Environment and Breast Cancer: Science Review


Evidence From Humans
 
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Exposure to polychlorinated biphenyl (PCB) congeners measured shortly after giving birth and subsequent risk of maternal breast cancer before age 50
Cohn, B.A., Terry, M.B., Plumb, M., Cirillo, P.M. Breast Cancer Research and Treatment. 2012. 136:1, 267-275.
Topic area
Environmental pollutant - PCBs
Study design
Nested case-control
Funding agency
Breast Cancer and the Environment Research Program
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
No analysis based on menopausal status (all cases in analysis were premenopausal)
Number of Controls
Controls: 112
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
112 cases were from participants in the Child Health and Development Studies, residents of the Oakland, CA area and members of the Kaiser Permanente Health Plan who sought obstetric care between 1959 and 1967. Cases were identified as women with incident invasive or non-invasive breast cancer diagnosed before age 50 through the California Cancer Registry, or deaths due to breast cancer before age 50. 112 controls, from the same cohort, were matched by year of birth.
Exposure Investigated
Exposures investigated
Blood was collected 1-3 days after delivery and measured for PCB congeners in serum, in the following groups: Potentially estrogenic: 101, 187, 201. Anti-estrogenic, dioxin-like: 66, 74, 105, 118, 156, 167, 138, 170. Anti-estrogenic, limited dioxin-like:
Exposure assessment comment
Because PCBs are persistent chemicals, early postpartum levels reflect exposure during pregnancy and perhaps childhood. PCB congeners were grouped into estrogenic and persistent; antiestrogenic, immunogenic, dioxin-like; and limited dioxin-like activity; and phenobarbital, CYP1A/2B inducers. Nonsignificant congeners (p>0.05) were removed from the model. The model was further refined by adjustment for additional variables, and PCBs 187, 167, and 203 remained significant, and were included in the analyses. Serum samples were collected from 1959 to 1967, an average of 17 years before diagnosis.
Early life exposures considered
Blood samples were collected right after pregnancy, reflecting sensitive window when breast cells are rapidly proliferating and, in a first full-term pregnancy (as was the case for some women in CHDS), differentiating.
Breast cancer outcome investigated
Primary incident breast cancer
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.
Blood lipids (total cholesterol, total triglycerides), race, parity, lactation, BMI, year of blood sampling. Adjustment for p,p'-DDT, o,p'-DDT, and p,p'-DDE did not affect PCB associations with breast cancer (data not shown).
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
No
Strength of associations reported
Highest compared to lowest quartile in blood:
PCB 167: OR 0.24 (95% CI 0.07-0.79)
PCB 187: OR 0.35 (95% CI 0.11-1.14)
PCB 203: OR 6.43 (95% CI 1.85-21.73)
PCB 203/187+167 (post hoc) score: OR 2.81 (95% CI 1.11-7.09)
Results Comments
Effect estimates for individual PCBs were not adjusted for confounders. The post hoc score intends to describe the net effect of PCB exposure in the study. The PCBs analyzed included PCB 187, which is estrogenic; PCB 167, which is dioxin-like and anti-estrogenic; and PCB 203, which is a CYP1A/2B inducer. Authors reported finding no association with PCB groupings (see "Exposures investigated") or with sum of total PCBs (data not shown).
Reviewers Comments
This is the first study to look at PCB levels in women in the critical period for the breast, directly after giving birth, and the association with breast cancer. Findings of associations for some congeners and not others of similar biological activity requires further confirmation because of the possibility that post hoc analysis reflects chance.