Intrauterine environments and breast cancer risk: meta-analysis and systematic review

Abstract

Introduction Various perinatal factors, including birth weight, birth order, maternal age, gestational age, twin status, and parental smoking, have been postulated to affect breast cancer risk in daughters by altering the hormonal environment of the developing fetal mammary glands. Despite ample biologic plausibility, epidemiologic studies to date have yielded conflicting results. We investigated the associations between perinatal factors and subsequent breast cancer risk through meta-analyses.

Epidemiology of breast cancer in young women

“…Birth characteristic including gestational age, birth weight and birth length are associated with maternal hormone levels. Epidemiological data seem to support the hypothesis that hormonal exposure in uterus increases the risk of breast cancer in adulthood [26].…”

Neonatal growth and breast cancer risk in adulthood

“…In the base of the study, on which we relied, birth size indicators (birth weight, birth length, and placental weight) were very weakly positively related to risk, although mutual adjustment of these indicators tended to increase the positive trends (Ekbom et al, 1997). However, when a true but weak association is investigated in many studies, some are bound to generate non-significant or even null results (Michels and Xue, 2006;Park et al, 2008). We had no information about adult life risk factors for breast cancer (e.g., age at menarche), but even if associations of such factors with postnatal growth were to be found, they would probably have been placed as intermediates (which should not be controlled for) rather than as confounders (which should).…”

“…It has been postulated that the likelihood of breast cancer depends on the number of mammary stem cells, which is determined in early, including intrauterine life, as well as on the early postnatal levels of growth-enhancing mammotropic hormones, which affect the replication rate of such stem cells (Trichopoulos, 1990;Adami et al, 1995;Trichopoulos et al, 2005Trichopoulos et al, , 2008. Birth size is known to influence breast cancer risk (Michels and Xue, 2006;Park et al, 2008), and there is compelling evidence that periadolescent growth (Ahlgren et al, 2004) and adult height (Tretli 1989;World Cancer Research Fund/American Institute for Cancer Research, 2007) are also associated with this risk. Using haematopoietic stem cells as probable correlates of the difficult-to-measure mammary stem cells, the size of their pool was positively associated with both umbilical cord growth hormones and birth weight (Savarese et al, 2007;Strohsnitter et al, 2008).…”

“…There is much evidence that birth size of women influences their breast cancer risk (Michels and Xue, 2006;Park et al, 2008), particularly before menopause (World Cancer Research Fund/ American Institute for Cancer Research, 2007). No study, however, has investigated neonatal growth in relation to breast cancer risk, even though neonatal growth could be of particular importance, as it is strongly associated with neonatal IGF-1 levels (Albertsson-Wikland et al, 1998;Ogilvy-Stuart et al, 1998;Hikino et al, 2001;Skalkidou et al, 2003).…”

New concepts of breast cancer aetiology

“…Some speculate that the foetal hormonal environment associated with large birth size may alter programming of the breast, making it more susceptible to cancer initiation by endogenous hormone levels and other carcinogens later in life (31).…”