Breast Cancer Research and Treatment

, Volume 134, Issue 2, pp 783–791 | Cite as

Adolescent intakes of vitamin D and calcium and incidence of proliferative benign breast disease

  • Xuefen Su
  • Graham A. Colditz
  • Laura C. Collins
  • Heather J. Baer
  • Laura A. Sampson
  • Walter C. Willett
  • Catherine S. Berkey
  • Stuart J. Schnitt
  • James L. Connolly
  • Bernard A. Rosner
  • Rulla M. Tamimi


Vitamin D and calcium have been shown to have protective effects against breast cancer development in animal studies. Vitamin D and calcium play important anticarcinogenic roles in animal studies. Exposures between menarche and first birth may be important in breast development and future breast cancer risk. However, the relations between adolescent vitamin D and calcium intake and the risk of proliferative benign breast disease (BBD), a marker of increased breast cancer risk, have not yet been evaluated. We examined these associations in the Nurses’ Health Study II. Among the 29,480 women who completed an adolescent diet questionnaire in 1998, 682 proliferative BBD cases were identified and confirmed by centralized pathology review between 1991 and 2001. Hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated by Cox proportional hazards regression and adjusted for potential confounders. A suggestive inverse association was observed between adolescent total vitamin D intake and proliferative BBD. Women in the highest quintile of vitamin D intake during adolescence had a 21 % lower risk (multivariate HR (95 % CI): 0.79 (0.61, 1.01), p-trend = 0.07) of proliferative BBD than women in the lowest quintile. Results were essentially the same when the analysis was restricted to prospective cases (n = 142) diagnosed after return of the adolescent diet questionnaire and independent of adult vitamin D intake. Adolescent total milk intake was positively associated with proliferative BBD (≥3 servings/day vs. <1 serving/day HR (95 % CI): 1.41 (0.91, 2.17), p-trend = 0.03), after additional adjustment for total vitamin D. Calcium intake during adolescence was not associated with proliferative BBD (p-trend = 0.91). Vitamin D intake during adolescence may be important in the earlier stage of breast carcinogenesis. These findings, if corroborated, may suggest new pathways and strategies for breast cancer prevention.


Adolescent diet Vitamin D Calcium Proliferative BBD 



Atypical hyperplasia


Benign breast disease


Confidence interval


Food-frequency questionnaire


Hazard ratio


High school food-frequency questionnaire


Intraclass correlation coefficients


Nurses’ Health Study


Nurses’ Health Study II


Oral contraceptive



This work was supported by the National Institutes of Health Public Health Service Grants [grant numbers CA046475, CA050385, CA089393], and the Breast Cancer Research Foundation. Funding was provided in part by supporters and public donors of the Campaign for Cancer Prevention (, directed by Eric L. Ding. We also especially thank Causes founders Joseph Green and Sean Parker, as well as the entire dedicated staff of Causes (San Francisco, CA) and the Nurses’ Health Study II participants for their dedication to this study.

Ethical standards

The study complies with the current laws of the United States of America.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Xuefen Su
    • 1
    • 2
    • 3
  • Graham A. Colditz
    • 3
    • 4
  • Laura C. Collins
    • 5
  • Heather J. Baer
    • 3
    • 6
  • Laura A. Sampson
    • 2
    • 7
  • Walter C. Willett
    • 2
    • 3
    • 7
  • Catherine S. Berkey
    • 2
  • Stuart J. Schnitt
    • 5
  • James L. Connolly
    • 5
  • Bernard A. Rosner
    • 2
    • 8
  • Rulla M. Tamimi
    • 2
    • 3
  1. 1.School of Public Health and Primary Care, Faculty of MedicineChinese University of Hong KongHong KongPeople’s Republic of China
  2. 2.Channing Laboratory, Department of MedicineBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  4. 4.Alvin J. Siteman Cancer Center and Department of SurgeryWashington University School of MedicineSt. LouisUSA
  5. 5.Department of PathologyHarvard Medical School and Beth Israel Deaconess Medical CenterBostonUSA
  6. 6.Division of General MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  7. 7.Department of NutritionHarvard School of Public HealthBostonUSA
  8. 8.Department of BiostatisticsHarvard School of Public HealthBostonUSA

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