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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention

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Research Articles

History of Gestational Diabetes Mellitus and Risk of Incident Invasive Breast Cancer among Parous Women in the Nurses' Health Study II Prospective Cohort

Camille E. Powe, Deirdre K. Tobias, Karin B. Michels, Wendy Y. Chen, A. Heather Eliassen, JoAnn E. Manson, Bernard Rosner, Walter C. Willett, Frank B. Hu, Cuilin Zhang, Janet W. Rich-Edwards and Kathryn M. Rexrode
Camille E. Powe
Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts.
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Deirdre K. Tobias
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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Karin B. Michels
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Department of Obstetrics, Gynecology and Reproductive Biology, Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, Massachusetts.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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Wendy Y. Chen
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
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A. Heather Eliassen
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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JoAnn E. Manson
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Boston, Massachusetts.
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Bernard Rosner
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
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Walter C. Willett
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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Frank B. Hu
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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Cuilin Zhang
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Rockville, Maryland.
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Janet W. Rich-Edwards
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Boston, Massachusetts.
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Kathryn M. Rexrode
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
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  • For correspondence: krexrode@partners.org
DOI: 10.1158/1055-9965.EPI-16-0601 Published March 2017
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Tables

  • Table 1.

    Characteristics of 86,972 parous U.S. women in the NHS II cohort in 1989, by history of GDM

    No history of GDM n = 81,784History of GDM n = 5,188
    Agea35.0 ± 4.733.8 ± 4.4
    Lifestyle factors
     BMI23.9 ± 4.725.8 ± 5.9
      Normal weight (BMI < 25.0), %7155
      Overweight (BMI 25.0–29.9), %1825
      Obese (BMI ≥ 30), %1020
     BMI at age 18b21.0 ± 3.021.5 ± 3.6
      Normal weight at 18 (BMI < 25.0), %9187
      Overweight/obese at 18 (BMI ≥ 25.0), %812
     Height (inches)64.9 ± 2.664.5 ± 2.6
     Total physical activity (MET-hrs/week)23.7 ± 35.221.8 ± 33.0
     Alternative Healthy Eating Index scoreb47.9 (10.7)47.2 (10.5)
     Fruit and vegetable intake (servings/day)b4.2 ± 2.34.3 ± 2.5
     Alcohol intake (g/day)b2.9 ± 5.62.2 ± 4.8
     Smoking total pack years7.4 ± 60.76.9 ± 55.4
     Smoking status, %
      Never6666
      Past2221
      Current smoker1213
     Current multivitamin use, %4647
    Other risk factors
     Age at menarche, %
      ≤10 years710
      11–12 years4648
      13–14 years3835
      ≥15 years87
     Regularity of menses at ages 18–22, %
      Regular or very regular7472
      Usually or always irregular2225
     Age at first birth (years)26.5 ± 4.527.6 ± 5.0
     Parity (pregnancies ≥6 months)1.8 ± 1.11.8 ± 1.2
     Birth indexc16.1 (14.3)14.3 (14.8)
     Total breastfeeding, %b
      None1513
      <6 months1313
      ≥6 months4643
     Oral contraceptive use, %
      Never1516
      Past7372
      Current1212
     History of pregnancy-induced hypertension1020
     Mammography screening among women >40 years old, %
      <40 years old8080
      ≥40 years old, with screening1111
      ≥40 years old, no screening55
      ≥40 years old, mammography for symptoms44
     Hysterectomy55
     Bilateral oophorectomy11
     Family history of diabetes, %1428
     Family history of breast cancer, %65
     Personal history of benign breast disease, %b2930
     Race/ethnicity, %
      White9693
      Black23
      Asian23
    • NOTE: Values represent means ± SD unless otherwise indicated and are standardized to the age distribution of the study population. Values of categorical variables may not sum to 100% due to rounding.

    • ↵aValue is not age adjusted.

    • ↵bMissing data on BMI at age 18 in 1% of participants, food frequency and alcohol intake in 16.3% of participants, breastfeeding in 14.6% of parous participants, and history of benign breast disease in 3.6% of participants. All other data were missing in less than 1% of participants.

    • ↵cBirth index was calculated by summing total years from each birth to current age (or age at menopause for postmenopausal women) over all births.

  • Table 2.

    Association between history of GDM and incident invasive breast cancer risk

    No GDMGDM
    HR (95% CI)HR (95% CI)P
    Cases, no.2,277100
    Person-yearsa923,69458,384
    Age adjusted1.00 (reference)0.68 (0.55–0.84)0.0003
    Multivariable adjusted1.00 (reference)0.68 (0.55–0.84)0.0004
    • NOTE: Multivariable model additionally adjusts for BMI at age 18 (continuous), weight gain since age 18 (continuous), height (continuous), total physical activity (MET-hours/week, quintiles), alcohol intake (none, 1–14 grams/day, ≥15 grams/day), age at menarche (≤10 years old, 11–12, 13–14, ≥15), birth index (continuous), total breastfeeding (none, <6 months, ≥6 months), menopausal status (premenopausal, postmenopausal, unknown), hormone therapy use (never, ever use of estrogen + progesterone, past: estrogen only or other, current: estrogen only or other), family history of breast cancer in mother or sister (yes/no), personal history of benign breast disease (yes/no), white race/ethnicity (yes/no), and mammography within the past 2 years (<40 years old, ≥40 and no mammography, ≥40 and mammography for screening, ≥40 and mammography for abnormality/symptoms).

    • ↵aPerson-years are calculated as the time from age at first birth or first GDM pregnancy, through the end of follow-up (the date of incident breast cancer diagnosis, death, or last questionnaire return through May 31, 2013).

  • Table 3.

    Association between history of GDM and incident invasive breast cancer risk, stratified by risk factors

    Cases, no.No GDMGDM
    Stratified by risk factorsNo GDM/GDMHR (95% CI)HR (95% CI)Pinteraction
    Current BMI category (kg/m2)a
     Normal (<25.0)1,116/491.00 (reference)0.97 (0.72–1.32)0.04
     Overweight (25.0–29.9)646/251.00 (reference)0.50 (0.32–0.78)
     Obese (≥30.0)512/261.00 (reference)0.50 (0.32–0.77)
    Age at first birth
     <30 years1,707/591.00 (reference)0.57 (0.39–0.83)0.85
     ≥30 years570/411.00 (reference)0.89 (0.64–1.24)
    Family history of breast cancer
     No1,900/831.00 (reference)0.65 (0.52–0.83)0.96
     Yes377/171.00 (reference)0.76 (0.44–1.31)
    Family history of diabetes
     No1,669/621.00 (reference)0.75 (0.57–0.98)0.33
     Yes608/381.00 (reference)0.59 (0.41–0.85)
    Physical activity
     Low (Q1–Q3)1,457/581.00 (reference)0.56 (0.42–0.74)0.04
     High (Q4–Q5)820/421.00 (reference)0.98 (0.70–1.37)
    Total lifetime breastfeeding
     None to <6 months933/291.00 (reference)0.55 (0.37–0.81)0.08
     ≥6 months1,344/711.00 (reference)0.77 (0.59–0.99)
    • NOTE: Multivariable model adjusts for age, BMI at age 18 (continuous), weight gain since age 18 (continuous), height (continuous), total physical activity (MET-hours/week, quintiles), alcohol intake (none, 1–14 grams/day, ≥15 grams/day), age at menarche (≤10 years old, 11–12, 13–14, ≥15), birth index (continuous), total breastfeeding (none, <6 months, ≥6 months), menopausal status (premenopausal, postmenopausal, unknown), hormone therapy use (never, ever use of estrogen + progesterone, past: estrogen only or other, current: estrogen only or other), family history of breast cancer in mother or sister (yes/no), personal history of benign breast disease (yes/no), white race/ethnicity (yes/no), and mammography within the past 2 years (<40 years old, ≥40 and no mammography, ≥40 and mammography for screening, ≥40 and mammography for abnormality/symptoms).

    • ↵aMultivariable model is adjusted for current BMI (continuous).

  • Table 4.

    Association between history of GDM and incident invasive breast cancer risk, by intermediate type II diabetes status

    No GDM or type II diabetesGDM onlyType II diabetes onlyBoth GDM and type II diabetes
    HR (95% CI)HR (95% CI)HR (95% CI)HR (95% CI)
    All women
     Cases, no.2,22495535
     Person-years907,82353,63520,5765,982
     Age adjusted1.00 (reference)0.72 (0.58–0.90)0.63 (0.37–1.07)0.23 (0.09–0.61)
     Multivariable model1.00 (reference)0.72 (0.58–0.89)0.69 (0.40–1.18)0.26 (0.10–0.68)
    • NOTE: Multivariable model adjusts for age, BMI at age 18 (continuous), weight gain since age 18 (continuous), height (continuous), total physical activity (MET-hours/week, quintiles), alcohol intake (none, 1–14 grams/day, ≥15 grams/day), age at menarche (≤10 years old, 11–12, 13–14, ≥15), birth index (continuous), total breastfeeding (none, <6 months, ≥6 months), menopausal status (premenopausal, postmenopausal, unknown), hormone therapy use (never, ever use of estrogen + progesterone, past: estrogen only or other, current: estrogen only or other), family history of breast cancer in mother or sister (yes/no), personal history of benign breast disease (yes/no), white race/ethnicity (yes/no), and mammography within the past 2 years (<40 years old, ≥40 and no mammography, ≥40 and mammography for screening, ≥40 and mammography for abnormality/symptoms).

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Cancer Epidemiology Biomarkers & Prevention: 26 (3)
March 2017
Volume 26, Issue 3
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History of Gestational Diabetes Mellitus and Risk of Incident Invasive Breast Cancer among Parous Women in the Nurses' Health Study II Prospective Cohort
Camille E. Powe, Deirdre K. Tobias, Karin B. Michels, Wendy Y. Chen, A. Heather Eliassen, JoAnn E. Manson, Bernard Rosner, Walter C. Willett, Frank B. Hu, Cuilin Zhang, Janet W. Rich-Edwards and Kathryn M. Rexrode
Cancer Epidemiol Biomarkers Prev March 1 2017 (26) (3) 321-327; DOI: 10.1158/1055-9965.EPI-16-0601

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History of Gestational Diabetes Mellitus and Risk of Incident Invasive Breast Cancer among Parous Women in the Nurses' Health Study II Prospective Cohort
Camille E. Powe, Deirdre K. Tobias, Karin B. Michels, Wendy Y. Chen, A. Heather Eliassen, JoAnn E. Manson, Bernard Rosner, Walter C. Willett, Frank B. Hu, Cuilin Zhang, Janet W. Rich-Edwards and Kathryn M. Rexrode
Cancer Epidemiol Biomarkers Prev March 1 2017 (26) (3) 321-327; DOI: 10.1158/1055-9965.EPI-16-0601
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