Breast cancer and PCBs: true or false association?

The issue of a possible association between polyŽ . chlorinated biphenyls PCBs and increased risk of breast cancer is important. Numerous epidemiological studies have examined the relationship, but the Ž results are not consistent Moysich et al., 1998; Dorgan et al., 1999; Aronson et al., 2000; Stellman et al., 2000; Zheng et al., 2000; Laden et al., 2001a; . Lucena et al., 2001 . Meanwhile, experimental studies had demonstrated that some PCBs have oestrogenic activity and enhance proliferation of breast Ž tumour cells Safe, 1992; Jansen et al., 1993; Wolff . and Toniolo, 1995 . Ž . Recently, Laden et al. 2001b reported no relationship based on results of pooled analysis of five Ž US studies. Total PCBs, and only few PCB n-118, . 138, 153 and 180 were analysed in serum. Meanwhile, it is feasible to use blood sera to obtain and analyse PCBs. Adipose tissue PCB levels have been regarded as a preferred indicator of human exposure. Levels in breast adipose tissue are known to be higher and more representative of the cumulative internal exposure at the target site for breast cancer ŽArchibeque-Engle et al., 1997; Angulo et al., 1999; . Lopez-Carrillo et al., 1999 . Archibeque-Engle et al. Ž . 1997 did not find a significant relationship between serum concentrations and tissue residues for 15 compounds analysed. Based on the lack of correlation between breast adipose tissue and serum, as well as an absence of some compound residues in serum, the authors emphasized that adipose tissue should be analysed in addition to serum to fully understand the relationship between organochlorine compounds and breast cancer. In adipose tissue a positive association with indiŽ vidual PCBs has been demonstrated Aronson et al., . 2000; Stellman et al., 2000; Lucena et al., 2001 . However, in a hospital-based case control study, Ž . Zheng et al. 2000 , analysing nine PCBs in breast fat, reached the conclusion that PCBs are not a risk factor for breast cancer. Breast cancer risk associated with PCBs varies according to specific PCB Ž . congeners Safe, 1992 , and Zheng et al. mentioned a possible carcinogenic effect based on the total level of PCBs after failure to find positive association with individual congeners. We think that every PCB could have a different effect on human cells, and some have oestrogenic activity while others have anti-oestrogenic activity. Therefore, the conclusions of Zheng et al. are not justified, especially considering that among all PCBs evaluated the only potentially oestrogenic PCB was PCB n-187. Furthermore, Ž the study included fewer controls than cases 186 . versus 304 , making the possibility of demonstrating such risk, if present, more difficult. In a similar hospital-based case control study, we measured the levels of eleven PCB congeners in breast fat of all women subjected to surgical interference because of breast lumps, in our university Ž hospital over a 10-month period Lucena et al., . 2001 . A highly positive association was found between breast cancer risk and PCB n-28, a PCB not measured by Zheng et al. Although our findings were based on a smaller sample size, PCB n-28 in the multivariate analysis was found to be the most significant risk factor with odds ratio of 9.6 and quite Ž . satisfactory confidence interval 95% CI 3.8, 24.4 . Based on these findings, we would like to raise concerns about the rising incidence of breast cancer in developed countries, where large numbers of women are exposed to PCBs. Further research in this area is essential, especially into the possibility that individual congeners have different impacts on human cells.