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Original Investigation
March 2017

Association of Serum Level of Vitamin D at Diagnosis With Breast Cancer SurvivalA Case-Cohort Analysis in the Pathways Study

Author Affiliations
  • 1Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York
  • 2Division of Research, Kaiser Permanente Northern California, Oakland
  • 3Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York
  • 4Department of Epidemiology and Biostatistics, University of California, San Francisco

Copyright 2017 American Medical Association. All Rights Reserved.

JAMA Oncol. 2017;3(3):351-357. doi:10.1001/jamaoncol.2016.4188
Key Points

Question  What is the association of serum vitamin D levels at the time of diagnosis with breast cancer survival?

Findings  In this cohort study of 1666 women with breast cancer, higher serum 25-hydroxyvitamin D levels were independently associated with better outcomes, including overall survival. Compared with women with the lowest third of 25-hydroxyvitamin D levels, those with the highest third had reduced hazards of all-cause death after full adjustment, and the associations were stronger in premenopausal women.

Meaning  This study provides compelling observational evidence of vitamin D’s benefits for breast cancer progression and mortality.


Importance  There are long-standing interests in the potential benefits of vitamin D for preventing breast cancer recurrence and mortality, yet data from prospective cohort studies are limited.

Objective  To investigate a serum biomarker of vitamin D status, 25-hydroxyvitamin D (25OHD) measured at the time of breast cancer diagnosis, to determine the association with prognosis.

Design, Setting, and Participants  The Pathways Study is a prospective cohort study of breast cancer survivors established in 2006. Enrollment was completed in 2013; follow-up is ongoing. The cohort was established in Kaiser Permanente Northern California, a large integrated health care delivery system in northern California. Women with a diagnosis of incident invasive breast cancer were typically consented and enrolled within 2 months of diagnosis. The overall enrollment rate was 46% (4505 of 9820). Participants are followed for health outcomes and comorbidities at 12, 24, 48, 72, and 96 months after baseline interview. A case-cohort design was used for efficiency assay of 25OHD, selecting 1666 cohort members with serum samples and ensuring representation in the subcohort of races and clinical subtypes. The data analysis was performed from January 5, 2014, to March 15, 2015.

Main Outcomes and Measures  Primary outcomes are breast cancer recurrence, second primary cancer, and death.

Results  Mean (SD) age was 58.7 (12.4) years. Serum 25OHD concentrations were lower in women with advanced-stage tumors, and the lowest in premenopausal women with triple-negative cancer. Levels were also inversely associated with hazards of disease progression and death. Compared with the lowest tertile, women with the highest tertile of 25OHD levels had superior overall survival (OS). This association remained after adjustment for clinical prognostic factors (hazard ratio [HR], 0.72; 95% CI, 0.54-0.98). Among premenopausal women, the association with OS was stronger, and there were also associations with breast cancer–specific survival and invasive disease–free survival (OS: HR, 0.45; 95% CI, 0.21-0.96; breast cancer–specific survival: HR, 0.37; 95% CI, 0.15-0.93; invasive disease–free survival: HR, 0.58; 95% CI, 0.34-1.01; all after full adjustment).

Conclusions and Relevance  Serum 25OHD levels were independently associated with breast cancer prognostic characteristics and patient prognosis, most prominently among premenopausal women. Our findings from a large, well-characterized prospective cohort provide compelling observational evidence on associations of vitamin D with lower risk of breast cancer morbidity and mortality.