Polychlorinated Biphenyls (PCBs)
CATEGORY: IARC probable, NTP reasonably anticipated, Endocrine disruptor
USED IN: Banned in U.S. in 1976, but two-thirds of insulation fluids, plastics, adhesives, paper, inks, paints and dyes manufactured before the ban are still in use
Although the EPA banned the use of PCBs in new products in 1976, as many as two-thirds of all insulation fluids, plastics, adhesives, paper, inks, paints, dyes and other products containing PCBs manufactured before the ban remain in use today. The remaining one-third was discarded, which means that these toxic compounds eventually made their way into landfills and waste dumps (Robinson, 1990).
Levels of PCBs were high before being banned in the United States, but generally their presence in human tissues has decreased slowly over the past decades (Hagmar, 2006). Exposures were high, though, between childhood and young adulthood for many women who are now facing breast cancer diagnoses. PCB levels in neonatal cord serum were correlated with the distance of mothers’ residences from a Superfund site; levels were lower after site remediation (Choi, 2006).
The science on PCBs is complicated. There are more than 200 individual PCBs, classified in three types based on their effects on cells. One type acts like an estrogen. A second type acts like an anti-estrogen. A third type appears not to be hormonally active, but can stimulate enzyme systems of animals and humans in a manner similar to the way certain drugs (such as phenobarbital) and other toxic chemicals do (Connor, 1997). Additionally, metabolites of PCBs can alter the expression of genes involved in hormone synthesis, indicating that these compounds may act as endocrine disruptors through mechanisms not directly involving estrogen or other hormone receptors (Braathen, 2009). PCBs with relatively low chlorination levels may induce damage to DNA in isolated breast tumor cells in vitro. The presence of estrogen receptors in the cells (ER+ cells) may actually offer protection against damage (Lin, 2009).
Most studies have looked at total PCB levels without identifying individual types. A few studies, however, have looked at relationships between cancer status and particular PCBs. For example, a 2004 case-control study found significantly higher total blood levels of PCBs, particularly PCB 153, in women with breast cancer than in presumably healthy women. PCB 153 has been shown to exhibit estrogen-like activity in animal and in vitro studies (Charlier, 2004). Another study measured several types of PCBs, along with DDE, in breast biopsy tissue. Compared with healthy women, pre-menopausal women with breast cancer had significantly higher levels of PCBs 105 and 118, while post-menopausal women with breast cancer had higher levels of PCBs 170 and 180 (Aronson, 2000). Interestingly, none of these four PCBs were shown to have estrogenic activity in a study using MCF-7 cell proliferation to test estrogen responses of compounds (Decastro, 2006).
Another report has implicated PCBs in breast cancer recurrence among women with non-metastatic breast cancer. The study found that women with the highest levels of total PCBs, as well as of PCB 118, in their fat tissues were almost three times as likely to have recurrent breast cancer as women with lower levels (Muscat, 2003).
Some studies have found no link between PCBs and breast cancer (Salehi, 2008). New evidence suggests that some of these compounds may have their greatest impact on women with particular susceptibilities and that looking broadly at large samples will not tell the full story of cancer risk as influenced by PCB exposures. Thus, more study is needed to determine the effect of PCB exposure on breast cancer development in specific populations. For example, researchers evaluating data from the Nurses’ Health Study revisited the issue of PCBs and breast cancer risk and revised their conclusion concerning the link between PCBs, DDE and breast cancer. In studies of PCBs and DDE in blood, they had previously concluded that exposure to these chemicals was unlikely to explain high breast cancer rates (Laden, 2001). In 2002, new evidence regarding variations in individual susceptibility due to genetic differences prompted these researchers to call for additional studies (Laden, 2002). In a new study examining occupational exposures to PCBs in electrical capacitor production workers and later breast cancer incidence, no overall relationship between exposure levels or duration and disease incidence was observed for female workers in general. But for non-white women, a significant relationship was found between incidence of breast cancer and earlier PCB exposure duration as well as cumulative exposure amounts (Silver, 2009).
In vitro studies of human breast cancer cells have demonstrated that various specific types of PCBs promote the proliferation of breast cancer cells in culture by stimulating estrogen-receptor-mediated pathways (Andersson, 1999; Gierthy, 1997) and the activation of key enzymes and cellular changes that are characteristic of transformation of cells to a malignant state (Hatakeyama, 1999).
