Early life socioeconomic environment and mammographic breast density

In examining early life SES in relation to mammographic density, we aimed to further clarify the role of early life factors in the development of breast cancer risk, and identify possible life-course pathways. Specifically, we examined whether parental education and family income at birth were associated with mammographic density, assessed from mammograms obtained in midlife, after accounting for: 1) birth and childhood characteristics relevant to breast cancer risk, and 2) established risk factors for breast cancer in later life periods. We observed significantly smaller dense area for the highest family income level at birth and higher percent density for the highest parental educational attainment, but only the association between family income and dense area remained after adjustment for factors from different periods of life.

Percent density and dense area respectively capture the relative and absolute amount of fibroglandular tissues on mammograms. Both measures have similar positive associations with the risk of breast cancer and most risk factors for breast cancer [24, 27, 35]. Nondense area has been inversely associated with breast cancer risk although this association may not be independent of the effect of measures of dense area on risk [24]. Measures of body size such as BMI are more strongly associated with percent density and with nondense breast area than with dense area, as the former two measures reflect the amount of fat tissue in the breast [36]. In our study, adult BMI explained a large amount of variation in percent density and nondense area, including differences in these measures of density by parental education, suggesting that any influence from early life SES on relative amount of dense tissue may be working through influencing general body size and fat tissue in the breast, rather than directly influencing the amount of dense breast tissue, where breast tumors develop. This is further substantiated by the lack of any associations between parental education and dense area.

The patterns of parental education in percent density parallel well-documented positive associations between adult SES and breast cancer risk [11–13], which have also been reported in some studies of adult SES and mammographic density [26, 37]. However, we observed an opposite pattern for early life family income and dense area. Importantly, the inverse association between family income and dense area persisted and was minimally altered by accounting for breast cancer risk factors across the life course. Childhood family has been positively associated with breast cancer risk in limited research [14], but little is known about its association with mammographic density. Given that differences in dense area were only observed for the two extreme categories of early life family income and the unexpected direction of this association, our results should be interpreted with caution. In a recent study of the New York City site of CPP birth cohort, we reported a significant positive association between a composite measure of parental SES at birth, composed of parental education, income and occupation and percent density, but did not observe any associations for dense and nondense areas after accounting for early life factors [38]. Here, we examined the same composite early life SES measure available for the New England CPP, but not the CHDS, and did not find any associations with any measures of mammographic density. These CPP cohorts differ in their racial and ethnic diversity as well as overall sample size. Specifically, racial/ethnic minorities represented less than a quarter of the study population for the current analysis, but included over 60% of the New York-CPP cohort. Income and education are the most widely used indicators of SES in the U.S., and while these measures tend to be correlated, at times they show differential associations with health outcomes. In particular, these measures of SES are less strongly correlated, and individually may have weaker associations with many health outcomes in racial/ethnic minority populations [39, 40]. Nonetheless, our results, if replicated in other studies, point to the possibility that the associations between early life SES and mammographic density may be independent of and similar in strength as the associations with other established risk factors. Further research is also needed o clarify the direction of these associations, which is important for understanding whether SES influences on breast cancer risk is mediated through mammographic density.

The main strengths of our study include the collection of prospective data on early life factors and detailed data on breast cancer risk factors in adulthood, which together with highly reliable measures of mammographic density offer a thorough evaluation of the influence of early life socioeconomic factors on breast cancer risk. We lacked data for exposures during puberty and adolescence, critical life periods for breast cancer risk development, that are characterized by rapid growth, breast development and hormone production and slow differentiation of breast tissue [41–43]. Certain exposures such as BMI, cigarette smoking, and alcohol consumption in adolescence have been linked to breast cancer as well as mammographic density in a few studies [44–49], but focused research on SES during adolescence and subsequent breast cancer risk is extremely limited and merits further attention. Studies of mammographic density that rely on routine clinical mammography inherently include populations with greater access to healthcare. However, mammography is among the most widely used screening tests [50, 51]; nearly 80% of the participants in our adult follow up study population had undergone mammography, and thus, were included in this analysis. Participants with and without mammograms did not have statistically significant differences in many key factors in this analysis, including childhood family income, maternal and paternal education, maternal or self-reported race/ethnicity, birthweight and childhood weight, maternal smoking during pregnancy, age at follow up, BMI, menopausal status, adult SES and alcohol intake; the two groups were different in terms of adult smoking. Our study attained high tracing and participation rates, which were similar to or higher than other follow-up studies of other sites of the Collaborative Perinatal Project [52, 53]. Our study results are most generalizable to premenopausal and non-Hispanic white women, who comprised the majority of our study population. Mammographic density changes around the time of menopause, and different cross-sectional associations may be observed according to menopausal status [27, 54]. Racial/ethnic differences in mammographic breast density and/or its associations with breast cancer risk factors have been noted in some studies [55–59]. Studies examining life course SES and mammographic density in racially/ethnically diverse women are further warranted given the potential interaction between race/ethnicity and SES; however, currently few birth or prospective cohort studies with reliable early life data have sufficiently large representation of racial/ethnic minorities.