Breast Cancer, PCBs and Dioxin
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This health section includes summaries of 128 studies on the links between breast cancer and exposure to PCBs or dioxin.
At least 24 studies of human populations show a possible link between PCBs and breast cancer. More than 50 additional laboratory studies illustrate in animals or cell cultures how PCBs may cause or promote breast cancer. Also, three studies of humans show a link between dioxin and breast cancer. These last three are important because certain PCBs are dioxin-like and PCBs are frequently contaminated with dioxins.
On the other hand, approximately 13 human studies did not show that PCBs increase breast cancer risk. Nevertheless, several such studies, when re-examined statistically, have found that certain PCBs were associated with risks, or that certain subgroups of women appeared to be more vulnerable to PCBs.
Scientists warn us not to make broad statements about PCBs, because PCB mixtures and human exposure routes are highly variable.
Possible explanations for differing results:
- Total vs. Individual PCB Exposures Many of the studies which found no PCB correlation with breast cancers measured only total PCBs in women, not any of the individual 209 different kinds of PCBs. This is important, because some PCBs are estrogenic, while others are anti-estrogenic, so PCBs may have opposite effects depending on the relative abundance of each type in the PCB mixture that women are exposed to. Several studies in women found that higher concentrations of certain kinds of PCBs were associated with a significantly higher breast cancer risk. Some researchers speculate that anti-estrogenic PCBs may suppress breast cancer.
- Timing of PCB Exposure Almost all of the human population studies measured only the current PCB concentrations in the women’s bodies. They had no information about the PCB levels the women were exposed to in their childhood or even when they were developing in their mothers’ wombs. Many scientists believe that breast cancers, and other hormone-sensitive cancers such as prostate cancer, may start at very young ages and lie dormant for many years before being triggered to grow later in adulthood. Even with adult exposures, toxicologists have proven that for many chemicals, cancer may not develop until 10, 20 or even 30 years after the exposure occurred. This may be true of PCBs as well, which makes it difficult to study.
- Women’s Individuality Many of the studies looked at women in general, and didn’t do careful statistical analysis of them in sub-groups of younger, older, post-menopausal, pre-menopausal, mothers, childless, breastfeeders, non-breastfeeders, bodyweight, etc. Many of these conditions involve specific vulnerabilities which could be lost in a generalized study. In several other cases, detailed studies found links between a specific type of PCB and a specific type of woman. For example: PCB 118 and 156 in pre-menopausal women. And in older ages, PCBs may represent an unnaturally high and unhealthy estrogenic exposure long after a woman has passed through menopause and her estrogen levels are supposed to be low.
- Genetic Vulnerabilities Several studies found that women with certain genetic traits, or of certain races, had statistically significant increases in breast cancer risk associated with PCB exposure.
- Temporary vs. Persistent Several studies found that the lighter-weight PCBs (with fewer chlorines attached around the edges) tended to be more estrogenic than the heavier PCBs. It would be logical to think that these lighter PCBs may increase breast cancer, just as higher levels of natural estrogen do, or as estrogen replacement therapy does.
- Parent Chemicals or Metabolites Several studies found that when PCBs gradually break down inside our bodies, they are metabolized into related compounds which are sometimes more estrogenic than the original PCBs. One study described a hydroxylated PCB which was 10 times as estrogenic as its parent PCB, and equal to natural estrogen in potency. It appears that few of the 40 human PCB studies listed here measured these PCB metabolites in relation to the women’s breast cancer risk, which means they may have missed an important factor.
Unfortunately, lighter PCBs are hard to track. They are more transient in the human body, so they don’t accumulate the way heavy PCBs do. This means that a measure of the total PCB mixture in a woman’s body today may completely misrepresent her lifetime exposure to PCBs, especially to the lighter-weight, estrogenic PCBs. The heavier PCBs might serve as a “marker” for past exposures to light-weight PCBs, but the type of exposure may matter a great deal. Heavier PCBs are more likely to stick to particles and bioaccumulate up the food chain to higher concentrations in fish, ducks and other meats. In contrast, lighter PCBs are more likely to dissolve into water or volatilize into the air. Lighter PCBs are also easier to absorb through skin.
This means that women who eat a lot of contaminated fish and ducks have a different kind of PCB exposure when compared with women who don’t eat contaminated fish but who live next to a PCB contaminated site which is volatilizing PCBs into the air and water. The women primarily exposed by air are getting a greater percentage dose of estrogenic PCBs. The fish-eaters get a higher percentage dose of the anti-estrogenic PCBs (though this may still not be enough to neutralize the estrogenic PCBs).
The ratio of estrogenic vs. anti-estrogenic PCBs could be very important. A few studies found that total PCB levels were higher in women free of breast cancer, implying that PCBs were not linked to breast cancer; however, if the women with seemingly lower PCBs were exposed to a higher percentage of estrogenic PCBs throughout their lives this may explain why they had higher breast cancer rates.
The lighter-weight PCBs may be like a hit-and-run driver, impossible
to identify as the culprit because they’ve largely disappeared by the time
a woman actually develops the disease.
According to science writer Micheal Castleman, natural estrogen may be metabolized along two paths, "good" and "bad," which balance each other's effects. Xenoestrogens [such as PCBs] appear to block the good estrogen path, allowing bad metabolized estrogen to promote tumor growth. Metabolism of the natural estrogen known as estradiol, produces both 2-hydroxyestrone (2-OHE1 or "good" estrogen) and 16-alpha hydroxyestrone (16 alpha-OHE1, "bad" estrogen). The 16 alpha-OHE1 stimulates uncontrolled cell division, a trait associated with cancer. Xenoestrogens appear to block the 2-OHE1 pathway and increase levels of 16 alpha-OHE1. (from: Why? by Michael Castlemen, online at: http://www.motherjones.com/mother_jones/MJ94/castleman.html)
- Low or High Doses Two studies found that some PCB mixtures were estrogenic at lower concentrations, but not at higher concentrations. One of the research teams speculated that the higher doses appeared to be directly toxic enough to mask or counteract any estrogenic effect, while the lower PCB doses may be able to slip under this threshold and behave like estrogen without triggering other effects. This could cause extreme difficulty in interpreting PCB exposure and disease data, because a PCB/cancer link may not follow a simple dose/response formula. It may help explain why some of the studies found that breast cancer patients actually had significantly lower levels of PCBs in their bodies than cancer-free patients. In all of those cases, the researchers concluded that they found no link between PCBs and breast cancer, but they didn’t account for this possible threshold effect.
- Non-estrogenic Carcinogen Some of the studies indicate that PCBs and dioxins may cause breast cancer through mechanisms other than the estrogen pathway. For example, some PCBs and dioxins may be causing DNA breakage or other genetic damage, resulting in cancer. This has nothing to do with estrogen.
- Blood or Tissue Samples Some studies measured PCBs circulating in the bloodstream, while others measured PCBs in fat tissue, particularly in breast fat tissue. The researchers don’t appear to agree on whether it matters. Some provide evidence that blood samples miss the true exposure of the breast to PCBs accumulated in breast fat over time. Others provide evidence that blood samples are similar enough to fat samples for study purposes.
- Samples Taken Before or After Chemotherapy Starts Some researchers question study findings where blood or tissue samples were taken from women after they had already started chemotherapy for breast cancer. They are concerned that the women’s body chemistry (including circulating PCB levels in the blood) could be greatly altered by the stress and treatment. This might skew the study results when these women are compared to non-cancerous women.
- PCBs May Make Tumors Worse Some researchers found evidence that while certain PCBs didn’t increase the rate of breast cancer in their study, the PCBs seemed to make tumors larger and more aggressive, leading to a poorer prognosis for the women.
- Synergy Some researchers found that PCBs may multiply or enhance the cancer-causing effect of other carcinogens, by stimulating the production of certain enzymes which activate the other chemicals or through other combinations of processes. This means that if other toxic chemical exposures have occurred, PCBs may tip the balance and promote the development of cancer in cases where the other chemicals wouldn’t have caused cancer alone. (see Enzymes)
- Breastfeeding If a woman has never breastfed a baby, this is a proven risk factor for developing breast cancer. Is it only a coincidence that breastfeeding is the only mechanism whereby a woman can eliminate a large percentage of PCBs and other organochlorines from her body? The true risk factor may be the PCBs and other toxic chemicals stored in the woman's body, not the lack of breastfeeding. (see Breastfeeding.)
- Biased Research? Several of the studies which found no link between PCBs and breast cancer were paid for by industries which have a financial stake in large PCB pollution liability cases, such as General Electric. There also appears to be a well-funded cluster of researchers who are all associated with Dr. Safe at Texas A&M University, and determined to discount PCB breast cancer claims. Safe has earned a reputation for his opposition to PCB (and other chemical) cancer claims and is frequently funded as an industry consultant. Many of their studies listed here focus on highlighting certain types of PCBs or PCB metabolites which are anti-estrogenic, with the implication that PCBs and their metabolites are beneficial in estrogen-sensitive cancers. They chose not to focus on the estrogenic varieties which have the opposite effect.
Breast Cancer Rates Are Higher in Green Bay
In Wisconsin, researchers have found three breast cancer population clusters, where the disease rate is much higher than average. Two of them are in zip codes on the east side of the City of Green Bay, in the old downtown along the Fox River and along the east shore of the Bay. (Zip codes 54301 and 54311) (The other zip code was in Shorewood, just north of Milwaukee on Lake Michigan.) The statistics were age-adjusted so results wouldn’t be skewed.
In general, Wisconsin’s breast cancer rate among women aged 65 and older is higher than the national average. Dr. Patrick Remington, Director of the University of Wisconsin’s Comprehensive Cancer Center, in Madison, conducted a study to determine whether the cancer clusters are true or just statistical mistakes. Verbally, he told us that the indepth analysis shows local rates in these 3 zip codes are truly higher than average. (3/24/01) He also dismissed claims made by a few local Green Bay doctors that the high rates were due to the presence of several hospitals and clinics in the area, because the statistics are based on the home address of the women. Unfortunately, the Center has no firm plans to study whether our high local breast cancer rates are linked to PCBs, dioxins, furans, or other contaminants.
As explained earlier, women primarily exposed to PCBs by air are getting a greater percentage dose of lighter-weight, estrogenic PCBs. (...and higher estrogen has been linked to breast cancer.) The two east-side Green Bay zip codes are both downwind of the last 7 miles of the Fox River, and the southern end of Green Bay, where more than 90% of the river's total PCB contamination is concentrated. PCBs are actively volatilizing into the air off the surface of the river and bay, and scientists estimate that City of Green Bay air concentrations of PCBs are 2 to 3 times higher than in the rest of Wisconsin. Unfortunately, it's impossible to measure a woman's lifetime exposure to these kinds of PCBs because the light-weight varieties are more transient and pass through the body relatively quickly --- they don't stay and accumulate like the heavier PCBs do. (see Breathing Local Air)
It is possible that PCBs could be linked to the local Breast Cancer rate, but we would need a full epidemiological (population-based) study in order to make this link, and it may be impossible to account for all the variables listed above.
The High Cost of Breast Cancer
Breast cancer is the second largest cause of cancer death in women in the U.S. (after lung cancer), according to the American Cancer Society. It is the most common cancer among women, excluding non-melanoma skin cancers. More than 1.2 million people will be diagnosed with breast cancer this year worldwide, according to the World Health Organizations
The American Cancer Society estimates that in 2001 approximately 192,200 new cases of invasive breast cancer (Stages I-IV) will be diagnosed among women in the United States. Another 46,400 women will be diagnosed with ductal carcinoma in situ (DCIS), a non-invasive breast cancer. DCIS is the earliest form of breast cancer, confined to the milk ducts of the breast. Though much less common, breast cancer also occurs in men. An estimated 1,500 cases will be diagnosed in men in 2001. (from: Imaginis: Breast Cancer Statistics, http://imaginis.com/breasthealth/statistics.asp)
Approximately 40,600 deaths will occur from breast cancer (40,200 among women, 400 among men) in the United States. In the past few decades, the incidence of breast cancer increased from 1-in-20, up to today’s much higher rate of 1-in-8 women (figures have been adjusted to account for age and detection rate differences.) The incidence rate of breast cancer (number of new breast cancers per 100,000 women) increased by approximately 4% during the 1980s but leveled off to 100.6 cases per 100,000 women in the 1990s. According to Our Stolen Future, “A contemporary woman's risk of breast cancer is 54% greater than was her mother's at the same age among blacks, and 41% greater among whites."
One small comfort: the death rates from breast cancer declined significantly between 1992 and 1996, with the largest decreases among younger women. Medical experts attribute the decline in breast cancer deaths to earlier detection and more effective treatments.
According to the American Cancer Society, only 25-30% of breast cancer cases can be explained by known risk factors, such as family history, lifestyle and diet. Inherited genetic mutations account for only 5%. This means 70-75% of breast cancer cases are unexplained by standard risk factors and may well be related to environmental exposure to toxins. PCBs may be one cause.
Sections on Breast Cancer and PCBs:
Table of Contents Introduction Summary of Study Results Studies of Breast Cancer, PCBs and Dioxin (128 studies in 2 parts) Links to More Information References
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