in urine from occupationally exposed populations, and methylene chloride has been detected in urine from general population

Ethylene oxide, propylene oxide Tobacco smoke, food and medical sterilization, vehicle exhaust, paint DNA and hemoglobin adducts in blood; mercapturic acid metabolites in urine
Flame retardants and degradation products [2,2-bis(bromomethyl)-1,3-propanediol, 2,3-dibromo-1-propanol] Flame retardants; primarily used in plastics and foams Parent compound or metabolite in urine
Heterocyclic amines Grilled meat Parent compound, protein adducts, and DNA adducts in blood; parent compound in urine and hair
Hormones and endocrine disruptors (e.g., endogenous and exogenous estrogens and estrogen mimics) Pharmaceutical hormones, consumer products, and commercial chemicals with hormonal activity Clinical and research methods are available to measure endogenous hormone levels in blood and urine; the MCF-7 cell proliferation assay has been used to measure estrogenic activity in extracts of adipose tissue from breast cancer cases and controls; development of methods to conduct this assay in blood, and to distinguish endogenous and exogenous estrogen signals, would allow integrated assessments of exposure to xenoestrogens
MX Water disinfection Urinary trihaloacetic acids are used as exposure biomarkers for chlorinated drinking water, but improved exposure biomarkers are needed for MX and other highly genotoxic disinfection by-products
Nitro-PAHs (e.g., 1-nitropyrene) Diesel exhaust Hemoglobin adducts in blood, metabolites in urine
Ochratoxin A Mycotoxin in grains, nuts, pork; also present in moldy environments Ochratoxin A and its metabolites in blood, urine, breast milk
PAHs (e.g., BaP) Vehicle exhaust, tobacco smoke, charred food

Protein adducts and DNA adducts in blood; oxidized metabolites in urine; parent compounds measured in hair, breast milk

(Improved exposure biomarkers are needed)

PFOA, related compounds Grease-, water-, and stainproof coatings; contaminated drinking water Parent compound in blood and breast milk
Pharmaceuticals (non­hormonal) A number of over-the-counter, veterinary, and prescription medicines that induce mammary tumors Few exposure biomarkers have been developed for use in the general population, but in many cases LC-MS/MS methods have been reported for the parent compound in plasma or metabolites in urine; in some cases exposure can be ascertained from self-report or medical records
Styrene Building materials and consumer products made from polystyrene; indoor air, cigarette smoke, polystyrene food packaging Parent compound in whole blood; urinary mercapturic and mandelic acid metabolites