title: Improved clinical outcomes associated with vitamin D supplementation during adjuvant chemotherapy in patients with HER2+ nonmetastatic breast cancer.
abstract: BACKGROUND
  Vitamin D (VD) supplementation has pleiotropic effects that extend beyond their impact on bone health, including the disruption of downstream VD receptor signaling and human epidermal growth factor receptor 2 (HER2) signaling through the ErbB2/AKT/ERK pathway. In the present study, we examined our institutional experience with patients having nonmetastatic HER2-positive (HER(+)) breast cancer and hypothesized that those patients who received VD supplementation during neoadjuvant chemotherapy would have improved long-term outcomes.
  
  
  METHODS
  We performed a retrospective review of all patients (n = 308) given trastuzumab-based chemotherapy between 2006 and 2012 at the University of Miami/Sylvester Comprehensive Cancer Center (UM/SCCC). We identified 2 groups of patients for comparison-those who received VD supplementation during neoadjuvant chemotherapy (n = 134) and those who did not (n = 112). Univariate and multivariate Cox proportional hazard regression models were fitted to overall survival (OS) and disease-free survival (DFS).
  
  
  RESULTS
  More than half of the patients received VD during neoadjuvant chemotherapy (54.5%), with 60% receiving a dose < 10,000 units/wk and 33.3% having a VD deficiency at the start of therapy. In our final multivariate model, VD use was associated with improved DFS (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.15-0.88; P = .026], whereas larger tumor size was associated with worse DFS (HR, 3.52; 95% CI, 1.06-11.66; P = .04). There were no differences in OS based on any of the categories, including VD use, tumor size, number of metastatic lymph nodes, age at diagnosis, or lymphovascular invasion (LVI).
  
  
  CONCLUSIONS
  VD supplementation in patients with nonmetastatic HER2(+) breast cancer is associated with improved DFS.
authors.affiliation: Department of Hematology and Oncology, Emory Winship Cancer Center, Atlanta, GA. Electronic address: simonzeichner@gmail.com.
authors.forename: Simon B
authors.initials: SB
authors.lastname: Zeichner
authors.affiliation: Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL; Sylvester Comprehensive Cancer Center at University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Tulay
authors.initials: T
authors.lastname: Koru-Sengul
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Nikesh
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Psychology, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Advanced Analytics, United HealthCare, Metairie, LA.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Markward
authors.affiliation: Department of Solid Tumor Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Montero
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, FL; Sylvester Comprehensive Cancer Center at University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Stefan
authors.initials: S
authors.lastname: Glück
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, FL; Sylvester Comprehensive Cancer Center at University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Orlando
authors.initials: O
authors.lastname: Silva
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, FL; Sylvester Comprehensive Cancer Center at University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Ahn
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000178:diet therapy* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D019587:Dietary Supplements; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D014807:Vitamin D; C508053:ERBB2 protein, human
keywords: Calcitriol; ErbB2/AKT/ERK pathway; Pleiotropic effects; Trastuzumab; Vitamin D receptor; Vitamin D supplementation