Our findings suggested null associations for maternal age and birth order in relation to adult breast cancer risk in the full study population. Breastmilk exposure in infancy was associated with a small decrease in the odds ratio for breast cancer overall. However, this relation was not observed among first-born women. Consistent with our initial hypotheses, higher birth order was associated with reduced breast cancer risk only among breastfed women. However, maternal age was related to an unexpected inverse association with breast cancer risk among women who were not breastfed. To our knowledge, no previous study has reported on potential interactions of birth order or maternal age with breastmilk exposure in determining adult breast cancer risk.
Previous reports have generally suggested a protective effect of younger maternal age in relation to adult breast cancer risk.21, 25, 26, 28, 43, 46, 50
However, an approximately equal number of reports detected weak or statistically non-significant positive trends 24, 27, 33, 36, 52, 54
or found no association.23, 29, 35, 37, 39, 41, 55
In 2005, Forman et al. recalculated previous findings to create a uniform reference group of maternal age 20−24.53
Of 12 studies, only two detected a statistically significant increase in breast cancer risk among women with mothers older than 25 43
or 35−39 years.26
Although many publications of the independent effects of birth order in relation to breast cancer risk have indicated null or statistically non-significant associations 17, 21, 24, 25, 29, 35, 36, 43, 47, 48, 50, 51, 54, 55
, at least three studies have shown inverse associations between birth order and breast cancer risk, either overall, or among subgroups of premenopausal women 28, 32, 46
Within the substantial literature of breastmilk consumption in infancy in relation to adult breast cancer risk, two reviews 42, 53
and a meta-analysis 57
suggest that women exposed to breastmilk as infants may have a 20−35% reduction in breast cancer risk. A third review concluded that while early viral etiology hypotheses58
have clearly not been upheld, results regarding the association between breastmilk exposure and breast cancer risk have been largely inconsistent. 49
A predominant explanation for potential decreases in breast cancer incidence according to high birth order and younger maternal age is variation in the in utero
hormonal environment and the potential creation of a “fertile soil” for breast carcinogenesis in adult life 59
. Hormonal profiles differ according to parity with higher estrogen levels in first pregnancies.60, 61
One early study also provided evidence of higher estrogen levels during pregnancy among women age 20−24 years old compared to both younger and older women.62
However, a second, more recent study did not detect differences in estrogen levels during pregnancy according to maternal age.63
Another theory suggests that older maternal age results in a greater probability of genetic mutation and chromosomal aberrations; however, some controversy remains whether these effects are independent of paternal age.64
In our study, information about paternal age was not collected during the telephone interview and was therefore unavailable for analysis.
Previous investigations of breastmilk exposure in infancy have highlighted differences relative to bottle-feeding in terms of nutrition, immunologic activity, and hormonal exposures. Other studies have indicated that environmental contaminant exposure is higher in breastfed infants compared to formula-fed infants. 65-69
Duration of breastfeeding has demonstrated a dose-response relation with PCB and DDT exposure in the infant.11, 69-72
Information on duration of breastfeeding in infancy was not available in our study.
Other limitations of our study should be considered. Birth order and maternal age were evaluated as proxies for potential relative concentration of persistent organic pollutants in breastmilk. The study questionnaire did not explicitly ask whether a participant's older siblings were breastfed in infancy. Therefore, our interpretation of the potential interaction between birth order and breastfeeding status is dependent on the assumption that if a woman was breastfed in infancy, then her older siblings were breastfed as well.
Confidence in our findings is strengthened by the high response rates, use of a standardized instrument with high reproducibility, and multivariable adjustment scheme. Self-reported exposure to breast-milk in infancy has been highly correlated with mother's reports (r=0.74).73
Being breastfed in infancy may also be correlated with the decision to breastfeed as an adult, a behavior known to reduce breast cancer risk.74
We additionally adjusted model estimates for duration of adult breastfeeding; odds ratios remained unchanged.
These findings suggest that maternal age and birth order associations with adult breast cancer risk may differ according to exposure to breastmilk in infancy.