BMC Cancer (2001) 1:8 http://www.biomedcentral.com/1471-2407/1/8 of up to 10% of ERN tumors is found to respond to the therapy as well [43,44]. In this study tamoxifen was pref- erably administered to postmenopausal patients, but 26.3% of the patients who received this treatment had an ERN tumor. Tamoxifen competes with endogenous es- trogen in binding to the receptor, and may therefore also block a possible effect of an estrogenic compound. How- ever, adjustment for tamoxifen therapy in survival anal- yses on a sub-sample of the cohort (80 cases) did not substantially alter the observed results. The present study has several strengths. The participants were select- ed independently of risk of breast cancer and were fol- lowed for 17 years with regard to development of the disease. This time span allows the breast cancer to devel- op and takes into account the presumed long latency of this cancer. Furthermore, it is possible to give a long- term estimate for overall survival, as the median follow up with regard to death was 7.2 years. The substantial amount of information collected on the participants in the CCHS and the linkage to several relevant registries assured the ability to adjust for potential confounding, when evaluating both breast cancer risk and prognosis. The observed differences between cases eligible for and not eligible for assessing ER are unlikely to have affected the findings on breast cancer risk. Parity would be ex- pected to be associated with lower organochlorine con- centrations, as lactation is a main route by which these substances are excreted. Younger age would mean short- er duration of exposure and less accumulation. Thus, the study subjects included in the present study could have lower serum organochlorine concentrations and slightly lower risk of breast cancer than the CCHS cohort in gen- eral. Exclusion of cases diagnosed within 5 years of se- rum sampling did not affect the present results on risk and survival, and neither did mutual adjustment for or- ganochlorine compounds. The Danish unique 10-digit ID-number issued to all per- sons living in and entering the country (by birth or immi- gration) insure the completeness of the undertaken linkages. Since 1942, the Danish Cancer Registry has reg- istered all cases of cancer occurring in the entire Danish population; the registry is regarded virtually complete [45]. DBCG has since 1976 been notified about new breast cancer cases by all Danish hospital departments [46]. The present study was not designed as a classical survival study and blood samples for assessment of organochlo- rine exposure was taken on average 8.7 years before the patients were diagnosed with breast cancer. Given the changes in organochlorine concentrations over time, the study only indirectly addressed the question whether es- trogen or estrogenic compounds determined in 1976-78 may interfere with the prognosis of ERP tumors. On the other hand, breast cancer is estimated to take several (8- 10) years to reach a clinical detectable size, which mean that assessment of organochlorine exposure at the time of diagnosis will not reflect the level at tumor initiation. Even though this study included more breast cancer cas- es than most of the previous studies dealing with the or- ganochlorine issue, it still has limited statistical power, especially in the analyses of ERN tumors. Conclusion The present study does not support the hypothesis that estrogen related risk factors or potential estrogenic orga- nochlorines increase the risk of developing ERP tumors. In fact, it shows that exposure to dieldrin increases the risk of developing ERN tumors, which are larger and more often spread at the time of diagnosis. However, this finding should be interpreted with caution due to the limited number of ERN cases, so whether exposure to es- trogenic organochlorine compounds affect the risk and prognosis of a hormone-responsive breast cancer needs to be clarified. Competing interests: None declared Acknowledgement The authors thank Merete Appleyard, the Copenhagen City Heart Study, for competent help with identifying the cohort and locating the serum sam- ples for chemical analysis and Dr John W Brock, Centers for Disease Con- trol and Prevention in Atlanta, USA for performing the organochlorine analyses. This study was supported through the Boston University Super- fund Basic Research Center by the National Institute of Environmental Health Sciences, (ES07381), the Danish Medical Council, and the Danish Health Foundation. References 1. Ahlborg UG, Lipworth L, Titus-Ernstoff L, Hsieh C-C, Hanberg A, Baron J, Trichopoulos D, Adami H-O: Organochlorine com- pounds in relation to breast cancer, endometrial cancer, and endometriosis: an assessment of the biological and epidemi- ological evidence. Crit Rev Toxicol 1995, 25:463-531 2. Soto AM, Chung KL, Sonnenschein C: The pesticides endosulfan, toxaphene, and dieldrin have estrogenic effects on human estrogen-sensitive cells. Environ Health Perspect 1994, 102:380-3 3. Bustos S, Denegri JC, Diaz F, Tchernitchin AN: p,p'-DDT is an es- trogenic compound. Bull Environ Contam Toxicol 1988, 1:91-8 4. Toniolo PG: Endogenous estrogens and breast cancer risk: the case for prospective cohort studies. Environ Health Perspect 1997, 10(suppl 3):587-592 5. Dorgan JF, Longcope C, Stephenson HE Jr, Falk RT, Miller R, Franz C, Kahle L, Campbell WS, Tangrea JS, Schatzkin A: Serum sex hor- mone levels are related to breast cancer risk in postmeno- pausal women. Environ Health Perspect 1997, 105(suppl 3):583-585 6. Early Breast Cancer Trialists Collaborative Group: Systemic treat- ment of early breast cancer by hormonal, cytotoxic or im- mune therapy. Lancet 1992, 339:71-85 7. Zhu K, Bernard LJ, Levine RS, Williams SM: Estrogen receptor sta- tus of breast cancer: a marker of different stages of tumor or different entities of the disease. Medical Hypothesis 1997, 49:69- 75 8. Wolff MS, Toniolo PG, Lee EW, Rivera M, Dubin N: Blood levels of organochlorine residues and risk of breast cancer. J Natl Can- cer Inst 1993, 85:648-5 9. Krieger N, Wolff MS, Hiatt RA, Rivera M, Vogelman J, Orentreich N: Breast cancer and serum organochlorines: A prospective