Authors
Woolcott CG, Aronson KJ, Hanna WM, SenGupta SK, McCready DR, Sterns EE, Miller AB.

Title
Organochlorines and breast cancer risk by receptor status, tumor size, and grade (Canada).

Journal
Cancer Causes and Control

Summary
The general population is exposed to organochlorines through high-fat foods of animal origin (e.g., meat, dairy products). Many organochlorines accumulate in fatty tissues including the breast and some have estrogenic or other hormonal activity. In some studies, women with breast cancer had higher levels of some chlorinated compounds including PCBs (polychlorinated biphenyls) and pesticides compared with controls (Høyer et al., 1998, Liljegren et al., 1998), although in other studies, the cases had lower or similar levels. The discrepancies in the results of these studies may be due to the study populations and their different susceptibilities. The objective of this study was to determine the association between organochlorines in breast adipose tissue and different subtypes of breast cancer.
The authors of the present study used a hospital-based case-control study to determine the association between organochlorines measured in breast adipose tissue and subtypes of breast cancer based on hormone receptor status (estrogen and progesterone), tumour size, and histological grade. The study was conducted from 1995 to 1997 in Kingston and Toronto, Canada. Among women who had a diagnostic breast biopsy, 0.2-1 g of breast tissue was used for analysis of 14 PCB congeners and 10 pesticides. The organochlorines measured comprised 14 PCB congeners: p,p'-DDT, p,p'-DDE, cis-nonachlor, trans-nonachlor, oxychlordane, hexachlorobenzene (HCB), mirex, and ß-hexachlorocyclohexane (ß-HCH), a-chlordane, and -chlordane. Total PCBs were estimated from the sum of PCBs 138 and 153 (multiplied by 5.2 to approximate the level of the commercial PCB mixture, Arochlor 1260). Organochlorines were determined in the 217 cases and in 213 controls that matched to the cases by age and study site. The questionnaire collected information about known and suspected risk factors that were considered as potential confounders in the analyses. Tumours were classified as receptor-positive if more than 10% of cells stained positive for the receptor in immunohistochemistry or the concentration of receptor was greater than 10 fmol/mg cytosolic proteins in enzyme immunoassay. Cases were considered to have positive receptor status when at least one assay outcome measure was positive. Tumor grade and size were classified by the pathology reports.
Overall, the control group had lower breast adipose tissue concentrations of all organochlorines. When adjusted for age, the concentrations of total PCBs, DDE, and ß-HCH were significantly higher in ER-negative than ER-positive cases (p < 0.05). The concentrations of cis-nonachlor and ß-HCH were significantly higher in cases with larger tumours than cases with smaller tumours (p < 0.05). The concentrations of PCBs 153 and 183, DDE, DDT, HCB, and ß-HCH were higher among cases with more poorly differentiated tumors than cases with better differentiated tumors (p < 0.05). Furthermore, concentrations of organochlorines were generally higher in cases with tumours of poorer prognosis (ER-negative, PR-negative, size>2 cm, histologic grade III). After adjustment for all confounders, associations between organochlorines and breast cancer did not vary significantly by hormone receptor status, tumour size, or histological grade. The odds ratios for PCBs and DDE, although not significant, were higher for ER-negative than for ER-positive breast cancers. The ORs of PCBs and DDE were higher with risk of ER-negative than ER-positive breast cancer. The OR for the association with risk ER-negative breast cancer was 2.4 (95% confidence interval CI 1.0-5.4) and it was 1.1 for ER-positive (95% CI 0.6-1.9).
One of the advantages of this study is that exposure assessment was done in breast adipose tissue. Measurements made in adipose tissue have the advantage over measurements in blood because they offer an excellent measure of increasing internal exposure at the target site. The concentrations of organochlorines in breast adipose tissue are 200-1000 times higher than in blood. This study suggests that breast tissue organochlorine levels may be more strongly associated with breast tumours that have poor prognoses, but additional studies are needed to confirm this finding.