Breast Cancer Studies Link PCBs With Disease

Breast cancer research suggests a link with PCB chemical exposure. Breast cancer studies are listed here.

Studies of Breast Cancer, PCBs and Dioxin

The following 129 breast cancer studies may not include all research on this topic. For more, visit the TOXNET database operated by the National Library of Medicine (the source of these abstracts). Keep in mind that these studies are not all equal in size or quality. Several studies examined the risks of only a few of the 209 kinds of PCBs. Some of the breast cancer research was published in peer-reviewed journals, while other studies were simply presented at conferences. For more information, please visit the Breast Cancer Table of Contents and Introduction.

New Study - To be published soon in Environmental Health Perspectives (link)

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.

In Wisconsin, Great Lakes fish consumption is an important source of exposure to PCBs, DDT, PBDE and other halogenated hydrocarbons—all of which may act as potential risk factors for breast cancer. The association between sport-caught fish consumption and breast cancer incidence was examined as part of an ongoing population-based case-control study. Breast cancer cases 20-69 years of age, diagnosed in 1998-2000 (n=1,481), were identified from the statewide cancer registry. Female controls of similar age were randomly selected from population lists (n=1,301). Information about all sport-caught (Great Lakes and other lakes) fish consumption and breast cancer risk factors was obtained through telephone interviews. After adjustment for known and suspected risk factors, the relative risk of breast cancer for women who had recently consumed sport-caught fish was similar to women who had never eaten sport-caught
fish (relative risk 1.00, 95% CI 0.86-1.17). Frequency of consumption and location of sport-caught fish was not associated with an increased risk of breast cancer. While recent Great Lakes fish consumption was not associated with postmenopausal breast cancer (relative risk 0.78, 95% CI 0.57–1.07), risk associated with premenopausal breast cancer was elevated (relative risk 1.70, 95 % CI 1.16–2.50). This study demonstrates no overall association between recent sport-caught fish consumption and breast cancer, although there may be an increased breast cancer risk for subgroups of women who are young and/or premenopausal. (McElroy, et al, 2003)

Study #1

Women who ate contaminated fish had an elevated incidence of breast cancer compared to those who ate less-contaminated fish

In Sweden the main exposure route for both polychlorinated biphenyls (PCB) and other persistent organochlorine compounds is through consumption of fatty fish species from the Baltic Sea (the eastern coast of Sweden). Cohorts of fishermen's wives from the Swedish east and west coasts were established. Interviewed east and west coast cohort women ate locally caught fish at least twice as often as women from the general population. The east coast cohort women displayed during the period 1968-1989 an increased breast cancer incidence and mortality in ischemic heart disease as compared with the west coast cohort. Due to lack of individual data on exposure and confounding factors, it is not possible to conclude that the differences were caused by fish intake. Infants from the east coast cohort had during the period 1973-1991 an increased risk for low birth weight, as compared with infants from the west coast cohort. A nested case-referent study within the east coast cohort indicated an increased risk (incomplete abstract) (Rylander, 1997)

Additional information from this Rylander study: “Fishermen's wives who eat organochlorine-contaminated fish [including high PCB levels] from the Baltic sea (east coast of Sweden) had an elevated incidence of breast cancer compared to women eating less-contaminated fish from the west coast of Sweden.[23] Among the group of 2175 women, 38 cancers were expected and 49 were observed.” (From: http://www.monitor.net/rachel/r573.html)

Study #2

Relative levels of specific PCB congeners were, in general, highly correlated with each other, with the exception of PCB 180, a heptachlorobiphenyl (Wisconsin Study)

Specific congeners of PCBs may differ with respect to their human health risks. For epidemiologic studies, however, measuring levels of specific congeners--as compared with estimating the concentration of total PCBs present, may be of limited value if levels of specific congeners are highly correlated. We examined the correlations among levels of specific congeners in three groups: controls from a case-control study of breast cancer in North Carolina and two groups from Wisconsin with exposure to fish from contaminated waters. Levels of specific congeners were, in general, highly correlated (Pearson r > 0.80). However, the level of congener 180, a heptachlorobiphenyl, tended to be less correlated with levels of lower-chlorinated biphenyls. Among the implications of these findings are that measurement of a select group of congeners may yield essentially the same information as measurement of a large panel, and may be more cost efficient. (DeVoto et al, 1997)

Study #3

results suggest that exposure to dioxin-like PCBs increases breast cancer risk
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

Some reports indicate that exposure to specific polychlorinated biphenyl (PCB) congeners is related to breast cancer risk. The authors recruited participants in a case-control study from October 1994 to March 1997 to assess the relation between breast cancer risk and concentrations of 14 PCB congeners measured in plasma lipids by high-resolution gas chromatography. Participants were incident cases of breast cancer in 314 women and 523 women without cancer (the “controls”) from the Quebec City region (Canada). Compared with controls, cases had significantly higher concentrations of PCB 99 (p = 0.02), PCB 118 (p = 0.03), and PCB 156 (p = 0.006). Associations were found between breast cancer risk and either PCB 118 (odds ratio (OR) = 1.60, 95% confidence interval (CI): 1.01, 2.53; fourth vs. first quartile) or PCB 156 (OR = 1.80, 95% CI: 1.11, 2.94; fourth vs. first quartile) concentration. Breast cancer risk was also associated with a total concentration of the three mono-ortho-substituted congeners 105, 118, and 156 expressed as 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (OR = 2.02, 95% CI: 1.24, 3.28; fourth vs. first quartile). These results suggest that exposure to dioxin-like PCBs increases breast cancer risk. Alternatively, the results may be explained by differences between cases and controls regarding metabolic pathways involved in the biotransformation of both mono-ortho PCBs and estrogens. (Demers et al, 2002)

Additional information: “The study also found that women with high levels of a combination of three PCBs that mimic the cancer-causing chemical dioxin--PCBs 105, 118 and 156--were about twice as likely to have breast cancer. These chemicals are known as mono-ortho PCBs. This risk was also greater in premenopausal women. The study is the second large study to suggest a link between mono-ortho PCBs and breast cancer. Although the study only analyzed three of this type of PCB, Ayotte and colleagues point out that PCBs 105, 118 and 156 composed a "major fraction" of dioxin-like chemicals in a study of breast milk in southern Quebec. Results suggest that some persistent environmental contaminants that accumulate in the body of women with age and are similar in structure to dioxin may be a risk factor for breast cancer.” From: http://www.yourlawyer.com/practice/panews.htm?parea=Toxic%20Substances&&story_id=284

Study #4

certain PCBs (28 and 52) were associated with malignant breast lesions, with PCB 28 the most important risk factor

The chronic effects of polychlorinated biphenyls (PCBs) are a public health concern, and a potential relationship with breast cancer has been postulated. The purpose of this study was to examine the possible relationship between PCBs and breast cancer. All women (134) treated by excision biopsy because of breast lump at Reina Sofia University Hospital, Cordoba, Spain over a period of 10 months were included in our study. They were all administered a questionnaire by interview, calculation of body mass index, histopathological examination of excised mass and chemical estimation of PCB congener levels in breast fat. The collected samples were from 65 (48.5%) women with benign lesions and 69 (51.5%) with malignant lesions. The variables associated with malignant lesions on univariate analysis were age, lactation period, overweight, PCB n-28 and PCB n-52. On the multivariate analysis PCB n-28 was found to be the most important risk factor (OR 9.6, 95% CI 3.8-24.4). Other risk factors were identified as age, drinking alcohol, low parity and overweight. If these findings can be confirmed in a large study population, however, they may have important implications for breast cancer risk. (Lucena et al, 2001)

Study #5

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
total PCBs did not differ significantly between cancer cases and controls

To assess a possible etiological role of organochlorine compounds in breast cancer development on Long Island, a high-risk region of New York State, concentrations of organochlorine pesticides and polychlorinated biphenyls (PCBs) were measured in the adipose tissue of 232 women with breast cancer and 323 hospital controls admitted to surgery for benign breast disease or non-breast-related conditions. Seven pesticide residues and 14 PCB congeners were assayed via a supercritical fluid extraction method followed by gas chromatography with electron capture detection. After adjustment for age and body mass index, which were strongly correlated with organochlorine levels, adipose concentrations of 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene, total pesticides, and total polychlorinated biphenyls (PCBs) did not differ significantly between cases and controls. The relative abundance of individual pesticide species and PCB congeners was similar in cases and controls. Odds ratios adjusted for age, BMI, hospital, and race gave no evidence of a dose-response for 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene, total pesticides, or total PCBs, whether stratified by estrogen receptor status or not. Breast cancer risk among Long Island residents was not elevated compared with residents of the adjacent New York City borough of Queens. We did not confirm a previously reported association between breast cancer risk and levels of PCB congener 118 (2,3',4,4',5-pentachlorobiphenyl), nor did we observe an association with the most abundant congener 153 (2,2',4,4',5,5'-hexachlorobiphenyl), a strong inducer of phase I enzymes that was reported recently to have estrogenic properties. Only PCB congener 183 (2,2',3,4,4',5',6-heptachlorobiphenyl), which is also an inducer, was significantly associated with risk, with an adjusted odds ratio of 2.0 (95% confidence interval, 1.2-3.4) in women with adipose levels >5.67 ng/g; the biological importance of this observation is unclear without confirmation in additional studies. Although neither the present nor other studies have provided convincing evidence of an association between body burden of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane and PCBs with cancer of the breast, these compounds are rated as "possible" and "probable" human carcinogens, respectively, by the International Agency for Research on Cancer. Investigations of associations with cancer at other sites should be carried out. (Stellman et al, 2000)

Additional information: “The researchers found an apparent association with increased risk for breast cancer only with the PCB congener 183, which accounts for about 9% of total PCBs. Little is known about this compound's toxicity, except that it weakly induces enzymes which may activate some carcinogens. However, no association was found between risk for breast cancer and the most abundant PCB congener, 153, which is a much stronger inducer and which has also been found to have estrogenic properties. The meaning of the finding for congener 183 is unclear, and the observation needs to be confirmed in other studies now in progress. The research team did not confirm a previously reported association with PCB congener 188.”
[from http://epi.grants.cancer.gov/LIBCSP/projects/EpidemiologyBC.html]

Study #6

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

OBJECTIVE: To prospectively evaluate if repeated measurements of organochlorine exposure provide a more precise measure of breast cancer risk. METHODS: In the Copenhagen City Heart Study (CCHS) participants donated blood twice, in 1976-1978 and 1981 1983. Information on breast cancer risk factors was obtained through standardized questionnaires. A cohort nested case-control study of 155 cases and 274 matched breast cancer-free controls who had participated in both CCHS examinations was conducted. The average serum organochlorine concentration over the course of the two examinations was used, testing a possible association between organochlorine exposure and breast cancer risk. RESULTS: A high serum concentration of p,p'-DDT over the course of the two examinations was associated with a more than three-fold significantly increased risk of breast cancer, and a dose-response relationship was apparent. Furthermore, the risk of breast cancer increased with increasing serum concentrations of PCB congener 118 and 138 and the total amount of DDT isomers (sigmaDDT), but the trends were not significant. CONCLUSION: This study provides new evidence of the adverse effect of some organochlorines on breast cancer risk. Furthermore, repeated assessment of exposure during a relevant time period may provide a more precise risk estimate than a single measurement. (Hoyer et al, 2000b)

Study #7

PCBs tended to be more strongly associated with risk of larger and higher-grade breast tumors (tumors with a poor prognosis)
The odds ratio of PCB risk was higher for non-estrogen-sensitive breast cancers than for estrogen-positive cancers
The concentrations of organochlorines in breast adipose tissue are 200-1000 times higher than in blood

OBJECTIVE: We evaluated the association between organochlorines and breast cancer subtype defined by the tumor characteristics: estrogen receptor status, progesterone receptor status, tumor size, and grade. METHODS: A case-control study was conducted from 1995 to 1997 in Kingston and Toronto, Canada. Breast adipose tissue, taken from 217 cases and 213 biopsy controls frequency-matched on age, was analysed for 14 polychlorinated biphenyl (PCB) congeners and 10 pesticides. RESULTS: Adjusting for age, geometric means of several organochlorines differed by estrogen receptor status and tumor grade (p < 0.05). Odds ratios (ORs) for each organochlorine relative to the common control group for breast cancers of differing subtype were compared using polytomous logistic regression. Although the ORs did not differ significantly by subtype, the ORs of PCBs and p, p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) were higher with risk of estrogen receptor-negative breast cancer than estrogen receptor-positive breast cancer. One of the most extreme differences was with DDE, where the OR for the association with risk of estrogen receptor-negative breast cancer was 2.4 (95% confidence interval (CI) 1.0-5.4) in the uppermost tertile relative to the lowest, whereas the corresponding OR for risk of estrogen receptor-positive breast cancer was 1.1 (95% CI 0.6-1.9). PCBs also tended to be more strongly positively associated with risk of larger and higher-grade tumors. CONCLUSIONS: The association between organochlorines and breast cancer risk did not significantly differ by subtype, but many PCBs were more strongly associated with tumors of poor prognosis. (Woolcott et al, 2001)

Additional information: “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). 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. [From EM-Com http://www.emcom.ca/summaries/woolcott.shtml]

Study #8

women with above average PCB levels had increased breast cancer risk associated with the presence of certain genetic markers
PCBs may modify genetic effects on postmenopausal breast cancer risk through increased enzyme induction or by activation by specific PCB congeners

In experimental systems, polychlorinated biphenyls (PCBs) induce cytochrome P4501A1 (CYP1A1), which is involved in metabolism of steroid hormones and polycyclic aromatic hydrocarbons in humans. A genetic polymorphism coding for a valine to isoleucine substitution in exon 7 has been associated with lung cancer risk in Japanese populations. In a previous study, we found no association between CYP1A1 genotype and breast cancer risk. However, we were interested in determining whether genotype would relate to risk when PCB body burden was taken into account. In a subset of a case-control study in western New York, 154 postmenopausal women with incident, primary, histologically confirmed postmenopausal breast cancer and 192 community controls were interviewed and underwent phlebotomy. Serum levels of 56 PCB peaks were determined by high resolution gas chromatography with electron capture. PCR-RFLP analyses of the CYP1A1 polymorphism were performed. Unconditional logistic regression was used to compute adjusted odds ratios and 95% confidence intervals. Among women with serum PCB levels above the median of the distribution in the control group, there was increased risk of breast cancer associated with the presence of at least one valine allele, compared with women who were homozygous for the isoleucine alleles (odds ratio, 2.93; 95% confidence interval, 1.17-7.36). Among women with low PCB body burden, no association between CYP1A1 genotype and breast cancer risk was observed. Adjustment for serum lipids and body mass index did not affect the magnitude of the observed associations. PCB body burden may modify the effect of the polymorphism on postmenopausal breast cancer risk through increased CYP1A1 enzyme induction or by activation by specific PCB congeners. These results should be considered preliminary, pending replication by other studies. (Moysich et al, 1999)

Study #9

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

Environmental exposure to organochlorine compounds has been associated with a potential role in breast cancer etiology, but results from previous investigations yielded inconsistent results. In this case-control study, we examined the effect of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), hexachlorobenzene (HCB), mirex, and several measures of polychlorinated biphenyls (PCBs) on postmenopausal breast cancer risk. The study sample included 154 primary, incident, histologically confirmed, postmenopausal breast cancer cases and 192 postmenopausal community controls. Usual diet, reproductive and medical histories, and other lifestyle information was obtained by an extensive in person interview. Serum levels (ng/g) of DDE, HCB, mirex, and 73 PCB congeners were determined by gas chromatography with electron capture. PCB exposure was examined as total measured PCB levels, total number of detected PCB peaks, and three PCB congener groups. In the total sample, there was no evidence of an adverse effect of serum levels of DDE [odds ratio (OR), 1.34; 95% confidence interval (CI) 0.71-2.55], HCB (OR, 0.81; 95% CI, 0.43-1.53), or mirex (OR, 1.37; 95% CI, 0.78-2.39). Further, higher serum levels of total PCBs (OR, 1.14; 95% CI, 0.61-2.15), moderately chlorinated PCBs (OR, 1.37; 95% CI, 0.73-2.59), more highly chlorinated PCBs (OR, 1.19; 95% CI, 0.60-2.36), or greater number of detected peaks (OR, 1.34; 95% CI, 0.72-2.47) were not associated with increased risk. There was some indication of a modest increase in risk for women with detectable levels of less chlorinated PCBs (OR, 1.66; 95% CI, 1.07-2.88). Among parous women who had never lactated, there was some evidence for increased risk, associated with having detectable levels of mirex (OR, 2.42; 95% CI, 0.98-4.32), higher serum concentrations of total PCBs (OR, 2.87; 95% CI, 1.01-7.29), moderately chlorinated PCBs (OR, 3.57; 95% CI, 1.10-8.60), and greater numbers of detected PCB congeners (OR, 3.31; 95% CI, 1.04-11.3). These results suggest that an increase in risk of postmenopausal breast cancer associated with environmental exposure to PCBs and mirex, if at all present, is restricted to parous women who had never breast-fed an infant. Future studies should consider lactation history of participants, as well as use similar epidemiological and laboratory methodologies, to ensure comparability of results across studies. (Moysich et al, 1998)

Study #10

co-planar PCBs 77, 126 and 169 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

In a case-control study on 43 patients operated for invasive breast cancer (cases) and 35 patients operated for benign breast disease (controls) adipose tissue concentrations of polychlorinated biphenyls (PCBs), 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and hexachlorobenzene (HCB) were investigated. Approximately 10 g of breast tissue free from tumour was taken and frozen until analysis. No significant difference for the sum of non co-planar PCBs or DDE was found between cases and controls. For postmenopausal women the odds ratio (OR) was increased for co-planar PCB #77 > 4.5 pg/g lipid (OR = 5.8, 95% confidence interval (CI) = 0.8-42), PCB #126 > 145 pg/g lipid (OR = 2.2, 95% CI = 0.2-18), PCB #169 > 90 pg/g lipid (OR = 7.8, 95% CI = 0.6-96), and for HCB > 40 ng/g lipid (OR = 1.9, 95% CI = 0.4-7.2) adjusted for age and parity. The risk increased further for postmenopausal women with oestrogen receptor positive tumours yielding for PCB #77 adjusted OR 33 (95% CI 1.8-588), PCB #126 OR not calculable (no unexposed cases), PCB #169 OR 8.6 (95% CI 0.5-136) and hexachlorobenzene OR 7.1 (95% CI 1.1-45). Also for the sum of PCB > 1230 ng/g lipid adjusted OR increased to 1.8 (95% CI 0.4-7.3) whereas the results were similar for DDE. (Liljegren et al, 1998)

Study #11

clear associations with breast cancer risk were demonstrated in this study for some PCBs measured in breast adipose tissue
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.
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.

Numerous studies have examined the relationship between organochlorines and breast cancer, but the results are not consistent. In most studies, organochlorines were measured in serum, but levels in breast adipose tissue are higher and represent cumulative internal exposure at the target site for breast cancer. Therefore, a large 3-year hospital-based case-control study was conducted in Ontario, Canada to evaluate the association between breast cancer risk and breast adipose tissue concentrations of several organochlorines. Women scheduled for excision biopsy of the breast were enrolled and completed a questionnaire. The biopsy tissue of 217 cases and 213 benign controls frequency matched by study site and age in 5-year groups was analyzed for 14 polychlorinated biphenyl (PCB) congeners, total PCBs, and 10 other organochlorines, including p,p'-1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene. Multiple logistic regression was used to assess the magnitude of risk. While adjusting for age, menopausal status, and other factors, odds ratios (ORs) were above 1.0 for almost all organochlorines except five pesticide residues. The ORs were above two in the highest concentration categories of PCB congeners 105 and 118, and the ORs for these PCBs increased linearly across categories (Ps for trend < or =0.01). Differences by menopausal status are noted especially for PCBs 105 and 118, with risks higher among premenopausal women, and for PCBs 170 and 180, with risks higher among postmenopausal women. Clear associations with breast cancer risk were demonstrated in this study for some PCBs measured in breast adipose tissue. (Aronson et al, 2000)

Additional information: “This study was the largest of its kind ever done – by 2000. Previous studies of chemicals in the bodies of women with breast cancer had failed to show a link to PCBs. But Dr. Aronson, an epidemiologist, says most past studies have looked at pollutants carried in the bloodstream. And PCBs, being an oil, lodge for many years in the body fat of humans and wildlife alike. The 24 organochlorines in her study included several banned pesticides -- mirex, hexachlorobenzene, DDT and the chemical that DDT forms when it breaks down, DDE. "We're looking at 24 organochlorines and there are 15,000 of them out there" in the environment. Some chemicals, nicknamed "gender-benders," mimic the action of the hormone estrogen and trick the body's hormone system. It has been suggested that this is the way pollution causes breast cancer. But Dr. Aronson says there's nothing so devious about these chemicals because they don't act like estrogen on women's hormone systems. They just cause cancer, and that's that.” [From http://groups.yahoo.com/group/women-csd/message/17]

Study #12

PCBs increased the relative breast cancer risk in postmenopausal women who had certain genetic characteristics
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

There is concern that exposures to the environmental chemicals polychlorinated biphenyls (PCBs) may contribute to breast cancer risk. An individual's susceptibility to the effects of PCBs may be partially determined by polymorphisms in the gene encoding the biotransformation enzyme cytochrome P450 1A1 (CYP1A1). PCB exposure induces CYP1A1 activity, and PCBs themselves or other xenobiotics can be metabolized to carcinogenic intermediates in the presence of the variant genotype. A previous case-control study provided evidence of an interaction between high exposures to PCBs and the CYP1A1-exon 7 polymorphism (the A to G transition at nucleotide 4889), leading to a significant increase in postmenopausal breast cancer risk. We examined the interaction of PCBs with the CYP1A1-MspI (the T to C transition at nucleotide 6235) and exon 7 polymorphisms among 367 breast cancer case-control pairs (293 postmenopausal pairs) in the Nurses' Health Study. Although there was no independent association of either the CYP1A1 variants or PCBs with breast cancer risk, the relative risk among the postmenopausal women with plasma PCB levels in the highest third of the distribution in the control group and at least one exon 7 variant allele compared with women who were homozygous for the wild-type allele and who had PCB levels in the lowest third was 2.78 (95% confidence interval, 0.99-7.82). The majority of studies have concluded that exposure to PCBs is unlikely to be a major cause of breast cancer, but these findings indicate that further studies of genetically susceptible populations are warranted. (Laden et al, 2002)

Study #13

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]

Organochlorines are persistent and highly lipophilic environmental contaminants which bioaccumulate in the food chain. Some of these chemicals, 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and polychlorinated biphenyls (PCBs), have been suggested to be of significance in the aetiology of breast cancer. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an anti-oestrogen in animal studies and should be thus lower the risk of breast cancer. The other isomers of polychlorinated dibenzo-p-dioxins (PCDDs) or the chemically related polychlorinated dibenzofurans (PCDFs) have not been tested regarding carcinogenesis of the breast. The purpose of this study was to investigate whether PCDDs or PCDFs influence the risk for breast cancer. Consecutive patients who underwent surgery for a breast disease between 1993 and 1995 were recruited for the study. Cases were 22 patients with infiltrative breast cancer and controls were 19 patients operated for a benign breast disease during the same time period. Approximately 10 g of breast tissue free from tumour was taken from the specimen and frozen until analysis. Fat was extracted, cleaned and analysed with a high-resolution gas chromatograph coupled to a high-resolution mass spectrometer. Median concentrations of octachlorinated dibenzo-p-dioxin (OCDD) were 598 (170-14,880) and 396 (103-1,847) pg/g lipid in the cases and in the controls, respectively. In a multivariate logistic regression analysis controlling for other risk factors for breast cancer increased odds ratio (OR) was obtained for OCDD: 401-1000 pg/g lipid yielded OR 3.8, 95% confidence interval (CI) 0.4-39, > 1000 pg/g lipid gave OR 5.2, CI 0.4-72. When the lipid OCDD variable was examined as a continuous risk factor there was a 1.09 (9%), CI 0.95-1.25, increase in the adjusted OR for breast cancer per 100 unit (pg/g lipid) increase in OCDD. No differences were found between cases and controls for the other six tested PCDDs. Mean concentration of TCDD was in the cases 3.6 (1.0-7.9) and in the controls 3.3 (1.1-6.3) pg/g lipid. For PCDFs no significant differences were found between cases and controls. The results were not changed if oestrogen or progesterone receptor status, S-phase fraction and DNA ploidy were considered. Breast tissue concentration of OCDD was increased in cancer patients, whereas the concentrations of other PCDDs and PCDFs were equal in cases and controls. (Hardell et al, 1996)

Study #14

Elevated levels of PCBs were found in fat samples from women with cancer, compared with those who had benign breast disease

The etiology of human breast cancer is unknown; accepted risk factors, e.g., menstrual, reproductive, and family histories, are implicated in less than half of all cases. Various halogenated hydrocarbons--acting as either co-carcinogens or promoting agents--which are derived from the environment and are concentrated in human fatty stores, may also play a role in breast cancer risk. A pilot study was undertaken to measure and compare levels of chemical residues in mammary adipose tissue from women with malignant and nonmalignant breast disease. Elevated levels of polychlorinated biphenyls, bis (4-chlorophenyl)-1,1 dichloroethene, and bis(4-chlorophenyl)-1,1,1 trichloroethane were found in fat samples from women with cancer, compared with those who had benign breast disease. These results, although preliminary, suggest a role for environmentally derived suspect carcinogens in the genesis of mammary carcinoma. Study looked at 20 breast cancer cases and 20 controls.. (Falck et al, 1992)

Study #15

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

We examined plasma dichlorodiphenyldichloroethene (DDE) and total polychlorinated biphenyl (PCB) levels in relation to breast cancer in a population-based, case-control study of African-American women (292 cases and 270 controls) and white women (456 cases and 389 controls) in North Carolina. Adjusted odds ratios (ORs) for breast cancer comparing the highest to lowest third of DDE were 1.41 [95% confidence interval (CI), 0.87-2.29] in African-American women and 0.98 (95% CI, 0.67-1.43) in white women. ORs comparing the highest to lowest third of total PCBs were 1.74 (95% CI, 1.00-3.01) in African-American women and 1.03 (95% CI, 0.68-1.56) in white women. Among African-Americans, the OR for total PCBs was highest for obese women (body mass index 234.2; OR, 4.92; 95% CI, 1.63-14.83). In contrast, the OR for DDE was highest for the leanest African-American women (body mass index, <25; OR, 3.84; 95% CI, 0.98-15.08). ORs for DDE were not elevated among women who lived or worked on farms or elevated among farming women who reported exposure to pesticides. Our results suggest absence of a strong effect for DDE or total PCBs in breast cancer but lend support for associations among subgroups of women. In our study, factors such as income, parity, breastfeeding, race/ethnicity, and body mass index influenced the relationship of organochlorines and breast cancer. Differing distributions of such factors may explain some of the inconsistencies across previous studies. (Millikan et al, 2000)

Study #16

higher PCBs exposures were linked with a statistically significant increase in breast cancer risk among women in the middle tertile of body mass index

BACKGROUND: Environmental exposure to organochlorines has been examined as a potential risk factor for breast cancer. In 1993, five large U.S. studies of women located mainly in the northeastern United States were funded to evaluate the association of levels of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and polychlorinated biphenyls (PCBs) in blood plasma or serum with breast cancer risk. We present a combined analysis of these results to increase precision and to maximize statistical power to detect effect modification by other breast cancer risk factors. METHODS: We reanalyzed the data from these five studies, consisting of 1400 case patients with breast cancer and 1642 control subjects, by use of a standardized approach to control for confounding and assess effect modification. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) by use of the random-effects model. All statistical tests were two-sided. RESULTS: When we compared women in the fifth quintile of lipid-adjusted values with those in the first quintile, the multivariate pooled OR for breast cancer associated with PCBs was 0.94 (95% CI = 0.73 to 1.21), and that associated with DDE was 0.99 (95% CI = 0.77 to 1.27). Although in the original studies there were suggestions of elevated breast cancer risk associated with PCBs in certain groups of women stratified by parity and lactation, these observations were not evident in the pooled analysis. No statistically significant associations were observed in any other stratified analyses, except for an increased risk with higher levels of PCBs among women in the middle tertile of body mass index (25-29.9 kg/m(2)); however, the risk was statistically nonsignificantly decreased among heavier women. CONCLUSIONS: Combined evidence does not support an association of breast cancer risk with plasma/serum concentrations of PCBs or DDE. Exposure to these compounds, as measured in adult women, is unlikely to explain the high rates of breast cancer experienced in the northeastern United States. (Laden et al, 2001)

Study #17

Overall results do not support the hypothesis that exposure to PCBs increases the risk of breast cancer (but see specific categories above)
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.

The environmental organochlorines 2,2-bis(p-chlorophenyl)1,1,1,trichloroethane (DDT) and polychlorinated biphenyls (PCBs) have been implicated as potential causes of female breast cancer. We continued follow-up of our 1997 case-control study nested in the Nurses' Health Study cohort, adding 143 postmenopausal cases and controls to the original 238 pairs, and examining specific PCB congeners for the first time. We measured plasma levels of 2,2-bis(p-chlorophenyl)ethylene (DDE), the major metabolite of DDT, and PCBs prospectively, comparing women who were diagnosed with breast cancer between 1 month and 4 years after blood collection with control women in whom breast cancer did not develop. Median concentrations of lipid-adjusted DDE, total PCBs, and PCB numbers 118, 138, 153 and 180, assessed individually, were similar among the cases and controls. The multivariate relative risk of breast cancer for women in the highest quintile of exposure as compared with women in the lowest quintile was 0.82 for DDE (95% confidence interval [CI]: 0.49-1.37) and 0.84 for total PCBs (95% CI: 0.47-1.52), 0.69 for PCB 118 (95% CI: 0.39-1.22), 0.87 for PCB 138 (95% CI: 0.50-1.50), 0.83 for PCB 153 (95% CI: 0.47-1.48), and 0.98 for PCB 180 (95% CI: 0.55-1.75). Sub-group analyses were also performed. Overall, our results do not support the hypothesis that exposure to DDT and PCBs increases the risk of breast cancer. (Laden et al, 2001)

Additional discussion: “The purpose of this study was to expand upon a previously implemented case - control study in order to determine the association of breast cancer risk with specific PCB congeners, as well as total PCBs and DDE, and to evaluate this risk with respect to potentially susceptible subgroups, such as those defined by lactation, body mass index and other breast cancer risk factors. This study added an additional 143 post - menopausal cases (those with histologically confirmed breast cancer) and controls to an existing sample of 238 pairs. Levels of specific PCB congeners and organochlorines within blood samples provided by cases and controls were analyzed. The authors cite that the addition of the 143 cases - controls did not significantly alter the relationships observed within the original study. No significant association of DDE, sum of PCBs or the individual congeners with breast cancer was observed. While the investigators noted a slight increase in breast cancer risk among nulliparous women with increasing levels of total PCBs and congener 118, 138, and 153, however, the observation was made based on few cases, and therefore cannot be considered significant. It must be acknowledged that nulliparity in itself is a known risk factor for developing breast cancer.” (from the McMaster University School of Nursing (Environment and Cancer Working Group) http://www.fhs.mcmaster.ca/ecwg/pcbarticles.htm

Note: Though this abstract claims: “Overall, our results do not support the hypothesis that exposure to DDT and PCBs increases the risk of breast cancer,” these same researchers later modified this statement with additional analysis (see later Laden study above.)

Study #18

the most important predictors of PCBs were age, serum cholesterol, and residence in the Midwest or Northeast

We evaluated predictors of plasma concentrations of dichlorodiphenyldichloroethylene (DDE), a metabolite of dichlorodiphenyltrichloroethane (DDT), and polychlorinated biphenyls (PCBs) in a group of 240 women, controls from a breast cancer case-control study nested in the Nurses' Health Study. We considered personal attributes such as age, serum cholesterol, region of residence, adiposity, lactation, and dietary intake. DDE levels increased 0.17 ppb/year of age (p = 0.0003), and PCBs increased 0.08 ppb (p = 0.0001). DDE and PCBs increased 0.20 (p = 0.02) and 0.13 ppb (p = 0.001), respectively, per 10 mg/dl serum cholesterol. Women living in the western United States had higher levels of DDE (mean = 11.0 ppb; p = 0.003), and women in the Northeast and Midwest had higher levels of PCBs (mean = 5.6 ppb; p = 0.0002) as compared to women from other parts of the country (mean DDE = 6.3; mean PCBs = 4. 5 ppb). Levels of DDE could not be predicted from consumption of meat, fish, poultry, dairy products, vegetables, fruits, and grains. There was a positive association between fish consumption and PCB concentrations among women in the Northeast and Midwest. Using data from the cases in the nested case-control study to assess the predictive ability of the models, we confirmed that the most reliable predictors of DDE were age and serum cholesterol, and the most important predictors of PCBs were age, serum cholesterol, and residence in the Midwest or Northeast. The null results for the majority of the food variables suggest that specific dietary factors, other than fish, are not currently a substantial contributor to human exposure to DDE and PCBs. (Laden et al, 1999)

Study #19

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

The role of environmental organochlorine exposure to breast cancer risk was evaluated, taking into account estrogen receptor (ER) status of primary tumors. Forty one women, aged 40 to 69 years, undergoing a biopsy for breast mass volunteered for the study. Mammary infiltration adenocarcinoma was diagnosed in 20 of the women while benign breast disease was found in 17 others. ER levels were measured in the cytoplasm of breast cancer cells. Fat and plasma organochlorine concentrations were also measured. Although adipose tissue and plasma concentrations of most organochlorines were higher in case patients than in control subjects, a statistically significant difference was noted only for hexachlorobenzene (118741) in plasma. Control subjects were compared with ER negative and ER positive case patients. Mean adipose tissue concentrations of organochlorines in ER negative case patients were generally lower than those in controls. In ER positive case patients, median and mean DDE (72559) fat concentrations were substantially higher than controls. The findings suggest that women with hormone responsive breast cancer, but not those with hormone nonresponsive breast cancer, have a higher DDE body burden than women with benign breast diseases. The authors feel that these findings support the hypothesis that exposure to estrogenic organochlorine may affect the incidence of hormone responsive breast cancer. (Dewailly et al, 1994)

Study #20

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

PESTAB. Malignant tissue and adjacent, apparently normal, glandular and adipose tissue from nine women with adenocarcinoma of the breast and mammary gland and adjacent adipose tissue from five healthy accident victims were analyzed for organochlorine compounds using electron capture gas chromatography. In the normal tissues, the p,p'-DDE content was greater than that of p,p'-DDT, whereas the reverse was true in the neoplastic tissue. o,p'-DDT was greatly increased in the malignant tissue compared with the normal tissue, and o,p'-DDD was also fairly high compared with control values. The concentrations of total DDT and PCBs in the cancer patients were higher in the malignant tissue than in the adjacent mammary and adipose tissues. The values obtained in the normal tissues from the cancer patients were similar to those in the tissues from the healthy control subjects. The concentration of individual chlorinated biphenyls was also highest in the extracted lipids of malignant tissue. The results suggest different rates of metabolism of the organochlorine compounds in the malignant and normal tissues. (Wasserman et al, 1976)

Study #21

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
PCBs may play a role in breast cancer as a result of their carcinogenic, immunotoxic, and, sometimes, estrogenic properties

Persistent chlorinated hydrocarbons assimilated through the diet may, as a result of their carcinogenic, immunotoxic, and, at least in regard to certain of these substances, estrogenic properties, play a role in the etiology of human breast cancer. As a consequence, increased concentrations of these ubiquitous environmental contaminants may be found in breast tissue of women suffering from malignant breast disease. To examine this possibility, surgically removed breast tissue samples from 65 women in Hesse, Germany were examined by capillary gas chromatography for p, p'-dichloro(diphenyl)trichloroethane (p,p'-DDT), p, p'-dichloro(diphenyl)-dichloroethane (p,p'-DDD), p, p'-dichloro(diphenyl)dichloroethene (p,p'-DDE), hexachlorobenzine (HCB), alpha-, beta-, and gamma-hexachlorocyclohexane (HCH) as well as the polychlorinated biphenyls (PCB) no. 28, 31, 49, 52, 101, 105, 118, 138, 153, 156, 170, and 180. Of the 65 patients, 45 were diagnosed with breast cancer. The control group of 20 women suffered from benign breast disease such as mastopathy. After statistical adjustment for age differences, higher concentrations of p,p'-DDT, p, p'-DDE, HCB as well as PCB-congeners no. 118, 138, 153, and 180 were detected in tissue from women with breast cancer than in tissue from control persons. These differences were weakly significant for p, p'-DDE (p = 0.017), for PCB 118 (p = 0.042) and for PCB no. 153 barely not significant (p = 0.083). On an average, a 62% higher concentration of p,p'-DDE was found in cancer tissue (cancer patients: 805 microg/kg fat; controls: 496 microg/kg fat) and 25% higher concentration of PCB no. 118 (81 microg/kg fat; 65 microg/kg fat). The concentrations of beta-HCH, PCB no. 156 and 170 were lower (not significant) in cancer tissue than in tissue from women with benign disease. PCB-congeners no. 105 and 149 as well as gamma-HCH could only be detected in individual tissue samples; congeners no. 28, 31, 49, 52, and 101 as well as alpha-HCH and p,p'-DDD were not detected in any of the samples. To rule out the possibility that the concentrations of chlorinated hydrocarbons measured were influenced by the surgical procedure, 20 samples of tissue that were at a distance (minimum 1 cm and maximum 3 cm) from the tumor, tissue that was in direct proximity to the tumor (no more than 5 mm from the tumor), and tumor tissue itself (center of tumor) were separately prepared and analyzed. The average concentrations of chlorinated hydrocarbons varied to differing degrees and only minimally in tumor and surrounding breast tissue, indicating that the surgical procedure did not influence the results. (Guttes et al, 1998)

Study #22

PCBs were associated with a moderate increase in the odds of breast cancer

BACKGROUND: We conducted a population-based case-control study to describe the relationship between occupational exposure to estrogenic chemicals and the occurrence of breast cancer in Cape Cod, Massachusetts. METHODS: Incident cases of breast cancer (n = 261) diagnosed from 1983 through 1986 and controls (n = 753) were interviewed to gather information on breast cancer risk factors and all full-time jobs held since age 18. Blinded exposure assessments were employed using the data from the NIOSH National Occupational Exposure Survey, chemical production and usage information, and the expert judgement of a certified industrial hygienist. RESULTS: Overall, 29.5% of cases and 32.5% of controls had probable occupational exposure to one or more xenoestrogens. Probable exposure to nonylphenol (21.5% of cases, 21.4% of controls), butyl benzyl phthalate (10.0% of cases, 13.2% of controls), BHA (7.3% of cases, 9.6% of controls), bisphenol A (9.6% of cases, 11.6% of controls), and 4-tert-butylphenol (2.7% of cases and 5.3% of controls) were relatively commons, while probable exposure to the other xenestrogens was rare. Only PCBs and 4-octylphenol were associated with moderate increase in the odds of breast cancer (PCBs: 5 exposed cases and 6 exposed controls, adjust odds ratio: 3.2, 95% CI = 0.8-12.2, and 4-octylphenol: 6 exposed cases and 5 exposed controls, adjusted odds ratio: 2.9, 95% CI = 10.8). (Aschengrau et al, 1998)

Study #23

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

In the present study, four structurally diverse polychlorinated biphenyls (PCBs) were chosen from a set of 20 PCBs selected to represent the 154 tetra- through hepta-chlorinated biphenyls. The purpose was to determine estrogenic activities of the chosen PCBs and five of their hydroxylated derivatives (OH-PCBs). A human breast cancer cell line (MCF-7) and primary cultures of rainbow trout (Oncorhyncus mykiss) hepatocytes were used to determine estrogenic effects. The PCBs 2,2',4,6,6'-pentachlorobiphenyl (104) and 2,2',3, 4', 5,6,6'-heptachlorobiphenyl (188), and the hydroxylated PCBs 2,2', 4',6'-tetrachloro-4-biphenylol (4'-50), 2',4', 6'-trichloro-4-biphenylol (4'-30), 2',3,5, 5'-tetrachloro-4-biphenylol (4'-72), 2',3,3',5', 6'-pentachloro-4-biphenylol (4'-112), and 2',3,4',5, 6'-pentachloro-4-biphenylol (4'-121) significantly increased MCF-7 cell proliferation. The coaddition of hydroxytamoxifen, an estrogen antagonist, inhibited increased cell proliferation. The activity of the hydroxylated PCBs 4'-50 and 4'-30 was significantly higher at all nominal concentrations tested as compared to the corresponding PCB, viz., PCB 104. The hydroxylated PCBs 4'-50, 4'-30, 4'-72 and 4'-112 induced vitellogenin synthesis in rainbow trout hepatocytes. Significant differences were found in the MCF-7 system between the parent PCB and its hydroxylated derivative, viz., for 4'-50/4'-30 and 104, and in the rainbow trout hepatocyte assay between 4'-112 and 112, respectively. No activity was observed for PCB 58 in any of the two assays in the present study. Even though cells from two different species (human and fish) are used in the present study, the results obtained by the two methods agree fairly well. In both studies the hydroxylated PCBs were more active than the PCBs, and 4'-30 was the most active compound second only to 17beta-estradiol. (Andersson et al, 1999)

Study #24

Tumors in patients who inadvertently consumed PCBs in 1968 have included one or more occurrences of breast cancer

The general toxic effects and the carcinogenic potential of the polychlorinated biphenyls (1336363) (PCBs) were reviewed. Low level exposure of primates to PCBs has caused widespread deleterious effects that persist indefinitely. General effects of the PCBs in man and in nonhuman primate experimental animals were discussed. In man, the effects have included fatigue, headaches, digestive disorders, menstrual disturbances, and hyperpigmentation in infants born to mothers exposed to PCBs. In experimental animals, the most consistent tissue modification has been a marked hypertrophy of the liver. Biochemical implications of the PCBs as possible carcinogens were discussed in terms of several metabolites and their association with cellular macromolecules. Morphological changes and tumor development associated with chronic feeding of PCBs to rodents and monkeys were described, including neoplastic liver nodules, liver adenofibrosis, hepatocellular carcinomas, and hyperplastic and metaplastic alterations of the stomach. Preliminary observations on the association of PCBs and tumor development in man were reviewed. Tumors in patients who inadvertently consumed PCBs in 1968 have included one or more occurrences of stomach, liver, lung, and breast cancers, malignant melanomas, and a malignant lymphoma. The author concludes that although there is only suggestive evidence that persons exposed to PCBs have a higher incidence of cancer, the data that have been obtained in lower animals warrant concern in man, and that until a better understanding of the potential danger of low level, long term exposure is established, it appears that any level of exposure may be injurious to human health. (Allen et al, 1977)

Study #25

Women with certain genetic characteristics (CYP1A1) combined with higher PCB exposure have been found to have a moderately increased breast cancer risk.

We had previously determined that the NAT2 slow acetylator genotype and cigarette smoking is a risk factor for postmenopausal Caucasian women. This year, diet and meat consumption was not found to be a risk factor for breast cancer. Analysis for NAT1 did not reveal additional risks. Other genetic analyses are completed for MEH3, MEH4, CYP2D6, SOD, GSTM1, GST-T and CYP1A1. CYP1A1 data have been studied in relation to PCB exposure, and a modest risk has been found in women with the highest PCB body burdens. Currently, 215 blocks have been received for p53 analysis, 93 have been immunohistochemical stained, and SSCP is in progress. To corroborate the epidemiological data, 38 breast cell strains have been established and metabolism is being studied in relation to genotypes. Methodological conditions are being addressed. Finally, to identify smoking-related risk, we have been studying smoking behavior and addiction, where, genetic polymorphisms in dopamine receptors have been associated with depressi (incomplete abstract) (Shields, 1998)

Study #26

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]

To examine the role of estrogenic organochlorine compounds in the development of human breast cancer, scientific literature addressing the relationship between exposure to organochlorine pesticides, 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (50293) (DDT) in particular, and human breast malignant neoplasm incidence were reviewed. The increased incidence of breast cancer among females was discussed and implicated with the increasing levels of external hormonal influences on estrogen receptor content. The role of estrogen in female physiology was described. Risk factors for breast cancer included a family history of the disease, lifetime exposure to estrogen, use of estrogen supplements, exposure to ionizing radiation, diet, and exposure to environmental carcinogens. The history, pharmacokinetics, and estrogenic activity of DDT were discussed. Studies have indicated the carcinogenicity of DDT, although epidemiological data have not strongly supported this observation and a mechanism of action has not been established. Some species of DDT have been shown to exhibit weak estrogenic activity. Elevated levels of polychlorinated biphenyls (PCBs) and DDT metabolites have been found in some breast cancer patients, though not enough to establish a definitive causal relationship. The authors conclude that exposure to organochlorine pesticides such as DDT is minimal enough to make this a negligible risk factor for the development of breast cancer, but that additional studies are needed to better understand the risk presented by xenoestrogens. (Houghton et al, 1995)

Study #27

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

BACKGROUND: Polychlorinated biphenyls (PCB) have been a major environmental health concern because of their wide distribution and persistence in the environment. Estimating joint effects of all congeners in a single analysis is complicated by correlation among exposure levels, and the resulting collinearity makes the results difficult to interpret. METHODS: Patients with breast-related surgery at Yale-New Haven Hospital were interviewed using a standardized questionnaire, and breast adipose tissue samples were analysed for nine PCB congeners (74, 118, 138, 153, 156, 170, 180, 183, 187). The study recruited 490 women (304 cases and 186 controls) between 1994 and 1997. Logistic ridge regression was used to analyse the instability caused by collinearity. RESULTS: Although total PCB did not appear to be associated with breast cancer risk, significant differences in effect were observed among the nine congeners. Logistic ridge regression demonstrated a protective effect on breast cancer risk for a potentially anti-oestrogenic and dioxin-like congener, 156, while two phenobarbital, CYP1A and CYP2B inducers had an adverse effect, 180 and 183. This analysis also suggested that a protective effect for another phenobarbital congener, 153, was largely explained by instability caused by collinearity. CONCLUSIONS: These results indicate that studies of PCB congeners and health require an in-depth statistical analysis in order to better understand the complex issues related to their collinearity. (Holford et al, 2000)

Additional discussion: “This study expands upon the data collected in Zheng et al's (2000) study on breast cancer risk associated with congeners of PCBs. The same nine congeners are evaluated as per Zheng et al (2000); however, as opposed to using an unconditional logistic regression modelling method as with Zheng (2000) et al's study, a linear logistic regression model was used for statistical analysis, in order to determine the joint effects of individual congeners. While the study confirmed that total PCB exposure is not related to increased breast cancer risk, investigators found that various congeners demonstrated significant differences. While congener 156 was found to have protective effects, congeners such as 180 and 183 were found to be associated with increased risk. As with Zheng et al's study (2000), the use of women with benign breast disease in the control group has the potential to act as a confounder.” [from the McMaster University School of Nursing , Environment and Cancer Working Group]
http://www.fhs.mcmaster.ca/ecwg/pcbarticles.htm

Study #28

PCBs were higher for breast cancer case patients than for control subjects, but it was not a significant association (serum study)
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

Organochlorines such as DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and PCBs (polychlorinated biphenyls), which have been used extensively as insecticides and as fluid insulators of electrical components, respectively, are known to be persistent environmental contaminants and animal carcinogens. These agents have been found in human tissue due to their inefficient metabolism and their solubility in lipids, which lead to lifelong sequestration in adipose tissue. Their association with human cancer occurrence, however, has been explored only marginally, with most studies having 20 or fewer cases. This blinded study was designed to determine whether exposure to PCBs and to DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene], the major metabolite of DDT, is associated with breast cancer risk in women. We analyzed sera from the stored blood specimens of 14,290 participants enrolled between 1985 and 1991 in the New York University Women's Health Study, a prospective cohort study of hormones, diet, and cancer. Cohort members who developed breast cancer were included as case patients in our nested case-control study. DDE and PCBs were measured by gas chromatography in the sera of 58 women with a diagnosis of breast cancer 1-6 months after they entered the cohort and in 171 matched control subjects from the same study population who did not develop cancer. The two groups of women were comparable in age (average of 63 among the cancer cases, and 59 among the non-cancer control group). There were appreciably more smokers among the non-cancer controls (15 out of 20) than among the cancer group (6 out of 20). Average height and weight were nearly identical for the two groups. The mean concentrations of PCBs, DDT, and DDE were 50% to 60% higher in the women with cancer. Concentrations in the fatty tissues of the cancer cases were: DDT 216 ppb [parts per billion], DDE 2200 ppb, PCBs 1965 ppb. (equals 19.65 ppm, or parts per million PCBs). Mean levels of DDE and PCBs were higher for breast cancer case patients than for control subjects, but paired differences were statistically significant only for DDE (P = .031). After adjustment for first-degree family history of breast cancer, lifetime lactation, and age at first full-term pregnancy, conditional logistic regression analysis showed a fourfold increase in relative risk of breast cancer for an elevation of serum DDE concentrations from 2.0 ng/mL (10th percentile) to 19.1 ng/mL (90th percentile). For PCBs, the relative risk for a change in serum levels from 3.9 ng/mL (10th percentile) to 10.6 ng/mL (90th percentile) was less than twofold, a nonsignificant association that was further reduced after adjustment for DDE. In this population of New York City women, breast cancer was strongly associated with DDE in serum but not with PCBs. These findings suggest that environmental chemical contamination with organochlorine residues may be an important etiologic factor in breast cancer. Given the widespread dissemination of organochlorine insecticides in the environment and the food chain, the implications are far-reaching for public health intervention worldwide. (Wolff et al, 1993)

Study #29

PCB-118 and 138 were associated with increased breast cancer when blood was collected close to the time of diagnosis
women with higher serum levels of PCBs showed no increased risk of breast cancer overall

OBJECTIVE: To prospectively evaluate relationships of organochlorine pesticides and polychlorinated biphenyls (PCBs) with breast cancer, we conducted a case-control study nested in a cohort using the Columbia, Missouri Breast Cancer Serum Bank. METHODS: Women donated blood in 1977-87, and during up to 9.5 years follow-up, 105 donors who met the inclusion criteria for the current study were diagnosed with breast cancer. For each case, two controls matched on age and date of blood collection were selected. Five DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] analogs, 13 other organochlorine pesticides, and 27 PCBs were measured in serum. RESULTS: Women in the upper three quartiles of hexachlorobenzene were at twice the risk of breast cancer compared to those in the lowest quartile. However, there was no evidence for a dose-response relationship, and the association was limited to women whose blood was collected close to the time of diagnosis. Women with higher serum levels of other organochlorine pesticides and PCBs showed no increased risk of breast cancer overall, although positive associations were suggested for PCB-118 and PCB-138 when blood was collected close to the time of diagnosis. CONCLUSIONS: Results of this study do not support a role for organochlorine pesticides and PCBs in breast cancer etiology. (Dorgan et al, 1999)

Study #30

Dioxin exposure increased breast cancer mortality, but not breast cancer incidence [certain PCBs are dioxin-like, or are frequently contaminated with dioxin]

Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin or TCDD) can arise as a contaminant in the production of herbicides. It causes chloracne in those exposed to it but its human carcinogenicity has been a matter of dispute. We report here a mortality follow-up of 1583 workers (1184 men, 399 women) employed in a chemical plant in Germany that produced herbicides, including processes contaminated with TCDD. Production of TCDD was reduced from 1954 after an outbreak of chloracne. Vital status up to 1989 was determined for 97.1% of workers hired between 1952 and 1984, and 367 deaths (313 men, 54 women) were recorded. A malignant neoplasm was the underlying cause of death in 93 men and 20 women. Standardised mortality ratios (SMR) were calculated with, as references, national mortality statistics for West Germany and deaths in a cohort of male gas workers; for total cancer mortality they were 1.24 (95% confidence interval 1.00-1.52) and 1.39 (1.10-1.75), respectively, among men. Cancer mortality was increased among men with 20 or more years of employment (SMR = 1.87 [Germany] and 1.82 [gas workers]) and among men who began employment before 1955 (SMR = 1.61 and 1.87). The group with suspected highest exposure to TCDD had SMRs of 1.42 and 1.78. Only 7% of cohort women worked in the high exposure locations in the plant, compared with 39.6% of men, and no increased risk of cancer mortality was observed among women; but breast cancer mortality was raised (SRM = 2.15). These results, together with a US occupational study and a German investigation of accidental exposure, support the hypothesis that TCDD is a human carcinogen. (Manz et al, 1991)

Study #31

dioxin was significantly related with breast cancer incidence among women [certain PCBs are dioxin-like, or are frequently contaminated with dioxin]
breast cancer incidence increased more than 20 years after exposure of younger women (but not earlier)
dioxin disrupts multiple endocrine pathways
dioxin caused increased mortality from all cancer combined

2,3,7,8-Tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD or dioxin), a widespread environmental contaminant, has been shown to disrupt multiple endocrine pathways. The International Agency for Research on Cancer classified TCDD as a known human carcinogen, primarily based on occupational studies of increased mortality from all cancers combined. Using data from the Seveso Women's Health Study (SWHS), we examined the association between individual serum TCDD levels and breast cancer risk in women residing around Seveso, Italy, in 1976, at the time of an industrial explosion that resulted in the highest known population exposure to TCDD. The SWHS cohort comprises 981 women who were infants to 40 years old in 1976, resided in the most contaminated areas at the time of the explosion, and had archived sera that was collected soon after the explosion. For each woman, serum TCDD exposure was measured by high-resolution mass spectrometry. Cancer cases were identified during interview and confirmed by medical record. At interview, 15 women (1.5%) had been diagnosed with breast cancer and serum TCDD levels for cases ranged from 13 to 1,960 ppt. Cox proportional hazards modeling showed that the hazard ratio for breast cancer associated with a 10-fold increase in serum TCDD levels (log(subscript)10(/subscript) TCDD) was significantly increased to 2.1 (95% confidence interval, 1.0-4.6). Covariate-adjusted results were not different. Individual serum TCDD is significantly related with breast cancer incidence among women in the SWHS cohort. Continued follow-up of the cohort will help shed light on the possible role of TCDD in the pathogenesis of breast cancer. (Warner et al, 2002)

Study #32

dioxin exposure resulted in a higher breast cancer incidence [certain PCBs are dioxin-like, or are frequently contaminated with dioxin]

One of the largest environmental polluters in Chapaevsk (Samara Region, Russia) is the Middle Volga chemical plant. From 1967 to 1987, it produced hexachlorocyclohexane (lindane) and its derivatives. Currently, it produces crop protection chemicals (liquid chlorine acids, methyl chloroform, vinyl chloride, and some other chemicals). Dioxins were detected in air (0.116 pg/m3), in soil (8.9-298 ng/kg), in the town's drinking water (28.4-74.1 pg/liter), and in the cow's milk (the content of 2,3,7,8-TCDD was 17.32 pg TEQ/g fat). The mean content of dioxins in seven pooled samples of human milk (40 individual trials) was 42.26 pg TEQ/g fat, in four female workers' blood samples -412.4 pg TEQ/g fat, in six residents blood samples (those who lived 1-3 km from the chemical plant) -75.2 pg TEQ/g fat, in four residents' blood samples (5-8 km from the plant) -24.5 pg TEQ/g fat. To assess cancer risk and reproductive health status, official medical statistical information was used. In general, the male cancer mortality observed rate in Chapaevsk is higher than expected. The SMR is higher for lung cancer 3.1(C.I. 2.6-3.8), urinary organs 2.6(C.I. 1.7-3.6). Chapaevsk women have a higher risk overall due to breast cancer 2.1(C.I. 1.6-2.7) and cervix cancer 1.8(C.I. 1.0-3.1). The incidence rates were higher for lung cancer in males and for female breast cancer in all age groups compared to Russia and Samara Region in 1998. Significant disruptions in reproductive function were detected. The mean frequency of spontaneous abortions in the last seven years was statistically higher 24.4% in Chapaevsk (compared to other of the towns region). The average rate of premature labor was 45.7 per 1000 women in Chapaevsk that is significantly higher than in most Samara Region towns. The frequency of newborns with low birth weight was 7.4%. In Russia and in most of the Samara Region towns, this rate is lower (6.2-5.1%) but not statistically different. For the determination of congenital morphogenetic conditions (CMGC), 369 children born between 1990 and 1995 were examined. The average number of CMGC per child was significantly higher, 4.5 for boys and 4.4 for girls. The first results indicated serious disruptions associated with high dioxin levels in human milk and blood in Chapaevsk. We suggest that Chapaevsk is an incredibly interesting site for further environmental-epidemiological research to assess the impact of dioxins on human health. (Revich et al, 2001)

Study #33

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

BACKGROUND: Environmental persistent organochlorines (POCs) biomagnify in the food chain, and the chemicals are suspected of being involved in a broad range of human malignancies. It is speculated that some POCs that can interfere with estrogen receptor-mediated responses are involved in the initiation and progression of human breast cancer. The tumor suppressor gene BRCA1 plays a role in cell-cycle control, in DNA repair, and in genomic stability, and it is often downregulated in sporadic mammary cancers. The aim of the present study was to elucidate whether POCs have the potential to alter the expression of BRCA1. METHODS: Using human breast cancer cell lines MCF-7 and MDA-MB-231, the effect on BRCA1 expression of chemicals belonging to different classes of organochlorine chemicals (the pesticide toxaphene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and three polychlorinated biphenyls [PCB#138, PCB#153 and PCB#180]) was measured by a reporter gene construct carrying 267 bp of the BRCA1 promoter. A twofold concentration range was analyzed in MCF-7, and the results were supported by northern blot analysis of BRCA1 mRNA using the highest concentrations of the chemicals. RESULTS: All three polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin reduced 17beta-estradiol (E2)-induced expression as well as basal reporter gene expression in both cell lines, whereas northern blot analysis only revealed a downregulation of E2-induced BRCA1 mRNA expression in MCF-7 cells. Toxaphene, like E2, induced BRCA1 expression in MCF-7. CONCLUSION: The present study shows that some POCs have the capability to alter the expression of the tumor suppressor gene BRCA1 without affecting the cell-cycle control protein p21Waf/Cip1. Some POCs therefore have the potential to affect breast cancer risk. (Rattenborg et al, 2002)

Study #34

No association was seen between PCBs and the onset of menopause (a breast cancer risk factor)

The effect of potential endocrine-modulating organochlorines on menopause has not been extensively examined. We evaluated the associations of plasma polychlorinated biphenyls (PCBs) and 1,1-dichloro-2,2-bis( -chlorophenyl)ethylene (DDE) with age at natural menopause. We analyzed data from 1407 women in a population-based, case-control study of breast cancer that was carried out in 1993-1996 in North Carolina. The adjusted hazard ratio estimating the rate of onset of natural menopause was 1.4 (95% confidence interval = 0.9-2.1) for the top decile of DDE compared with values below the median. This association is similar in magnitude to the association between smoking and menopause (hazard ratio = 1.4 [1.1-1.9]). No association was seen with PCBs. The suggested effect of DDE on timing of natural menopause encourages further research to corroborate these findings and evaluate potential mechanisms. Prospective studies, in which exposure measurements are taken before menopause, would be particularly useful. (Cooper et al, 2002)

Study #35

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

Methylsulfonyl (MeSO(2)) metabolites of polychlorinated biphenyls (PCBs) and 2,2-bis(4-chlorophenyl)-1,1-dichloroethene (4,4'-DDE), itself a metabolite of the insecticide 4,4'-DDT, are emerging as a major class of contaminants in the tissues of wildlife and humans. We investigated the antiestrogenic capacity and potencies of 3'- and 4'-MeSO(2)-2,2',4,5,5'-pentachlorobiphenyl (CB101) and -2,2',4,5'-tetrachlorobiphenyl (CB49), which are among the most environmentally persistent MeSO(2)-PCBs, and 3-MeSO(2)-4,4'-DDE on estrogen receptor (ER)-dependent gene expression in four cell-based bioassay systems. Congener- and concentration-dependent antagonism of 17beta-estradiol (E2)-induced gene expression, rather than induction of ER-dependent gene expression, was observed for the MeSO(2)-PCBs on lucifierase activity in stably transfected human breast adenocarcinoma T47D cells (ER-CALUX) and vitellogenin (vtg) production in primary hepatocytes from male carp fish (Cyprinus carpio) (CARP-HEP/vtg). 4'-MeSO(2)-CB101 and -CB49 had the highest antagonistic potency (i.e., maximum inhibition of about 70%, LOECs of 1.0 microM and 2.5 microM), whereas 3'-MeSO(2)-CB101 and -CB49 were less antagonistic; the precursor CB101 and MeSO(2)-PCB analog MeSO(2)-2,5-dichlorobenzene had no effect. Relative to the 4-MeSO(2)-PCBs, tamoxifen (IC(50), 0.06 microM and 0.7 microM) was about 40 and 7 times more potent in the ER-CALUX and CARP-HEP/vtg assays, respectively. Congener- and concentration-dependent effects on aryl hydrocarbon receptor-mediated induction of EROD activity (carp hepatocytes), luciferase expression (H4IIE rat hepatoma [H4IIE.luc] cell line), or cell viability were not observed. 3-MeSO(2)-4,4'-DDE was neither estrogenic nor antiestrogenic in either of the bioassays. Inhibitory trends for the MeSO(2)-PCBs in a bioassay based on stably transfected human embryonic kidney cell (HEK293-ERalpha-ERE) were similar to the ER-CALUX and CARP-HEP/vtg bioassays, whereas the antagonism was weaker in a related HEK293-ERbeta-ERE bioassay. Our findings suggest that the 4'-MeSO(2)-PCBs are antiestrogenic in vitro via a reversible or surmountable interaction with fish or human ER, and that the interaction with human ERalpha is apparently favored over ERbeta. MeSO(2)-PCB metabolites are persistent and bioaccumulative contaminants, and therefore, could be potentially active as environmental antiestrogens in wildlife and humans. (Letcher et al, 2002)

Study #36

available evidence does not suggest an association between organochlorines and breast cancer

Organochlorines are a diverse group of synthetic chemicals that include polychlorinated biphenyls (PCBs), dioxins, and organochlorine pesticides such as dichlorodiphenyl-trichloroethane (DDT), lindane, and hexachlorobenzene. Although use of DDT and PCBs has been banned in the United States since the 1970s, some organochlorine compounds have accumulated and persisted within the environment. As a result, measurable amounts can still be found in human tissue. Because some organochlorine compounds act as estrogen agonists or antagonists within in vitro and experimental animal systems, a possible association of breast cancer risk with organochlorine exposure has been hypothesized and investigated. Although a few studies support this hypothesis, the vast majority of epidemiological studies do not. While some of these compounds may have other adverse environmental or health effects, organochlorine exposure is not believed to be causally related to breast cancer. Women concerned about possible organochlorine exposure can be reassured that available evidence does not suggest an association between these chemicals and breast cancer. (Calle et al, 2002)

Study #3

study does not support the hypothesis that organochlorines increase breast cancer risk
study used only PCBs 118, 153, 138 and 180

Whether environmental contaminants increase breast cancer risk among women on Long Island, NY, is unknown. The study objective is to determine whether breast cancer risk is increased in relation to organochlorines, compounds with known estrogenic characteristics that were extensively used on Long Island and other areas of the United States. Recent reports do not support a strong association, although there are concerns with high risks observed in subgroups of women. Blood samples from 646 case and 429 control women from a population-based case-control study conducted on Long Island were analyzed. No substantial elevation in breast cancer risk was observed in relation to the highest quintile of lipid-adjusted serum levels of p,p'-bis(4-chlorophenyl)-1,1-dichloroethene (DDE) [odds ratio (OR), 1.20 versus lowest quintile; 95% confidence interval (CI), 0.76-1.90], chlordane (OR, 0.98; 95% CI, 0.62-1.55), dieldrin (OR, 1.37; 95% CI, 0.69-2.72), the sum of the four most frequently occurring PCB congeners (nos. 118, 153, 138, and 180; OR, 0.83; 95% CI, 0.54-1.29), and other PCB congener groupings. No dose-response relations were apparent. Nor was risk increased in relation to organochlorines among women who had not breastfed or were overweight, postmenopausal, or long-term residents of Long Island; or with whether the case was diagnosed with invasive rather than in situ disease, or with a hormone receptor-positive tumor. These findings, based on the largest number of samples analyzed to date among primarily white women, do not support the hypothesis that organochlorines increase breast cancer risk among Long Island women. (Gammon et al, 2002)

Study #38

blood samples collected after treatment, rather than before treatment, for characterizing PCB levels may lead to misclassification of exposure

Small studies have examined, with conflicting results, whether breast cancer risk is increased among women exposed to high levels of chlorinated hydrocarbons, as measured in breast fat tissue or peripheral blood collected prior to treatment (pretreatment blood). For a population-based, case-control study, collection of pretreatment blood is a labor-intensive effort. An alternative is to collect blood from cases at interview, as is done for controls, after breast cancer treatment has commenced (posttreatment blood). It is unknown whether treatment affects blood levels of the organochlorines 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) or polychlorinated biphenyls (PCBs). The purpose of this study was to determine whether pretreatment versus posttreatment blood samples yielded significantly different estimates of cumulative exposure to DDE and PCBs among newly diagnosed breast cancer patients. Two-ml blood samples were collected prior to and after treatment for breast cancer from 22 nonfasting women, ages 45-87 years, newly diagnosed with invasive disease. Treatment was defined as major surgery (mastectomy or node removal), radiation, hormones (tamoxifen), or chemotherapy. Pretreatment and posttreatment blood samples were assayed for DDE and PCBs in blinded, matched pairs. The reported concentrations (volume basis) were adjusted for estimated total plasma lipids. For DDE, mean differences in unadjusted [0.99 ng/ml; 95% confidence interval (CI), -0.36 to 2.34 ng/ml] and lipid-adjusted (0.05 microgram/g lipid; 95% CI, -0.04 to 0.13 microgram/g lipid) levels were small. For PCBs, the unadjusted (0.68 ng/ml; 95% CI, 0.05 to 1.30 ng/ml) and adjusted (0.070 microgram/g lipid; 95% CI, -0.009 to 0.149 microgram/g lipid) mean differences were of borderline statistical significance. The mean percent change in lipid-adjusted organochlorine levels did not vary substantially between treatment groups, except for those patients receiving chemotherapy [n = 5; 15.8% (DDE), 29.4% (PCBs)]. Adjusted mean differences also increased with increasing time between the pretreatment and posttreatment blood draws. In multiple regression models that included treatment, age, race, stage, and time between blood draws, only chemotherapy appeared to predict the percent change in adjusted pretreatment and posttreatment levels of DDE or PCBs (P = 0.10 and 0.06, respectively). Posttreatment blood samples drawn within 3 months of pretreatment samples, with the exception of those drawn after the commencement of chemotherapy, provide similar measures of DDE body burden levels among breast cancer cases. The use of blood samples collected after treatment, rather than before treatment, for characterizing PCB levels may lead to misclassification of exposure. (Gammon et al, 1996)

Study #39

no evidence of a relationship between PCBs and breast cancer risk

Information on the association between exposure to beta-hexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB) or polychlorinated biphenyls (PCBs) and the incidence of breast cancer is inconclusive. However, exposure to such compounds is a public health concern in Mexico and is subject to recent regulation. Serum levels of beta-HCH, HCB and PCBs were analysed in 95 histologically confirmed breast cancer cases and 95 hospital controls, 20-79 years of age, from Mexico City, enrolled between March 1994 and April 1996. After adjusting for established risk factors, there was no evidence of a relationship between beta-HCH, HCB and PCBs and breast cancer risk (OR for beta-HCH tertile 3 versus tertile 1: 1.05 95% CI 0.46-2.40; OR for HCB tertile 3 versus tertile 1: 0.46 95% CI 0.20-1.07; OR for PCBs 1.31 95% CI 0.33-5.21 for the high category of exposure). This study lends no support to the case for a role for beta-HCH, HCB or PCBs in breast cancer aetiology. (Lopez-Carrillo et al, 2002)

Study #40

the combined additive effect of 11 xenoestrogens (including PCBs) led to a dramatic enhancement of the hormone's action, even when each single agent was present below its no-observed-effect concentration

The low potency of many man-made estrogenic chemicals, so-called xenoestrogens, has been used to suggest that risks arising from exposure to individual chemicals are negligible. Another argument used to dismiss concerns of health effects is that endogenous steroidal estrogens are too potent for xenoestrogens to contribute significantly to estrogenic effects. Using a yeast reporter gene assay with the human estrogen receptor , we tested these ideas experimentally by assessing the ability of a combination of 11 xenoestrogens to affect the actions of 17ß-estradiol. Significantly, each xenoestrogen was present at a level well below its no-observed-effect concentration (NOEC). To derive accurate descriptions of low effects, we recorded concentration-response relationships for each xenoestrogen and for 17ß-estradiol. We used these data to predict entire concentration-response curves of mixtures of xenoestrogens with 17ß-estradiol, assuming additive combination effects. Over a large range of concentrations, the experimentally observed responses decisively confirmed the model predictions. The combined additive effect of the 11 xenoestrogens led to a dramatic enhancement of the hormone's action, even when each single agent was present below its NOEC. Our results show that not even sub-NOEC levels of xenoestrogens can be considered to be without effect on potent steroidal estrogens when they act in concert with a large number of similarly acting chemicals. It remains to be seen to what degree these effects can be neutralized by environmental chemicals with antiestrogenic activity. Nevertheless, potential human and wildlife responses induced by additive combination effects of xenoestrogens deserve serious consideration. Study included two types of PCBs and three PCB metabolites [breakdown products]. (Rajapakse et al, 2002) (For more discussion of this study, visit this website: http://ourstolenfuture.org/NewScience/synergy/2002-08rajapakseetal.htm)

Study #41

past exposure to PCBs may affect the risk of developing breast cancer

There is an increasing concern about environmental exposure to multiple chemicals and adverse changes in reproductive development, function, or behaviour in wildlife. The major group of environmental chemicals, such as organochlorine pesticides, polychlorinated biphenyls (PCBs) and other xenoestrogens are currently known to have estrogenic effects in vertebrates or fishes. Recent studies suggest that past exposure to such estrogenic compounds may affect the risk of developing breast cancer, precocious puberty, or impaired fertility in man. (Charlier et al, 2002)

Study #42

PCB residues were lower in the blood of breast cancer cases (serum study)

An investigation was conducted to detect residues of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and polychlorinated biphenyls (PCBs) in blood serum samples collected from a cohort of fasting females attending the health insurance outpatient clinic at Port Said between July 1999 and July 2000. Females involved in the study included 43 females diagnosed with invasive adenocarcinoma of the breast, 21 female suffering benign breast disease, and 11 normal healthy females. Serum was separated and its contents of DDE and PCBs were extracted and determined, using gas chromatography, equipped with electron capture detector. Mean residues of DDE detected in the three examined groups of females were 41+/-5.2, 48+/-6.2 and 31+/-2.5ng/g for breast cancer cases, benign breast disease cases and controls, respectively, indicating some significantly less residues in blood serum of control females. While PCBs residues detected were 54+/-17, 59+/-23 and 61+/-21ng/g, for the three groups, respectively. Residues of DDE detected in all females alike in the present study are about 15 times higher than residues detected in Canada and The Netherlands. (Ahmed et al, 2002)

Study #43

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
PCB levels were similar between breast cancer cases and controls (serum study)

OBJECTIVES: To report the levels of DDT, DDE, other chlorinated pesticides, and PCBs found in 131 Alaska Native women who had serum samples collected between 1980 and 1987 and to compare these levels to other published studies of DDE and PCB exposure among U.S. women. STUDY DESIGN: Review of data collected during a case-control study of the relationship between organochlorine chemicals and breast cancer. Data for case and control women were pooled in this analysis because case-control differences were found to be minimal and because serum samples pre-dated cancer diagnoses by 3 to 10 years. RESULTS: More than 99% of the women had detectable levels of p,p-DDE (mean 9.10 ng/mL or ppb). Mean total PCB level was 7.56 ppb. Levels of exposure varied by geographical location and ethnic identification, which maybe a reflection of dietary differences. Five of the organochlorines were detected in at least half of the study population. Results were recalculated using detection limits corresponding to other published studies of DDE and PCB levels in U.S. women. Alaska women had levels similar to those reported from New York women collected in the 1980s. We compared the PCB congener levels measured in Alaska Native women with levels reported in Arctic animals and found similar PCB congener profiles. The six most frequently detected contaminants in Alaska Natives were also detected in the marine mammal samples reported by Becker et al (5). CONCLUSIONS: Our study identified widespread Alaska Native exposure to organochlorines that originated outside of the Arctic, a finding also seen in other studies. Our results provide a reference baseline for exposure levels during the 1980s, but further research is necessary to assess temporal trends in exposure among Alaska Natives. Further, the need for national and international inter-laboratory standardization for testing for persistent organochlorines to facilitate comparisons between Alaska Natives and other American populations is clearly demonstrated. (Rubin et al, 2001)

Study #44

data do not support the hypothesis that oxidative DNA damage caused by exposure to organochlorines is an important risk factor in breast cancer

A study was conducted to test the hypothesis that oxidative DNA damage caused by exposure to organochlorines is an important risk factor in breast cancer. This is the first study that evaluates this hypothesis by measuring 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, polychlorinated biphenyl (PCB) congeners, and isomers of bis (4-chlorophenyl)-1,1,1-trichloroethane (DDT) and bis (4-chlorophenyl)-2,2,2-dichloroethane (DDE) in cancerous and noncancerous tissue. We measured these compounds in 44 primary tumors (cancerous) and 21 benign breast biopsy (noncancerous) tissues. Overall, no significant differences were observed in the level of the organochlorines between the tissues. The median concentration for 8-OHdG was 10.5 fmol/mg DNA (1.7/10(5) deoxyguanosine residues), and 8.5 fmol/mg DNA (1.4/10(5) deoxyguanosine residues) in cancerous and noncancerous tissue, respectively. These values are similar to background levels. No significant differences were observed in 8-OHdG levels in cancerous versus noncancerous tissue, and no correlation was demonstrated between the organochlorines and 8-OHdG. The data thus do not support the hypothesis that oxidative DNA damage caused by exposure to organochlorines is an important risk factor in breast cancer. (Charles et al, 2001)

Study #45

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

The role of organochlorine (OC) exposure in the etiology of breast cancer remains controversial. Thus, our objective was to determine whether the most abundant and toxic OCs found in human milk could, when ingested during the neonatal period, modulate the development of mammary tumors in the rat. We prepared a mixture composed of p,p'-dichlorodiphenyltrichloroethane (DDT), its major metabolite, p,p'-dichlorodiphenyldichloroethene (DDE), and 19 polychlorinated biphenyls (PCB) based on their concentrations found in the milk of Canadian women. Neonate rats at 1, 5, 10, 15, and 20 days of age were gavaged with this mixture, at 10, 100, and 1,000 times the amount that a human baby would consume. An additional group received 2.5 microg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg body weight (bw) by gavage at 18 days of age, instead of the mixture. On day 21, all treatment groups, except for a control group and a 1,000-mix group, received a single intraperitoneal injection of methylnitrosourea (MNU, 30 mg/kg bw), the initiator of the carcinogenic process. The average number of rats per treatment group was 33. Rats were sacrificed when their tumors reached 1 cm in size, or at 308 days of age. We prepared mammary tumors and mammary gland whole mounts for histologic analysis. There were no significant effects when only the malignant or only the benign tumors were considered. After all benign and malignant lesions were pooled, the number of mammary tumors differed among all MNU-treated groups (p = 0.02) with more lesions developing in the MNU-1,000[times] (median = 4.5; p = 0.05) and MNU-TCDD (median = 5.5; p = 0.07) compared to the MNU-0 rats (median = 2). Compared to the MNU-0 group, the percentage of rats that developed palpable tumors (benign plus malignant) was slightly higher (p = 0.06) in the MNU-TCDD group, but not in the MNU-1,000[times] group. The percentage of palpable tumors that were malignant was higher (p = 0.02) in the MNU-100[times] group (15/16, 94%) than in the MNU-0 group (10/18, 56%). The highest dose of the mixture delayed (p = 0.03) the development of tumors, but this was not observed with the MNU-TCDD treatment. These results suggest that neonatal exposure to high doses of organochlorines could favor the development of MNU-induced mammary lesions, but also delays the development of palpable tumors in the rat. (Desaulniers et al, 2001)

Study #46

wastewater treatment plant discharges have measurable PCBs and hormonal properties

The estrogenic activity (by E-screen bioassay), the concentrations of PCBs, PCDDs/PCDFs (and their resulting toxicity equivalents, TEQ) and several endocrine disrupting chemicals (EDCs: e.g., bisphenol A, nonylphenol, Butyl benzylpthalate (BBP), di-n-butylphthalate (DBP), 17alpha-ethynyl-estradiol or 4-octylphenol) have been analyzed from leachates of each step (before treatment, after biodegradation/sedimentation and after charcoal treatment) of a controlled landfill leachate treatment plant. The comparison of the effluent of the examined landfill leachate treatment plant with water from a nearby river in this study indicated no additional dioxin-like (e.g., TEQ: 0.027 compared to 1.01 pg TEQ/l; PCBs: 1.2 compared to 3.9 ng/l) or estrogenic impact (2.8 compared to 3.5 ng estradiol equivalents EE/l; analyzed by E-screen bioassay) from the leachate treatment plant into the surrounding water environment. The impact of dioxin-like compounds from uncleaned leachates into the final cleaned effluents could be sufficiently reduced by the leachate treatment plant for PCDDs (75%), PCDFs (62%), dioxin-like PCBs (97%), and the sum of TEQ (78%). The leachate treatment plant also achieved a reduction of the estrogenic activity as determined by E-screen (from 4.8 to 2.8 ng EE/l = 42%), by GC/MS for bisphenol A (>96% and nonylphenol (>98%) or by ELISA for estradiol (>80%). Additionally, for the validation of the E-screen, five known endocrine disrupting chemicals (EDCs: bisphenol A, BBP, DBP, 17 alpha-ethynyl-estradiol, 4-octylphenol) were analyzed. The EC50 values and estradiol equivalents factors (EEFs) for the five EDCs determined in this study were comparable to previously published data. The combined biological and chemical trace analysis data have provided valuable information on the relative contribution of natural, synthetic, and non-steroidal anthropogenic chemicals to the estrogenic and dioxin-like activity in leachates from a wastewater treatment plant, and water from a nearby river. (Behnisch et al, 2001)

Study #47

dioxin and certain PCBs increase the metabolism (breakdown) of hormones used in estrogen replacement therapy, potentially impacting estrogen-responsive breast tumors

Sulfate conjugates of the B-ring unsaturated estrogens, equilin, equilenin, and 8-dehydroestrone, and their 17alpha- and 17beta-dihydro analogues, constitute about 54% of Premarin (Wyeth-Ayerst), the most commonly prescribed estrogen formulation in estrogen replacement therapy. Despite the wide clinical use of Premarin, there have been very few studies on the metabolism of the B-ring unsaturated estrogens in humans and there is no information regarding the fate of these compounds in breast tissue or tumors. In this study, we investigated the metabolism of equilenin in two lines of human breast-cancer cells, MCF-7 and MDA-MB-231. MCF-7 cells respond to treatment with Ah-receptor agonists with induction of cytochromes P450 1A1 and 1B1, whereas in MDA-MB-231 cells P450 1B1 is predominantly induced. Metabolites of equilenin were identified and quantified by GC/MS utilizing a series of synthetic metabolite standards and deuterium-labeled analogues as internal standards. In the two cell lines, the same pathways of equilenin metabolism were observed. Equilenin was reduced at C-17 to the 17beta-dihydro form, with minimal production of the 17alpha-dihydro isomer. Both equilenin and 17beta-dihydroequilenin were hydroxylated at the C-4 position, and the resultant catechol metabolites were methylated to form 4-methoxyequilenin and 4-methoxy-17beta-dihydroequilenin. Rates of equilenin metabolism were markedly elevated in cultures exposed to the Ah-receptor agonists, 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3,4,4',5-tetrachlorobiphenyl [PCB], implicating the activities of P450s 1A1 and 1B1 in the metabolism. The 2-hydroxylation pathways of equilenin and 17beta-dihydroequilenin metabolism were not observed. In microsomal reactions with cDNA-expressed human enzymes, both P450s 1A1 and 1B1 catalyzed the 4-hydroxylation of 17beta-dihydroequilenin, whereas with 17beta-estradiol as substrate P450 1A1 catalyzes predominantly 2-hydroxylation and P450 1B1 predominantly 4-hydroxylation. Since P450 1B1 is constitutively expressed and both P450s 1A1 and 1B1 are inducible in many extrahepatic tissues including the mammary epithelium, these results indicate the potential for 4-hydroxylation of equilenin and 17beta-dihydroequilenin in extrahepatic, estrogen-responsive tissues. (Spink et al, 2001)

Study #48

humans may be exposed to PCBs in their homes

In order to characterize typical indoor exposures to chemicals of interest for research on breast cancer and other hormonally mediated health outcomes, methods were developed to analyze air and dust for target compounds that have been identified as animal mammary carcinogens or hormonally active agents and that are used in commercial or consumer products or building materials. These methods were applied to a small number of residential and commercial environments to begin to characterize the extent of exposure to these classes of compounds. Phenolic compounds, including nonylphenol, octylphenol, bisphenol A, and the methoxychlor metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), were extracted, derivatized, and analyzed by gas chromatography/mass spectrometry (GC/MS)-selective ion monitoring (SIM). Selected phthalates, pesticides, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) were extracted and analyzed by GC/MS-SIM. Residential and workplace samples showed detectable levels of twelve pesticides in dust and seven in air samples. Phthalates were abundant in dust (0.3-524 micrograms/g) and air (0.005-2.8 micrograms/m3). Nonylphenol and its mono- and di-ethoxylates were prevalent in dust (0.82-14 micrograms/g) along with estrogenic phenols such as bisphenol A and o-phenyl phenol. In this 7-sample pilot study, 33 of 86 target compounds were detected in dust, and 24 of 57 target compounds were detected in air. In a single sample from one home, 27 of the target compounds were detected in dust and 15 in air, providing an indication of chemical mixtures to which humans are typically exposed. (Rudel et al, 2001)

Study #49

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]

Polychlorinated biphenyls (PCBs) are ubiquitous environmental persistent contaminants giving rise to potential health hazard. Some PCBs exert dioxin-like activities mediated through the aryl hydrocarbon receptor. Although reports on interaction with other nuclear receptors are sparce, some congeners are hypothesized to possess endocrine disruptive potential. Here we present evidence that the three PCBs most abundant in biological extracts, 2,2',3'4,4',5-hexachlorobiphenyl (PCB#138), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB#153), and 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB#180) have pleiotropic effects on the estrogen- and androgen-receptor. In MCF-7 cells a slightly increased cell proliferation was observed at low concentrations (1-10 nM) in cells co-treated with 0.01 nM 17beta-Estradiol, whereas the compounds inhibited cell growth significantly at 1 and 10 microM. In reporter gene (ERE-tk-CAT) analysis the three congeners exhibited a significantly estrogen receptor-ligand mediated decrease of the chloramphenicol transferase activity in both control and 10 nM 17beta-estradiol induced MCF-7 cells. In addition, PCB#138 elicited a dose-dependent antagonistic effect on androgen receptor activity in transiently co-transfected Chinese Hamster Ovary cells with an IC(50), of 6.2 microM. In summary, this study indicate that the di-ortho, multiple-chloro substituted biphenyls, PCB#138, PCB#153 and PCB#180, can compete with the binding of the natural ligand to two nuclear receptors and thus possess the ability to interfere with sexual hormone regulated processes. (Bonefeld-Jorgensen et al, 2001)

Study #50

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

This study investigated the potential association between organochlorine exposure and breast cancer using stored sera collected from 1973 through 1991 from the Janus Serum Bank in Norway. Breast cancer cases were ascertained prospectively from among 25,431 female serum bank donors. A total of 150 controls were matched to cases by birth dates and dates of sample collection. One g of serum per subject was analyzed for a total of 71 organochlorine compounds. For 6 pesticides [B-hexachlorocyclohexane, heptachlor epoxide, oxychlordane, trans-nonachlor, p, p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, and p, p'-2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and 26 individual polychlorinated biphenyl (PCB) congeners there were >90% of samples over the limit of detection. There was no evidence for higher mean serum levels among cases for any of these compounds, nor any trend of increasing risk associated with higher quartiles of exposure. The remaining compounds (including dieldrin) were analyzed with respect to the proportion of cancer cases and controls having detectable levels; no positive associations were noted in these analyses. Our study did not confirm the recent findings of a Danish study of increased concentrations of dieldrin in the serum of breast cancer cases. The evidence to date on the association between serum organochlorines is not entirely consistent, but there is accumulating evidence that serum levels of p, p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and total PCBs are not important predictors for breast cancer in the general population. Studies to date have not been able to evaluate whether exposure to highly estrogenic, short-lived PCB congeners increases breast cancer risk, nor have they fully evaluated the risk associated with organochlorine exposure in susceptible subgroups or at levels above general population exposure, including women with occupational exposure. (Ward et al, 2000)

Study #51

study did not provide evidence that, for the teachers with breast cancer in the polluted school, a relevant exposure to genotoxic agents exists

Exposure to pollutants, in particular polychlorinated biphenyls (PCB), was established at a school built in 1966. Because of a statistically conspicuous increased frequency of breast cancer observed in the teachers of the school this study was performed to ascertain whether the teachers in the polluted school have an increased level of micronucleated cells (MN) or sister chromatid exchanges (SCE) as an expression of a raised cytogenetic risk. Teachers in a directly adjacent school served as one control group and those from a school about 30 km away as a second one. Each teacher had to answer a questionnaire and after venous blood samples had been taken, the number of MN and SCE in peripheral lymphocytes were determined. For the teachers in the polluted school, in addition, the length of stay in the building during the last month and year was recorded. Thereby no correlation with the number of MN and SCE was proven. In comparison with the two control groups, neither the number of MN nor SCE was increased in the teachers of the polluted school. Even if their predictive value for cancer risk assessment is disputed, MN and SCE have a high rating as standard procedures in the proof of an exposure to genotoxic agents. This study thus does not provide any evidence that, for the teachers in the polluted school, a relevant exposure to genotoxic agents exists. (Wiesner et al, 2000)

Study #52

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)

The simple and sensitive in vitro MCF-7 human breast cancer cell proliferation assay was used to examine the proliferation abilities of two Chinese commercial polychlorinated biphenyl (PCB) mixtures made in the 1960s. Chinese PCB3 and Chinese PCB5 were compared with 17 beta-estradiol (E2). All of the positive activities of these types of Chinese PCBs were significantly different compared to controls with respect to MCF-7 cell doubling time. At lower levels of 7.8 pg/ml and 182 pg/ml, the Chinese PCB3 showed 94% and 86% of relative proliferation effects compared to 17 beta-estradiol, respectively. Chinese PCB5, also showed higher cell proliferation activity at lower level of 8.3 pg/ml, with relative proliferation effect as high as 107% in comparison to 17 beta-estradiol. Thus, both PCBs seem to be different from corresponding Aroclor mixtures. However, Chinese PCBs did not express cell proliferation effects at higher levels of 9.1 ng/ml for Chinese PCB3 and 166 pg/ml and 8.3 ng/ml for Chinese PCB3. This may be due to cytotoxicity and/or antiestrogenic compounds in the mixtures. (Du et al, 2000)

Study #53

environmental exposure to PCBs may not substantially affect breast cancer risk

Experimental studies show that hormonal and nonhormonal activities of polychlorinated biphenyls (PCBs) are structure dependent, suggesting that the breast cancer risk associated with PCBs may vary according to specific PCB congeners. In 1994-1997, the authors conducted a case-control study of Connecticut women to investigate whether breast cancer risk is associated with body burden of PCBs and varies by PCB congeners. A total of 304 breast cancer cases and 186 controls aged 40-79 years were recruited into the study. Fresh breast adipose tissue was analyzed for PCBs. The age- and lipid-adjusted geometric mean tissue levels of total PCBs were not significantly different (p = 0.46) for the cases (478.6 parts per billion) and controls (494.1 parts per billion). The covariate-adjusted odds ratio was 0.7 (95% confidence interval: 0.4, 1.1) for all study participants when the third tertile was compared with the lowest tertile. No individual congeners or groups of congeners were associated with a significantly increased risk of breast cancer. Further stratification by type of breast disease; menopausal, parity, and lactation status; and body size also showed no significant association with body levels of PCBs. These results suggest that environmental exposure to PCBs may not substantially affect breast cancer risk. (Zheng et al, 2000)

Additional discussion: Study evaluated risks from “congeners 74, 118, 138, 153, 156, 170, 180, 183, and 187. Researchers adjusted f