Abstract
BackgroundParity and age at first pregnancy are well-established risk factors for breast cancer, but the effects of other characteristics of pregnancies are uncertain and the literature is inconsistent.MethodsIn a cohort of 83,451 parous women from the general population of the UK, which collected detailed information on each pregnancy and a wide range of potential confounders, we investigated the associations of length of gestation and birthweight of offspring in a woman’s pregnancies with her breast cancer risk, adjusting for a full range of non-reproductive as well as reproductive risk factors unlike in previous large studies.ResultsGestation of the first-born offspring was significantly inversely related to the risk of pre-menopausal breast cancer (p trend = 0.03; hazard ratio (HR) for 26–31 compared with 40–41 weeks, the baseline group, = 2.38, 95% confidence interval (CI) 1.26–4.49), and was borderline significantly related to risk of breast cancer overall (p trend = 0.05). Risk was significantly raised in mothers of high birthweight first-born (HR for breast cancer overall = 1.53, 95% CI 1.06–2.21 for ≥ 4500 g compared with 3000–3499 g, the baseline group). For gestation and birthweight of most recent birth, there were no clear effects. Analyses without adjustment for confounders (other than age) gave similar results.ConclusionsOur data add to evidence that short gestation pregnancies may increase the risk of breast cancer, at least pre-menopausally, perhaps by hormonal stimulation and breast proliferation early in pregnancy without the opportunity for the differentiation that occurs in late pregnancy. High birthweight first pregnancies may increase breast cancer risk, possibly through the association of birthweight with oestrogen and insulin-like growth factor 1 levels.
Highlights
Parity and age at first pregnancy are well-established risk factors for breast cancer, but the effects of other characteristics of pregnancies are uncertain and the literature is inconsistent
The large studies [15,16,17,18,19,20,21,22,23,24] have all been based on record linkage, and have generally not been able to adjust for non-reproductive confounders, which might be important since several factors such as maternal height, birthweight, smoking, and alcohol consumption, that are associated with the offspring’s birthweight and gestation [25,26,27,28,29,30,31], are known or likely risk factors for breast cancer
The recruitment questionnaire asked about several variables, including birthweight and gestation, the variables addressed in this paper, for each of the subject’s pregnancies, and about all known and likely causes of breast cancer
Summary
Parity and age at first pregnancy are well-established risk factors for breast cancer, but the effects of other characteristics of pregnancies are uncertain and the literature is inconsistent. One might expect that characteristics of the pregnancies, such as the length of gestation and the birthweight of the offspring, that are associated with maternal hormone levels [7,8,9,10,11,12,13,14] might affect breast cancer risk. Investigations of this have been far more limited, than for age at first birth and parity, and results have been inconsistent. With one exception for hormone receptor type [23], these studies have not analysed risks in subdivisions of breast cancer that may have different aetiological characteristics—by menopausal status at the time of breast cancer incidence, by in-situ versus invasive status, and by hormone receptor subtype
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