This is the first study to consider whether there is an association between reports of seeing a fogger truck and the risk of breast cancer. Among the LIBCSP population as a whole, there is little evidence that ever seeing a fogger truck was associated with an increase in risk of breast cancer, however, effect estimates were stronger among certain biologically susceptible subgroups. The strongest, most robust findings were observed for women with hormone receptor positive breast cancer.
Individuals with ER+PR+ tumors were 44% more likely to have reported ever seeing a fogger truck than were participants with other breast cancer subtypes. When restricted to those who were living at the residence ≤14 and ≤20 years of age, women with ER+PR+ tumors were similarly more likely to report seeing a fogger truck than other subtypes. ER+PR+ tumors, which include Luminal A and Luminal B tumors , are driven by estrogen and progesterone levels and most commonly associated with reproductive risk factors . This is consistent with xenoestrogenic activity of commercial DDT . Laboratory studies have found that p-p’-DDT enhances ER+PR+ tumor growth [40, 41]. Therefore, it would be expected to observe the strongest effect of DDT exposure among women with this hormonally active subtype. A stronger risk of ER+PR+ tumors was not found in a previous LIBCSP report that focused on p-p’-DDT and p-p’- DDE serum concentrations, but we did not consider self-reported exposure to fogger trucks in that analysis . ER+PR+ are the most common subtype of breast cancer in American women with approximately 70% of tumors classified as ER+PR+ or “hormonally responsive” . The high prevalence of ER+PR+ breast cancer underscores the need to better understand the etiology of these specific tumors in an effort to improve public health risk reduction strategies in the U.S.
When stratifying by birth cohort, we found that seeing a fogger truck was most detrimental among women who were 20 or younger at the time DDT was widely introduced in the U.S in 1945. It is plausible that any effect of seeing a fogger truck after those early years was masked by the ubiquitous exposure to DDT. This result suggests that seeing a fogger truck had the most detrimental effect before exposure became omnipresent. The increased risk observed for postmenopausal women is likely due to the fact that women diagnosed with premenopausal breast cancer in 1996–1997 were less likely to be born in the earlier birth cohorts where an effect of DDT on breast cancer risk was observed.
The proxy measure of a fogger truck used in this study suggests that p,p’-DDT, rather than the metabolite p,p’-DDE, may be the carcinogenic compound; a result that is consistent with laboratory evidence and the Cohn et al., study [12, 24]. This finding may also help to explain discrepancies in the previous literature that often relied on DDE measurements or did not investigate the association by tumor subtype.
Although the heterogeneity in the ORs for the associations between seeing a fogger truck and breast cancer by change in weight was not significant, the study power for evaluating the interaction was low because of the small number of LIBCSP participants who maintained or lost weight. The elevated risk of breast cancer among those who gained weight and reported seeing a fogger truck compared to those who did not see a fogger truck at their residence suggests that DDT may have a stronger or more detectable effect when stored in adipose tissue of women who gain and store weight over time.
There was not a large difference in the results when >1972 reports of exposure to fogger trucks were excluded. However, due to the possible use of other pesticides after 1972 by fogger trucks it was important to consider possible exposure misclassification and to better isolate the effects of DDT exposure.
p-p’-DDT and p-p’-DDE serum concentrations, a surrogate measure of long-term exposures, were not correlated with seeing a fogger truck at a residence, a surrogate measure of acute exposures. This result is not unexpected given the long period from exposure to blood collection in this study, and evidence that current organochlorine serum concentrations may be decoupled from exposure levels due to intakes from food sources  and differing metabolism and degree of organochlorine storage in individuals . As well, this measure of acute exposure is unlikely to be indicative of total DDT exposure levels as women were likely exposed to commercial DDT by sources outside their residences. This lack of correlation between serum concentrations and the fogger truck measure at least partially explains the discrepancies between the association found here and the previous LIBCSP publication focused on serum concentrations, which did not include the fogger truck exposure .
There was no increase in risk observed for reporting a fogger truck at multiple residences. Although the report of seeing a fogger truck may represent a single exposure, it is also possible that spraying occurred repeatedly at the residence which would make it difficult to discern exact exposure levels based on the questionnaire.
There was little evidence of an increased breast cancer risk for seeing a fogger truck with either of the two biologically susceptible windows investigated in this analysis, ≤14 and ≤20 years of age. Although cell sizes were small, slightly stronger estimates were observed among participants who reported seeing a fogger truck at their residence when they were 15–20 years of age.
The LIBCSP has extensive residential history information that allowed for the investigation of exposure during susceptible windows. A strength of this investigation is that the study cohort was alive during DDT use in the U.S., and was exposed at a range of ages. However, despite the relatively large, population-based sample size available, a larger sample would have provided a better opportunity to thoroughly investigate the subgroup analysis of biological windows of susceptibility. Additionally, due to the age of the study population, there were few premenopausal women who were within the hypothesized susceptible windows during the time periods where there was an effect observed for fogger truck exposure. Due to the case–control design of the study, we were not able to completely address age-period-cohort effects that would result in a more definitive case for critical windows of exposure. We were also unable to investigate any impact time spent outdoors or use of local produce that could have contributed to the understanding of this relationship.
Another potential limitation is differential recall bias. Cases who were concerned about their previous exposures to potentially harmful chemicals may have been more likely to report seeing a fogger truck. It is unlikely that this bias would differ by ER/PR status, yet it was when we assessed for potential heterogeneity among these subgroups that one of our strongest findings was observed. Approximately equal proportions of cases and controls reported that they believed that at least one environmental factor could cause breast cancer (69 percent and 68 percent, respectively) ; suggesting recall bias was not differential with respect to case–control status. It is difficult to hypothesize at what age seeing a fogger truck could be considered a memorable experience and likely to vary across individuals. Any variation in recall would not be expected to differ by case status and thus would bias estimates towards the null. To the best of our knowledge, the use of any other pesticides in fogger trucks before the DDT ban is unknown and any exposure misclassification resulting from the use of alternative pesticides would attenuate any effect on breast cancer risk, which we assume is attributable to DDT. Alternatively, it is also possible that our results could be due to an unknown chemical or chemicals and not attributable to DDT.
We did not observe significant heterogeneity when investigating breast cancer risk by birth cohort (data not shown) and therefore it is unlikely that truck sightings are proxies for age at diagnosis. From the lack of an increase in risk observed for seeing a truck among the 1946–1972 birth cohort, we can also conclude that seeing a fogger truck was not a proxy for being at a young and potentially susceptible age during DDT use.
Few studies have examined the association between DDT exposure during younger ages and subsequent breast cancer risk, and none have considered acute DDT exposures. Therefore, the study results reported here provide a novel perspective to the ongoing discussion about the relationship between DDT and breast cancer. The stronger association observed with a biologically susceptible subgroup, namely women with ER+PR+ breast cancer, provide support for an association between DDT and breast cancer risk. With the prevalence of DDT increasing with indoor residual spraying programs for malaria vector control outside the U.S. , the importance of understanding the health effects of DDT continues.