Abstract

BackgroundPerinatal factors have been associated with some adult health outcomes, but have not been well studied in young-onset breast cancer. We aimed to evaluate the association between young-onset breast cancer and perinatal exposures and to explore etiologic heterogeneity in the relationship between associated perinatal factors and estrogen receptor status of the tumor.MethodsWe addressed this in a sister-matched case-control study. Cases were women who had been diagnosed with ductal carcinoma in situ or invasive breast cancer before the age of 50. Each case had a sister control who was free of breast cancer up to the same age at which her case sister developed the disease. The factors considered were self-reported and included the mother’s preeclampsia in that pregnancy, mother’s smoking in that pregnancy, gestational hypertension, prenatal diethylstilbestrol use, and gestational diabetes, as well as low birth weight (less than 5.5 pounds), high birth weight (greater than 8.8 pounds), short gestational length (less than 38 completed weeks), and being breastfed or being fed soy formula.ResultsIn conditional logistic regression analyses, high birth weight (odds ratio [OR] = 1.59, 95% confidence interval [CI] 1.07–2.36) and preeclampsia (adjusted OR = 1.92, CI 0.824–4.5162) were positively associated with risk. The association with preeclampsia was stronger when the analysis was restricted to invasive breast cancer (OR = 2.87, CI 1.08–7.59). We also used case-only analyses to assess etiologic heterogeneity for estrogen receptor (ER)-positive versus estrogen receptor-negative cancer. Women who were born to a preeclamptic pregnancy and later developed young-onset breast cancer were at increased odds for the ER-negative type (OR = 2.27; CI 1.05–4.92).ConclusionThese results suggest that being born to a preeclamptic pregnancy may increase risk for young-onset breast cancer, especially for the ER-negative subtype.

Highlights

  • Perinatal factors have been associated with some adult health outcomes, but have not been well studied in young-onset breast cancer

  • There was a positive association between breast cancer and high birth weight (OR = 1.59, 95% confidence intervals (CI) 1.07– 2.36)

  • Participants who had a short gestational length (< 38 weeks) (OR = 1.26, 95% CI 0.83–1.92) and those whose mother smoked during their gestation (OR = 1.19, 95% CI 0.81–1.74) had estimated positive associations with breast cancer

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Summary

Introduction

Perinatal factors have been associated with some adult health outcomes, but have not been well studied in young-onset breast cancer. Breast cancer risk factors have been reported to vary across age of onset [2, 3], which suggests that there is etiologic heterogeneity of breast cancer associated with age at onset (young-onset vs older-onset). According to a provocative hypothesis proposed by Trichopoulos in 1990, some breast cancers may etiologically originate in utero [4]. He proposed that prenatal exposure to endogenous or exogenous hormones might influence the trajectory of breast cancer development later in life, implying that a critical window for carcinogenesis of the breast might begin during prenatal life. Some epidemiological studies have examined this hypothesis by using surrogate markers for in utero exposures to steroids and growth hormones

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