Environment and Breast Cancer: Science Review

Evidence From Humans
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Organochlorine exposures influence on breast cancer risk and survival according to estrogen receptor status: a Danish cohort-nested case-control study
Hoyer, A. P., Jorgensen, T., Rank, F., Grandjean, P. BMC Cancer. 2001. 1:1, 8.
Topic area
Environmental pollutant - Pesticides, organochlorines
Study design
Nested case-control
Funding agency
NIEHS Other: Boston University Superfund Basic Res
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Pre menopausal
Post menopausal
Number of Controls
Controls: 318
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Participants in the Copenhagen City Heart Study, which enrolled 10,317 women in 1976-1978. Cases between 25 and 80 years of age diagnosed with primary breast cancer between enrollment and 1993, identified by linkage to the Danish Cancer Registry. Controls matched on age and vital statistics.
Exposures investigated
Quartiles of serum organochlorine concentrations determined by gas chromatography for hexachlorobenzene (HCB), dieldrin, PCBs (sum of congeners), p,p'-DDE
Breast cancer outcome investigated
Primary breast cancer, ER positive and ER negative
Mortality from breast cancer
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Body weight, parity, menopausal status, HRT, smoking, alcohol consumption, household income, education; in survival analysis: tumor size, degree of spread, stage of disease
Description of major analysis
Conditional logistic regression; Cox proportional hazard method
Strength of associations reported
No significant association with ER+ or ER- tumors: HCB, PCBs, p,p'-DDE
No significant association with ER+ tumors: Dieldrin
Quartiles of dieldrin concentration for ER negative tumors: p trend = 0.01
quartile: cases/controls, OR (95% CI)
I (referent): 6/23
II: 5/23 OR=1.2 (0.3-5.4)
III: 13/23; OR=4.9 (0.9-28.3)
IV: 20/23; OR=7.6 (1.3-46.1)
No significant association between OC concentration and survival for ER+ tumors, though women with ER+ tumors and higher levels of dieldrin and PCB tended to have worse survival.
HIgher concentrations of HCB and PCB were associated with significantly higher survival in women with ER- tumors.
Higher concentration of dieldrin was associated (p trend =.06) with lower survival in women with ER- tumors.
Results Comments
Authors state, "Exposure to dieldrin increases the risk of developing ERN tumors, which are larger and more often spread at the time of diagnosis." However, the number of ER- cases is limited. Authors suggest the possibility that ER status may change during disease progression. A larger proportion of ER- tumors in this study were large.
BACKGROUND: The relationship between breast cancer and organochlorine exposure is controversial and complex. As estrogen receptor positive and negative breast cancer may represent different entities of the disease, this study was undertaken to evaluate organochlorines influence on breast cancer risk and survival according to receptor status. METHODS: The background material stems from the Copenhagen City Heart Study (Denmark 1976-78). The breast cancer risk was investigated in a cohort nested case-control design including 161 cases and twice as many breast cancer free controls. The cases served as a cohort in the survival analysis. Serum organochlorine concentrations were determined by gas chromatography. RESULTS: The observed increased breast cancer risk associated with exposure to dieldrin derived from women who developed an estrogen receptor negative (ERN) tumor (Odds ratio [OR] I vs. IV quartile, 7.6, 95% confidence interval [95% CI] 1.4-46.1, p-value for linear trend 0.01). Tumors in women with the highest dieldrin serum level were larger and more often spread at the time of diagnosis than ERP tumors. The risk of dying was for the remaining evaluated compounds higher among patients with ERP breast cancer when compared to those with ERN. In the highest quartile of polychlorinated biphenyls (SigmaPCB) it was more than 2-fold increased (Relative risk [RR] I vs. IV quartile, 2.5, 95% CI 1.1-5.7), but no dose-response relation was apparent. CONCLUSION: The results do not suggest that exposure to potential estrogenic organochlorines leads to development of an ERP breast cancer. A possible adverse effect on prognosis of hormone-responsive breast cancers needs to be clarified.
Author address
The Copenhagen Center for Prospective Population Studies, Harsdorffsvej 1B, 2tv, DK-1874 Frederiksberg C, Denmark. aph@post8.tele.dk
Reviewers Comments
Strength: 17 years follow-up, prospective OC measurement.