Similar to earlier reports in non-Hispanic white women, we found that early-life body size influences risk of premenopausal breast cancer in Hispanic women. There was a more consistent pattern of inverse associations for relative weight than for body build. US-born controls were more likely than foreign-born controls to report large childhood and adolescent body size, and particularly strong inverse associations with relative weight were found in US-born women and women with a current BMI ≥25 kg/m2. We found no associations with childhood or adolescent body size in postmenopausal women, except for some suggestive inverse associations in US-born women not currently using HT.
Consistent with our findings, the only other study that reported on adolescent body size and breast cancer risk in Hispanic women also found a suggestive inverse association with high BMI (≥22.5 vs. < 18.2) at age 15 years (OR=0.65, 95% 0.39-1.08, P
for trend = 0.09) (20
). Our findings for premenopausal breast cancer are also consistent with previous reports in mostly non-Hispanic white women. Inverse associations have been found for high relative weight (12
), heavy body build (15
), or high BMI (10
) at various ages in childhood or adolescence, although some studies did not find associations with adolescent body size (11
). We found inverse trends for relative weight at ages 10, 15, and 20 years and, consistent with other studies (15
), we found that the inverse association of premenopausal breast cancer risk with early-life body size was independent of current BMI, a strong predictor of premenopausal breast cancer risk in this study (26
). Similar to other cohort (19
) and case-control (27
) studies, we found the greatest reduction in premenopausal breast cancer risk in women who were heavy both in childhood or adolescence and adulthood.
Unlike some other studies that reported reduced risks of postmenopausal breast cancer risk associated with large adolescent body size (11
), the present study found little evidence of inverse associations in postmenopausal women, regardless of HT use, except for suggestive inverse associations among US-born women not currently using HT. In the Nurses’ Health Study (16
), the largest study on adolescent body size and breast cancer risk to date, inverse associations did not differ between pre- and postmenopausal women.
Given the small number of African American and non-Hispanic white subjects for whom we collected information on early-life body size, we restricted the analysis to Hispanic women. When we included women of all three race/ethnicities, the results for premenopausal women (276 cases, 345 controls) and postmenopausal women not currently using HT (312 cases, 511 controls) were essentially the same (data not shown).
Few studies have assessed whether the association with adolescent body size is modified by hormone receptor status (10
) and findings are inconsistent. In the Nurses’ Health Study (16
), the inverse association with adolescent body build among pre- and postmenopausal women combined was stronger for ER− tumors than ER+ tumors, and PR status was not found to be an important modifying factor. Other studies have also reported stronger inverse associations for ER− tumors with BMI at age 15 years in Hispanics (pre- and postmenopausal women combined) (20
), and with body build at age 7 years in a population of Swedish postmenopausal women (21
). In contrast, some studies found inverse associations with high BMI at age 18 years limited to ER+ premenopausal breast cancer (10
), and with high relative weight at age 12 years limited to PR-postmenopausal breast cancer (13
). In the present study, inverse associations of premenopausal breast cancer risk with large childhood and adolescent body size were more consistent for ER+ tumors, but associations were not significantly different by ER status.
Some potential limitations need to be considered when interpreting our results. The analyses for premenopausal women, particularly those for breast cancer defined by ER status, were limited by small sample sizes. Our findings suggest potentially different effects of early-life body size on breast cancer risk in US-born vs. foreign-born Hispanic women, but our sample size was too small to examine these complex interactions. Exposure ascertainment required recall of body size many years in the past and, thus, could be subject to errors in recall. To minimize recall error, we asked about comparative weight, which may be easier to recall than absolute weight at young ages (29
), and we used visual aids, such as line drawings of body figures, that have been validated as a reliable self-reported measure of adult (29
) and adolescent (28
) body size. Other studies have shown that self-reported body build at 18 years is strongly correlated with recorded BMI at age 18 years (28
), and that BMI measured at menarche is strongly correlated with body figures recalled 30 years later (30
). It is reassuring that, in our study, relative weight at age 10 years (among control women who had not started menstruation by age 10 years) was inversely associated with age at menarche, with mean ages of 13.4, 13.0, and 12.7 years for lighter, same, and heavier relative weight, respectively. This inverse trend is consistent with other reports (16
). When we adjusted the multivariate analyses for age at menarche, the inverse associations were not altered. Our findings on adolescent body size were stronger for relative weight compared to peers than for body build assessed by figure drawings, possibly due to better recall of the former adolescent body size measure. There is some evidence that birth size and infant growth may be related to breast cancer risk later in life and that the effect of adolescent body size may be mediated through these very early life factors (31
). We did not collect information on birth weight or infant growth, and therefore could not consider these factors in our analyses.
The biologic explanations for the inverse association between large adolescent body size and premenopausal breast cancer risk remain uncertain. Childhood obesity is associated with earlier menarche, a well established risk factor for breast cancer. This association seems incongruent with the observed inverse association with large adolescent body size. Several underlying mechanisms have been postulated (33
). It has been suggested that overweight adolescents experience slower pubertal growth and sexual maturation (8
), despite having, on average, an earlier onset of puberty (34
). Overweight adolescents may also experience a longer interval between menarche and the onset of regular menstrual cycles(14
), which may be indicative of a greater frequency of anovulatory cycles (6
) and, thus, lower cumulative exposure to ovarian sex hormones. Obesity in young girls has been associated with lower sex hormone binding globulin levels (35
) and higher androgen levels (6
); estrogen and progesterone concentrations, on the other hand, do not appear to vary with BMI in adolescence (35
). Obesity in young girls has been associated with higher levels of insulin (37
) and insulin-like growth factor-1 (38
), and it has been hypothesized that obesity at a young age could influence the metabolic set point for life through an insulin-related pathway (20
). Findings on hormone levels in young girls, however, are not consistent and not necessarily compatible with decreased breast cancer risk in adult life, suggesting complex biologic pathways. Furthermore, it is not known whether hormonal changes associated with adolescent obesity persist in adult life. It has also been suggested that higher levels of estrogen and other hormones in young overweight girls may induce earlier differentiation of breast tissue, with terminally differentiated cells being less susceptible to malignant transformation (16
), and that body fat at a young age influences the histologic constituents of breast tissue (11
Risk factors for breast cancer in Hispanic women have not been extensively studied. Interestingly, in the present analysis the inverse associations with early-life body size in premenopausal women were stronger for US-born than foreign-born Hispanics, and in postmenopausal women not currently using HT, they were limited to US-born Hispanics. The basis for this difference by country of birth is unclear; it is possible that correlates of and contributors to childhood body size differ across these populations. Large body size in childhood or adolescence was more frequently reported by US-born than foreign-born Hispanic women. Similarly, in a study of children from Mexican descent, the prevalence of obesity was considerably higher in those living in California than in Mexico (2
). It is possible that the earlier onset of childhood obesity in US-born Hispanics exerts a greater protective effect on breast cancer risk than in foreign-born Hispanics. US-born and foreign-born Hispanics also differ in other factors; foreign-born controls had higher levels of physical activity before age 20 years, later age at menarche, and shorter height (unpublished data), suggesting complex interactions between several early-life factors.
Given increasing trends of obesity in Hispanic children and adolescents (39
), it remains to be seen whether or not childhood and adolescent obesity today has the same underlying pathology or biologic consequences as it did in the past and, thus, whether it will lead to lower breast cancer incidence rates in the future. Furthermore, the potential benefit of adolescent obesity in reducing breast cancer risk need to be weighed against obesity-related risks of other chronic diseases, such as diabetes, which is increasingly prevalent in obese children and adolescents (40