Association of Serum Level of Vitamin D at Diagnosis With Breast Cancer Survival: A Case-Cohort Analysis in the Pathways Study.
OBJECTIVE
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.


METHODS
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.


METHODS
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
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.
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
Song
S
Yao
Division of Research, Kaiser Permanente Northern California, Oakland.
Marilyn L
ML
Kwan
Division of Research, Kaiser Permanente Northern California, Oakland.
Isaac J
IJ
Ergas
Division of Research, Kaiser Permanente Northern California, Oakland.
Janise M
JM
Roh
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
Ting-Yuan David
TD
Cheng
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
Chi-Chen
CC
Hong
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
Susan E
SE
McCann
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
Li
L
Tang
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
Warren
W
Davis
Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York.
Song
S
Liu
Division of Research, Kaiser Permanente Northern California, Oakland.
Charles P
CP
Quesenberry
Department of Epidemiology and Biostatistics, University of California, San Francisco.
Marion M
MM
Lee
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
Christine B
CB
Ambrosone
Division of Research, Kaiser Permanente Northern California, Oakland.
Lawrence H
LH
Kushi
D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D017697:Premenopause; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D017741:Survivors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
D014408:Biomarkers, Tumor; D014807:Vitamin D; C104450:25-hydroxyvitamin D