Abstract 130: Childhood and adolescent body size and risk of fatal breast cancer.
Authors: Warner Erica T. , Eliassen A. Heather , Chen Wendy Y. , Holmes Michelle D. , Willett Walter C. , Tamimi Rulla M. 
Published: August 2014

Background: Body size early in life is inversely associated with incidence of pre and postmenopausal breast cancer, but its relationship with fatal breast cancer is unclear. We prospectively examined the association between childhood and adolescent body size and risk of fatal breast cancer. Methods: Study participants include 76,261 women from Nurses’ Health Study (NHS) and 112,388 from Nurses’ Health Study II (NHS II). Self-reported body size at ages 5, 10 and 20 years was assessed with a validated 9-figure drawing in 1988 (NHS) and 1989 (NHSII). The outcome was defined as invasive breast cancer that led to breast cancer death. Cause of death was obtained from death certificates. We observed 922 cases of incident fatal breast cancer over 20 years of follow-up. Cox proportional hazards regression was used to calculate hazard ratios (HR) and confidence intervals (CI) for body size at each age, average childhood (ages 5 & 10) and adolescent (ages 10 & 20) body size, and change in body size up to age 20. Fatal and non-fatal cases were censored at the date of diagnosis. Results: Women who were largest at age 5 were 32% less likely to develop fatal breast cancer as compared to women that were leanest (HR: 0.68, 95% CI: 0.50, 0.91; p-trend &lt;0.0001) adjusted for current body mass index (BMI) and key breast cancer risk factors. Similar results were seen for age 10 (HR: 0.56, 95% CI: 0.43, 0.72), 20 (HR: 0.54, 95% CI: 0.30, 0.97), childhood (HR: 0.56, 95% CI: 0.40, 0.78) and adolescent (HR: 0.42, 95% CI: 0.16, 1.07) body sizes. Increases in body size were associated with lower risk of fatal breast cancer while, from age 5 to 10 only, decreasing in size increased risk (HR: 1.16, 95% CI: 1.29, 2.01). We found no evidence that associations differed by estrogen receptor status (p-heterogeneity &gt;0.15) or fatal vs. non-fatal (p-heterogeneity &gt;0.20). Conclusion: Larger body size at ages 5, 10 and 20 is associated with lower risk of fatal breast cancer in adulthood independent of current BMI. The association does not appear to be driven by estrogen-related mechanisms.

  Cases N = 922 Person-years Age-adj. HR (95% CI) MV HR* (95% CI) MV +Current BMI HR (95% CI) Figure at age 5 years 1 370 1,034,245 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) 2 243 922,357 0.92 (0.78, 1.09) 0.93 (0.79, 1.11) 0.93 (0.79, 1.10) 3 171 691,594 0.87 (0.73, 1.05) 0.89 (0.74, 1.07) 0.86 (0.71, 1.03) 4 84 390,941 0.72 (0.56, 0.91) 0.73 (0.57, 0.93) 0.69 (0.54, 0.87) ≥ 5 54 236,358 0.73 (0.55, 0.97) 0.73 (0.55, 0.98) 0.68 (0.50, 0.91) P for trend 0.001 0.002 &lt;0.0001 Figure at age 10 years 1 286 784,729 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) 2 286 944,240 1.00 (0.85, 1.19) 1.01 (0.86, 1.20) 1.00 (0.84, 1.18) 3 175 674,514 0.88 (0.72, 1.06) 0.90 (0.74, 1.09) 0.85 (0.70, 1.03) 4 101 479,532 0.70 (0.56, 0.88) 0.72 (0.57, 0.90) 0.65 (0.51, 0.82) ≥ 5 74 392,460 0.62 (0.48, 0.80) 0.63 (0.49, 0.81) 0.56 (0.43, 0.72) P for trend &lt;0.0001 &lt;0.0001 &lt;0.0001 Figure at age 20 years 1 103 143,078 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) 2 291 901,910 0.86 (0.56, 1.33) 0.87 (0.56, 1.35) 0.86 (0.55, 1.34) 3 324 1,175,790 0.79 (0.45, 1.36) 0.80 (0.46, 1.40) 0.75 (0.42, 1.34) 4 132 632,199 0.63 (0.48, 0.82) 0.64 (0.49, 0.84) 0.57 (0.43, 0.74) ≥ 5 72 322,528 0.65 (0.38, 1.12) 0.67 (0.39, 1.13) 0.54 (0.30, 0.97) P for trend 0.001 0.002 0.0005 *adjusted for age (months), time period (10 periods), birth weight (&lt;5.5, 5.5–6.9, 7–8.4, 8.5–9.9, ≥ 10 lbs), height (inches), recent alcohol consumption (0, 0.1–1.4, 1.5–4.9, 5.0–9.9, ≥ 10 g/day),age at menopause (years), menopausal status and PMH use (premenopausal, postmenopausal-never PMH, postmenopausal-past PMH, postmenopausal-current PMH, postmenopausal -missing PMH), parity and age at first birth (nulliparous, 1–2 pregnancies with age at first birth &lt;25, 1–2 pregnancies with age at first birth 25–29, 1–2 pregnancies with age at first birth ≥30, 3 or more pregnancies with age at first birth &lt;25, 3 or more pregnancies with age at first birth ≥25), oral contraceptive duration (never, &lt;12 months, 13–60 months, ≥60 months), history of benign breast disease (yes/no), first degree family history of breast cancer (yes/no), BMI (continuous).

Citation Format: Erica T. Warner, A. Heather Eliassen, Wendy Y. Chen, Michelle D. Holmes, Walter C. Willett, Rulla M. Tamimi. Childhood and adolescent body size and risk of fatal breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 130. doi:10.1158/1538-7445.AM2013-130