Kimberly A Bertrand1, Katie M O'Brien2, Lauren B Wright3, Julie R Palmer1, William J Blot4, A Heather Eliassen5, Lynn Rosenberg1, Sven Sandin6, Deirdre Tobias7,8, Elisabete Weiderpass9, Wei Zheng4, Anthony J Swerdlow3, Minouk J Schoemaker3, Hazel B Nichols10, Dale P Sandler2. 1. Slone Epidemiology Center at Boston University, Boston, MA, USA. 2. Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, USA. 3. The Institute of Cancer Research, London, UK. 4. Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA. 5. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 6. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 7. Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 8. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 9. International Agency for Research on Cancer (IARC)/World Health Organization (WHO), Lyon, France. 10. Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA.
Abstract
BACKGROUND: The history of gestational diabetes mellitus (GDM) has been associated with breast cancer risk in some studies, particularly in young women, but results of cohort studies are conflicting. METHODS: We pooled data from 257 290 young (age <55 years) women from five cohorts. We used multivariable Cox proportional-hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between GDM history and risk of breast cancer, overall and by oestrogen receptor (ER) status, before age 55 years, adjusted for established breast cancer risk factors. RESULTS: Five percent of women reported a history of GDM and 6842 women reported an incident breast-cancer diagnosis (median follow-up = 16 years; maximum = 24 years). Compared with parous women without GDM, women with a history of GDM were not at increased risk of young-onset breast cancer overall (HR = 0.90; 95% CI: 0.78, 1.03) or by ER status (HR = 0.96; 95% CI: 0.79, 1.16 for ER-positive; HR = 1.07; 95% CI: 0.78, 1.47 for ER-negative). Compared with nulliparous women, parous women with a history of GDM had a lower risk of breast cancer overall (HR = 0.79; 95% CI: 0.68, 0.91) and of ER-positive (HR = 0.82; 95% CI: 0.66, 1.02) but not ER-negative (HR = 1.09; 95% CI: 0.76, 1.54) invasive breast cancer. These results were consistent with the HRs comparing parous women without GDM to nulliparous women. CONCLUSIONS: Results of this analysis do not support the hypothesis that GDM is a risk factor for breast cancer in young women. Our findings suggest that the well-established protective effect of parity on risk of ER-positive breast cancer persists even for pregnancies complicated by GDM.
BACKGROUND: The history of gestational diabetes mellitus (GDM) has been associated with breast cancer risk in some studies, particularly in young women, but results of cohort studies are conflicting. METHODS: We pooled data from 257 290 young (age <55 years) women from five cohorts. We used multivariable Cox proportional-hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between GDM history and risk of breast cancer, overall and by oestrogen receptor (ER) status, before age 55 years, adjusted for established breast cancer risk factors. RESULTS: Five percent of women reported a history of GDM and 6842 women reported an incident breast-cancer diagnosis (median follow-up = 16 years; maximum = 24 years). Compared with parous women without GDM, women with a history of GDM were not at increased risk of young-onset breast cancer overall (HR = 0.90; 95% CI: 0.78, 1.03) or by ER status (HR = 0.96; 95% CI: 0.79, 1.16 for ER-positive; HR = 1.07; 95% CI: 0.78, 1.47 for ER-negative). Compared with nulliparous women, parous women with a history of GDM had a lower risk of breast cancer overall (HR = 0.79; 95% CI: 0.68, 0.91) and of ER-positive (HR = 0.82; 95% CI: 0.66, 1.02) but not ER-negative (HR = 1.09; 95% CI: 0.76, 1.54) invasive breast cancer. These results were consistent with the HRs comparing parous women without GDM to nulliparous women. CONCLUSIONS: Results of this analysis do not support the hypothesis that GDM is a risk factor for breast cancer in young women. Our findings suggest that the well-established protective effect of parity on risk of ER-positive breast cancer persists even for pregnancies complicated by GDM.
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