Cancer Causes & Control

, Volume 15, Issue 6, pp 591–600 | Cite as

Breast Cancer Risk and the Combined Effect of Environmental Estrogens

  • jesús m. ibarluzea
  • Mariana F. Fernández
  • Loreto Santa-Marina
  • Maria F. Olea-Serrano
  • Ana M. Rivas
  • Juan J. Aurrekoetxea
  • José Expósito
  • Miguel Lorenzo
  • Pablo Torné
  • Mercedes Villalobos
  • Vicente Pedraza
  • Annie J. Sasco
  • Nicolas Olea


Objective: The present study aimed to determine whether the combined effects of environmental estrogens measured as the total effective xenoestrogen burden (TEXB-alpha) are a risk factor for breast cancer over and above the risk potentially linked to specific pesticides.

Methods: We measured the levels of 16 organochlorine pesticides as well as TEXB in adipose tissue of 198 women at the time of breast cancer diagnosis. These were compared with findings in 260 age and hospital matched control women without breast cancer.

Results: The median levels of p,p′-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), aldrin, endosulfan ether and lindane (the pesticides detected in >40% of the study population) were higher in cases than controls, although the differences did not reach statistical significance. After adjusting for potential confounders, the odds ratio (OR) for breast cancer in women with detectable levels of aldrin was 1.55 (95% confidence interval (CI) 1.00–2.40). Among the postmenopausal women, the OR for aldrin and lindane was 1.84 (95% CI 1.06–3.18) and 1.76 (95% CI 1.04–2.98), respectively. Among cases with body mass index (BMI) below the median (28.6 kg/m2), the OR was 3.42 (95% CI 1.22–9.58) for women in the highest quartile of TEXB-alpha versus those in the lowest. The subgroup of leaner postmenopausal women showed an increased risk (OR: 5.67; 95% CI 1.59–20.21) for those in the highest tertile versus those in the lowest.

Conclusions: We found an increased risk for breast cancer in the leaner women, especially in the leaner postmenopausal subgroup, related to the TEXB-alpha. The pesticides aldrin and lindane are also individually associated with risk.

breast cancer environmental estrogens epidemiology organochlorine pesticides risk factors 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Wassermann M, Nogueira DP, Tomatis L, et al. (1976) Organochlorine compounds in neoplastic and adjacent apparently normal breast tissue. Bull Environ Contam Toxicol 15}: 478–484.Google Scholar
  2. 2.
    Unger M, Olsen J (1980) Organochlorine compounds in the adipose tissue of deceased people with and without cancer. Environ Res 23: 257–263.PubMedGoogle Scholar
  3. 3.
    Unger M, Kiaer H, Blichert-Toft M, Olsen J, Clausen J (1984) Organochlorine compounds in human breast fat from deceased with and without breast cancer and in a biopsy material from newly diagnosed patients undergoing breast surgery. Environ Res 34: 24–28.PubMedGoogle Scholar
  4. 4.
    Djordjevic MV, Hoffmann D, Fan J, Prokopczyk B, Citron ML, Stellman SD (1994) Assessment of chlorinated pesticides and polychlorinated biphenyls in adipose breast tissue using a supercritical fluid extraction method. Carcinogenesis 15}: 2581–2585.Google Scholar
  5. 5.
    Davis DL, Bradlow HL, Wolff M, Woodruff T, Hoel DG, Anton-Culver H (1993) Medical hypothesis: xenoestrogens as preventable causes of breast cancer. Environ Health Perspect 101: 372–377.PubMedGoogle Scholar
  6. 6.
    Wolff MS, Toniolo PG, Lee EW, Rivera LM, Dubin N (1993) Blood levels of organochlorine residues and risk of breast cancer. J Natl Cancer Inst 85: 648–652.PubMedGoogle Scholar
  7. 7.
    Dewailly E, Dodin S, Verreault R, et al. (1994) High organochlorine body burden in women with estrogen receptor-positive breast cancer. J Natl Cancer Inst 86: 232–234.PubMedGoogle Scholar
  8. 8.
    Olaya-Contreras P, Rodriguez-Villamil J, Posso-Valencia HJ, Olaya-Contreras P, Cortez JE (1998) Organochlorine exposure and breast cancer risk in Colombian women. Cad Saude Publica 14: 125–132.Google Scholar
  9. 9.
    Romieu I, Herná ndez-Avila M, Lazcano-Ponce E, Weber JP, Dewailly E (2000) Breast cancer, lactation history, and serum organochlorines. Am J Epidemiol 152: 363–370.PubMedGoogle Scholar
  10. 10.
    Falck F, Ricci A, Wolff MS, Godbold J, Deckers P (1992) Pesticides and polychlorinated biphenyl residues in human breast lipids and their relation to breast cancer. Arch Environ Health 47: 143–146.PubMedGoogle Scholar
  11. 11.
    Hoyer AP, Grandjean P, Jorgersen T, Brock JW, Hartvig HB (1998) }Organochlorine exposure and risk of breast cancer}. Lancet 352: 1816–1820.CrossRefPubMedGoogle Scholar
  12. 12.
    Hoyer AP, Jorgensen T, Brock JW, Grandjean P (2000) Organochlorine exposure and breast cancer survival. J Clin Epidemiol 53: 323–330.PubMedGoogle Scholar
  13. 13.
    Hoyer AP, Jorgensen T, Grandjean P, Hartvig HB (2000) Repeated measurements of organochlorine exposure and breast cancer risk (Denmark). Cancer Causes Control 11: 177–184.PubMedGoogle Scholar
  14. 14.
    Aronson KJ, Miller AB, Woolcott ChG, Sterns E, McCredy DR, Lickley LA (2000) Breast adipose tissue concentrations of polychlorinated biphenyls and other organochlorines and breast cancer risk. Cancer Epidemiol Biomarkers Prev 9: 55–63.PubMedGoogle Scholar
  15. 15.
    Dorgan JF, Brock JW, Rothman N, et al. (1999) Serum organochlorine pesticides and PCBs and breast cancer risk: results from a prospective analysis (USA). Cancer Causes Control 10: 1–11.CrossRefPubMedGoogle Scholar
  16. 16.
    Demers A, Ayotte P, Brisson J, Dodin S, Robert J, Dewailly E (2000) Risk and aggressiveness of breast cancer in relation to plasma organochlorine concentrations. Cancer Epidemiol Biomarkers Prev 9: 161–166.PubMedGoogle Scholar
  17. 17.
    Henderson AK, Rosen D, Miller GL, et al. (1995) Breast cancer among women exposed to polybrominated biphenyls. Epidemiology 6: 544–546.PubMedGoogle Scholar
  18. 18.
    Hardell L, Lindströ m G, Liljegren G, Dahl P, Magnuson A (1996) Increased concentrations of octachlorodibenzo-p-dioxin in cases with breast cancer-results from a case-control study. Eur J Cancer Prev 5: 351–357.PubMedGoogle Scholar
  19. 19.
    Hunter D, Hankinson S, Laden F, et al. (1997) Plasma organochlorine levels and the risk of breast cancer. N Engl J Med 337: 1253–1258.PubMedGoogle Scholar
  20. 20.
    Lopez-Carrillo L, Blair A, Lopez-Cervantes M, et al. (1997) Dichlordyltrichloroethane serum levels and breast cancer risk: a case-control study from Mexico. Cancer Res 57: 3728–3732.PubMedGoogle Scholar
  21. 21.
    Helzlsouer KJ, Alberg AJ, Huang HY, et al. (1999) Serum concentrations of organochlorine compounds and subsequent development of breast cancer. Cancer Epidemiol Biomarkers Prev 8: 525–532.PubMedGoogle Scholar
  22. 22.
    Mendoca GA, Eluf-Neto J, Andrada-Serpa MJ, et al. (1999) Organochlorines and breast cancer: a case-control study in Brazil. Int J Cancer 83: 596–600.PubMedGoogle Scholar
  23. 23.
    Krieger N, Wolff MS, Hiatt RA, Rivera M, Vogelman J, Orentreich N (1994) Breast cancer and serum organochlorines: a prospective study among white, black, and Asian women. J Natl Cancer Inst 86: 589–599.PubMedGoogle Scholar
  24. 24.
    Laden F, Collman G, Iwamoto K, et al. (2001) 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene and polychlorinated biphenyls and breast cancer: combined analysis of five US studies. J Natl Cancer Inst 93: 768–776.PubMedGoogle Scholar
  25. 25.
    van't Veer P, Lobbezoo IE, Martin-Moreno JM, et al. (1997) DDT (dicophane) and postmenopausal breast cancer in Europe: case-control study. BMJ 315: 81–85.PubMedGoogle Scholar
  26. 26.
    Stellman SD, Djordjevic MV, Britton JA, et al. (2000) Breast cancer risk in relation to adipose concentrations of organochlorine pesticides and polychlorinated biphenyls in Long Island, New York. Cancer Epidemiol Biomarkers Prev 9: 1241–1249.PubMedGoogle Scholar
  27. 27.
    Wolff MS, Zeleniuch-Jacquotte A, Dubin N, Toniolo P (2000) Risk of breast cancer and organochlorine exposure. Cancer Epidemiol Biomarkers Prev 9: 271–277.PubMedGoogle Scholar
  28. 28.
    Zheng T, Holford TR, Taylor Mayne S, et al. (2000) Risk of female breast cancer associated with serum polychlorinated biphenyls and 1,1-dichloro-2,2'-bis(p-chlorophenyl)ethylene. Cancer Epidemiol Biomarkers Prev 9: 167–174.PubMedGoogle Scholar
  29. 29.
    Laden F, Hankinson SE, Wolff MS, et al. (2001) Plasma organochlorine levels and the risk of breast cancer: an extended follow-up in the Nurses' Health Study. Int J Cancer 91: 568–574.CrossRefPubMedGoogle Scholar
  30. 30.
    Gammon MD, Wolff MS, Neugut AI, et al. (2002) Environmental toxins and breast cancer on Long Island.II. Organochlorine compound levels in blood. Cancer Epidemiol Biomarkers Prev 11: 686–697.PubMedGoogle Scholar
  31. 31.
    Safe SH (1997) Xenoestrogens and breast cancer. N Engl J Med 337: 1303–1304.PubMedGoogle Scholar
  32. 32.
    Laden F, Hunter DJ (1998) Environmental risk factors and female breast cancer. Annu Rev Public Health 19: 101–123.PubMedGoogle Scholar
  33. 33.
    Snedeker S (2001) Pesticides and breast cancer risk: a review of DDT, DDE, and Dieldrin. Environ Health Perspect 109: 35–47.Google Scholar
  34. 34.
    Laden F, Ishibe N, Hankinson SE, et al. (2002) Polychlorinated biphenyls, cytochrome P450 1A1, and breast cancer risk in the nurses' health study. Cancer Epidemiol Biomarkers Prev 11: 1560–1565.PubMedGoogle Scholar
  35. 35.
    Sasco AJ (2001) Epidemiology of breast cancer: an environmental disease? APMIS 109: 321–332.CrossRefPubMedGoogle Scholar
  36. 36.
    Soto A, Sonnenschein C, Chung KL, Fernandez MF, Olea N, Olea-Serrano MF (1995) The E-SCREEN Assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. Environ Health Perspect 103: 113–122.Google Scholar
  37. 37.
    Soto A, Ferná ndez MF, Luizzi M, Oles Karasko AS, Sonnenschein C (1997) Developing a marker of exposure to xenoestrogen mixtures in human serum. Environ Health Pespect 105: 647–663.Google Scholar
  38. 38.
    Shekhar PVM, Werdell J, Basrur VS (1997) Environmental estrogen stimulation of growth and estrogen receptor function in preneoplastic and cancerous human cells lines. J Natl Cancer Inst 89: 1774–1782.PubMedGoogle Scholar
  39. 39.
    Payne J, Scholze M, Kortenkamp A (2001) Mixtures of four organochlorines enhance human breast cancer cell proliferation. Environ Health Perspect 104: 391–397.Google Scholar
  40. 40.
    Sonnenschein C, Soto A, Ferná ndez MF, Olea N, Olea-Serrano MF (1995) Development of a marker of estrogenic exposure in human serum. Clin Chem 41: 1888–1895.PubMedGoogle Scholar
  41. 41.
    Pazos P, Pérez P, Rivas A, et al. (1998) Development of a marker of estrogenic exposure in breast cancer patients. Adv Exp Med Biol444: 29–40.PubMedGoogle Scholar
  42. 42.
    Rivas A, Olea N, Olea-Serrano MF (1997) Human exposure to endocrine-disrupting chemicals: assessing the total estrogenic xenobiotic burden. TRAC 16: 613–619.Google Scholar
  43. 43.
    Rivas A, Fernández MF, Cerrillo I, et al. (2001) Human exposure to endocrine disrupters: standardisation of a marker of estrogenic exposure in adipose tissue. APMIS 109: 185–197.CrossRefPubMedGoogle Scholar
  44. 44.
    Martínez Vidal JL, Moreno M, Garrido A, Olea-Serrano MF, Olea N (2000) Trace determination of alpha and beta endosulfan and three metabolites in human serum by GC-MS. Rapid Comm Mass Spectrometry 14: 939–946.CrossRefGoogle Scholar
  45. 45.
    Hernandez F, Pitarch E, Serrano R, Gaspar JV, Olea N (2002) Multiresidue determination of endosulfan and metabolic derivatives in human adipose tissue using automated liquid chromatographic cleanup and gas chromatographic analysis. J Anal Toxicol 26: 94–103.PubMedGoogle Scholar
  46. 46.
    Villalobos M, Olea N, Brotons JA, Olea-Serrano MF, Ruiz de Almodovar JM, Pedraza V (1995) The E-SCREEN assay: comparison among different MCF7 cell stocks. Environ Health Perspect 103: 844–850.PubMedGoogle Scholar
  47. 47.
    SPPS Inc. (1999) SPSS 9._0 Base Sintax Reference Guide. Chicago: SPSS Inc.Google Scholar
  48. 48.
    Haftenberger M, Lahmann PH, Panico S, et al. (2002) Overweight, obesity and fat distribution in 50-to 64-year-old participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Public Health Nutr 5: 1147–1162.CrossRefPubMedGoogle Scholar
  49. 49.
    Wolf MS, Anderson HA (1999) Correspondence re: J.M. Schildkrauut et al., Environmental contaminants and body fat distribution. Cancer Epidemiol. Biomark. Prev. 8: 179-183, 1999._ Cancer Epidemiol Biomarkers Prev 8: 951-952._Google Scholar
  50. 50.
    Kohlmeier L, Kohlmeier M (1995) Adipose tissue as a medium for epidemiologic exposure assessment. Environ Health Perspect 103: 99–106.Google Scholar
  51. 51.
    Agarwal VR, Takayama K, Van Wyk JJ, et al. (1998) Molecular basis of severe gynecomastia associated with aromatase expression in a fibrolamellar hepatocellular carcinoma. J Clin Endocrinol Metab 83: 1797–1800.CrossRefPubMedGoogle Scholar
  52. 52.
    Larner JM, Shackleton CHL, Roitman E, Schwartz PE, Hochberg RB (1992) Measurement of estradiol-17 fatty acid-esters in human tissues. J Clin Endocrinol Metab 75: 195–200.CrossRefPubMedGoogle Scholar
  53. 53.
    Moysich KB, Ambrosone CB, Mendola P, et al. (2002) Exposures associated with serum organochlorine levels among postmenopausal women from Westren New York State. Am J Ind Med 41: 102–110.CrossRefPubMedGoogle Scholar
  54. 54.
    Bigsby RM, Caperell-Grant A, Madhukar BV (1997) Xenobiotics released from fat during fasting produce estrogenic effects in ovariectomized mice. Cancer Res 57: 865–869.PubMedGoogle Scholar
  55. 55.
    Traina ME, Rescia M, Urbani E, et al. (2003) Long-lasting effects of lindane on mouse spermatogenesis induced by in utero exposure. Reprod Toxicol 17: 25–35.CrossRefPubMedGoogle Scholar
  56. 56.
    Schecter A, Toniolo P, Dai LC, Thuy LT, Wolff MS (1997) Blood levels of DDT and breast cancer risk among women living in the north of Vietnam. Arch Environ Contam Toxicol 33: 453–456.CrossRefPubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • jesús m. ibarluzea
    • 1
  • Mariana F. Fernández
    • 2
  • Loreto Santa-Marina
    • 3
  • Maria F. Olea-Serrano
    • 2
  • Ana M. Rivas
    • 2
  • Juan J. Aurrekoetxea
    • 1
  • José Expósito
    • 3
  • Miguel Lorenzo
    • 4
  • Pablo Torné
    • 5
  • Mercedes Villalobos
    • 6
  • Vicente Pedraza
    • 6
  • Annie J. Sasco
    • 7
  • Nicolas Olea
    • 2
  1. 1.Department of Health GuipuzkoaBasque CountrySpain
  2. 2.Laboratory of Medical InvestigationsHospital Clínico University of GranadaGranadaSpain
  3. 3.Department of Health GuipuzkoaBasque CountrySpain
  4. 4.Department of SurgeryTorrecárdenas HospitalAlmeríaSpain
  5. 5.Department of SurgeryHospital Clínico University of GranadaGranadaSpain
  6. 6.Department of RadiotherapyHospital Clínico University of GranadaGranadaSpain
  7. 7.International Agency for Research on Cancer and Institut National de la Santé et de la Recherche MédicaleLyonFrance

Personalised recommendations