Growth Patterns and the Risk of Breast Cancer in Women

Department of Epidemiology Research, Danish Epidemiology Science Center, Statens Serum Institut, Copenhagen, Denmark.
New England Journal of Medicine (Impact Factor: 55.87). 11/2004; 351(16):1619-26. DOI: 10.1056/NEJMoa040576
Source: PubMed


Adult height and body-mass index influence the risk of breast cancer in women. Whether these associations reflect growth patterns of the fetus or growth during childhood and adolescence is unknown.
We investigated the association between growth during childhood and the risk of breast cancer in a cohort of 117,415 Danish women. Birth weight, age at menarche, and annual measurements of height and weight were obtained from school health records. We used the data to model individual growth curves. Information on vital status, age at first childbirth, parity, and diagnosis of breast cancer was obtained through linkages to national registries.
During 3,333,359 person-years of follow-up, 3340 cases of breast cancer were diagnosed. High birth weight, high stature at 14 years of age, low body-mass index (BMI) at 14 years of age, and peak growth at an early age were independent risk factors for breast cancer. Height at 8 years of age and the increase in height during puberty (8 to 14 years of age) were also associated with breast cancer. The attributable risks of birth weight, height at 14 years of age, BMI at 14 years of age, and age at peak growth were 7 percent, 15 percent, 15 percent, and 9 percent, respectively. No effect of adjusting for age at menarche, age at first childbirth, and parity was observed.
Birth weight and growth during childhood and adolescence influence the risk of breast cancer.

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    • "for post-menopausal breast cancer per 5 cm difference in height [15]. A higher BMI has been recognised as a protective factor for pre-menopausal breast cancer, but a risk factor for post-menopausal tumour occurrence [16-18]; therefore we would estimate an increased risk of 4% for pre-menopausal cancer and a reduced risk of 10% for post-menopausal cancer for cabin crew. "
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    ABSTRACT: Background Many epidemiological studies point to an increased risk of breast cancer among female airline cabin crew. Possible causes include occupational factors (e.g. cosmic radiation exposure, chronodisruption), as well as lifestyle and reproductive factors. Aims To investigate the frequency of various risk factors in German flight attendants which are recognised to be associated with breast cancer. Methods 2708 current and former female cabin crew were randomly selected by a flight attendants’ union and mailed a questionnaire; 1311 responded (48% response). Descriptive statistics were used to compare the distribution of breast cancer risk factors with general German population data. Results On average, cabin crew were 3.0 cm (95% CI 2.7-3.3) taller than the comparison group, while their body mass index was 2.5 kg/m2 (95% CI 2.4-2.6) lower. We found less use of hormone replacement therapy, but longer average use of oral contraceptives. Nulliparity among respondents aged 45+ was 57% (95% CI 54%-60%) compared to 16%. Average age at first birth was 32.1 years (95% CI 31.7-32.4) vs. 25.5 years. The birth rate was 0.62 (95% CI 0.58-0.67), less than half the population average of 1.34. Alcohol consumption was considerably higher, whereas cabin crew tended to smoke less and performed more physical exercise. Conclusion We found important differences in terms of anthropometric, gynaecological, reproductive and lifestyle factors. Some of these differences (e.g. higher nulliparity, alcohol consumption, taller size) could contribute to a higher breast cancer risk, whereas others could lead to a reduction (e.g. increased physical exercise, lower BMI, less HRT use).
    Journal of Occupational Medicine and Toxicology 07/2014; 9(1):27. DOI:10.1186/1745-6673-9-27 · 1.62 Impact Factor
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    • "Aside from age at menarche and onset of regular menses, the other Tanner stages have been little studied in relation to breast cancer risk. There is weak evidence that earlier peak growth might increase breast cancer risk [9], but data are minimal, and there appear to have been no studies of risk by age at thelarche. "
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    ABSTRACT: Breast development and hormonal changes at puberty might affect breast cancer risk, but epidemiological analyses have focussed largely on age at menarche and not at other pubertal stages. We investigated associations between the timing of pubertal stages and breast cancer risk using data from a cohort study of 104,931 women (Breakthrough Generations Study, UK, 2003-2013). Pubertal variables were reported retrospectively at baseline. Breast cancer risk was analysed using Cox regression models with breast cancer diagnosis as the outcome of interest, attained age as the underlying time variable, and adjustment for potentially confounding variables. During follow-up (mean = 4.1 years), 1094 breast cancers (including ductal carcinoma in situ) occurred. An increased breast cancer risk was associated with earlier thelarche (age when breast growth begins; HR [95% CI] = 1.23 [1.02, 1.48], 1 [referent] and 0.80 [0.69, 0.93] for <=10, 11-12 and >=13 years respectively), menarche (initiation of menses; 1.06 [0.93, 1.21], 1 [referent] and 0.78 [0.62, 0.99] for <=12, 13-14 and >=15 years), regular periods (0.99 [0.83, 1.18], 1 [referent] and 0.74 [0.59, 0.92] for <=12, 13-14 and >=15 years) and age reached adult height (1.25 [1.03, 1.52], 1 [referent] and 1.07 [0.87, 1.32] for <=14, 15-16 and >=17 years), and with increased time between thelarche and menarche (0.87 [0.65, 1.15], 1 [referent], 1.14 [0.96, 1.34] and 1.27 [1.04, 1.55] for <0, 0, 1 and >=2 years), and shorter time between menarche and regular periods (1 [referent], 0.87 [0.73, 1.04] and 0.66 [0.50, 0.88] for 0, 1 and >=2 years). These associations were generally similar when considered separately for premenopausal and postmenopausal breast cancer. Breast duct development may be a time of heightened susceptibility to risk of carcinogenesis, and greater attention needs to be given to the relation of breast cancer risk to the different stages of puberty.
    Breast cancer research: BCR 02/2014; 16(1):R18. DOI:10.1186/bcr3613 · 5.49 Impact Factor
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    • "A substantial number of studies have explored prenatal origins of breast cancer [3] by linking early-life anthropometric factors to breast cancer risk [3-6]. Birth weight, taken as a proxy for prenatal exposures [4,6-10], and childhood height [6,8,11,12] are both positively associated with breast cancer, whereas higher body mass index (BMI; kg/m2) [8,11,13-15] in childhood seems to protect against breast cancer. However, the period in life when breast density is determined, and whether it may mediate the effect of early-life exposures on breast cancer risk, is unknown [1,2]. "
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    ABSTRACT: High breast density, a strong predictor of breast cancer risk, may be determined early in life. Childhood anthropometric factors have been related to breast cancer and breast density, but rarely simultaneously. We examine whether mammographic density (MD) mediates an association of birth weight, childhood body mass index (BMI) and height with the risk of breast cancer. A total of 13,572 women (50-69 years) in the Copenhagen mammography screening program (1991-2001) with childhood anthropometric measurements in the Copenhagen School Health Records Register were followed for breast cancer until 2010. Using logistic and Cox regression models we investigated associations among birth weight, height and BMI at ages 7-13 with MD (mixed/dense or fatty) and breast cancer, respectively. A total of 8,194 (60.4%) women had mixed/dense breasts and 716 (5.3%) developed breast cancer. Childhood BMI was significantly and inversely related to having mixed/dense breasts at all ages, with age at screening and birth cohort adjusted odds ratios (95% confidence intervals) ranging from 0.69 (0.66-0.72) at age 7 to 0.56 (0.53-0.58) at age 13, per one unit increase in z-score. No statistically significant associations were detected between birth weight and MD, height and MD, or birth weight and breast cancer risk. BMI was inversely associated to breast cancer risk, with age and birth cohort adjusted hazard ratios (HRs) of 0.91 (0.83-0.99) at age 7 and 0.92 (0.84-1.00) at age 13, whereas height was positively associated with breast cancer risk (age 7: 1.06 (0.98-1.14) and age 13: 1.08 (1.00-1.16)). After additional adjustment for MD, associations of BMI with breast cancer risk diminished (age 7: 0.97 (0.88-1.06) and age 13: 1.01 (0.93-1.11)), but remained with height (age 7: 1.06 (0.99-1.15) and age 13: 1.09 (1.01-1.17)). Among women 50 years and older, childhood body fatness was inversely associated to the breast cancer risk, possibly via a mechanism mediated by MD, at least in part. Childhood tallness was positively associated with breast cancer risk, seemingly via a pathway independent of MD. Birth weight was not associated with MD or breast cancer risk in this age group.
    Breast cancer research: BCR 01/2014; 16(1):R4. DOI:10.1186/bcr3596 · 5.49 Impact Factor
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