Our objective was to identify occupations associated with elevated rates of breast cancer. This issue has been largely neglected, possibly because of class  and gender bias . Many of the findings in this study are consistent with those from other studies of non-occupational risk factors for breast cancer related to the lifetime load of endogenous estrogens . These include the finding of an increased risk with duration of fecundity, decrease with the number of pregnancies and a not statistically significant decrease with length of breast-feeding . Similarly, the 28% increase associated with a 20 pack-year smoking history is consistent with other studies  indicating a general validity of the approach and findings. The observed socioeconomic status (SES) effect is less consistent with prior work. Although higher income and education have generally been associated with higher risk , our findings of an elevated risk in women with lower SES may have resulted from higher exposures to EDCs and carcinogens in the lower income manufacturing and agricultural industries of the geographic study area.
Band et al.  conducted a case–control study with 1018 cases in British Columbia. It was similar to this study but with separate analyses for large numbers of industry and occupation categories, classified as “usual” (longest held job) or ”ever/never,” and compared to all others. Because long durations of employment in one sector would tend to be associated with short durations in all other sectors, sectors conferring risk would be mutually negatively confounding when analyzed one at a time (i.e., the comparison group would have higher durations in the competing etiologic sectors). Beauty care, transportation, data-processing and food processing showed significant elevations for premenopausal breast cancer and laundry/drycleaning for postmenopausal cancer.
Villeneuve et al.  analyzed a case–control study (1230 cases) in two departments of France for each of 41 industry and 54 occupation categories individually, observing a statistically significant breast cancer excess after 10 years duration in motor vehicle manufacturing (obs/exp= 18/7=2.6(95% CI:1.0-6.3). This study also may have had negative exposure confounding causing diminished effect estimates.
Labrèche et al.  analyzed a case–control study in Montreal (556 cases) using an expert panel to estimate historical exposures to 300 substances. Analyses, limited to only 22 substances with > 5% prevalence, found significant excesses of postmenopausal cancer for polycyclic aromatic hydrocarbons (PAHs), and several polymeric fibers; results for chemicals involved in automotive plastics or canning operations were not reported.
Observing associations between breast cancer incidence and generically assigned exposure ratings in broad industrial categories in the present study suggests that the etiologic agents, whether as carcinogens or EDCs, are widely distributed possibly encompassing many compounds. The specific identification of causative agents should be possible in occupational studies with detailed compound-specific retrospective exposure assessments.
Many of the women in this study had a background in farming or in the automotive plastics sector and this provided sufficient statistical power to show consistency with our prior studies [26, 27]. Similarly, statistical power was sufficient to reliably identify elevated risks associated with food canning, bars-gambling and metalwork. In other sectors, such as construction, petrochemical, printing, and textile manufacturing sectors, there was a lack of statistical power.
This study found elevated breast cancer risk among women who had farmed. Agriculture in southwestern Ontario is diverse with tomato, corn and peach production being major activities. No additional risk, beyond what was found for farming in general, was observed for corn cultivation when atrazine was used but the labor-intensive activities there (detasseling) may have had low exposures. Several pesticides act as mammary carcinogens in animal bioassays ; many are EDCs . In several cohort studies no elevated risk was observed among farming women  but some of these studies did not examine specific exposures or their timing. The Agricultural Health Study , while inconclusive, found risk was elevated among postmenopausal women whose husbands used specific pesticides . A recent study found that young women exposed to DDT before the age of fourteen had an excess breast cancer risk before age fifty . Band et al.  found in pre- and postmenopausal cases (combined) elevated breast cancer risk in fruit and other vegetable farming (OR = 3.11, 90% CI 1.24-7.81). There was an even greater breast cancer risk among women ever employed in other vegetable farming (OR = 7.33, 90% CI 1.16-46.2). One important aspect of farming in terms of endocrine disruption is that employment tends to begin earlier than other occupations. This may impart particular risks for those in pre-pubescent or pre-parity windows of vulnerability .
The plastics manufacturing jobs held by the women who participated in this study involved primarily injection molding. Injection molding and related processes take molten mixtures of resins, monomer, multiple additives, and sometimes lamination films, and form them into plastic pieces of defined dimensions and configuration. Emissions of vapors or mists from these hot processes can include plasticizers, ultraviolet-protectors, pigments, dyes, flame-retardants, un-reacted resin components and decomposition products. Further exposure comes from skin contact in handling and performing finishing tasks .
Many plastics have been found to release estrogenic chemicals . Furthermore such additives as phthalates, and polybrominated diphenyl ethers (PBDE) have been identified as EDCs . Cumulative exposure to mixtures of various estrogenic chemicals may compound the effect . Some of the monomers present in the manufacturing of polymers (such as BPA, butadiene, and vinyl chloride) have been identified as mutagenic and/or carcinogenic . Several monomers, additives, and related solvents, such as vinyl chloride, styrene, and acrylonitrile have been identified as mammary carcinogens in animal studies .
A near doubling of the risk for female breast cancer was found among plastics and rubber industry workers (SIR = 1.8; 95% CI, 1.4-2.3) . Two other studies report increased breast cancer risk among rubber and plastics workers. Gardner et al. observed an OR of 1.4; 95% CI, 0.69-2.84, p=.26 after 10 years employment . Ji et al. observed an OR of 2.0; 95% CI, 0.9-4.3 for those who were ever employed as plastics process machine operators . Adding weight to this is a more than quadrupling of breast cancer risk found among male workers in the rubber and plastics industries (OR = 4.5; 95% CI, 0.7-28) . Villeneuve et al.  found an increased breast cancer risk among French plastics and rubber product makers (OR = 1.8; 95% CI, 0.9-3.5). Labrèche et al. recently found an excess risk of breast cancer for occupational exposure to acrylic fibers (OR = 7.69; 95% CI, 1.5-40) and for nylon fibers (OR =1.99; 95% CI, 1.0-3.9) when exposures occurred before age thirty-six . It was also reported that exposure to acrylic and rayon fibers and monoaromatic hydrocarbons doubled the risk of estrogen/progesterone positive tumours. The observation in this study of a robust association with automotive plastics manufacturing suggests that the risk factors are widespread and common in this sector. In the geographical study area, plastics production was primarily automotive. As a result, the non-automotive group was much smaller with less statistical power to detect associations. The absence of excess breast cancer incidence among non-automotive plastics workers could also be related to the types of polymers, additives and processes used in the manufacturing of automotive versus non-automotive products.
Food canning industry exposures could include pesticide residues and exposures specific to canning processes involving lead (historically) and coating emissions. Canning processing has been found to significantly reduce levels of residual pesticide  through washing, boiling, and peeling, which conceivably expose food processing workers. Some operations in this industry produce epoxy-coated cans at the food processing facility. In others, coated cans come from a supplier and are then hot washed. In either case, it is plausible that coating constituents are released into the plant atmosphere. Unlike typical consumer exposures that occur through ingestion of food packaged in epoxy-lined cans, the exposures to BPA from heated can liners experienced by canning workers occurs primarily through inhalation. The bioavailabilty of BPA that has been inhaled or absorbed dermally has been found to be eliminated at a slower rate than BPA ingested through food or drink . The associations observed for canning show higher specificity with respect to receptor type and menopausal status than was observed for automotive plastics. For etiologic effects, this would be expected because the relevant exposure in canning, if polymer-related, would be more homogeneous than that across diverse plastics manufacturing activities. There is little epidemiological research on this subject. However, Ji et al. found elevated breast cancer risk for work in food canning (OR = 3.5; 95% CI, 1.2-10.1) after adjusting for reproductive history and SES . Band et al. found elevated premenopausal breast cancer risk for work in food and beverage processing (OR = 3.45; 90% CI, 1.22-9.78) .
There were also important findings for those employed in bars or such gambling establishments as casinos and racetracks. The strong (OR = 2.28 after 10 years) (Table 6, model 4) but statistically significant (p=0.04 with one-tailed test) excess in breast cancer among bars-gambling workers implicates second-hand smoking . Environmental tobacco smoke has been identified as a major occupational health concern in the bars-gambling industries [61, 62]. The time period of lagged exposures studied here largely occurred prior to restrictive smoking regulations. Increase may also be related to disruption in circadian rhythms and decreased melatonin production resulting from work at night .
The findings for metal work, which includes foundries, metal stamping, fabrication and metalworking, have important implications for a broad range of blue collar industrial operations. Although these industries expose workers to metallic fume, metalworking fluids, PAHs, solvents, and other hazards [64, 65], there has been little epidemiological research on associated breast cancer risk. A weak association was found for breast cancer risk and soluble metalworking fluids . Several studies have found associations between PAH exposure and breast cancer risk [4, 66]. Petralia et al.  found elevated breast cancer risk among premenopausal women exposed to PAHs and benzene. Risk was found to be increased among young women exposed to solvents in a variety of industrial settings .
Despite the likely presence of diverse carcinogen or EDC exposures within industrial sectors, some distinct specificity of receptor-type associations was observed. Of sectors showing elevated breast cancer, automotive plastics and the metals-related sectors would be expected to have the most diverse mix of carcinogen and EDC exposures; the canning and bars-gambling sectors would be expected to have the least diverse. Our study found statistically significant associations with canning in two receptor types (ER+/PR- and ER-), one exhibiting a statistically significant interaction with prior farm work. If the association is etiologic, this suggests that more than one mechanism may be involved. There was also a statistically significant increase in ER- tumor status among women employed in farming. Although there has been little research in this area, Danish researchers noted an association between ER- tumor status and exposure to dieldrin . Whether or not the observed differences in hormone receptor status found in this study can be explained by the current level of understanding of the impact of EDC exposures on receptor status, they are indicative of the benefit of occupational investigations with more rigorous retrospective exposure assessments for investigating endocrine and other mechanistic aspects of breast carcinogenesis .
Finding distinct patterns for pre- versus postmenopausal breast cancer, such as increased premenopausal breast cancer among women employed in automotive plastics, adds confidence that exposure associations may be etiologic even though the exposure specificity is limited. Some of the events leading to a cancer diagnosis could occur throughout a woman’s life, i.e., both pre- and postmenopausal exposures could be involved in postmenopausal cases. Nevertheless, observing differences on menopausal status allows examination of some mechanistic hypotheses. Other studies of premenopausal breast cancer identified smoking  and such EDCs as benzene and PAHs  as risk factors.
Selection bias arising from participation that jointly depends on exposure history and case-status is unlikely to have played a significant role because study candidates did not know the intent of the study, and the participation rate among cases was relatively high. Among controls there would be even less likelihood of an exposure-driven decision. Uncontrolled confounding was undoubtedly present which is one reason why income terms were included in the model. Many lifestyle and health-related risk factors are associated with income. It would be quite unlikely for minor uncontrolled confounding to produce the strong specific associations observed.
Shift work was examined but did not produce statistically significant findings. In a study aggregating diverse workplaces, it is likely that exposures themselves depend on shift, making any shift-effect difficult to interpret. For example, not all employers operate a midnight shift and that shift can have maintenance, support and custodial activities that are absent in day-shift work and that could influence types or levels of exposures.
Exposure assessment based on survey instrument-derived work histories coded in NAICS and NOC categories has inevitable misclassification that dilutes or occludes observable associations . Changing trends in technology and manufacturing are a further source of misclassification, possibly playing a role in some sectors like food manufacturing and dry cleaning. In the case of the food sector, focus on the specific subsector for canning produced a stronger association.
Models using the additive relative rate specification fit less well than with the loglinear choice, which assumes an exponential rather than linear dependence on the exposure metric. This suggests that the weighting scheme assuming a 10-fold higher exposure with “high” vs. “moderate” may have understated this ratio.
There was an under-representation of potentially highly exposed migrant farm and greenhouse laborers because they were not treated at the regional cancer center. This exclusion may have underestimated the risk estimate. Furthermore the role of carcinogens and EDCs that are ubiquitous in society will be underestimated in this study against the inflated background.
While this study was unable to identify exposure to specific chemicals, associations were observed between breast cancer carcinogens and EDCs. EDCs and biological windows of vulnerability are not currently considered in the establishing of occupational exposure limits (OELs). These findings, along with mounting evidence from other recent studies of harm from low level EDC exposure, point to the need to re-evaluate OELs and their relevancy in regulatory protection.