Many of the 129 studies summarized below show a potential link between PCB chemical exposure and breast cancer; however, some of the study results conflict. 

• At least 25 studies of humans show a link between PCBs and breast cancer ( … this does not include the dozens of additional mechanistic laboratory studies which illustrate how PCBs may cause or promote breast cancer.)

• At least 3 additional studies of humans also show a link between dioxin and breast cancer (certain PCBs are dioxin-like, and PCBs are frequently contaminated with dioxins.)

• Approximately 13 human studies do not support the hypothesis that PCBs increase breast cancer risk; however, most of them measured only current levels of total PCBs in adult women, not individual PCB types or past exposures 20-30 years ago.   Several of these "negative results" studies, when reexamined statistically, have found that certain PCBs were associated with risks or that certain subgroups of women were more vulnerable.

(Each entry below represents one finding in a study unless otherwise noted.  Some studies had multiple findings.)

• recent Great Lakes fish consumption (GL salmon or lake trout eaten 5 years previously) was associated with a significant elevation in breast cancer risk for premenopausal and young women (Wisconsin)
• women who ate contaminated fish had an elevated incidence of breast cancer compared to those who ate less-contaminated fish (Sweden)
• PCBs increased the relative breast cancer risk in postmenopausal women who had certain genetic characteristics
• PCB 118 and 156 were linked to a 60% to 80% greater risk of breast cancer, with this risk more pronounced in premenopausal women
• women with high levels of a combination of PCBs 105, 118 and 156 were about twice as likely to have breast cancer. These are known as “mono-ortho” PCBs, which mimic dioxin.
• PCBs induce enzymes and can be metabolized (or metabolize other chemicals) into cancer-causing chemicals in the presence of certain genetic types
• further studies of genetically susceptible populations are warranted
• exposure to PCBs is unlikely to be a major cause of breast cancer 
• higher PCBs exposures were linked with a statistically significant increase in breast cancer risk among women in the middle tertile of body mass index 
• overall results do not support the hypothesis that exposure to PCBs increases the risk of breast cancer (but see specific categories above)
• the most important predictors of PCBs were age, serum cholesterol, and residence in the Midwest or Northeast
• three PCB congeners (numbers 138, 153 and 180) and dioxin altered the expression of tumor suppressor genes, and therefore have the potential to affect breast cancer risk
• no association was seen between PCBs and the onset of menopause (a breast cancer risk factor) 
• some PCB breakdown products are anti-estrogenic, with varying potencies and the potential to suppress breast cancer.
• some PCB breakdown products are persistent and bioaccumulative, and could be potentially active as environmental anti-estrogens in wildlife and humans
• one study which found negative results used PCBs 118, 153, 138 and 180
• blood samples collected after treatment, rather than before treatment, for characterizing PCB levels may lead to misclassification of exposure
• results suggest that exposure to dioxin-like PCBs increases breast cancer risk 
• past exposure to PCBs may affect the risk of developing breast cancer
• PCB residues were lower in the blood of breast cancer cases 
• the odds ratio of PCB risk was higher for non-estrogen-sensitive breast cancers than for estrogen-positive cancers
• PCBs tended to be more strongly associated with risk of larger and higher-grade breast tumors (tumors with a poor prognosis)
• Alaska women had PCB levels similar to New York women in the 1980s
• Alaska Native women had PCB levels and congener profiles similar to Arctic animals
• data do not support the hypothesis that oxidative DNA damage caused by exposure to organochlorines is an important risk factor in breast cancer 
• newborn exposure to high doses of a mixture of PCBs, DDT, DDE and dioxin (as found in human milk) could favor development of later breast tumors induced by other carcinogenic chemicals
• mixture delayed development of palpable breast tumors in the rat
• wastewater treatment plant discharges have measurable PCBs and hormonal properties
• dioxin and certain PCBs increase the metabolism (breakdown) of hormones used in estrogen replacement therapy, potentially impacting estrogen-responsive breast tumors
• three PCB congeners (#138, 153 and 180) have multiple effects on the estrogen- and androgen-receptors
• di-ortho, multiple-chloro substituted PCBs can compete with natural hormones to interfere with hormone regulated processes [such as breast cancer development or progression]
• certain PCBs (#28 and 52) were associated with malignant breast lesions, with PCB 28 the most important risk factor
• relative levels of specific congeners were, in general, highly correlated, with the exception of PCB 180, a heptachlorobiphenyl
• serum levels of total PCBs are not important predictors for breast cancer in the general population
• studies have not been able to evaluate whether exposure to highly estrogenic, short-lived PCB congeners increases breast cancer risk
• studies have not fully evaluated risk associated with PCB exposure in susceptible subgroups or at levels above general population exposure, including women with occupational exposure 
• study did not provide evidence that, for the teachers with breast cancer in the polluted school, a relevant exposure to genotoxic agents exists
• measurements 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
• two PCB congeners (180 and 183) were associated with breast cancer risk
• estimating joint effects of all PCB congeners in a single analysis is complicated by correlation among exposure levels
• studies of PCB congeners and health require in-depth statistical analysis to better understand complex issues related to their collinearity
• total PCB did not appear associated with breast cancer, but significant differences were observed among nine PCB congeners, with some having protective effects and others having adverse effects
• total PCBs did not differ significantly between cancer cases and controls (tissue study)
• PCB 183, which is also an inducer, was significantly associated with breast cancer risk in women with higher fat  levels  (PCB 183 accounts for about 9% of total PCBs)
• PCB 118 and 153 were not associated with breast cancer risk
• results suggest absence of a strong effect for total PCBs in breast cancer but lend support for associations among subgroups of women
• factors such as income, parity, breastfeeding, race/ethnicity, and body mass index influenced the relationship of organochlorines and breast cancer
• chinese PCBs produced cell proliferation rates similar to the effects of human estrogen hormone in human breast cancer cells
• cell proliferation was enhanced at lower PCB doses, but not at high PCB doses (possibly because of cell-toxicity or anti-estrogenic effects with the PCBs)
• environmental exposure to PCBs may not substantially affect breast cancer risk 
• data do not support hypothesis that PCB  exposure increases endometrial cancer risk (which is more sensitive to estrogens than breast tissue)
• past exposure to estrogenic organochlorines may not only affect the risk of developing breast cancer but also the survival 
• breast cancer risk increased with increasing serum levels of PCBs 118 and 138
• repeated assessment of exposure during a relevant time period may provide a more precise risk estimate than a single measurement
• changes in PCBs over time are influenced by metabolism, body mass index, and current organochlorine exposures, and each may affect interpretation of organochlorine levels in risk assessment models
• blood serum levels of PCB were correlated with body mass index
• PCB congeners exhibit a wide divergence of estrogenic response, enzyme activity and biological half-lives
• understanding breast cancer risk from PCB exposure requires attention to congener structures in complex mixtures and exposure changes over time
• PCBs are found in human tissue due to their inefficient metabolism and their solubility in lipids, which lead to lifelong sequestration in adipose (fat) tissue
• PCBs were higher for breast cancer case patients than for control subjects, but it was not a significant association
• in most studies, PCBs were measured in serum, but levels in breast adipose tissue are higher and represent cumulative internal exposure at the target site for breast cancer. 
• breast cancer odds ratios were above two in the highest concentration categories of PCB congeners 105 and 118, and the odds for these PCBs increased linearly across categories
• PCBs 105 and 118 produced higher risks among premenopausal women
• PCBs 170 and 180 produced higher risks among postmenopausal women. 
• clear associations with breast cancer risk were demonstrated in this study for some PCBs measured in breast adipose tissue
• dioxins and dioxin-like PCBs may inhibit estrogen action through the AHR/ARNT by competitively inhibiting ER alpha binding to imperfect ERE sites, adjacent to or overlapping XREs
• PCB #4 promoted foci formation in breast cancer cells, by stimulating the production of key proteins or structures in the cancerous tissue
• adipose tissue and plasma concentrations of most organochlorines were higher in case patients than in control subjects
• exposure to estrogenic organochlorines may affect the incidence of hormone responsive breast cancer
• total PCBs in breast cancer patients were higher in malignant tissue than in adjacent mammary and adipose tissues
• PCB values obtained in normal tissues from cancer patients were similar to those in the tissues from the healthy control subjects
• individual PCBs were highest in extracted lipids of malignant tissue
• PCBs 104 and 188, and 5 metabolized (hydroxylated) PCBs significantly increased breast cancer cell proliferation
• hydroxylated PCBs were more hormonally active than the PCBs, with one being nearly as potent as natural estrogen
• PCB concentrations among the non-cancerous “control” women were 147% higher in 1974 than 1989
• after 20 years of follow-up, exposure to relatively high concentrations PCBs showed no evidence of contributing to an increased risk of breast cancer 
• PCB-118 and 138 were associated with increased  breast cancer when blood was collected close to the time of diagnosis
• PCB 54 is estrogenic in breast cancer cells 
• a metabolite (breakdown product) of PCB 54 is 10 times as estrogenic as PCB 54
• two hydroxylated (metabolized) PCBs were estrogenic in two assays
• statistically significant predictors of PCB levels included age, serum lipids, parity, and fish consumption
• grouping with respect to degree of chlorination, enzyme induction, occurrence, and other toxicological aspects were useful for reducing PCB congeners into meaningful analytic units
• PCBs may modify genetic effects on postmenopausal breast cancer risk through increased enzyme induction or by activation by specific PCB congeners
• women with above average PCB levels had increased breast cancer risk associated with the presence of certain genetic markers 
• study found a modest increase in breast cancer risk for women with detectable levels of less chlorinated PCBs
• among parous women who had never lactated, there was some evidence for increased risk, associated with higher total PCBs in serum, moderately chlorinated PCBs, and greater numbers of detected PCB congeners
• co-planar PCBs 77 and 126 increased the odds ratio for breast cancer in postmenopausal women
• the risk increased further for postmenopausal women with estrogen-sensitive tumours, for PCBs 77, 126 and 169
• congener specific analysis of PCBs showed that some individual congeners were preferentially excluded from or concentrated in the breast cyst fluid
• levels of most congeners of PCBs were similar whether measured in fat or blood samples
• PCB congener patterns were similar in most human and wildlife samples, but different from PCB patterns found in people exposed to PCBs occupationally
• di-ortho PCBs 153 and 137 were found in all fat and over 98% of blood samples
• PCB 77 (dioxin-like) enhanced breast tumor development after the tumors were initiated by another toxic chemical
• PCB congeners can influence breast cancers
• PCB 80 is weakly estrogenic
• PCB 52 revealed no estrogenic properties 
• PCB 77 (dioxin-like) is estrogenic, highly toxic and bioaccumulates significantly
• one PCB congener can act as both an agonist and antagonist of estrogen and the magnitude of these effects can alter according to molecular environment
• studied levels of PCB 77 are similar to levels found in humans, so these results may be relevant
• PCBs may play a role in breast cancer as a result of their carcinogenic, immunotoxic, and, sometimes, estrogenic properties
• higher concentrations of PCBs 118, 138, 153, and 180 were found in women with breast cancer than in control persons
• breast cancer correlations were significant for PCB 118, and nearly significant for PCB 153
• PCB 156 and 170 were lower (not significant) in cancer tissue than in tissue from women with benign disease
• study found a slight increase in breast cancer risk among nulliparous women with increasing total PCBs and congeners 118, 138, and 153, however, it cannot be considered significant given the small sample size.
• PCBs were associated with a moderate increase in the odds of breast cancer
• the combined additive effect of 11 xenoestrogens (including PCBs)  led to dramatic enhancement of the hormone's action, even when each single agent was below its no-observed-effect concentration
• a significantly decreased trend in the incidence of mammary gland neoplasms compared to control was also noted for females receiving Aroclors 1242, 1254, and 1260.  (Study funded by General Electric Corp.)
• among PCBs, Heptachlor is estrogenic, whereas Aroclor 1221 and Aroclor 1254, both individually and in combination, are only weakly estrogenic
• adipose (fat) tissue levels of PCBs should be analyzed in addition to blood serum to fully understand the relationship of PCBs to breast cancer
• no significant relationship was found between serum concentrations and tissue residues for 15 of the 17 compounds analyzed
• sample PCB levels can vary up to 20% depending on sampling methods
• eleven of 13 hydroxylated metabolites of PCBs were anti-estrogenic, while 2 were estrogenic
• human metabolites of PCBs were not estrogenic in human breast cancer cells (industry consultants)
• changes in PCB levels within a 1 to 3-month period are minimal for noncancer patients and a single measure for estimating exposure is highly reliable for PCB
• PCB 126 (dioxin-like) significantly increased hydroxylation of estradiol in female rat livers
• hydroxylation has been suggested as responsible for development of estrogen-dependent tumors
• lower chlorinated, ortho substituted, non coplanar PCBs are weakly estrogenic
• free radicals and oxidative DNA damage are produced during oxidation of lower chlorinated PCBs 
• increased oxidative DNA damage is detected in human breast tumor tissue
• breast tissue concentration of OCDD [a form of dioxin] was increased in cancer patients, whereas concentrations of other dioxins and furans were equal in cases and controls   [Certain PCBs are dioxin-like, or contaminated with dioxins]
• guidelines provided for PCB half-lives 
• two PCB congeners (2,3,4-HCB, 2,4,5-HCB)  inhibit gap junctional intercellular communication (GJIC) in normal human breast epithelial cells, which could have tumor-promoting potential
• since the breast appears to be most susceptible to the carcinogenic effects of ionizing radiation during the first decade of life, exposure to other carcinogens during early breast development may be important in determining breast cancer risk
• it is not known whether exposure to PCBs in the womb or though breast milk can affect breast cancer rates in female offspring
• in addition to occupational exposures, environmental estrogens may have played a role in breast cancer in women and men in industrialized countries
• some congeners of PCB elicit very weak estrogenic responses in animals, while dioxin and related compounds have anti-estrogenic properties.
• coplanar PCBs significantly increase the ratio of 16 alpha-OHE1/2-OHE1 metabolites to values comparable to or greater than those observed after DMBA (a known breast carcinogen)
• the most abundant compounds found in fat tissue in both breast cancer cases and controls were p, p-DDE and PCB 
• PCBs were lower among white breast cancer patients compared with white controls
• elevated levels PCBs were found in fat samples from women with cancer, compared with those who had benign breast disease
• PCB 77 (dioxin-like) does not exhibit ER agonist activity but exhibits a broad spectrum of anti-estrogenic responses consistent with ligand-mediated AhR-ER crosstalk
• two hydroxylated metabolites of PCBs exhibited estrogenic activity, which was additive at high and low levels of estrogen receptor expression
• in addition to the hydroxylated metabolites, selected parent PCB congeners may also exhibit estrogenic and anti-estrogenic activities
• all but one of the tested hydroxylated PCBs competitively bound to the mouse and rat estrogen receptors
• structure and estrogen receptor binding relationships were different in the rat and mouse
• estrogenic activities were not dose-dependent
• several hydroxy-PCB congeners exhibited antiestrogenic activity
• two hydroxy-PCB congeners induced CAT activity in breast cancer cells transiently transfected with the Vit-CAT plasmid
• structure-estrogenicity/anti-estrogenicity relationships for these hydroxy-PCBs were complex and response-specific
• occupational exposure to relatively high levels of PCBs are not associated with an increased incidence of breast cancer
• E2 2-hydroxylase activity and the 16alpha-hydroxyestrone/2-hydroxyestrone metabolite ratio in breast cancer cells does not predict xenoestrogens or mammary carcinogens
• levels of  PCBs are not consistently elevated in breast cancer patients
• all of the hydroxy-PCB congeners inhibited one or more estrogenic responses
• one congener inhibited 17beta-estradiol-induced cell proliferation and CAT activity in breast cancer cells
• the dietary contribution of estrogenic industrial compounds is 0.0000025% of the daily intake of natural estrogenic flavonoids in the diet
• dioxin-like PCB congeners (numbers 81, 169, 77, 157, 105,  and 114) were anti-estrogenic, in descending order of potency
• PCB commercial mixtures (Aroclors 1221, 1232, 1248, 1254 and 1260) were inactive as anti-estrogens at the highest concentrations used in this study (10(-6)M)
• several dioxins and furans were also anti-estrogens
• PCBs and Dioxin induced enzymes which in turn can activate many potential mutagens and carcinogens in the mammary gland
• the accumulation of PCBs measured in breast fat tissue do not relate to the occurrence of mammary cancer
• PCBs have been detected in human milk samples. Their possible contribution to breast cancer has never been seriously studied (1983)
• the long-term and pernicious impacts of endocrine disruptors show our poor understanding of the complexities of life's mechanisms
• the collective exercise of wisdom, prudence and responsibility towards the essence and integrity of humanity has become, more than ever, an ethical, and perhaps even a survival, imperative
• no indication emerged of a relationship between PCB content in extractable breast fat tissue and the occurrence of breast cancer.
• most breast cancer risk factors can be linked to cumulative lifetime exposures to bioavailable estrogens
• the steep increase in breast cancers in high social strata is thought to reflect different cumulative exposures to endogenous or exogenous estrogens and proestrogens
• exogenous risk factors for breast cancer include exposure to PCBs
• tumors in patients who inadvertently consumed PCBs in 1968 have included one or more occurrences of breast cancer
• elevated levels of PCB metabolites have been found in some breast cancer patients, though not enough to establish a definitive causal relationship
• additional studies are needed to better understand the risk presented by xenoestrogens [such as PCBs]
• higher halogenated PCBs (especially, tetra-, penta-, and hexa- chlorinated biphenyls) act as promoters of carcinogenesis
• lower halogenated PCBs may be activated by hepatic and breast (milk) enzymes to oxygenated species that are electrophilic and bind to DNA
• PCBs have weak estrogenic activity and may enhance breast cancer formation by an estrogenic effect on breast epithelial cell growth
• PCBs inhibit gap junctional intercellular communication (GJIC) which may be involved in enhanced growth and breast cancer formation
• studies of breast cancer risk from organochlorine exposure have shown increased levels of  PCBs 
• PCBs exhibit endocrine-disrupting hormonal activity, and can interfere with the reproductive systems of human and other animals
• organochlorines appeared to be biphasic (at lower concentrations they stimulated breast cancer growth, and at higher levels they inhibited growth.)
• few studies provide information about long term exposure to low doses of  PCBs that would parallel exposure in young women
• laboratory data do not provide compelling evidence for PCB-dependent, estrogen mediated effects on breast cancer, although they do not exclude the possibility
• PCBs were estrogenic in animal studies, binding to estrogen receptors leading to increased uterine weights and blocking ovulation
• when hydroxylated, PCB congeners structurally resemble estradiol
• women with certain genetic characteristics (CYP1A1) combined with higher PCB exposure have been found to have a moderately increased breast cancer risk.
• a woman's lifetime exposure to endogenous hormones and breast cancer are strongly related
• PCBs mimic biological activity of estrogen and may contribute to an increased risk
• PCBs in breast tissue may influence formation of hydroxyl radicals in cells effecting oxidative DNA damage
• human milk can contain components [including PCBs] capable of causing genotoxic damage in human breast cells, which may be significant in breast cancer initiation 
• increases in male breast cancers may be part of larger trend of increasing male reproductive disorders, possibly linked to estrogenic environmental chemicals
• some studies have found higher breast tissue levels of organochlorines among breast cancer patients, but the findings are inconsistent.
• most studies on half-lives of PCBs, linked with increased risk of breast cancer, have been based on small sample sizes and a limited number of repeated measurements
• researchers need to adjust hormone measurements for systematic fluctuations over the menstrual cycle 
• certain dioxins and dioxin-like PCBs are anti-estrogenic and suppress tumors, which may make them useful in treating breast cancer  (industry consultant)
• increased incidences of breast cancer were found due to airborne pollutants [including PCBs]
• dioxin exposure may have implications in toxicity pathways other than the AhR signaling pathway
• dioxin disrupts multiple endocrine pathways
• dioxin caused increased mortality from all cancer combined
• dioxin was significantly related with breast cancer incidence among women
• breast cancer incidence increased more than 20 years after exposure of younger women (but not earlier)
• dioxin exposure resulted in a higher breast cancer incidence
• manmade estrogen disruptors [such as dioxin] may redirect estrogen metabolism in a more toxic pathway in breast cancer cells by altering the enzyme ratio
• few studies have addressed the molecular consequences of a combination of contaminants
• dioxin exposure of baby female rats in the womb increased the total proliferative compartment in terminal end buds (breast tissue) of the resulting adult female rats
• alteration of breast tissue differentiation (increased number of terminal end buds) is correlated with increased susceptibility to breast cancer from prenatal exposure to dioxin
• dioxin treatment resulted in an increased number of chemically-induced breast cancers in rats
• prevention of breast cancer may require intervention at an early age
• investigation of chemical exposures as possible etiologic factors for breast cancer has not been a research priority in the United States
• because breast cancer risk is strongly associated with reproductive hormones, environmental chemicals which mimic hormones should be investigated
• tamoxifen alone did not produce toxicity [tamoxifen is a common treatment for breast cancer]
• dioxin and tamoxifen together produced toxicity 9elevated liver dioxin retention and enhanced severity of liver pathology)
• dioxin exposure increased breast cancer mortality, but not breast cancer incidence
• breast cancer rates have increased, and the increase may be due to natural and synthetic chemical exposures which mimic hormones
• answers to mechanistic questions have not been and should not be the driving force behind public health policy
• cancer activists embrace a form of conservatism that advocates prudence in the face of exposure to estrogenic and other endocrine-disrupting chemicals
• unmet needs for cancer activists refer not so much to data gaps as to the failure to eliminate ongoing cancer hazards
• 15,000 manmade organochlorines are circulating in the environment; therefore, PCBs are only a tiny fraction of modern human organochlorine exposure

Comments from Upcoming Research Abstracts
 
• PCB accumulate in fat tissue (as in breast tissue) and have carcinogenic, estrogenic or anti-estrogenic properties
• the most prevalent PCBs were 153, 180, and 138. 
• octa-, Hepta- and Hexa-Dioxins and Penta-Furan are the major Dioxin congeners
• dioxin appears to be decreasing from 1980 levels in San Francisco women.
• dioxin and furan levels did not differ significantly between breast cancer cases and cancer-free cases.
• organochlorine levels during pregnancy may be associated with subsequent breast cancer
• associations between organochlorine exposure and breast cancer may be strongest among women who have never had children
• for these women, analyses may be most sensitive for detection of organochlorine effects because these analyses will capture both cumulative pubertal exposure and total exposure present prior to breast differentiation that follow first pregnancy
• total PCBs may be associated with increased breast cancer risk for Blacks and decreased risk for Whites
• some PCB congeners may be associated with decreased breast cancer risk while others may be associated with increased risk
• race differences in the composition of total PCBs may explain race differences in associations between total PCBs and breast cancer.
• individual congeners of PCBs can be either estrogenic or anti-estrogenic
• PCBs can act through a variety of mechanisms potentially leading to additive, antagonistic or synergistic effects
• microbial reductive dechlorination and metabolic transformation of PCBs within the body, may substantially alter the activity of these mixtures
• reductive dechlorination of PCBs may increase the estrogenic activity
• metabolism of PCBs further alters the estrogenic and anti-estrogenic activity of these mixtures
• elevated breast cancer risks were found with PCBs
• no association was observed for PCBs with breast cancer
• data support the theory of developmental windows and estrogenically-active xenobiotics [such as PCBs] playing a role in predisposition for mammary cancer
• few laboratory-based studies have been done concerning underlying PCB molecular mechanisms in normal human mammary epithelial cells
• dioxin suppressed breast tumors initiated by certain toxins, but not others
• PCB exposure may affect more than one hormone system, an outcome that could be missed by evaluating estrogenic activity alone

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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