title: Increased prevalence of vitamin D insufficiency in patients with breast cancer after neoadjuvant chemotherapy.
abstract: Patients with locally advanced breast cancer treated with neoadjuvant chemotherapy are at risk of cancer treatment-induced bone loss and consequently of increased skeletal morbidity. In addition, this situation could be worsened by the fact that only a minority of patients with breast cancer have sufficient vitamin D. A comprehensive evaluation of bone homeostasis is critical in this context. We retrospectively evaluated the serum levels of calcium, vitamin D, TRAIL, RANK ligand (RANKL), Osteoprotegerin (OPG), Bone TRAP, CrossLaps and DKK1 in 77 patients (median age: 50 years; range 25-74), with locally advanced breast cancer treated in our institute with anthracyclines-taxane neoadjuvant chemotherapy (7 cycles of 21 days/each) between March 2007 and August 2008. Serum samples were collected before the first (baseline) and the last treatment cycle. Variations and correlations between biomarker levels were evaluated. At baseline, 79.5 % of patients had vitamin D insufficiency (<30 ng/ml), increasing to 97.4 % at the end of the neoadjuvant chemotherapy (p < 0.0001). Calcium and RANKL serum concentrations were also significantly decreased, while OPG was significantly increased, resulting in lower RANKL/OPG ratio. Calcium and vitamin D, RANKL and vitamin D and RANKL and OPG levels were significantly correlated (Spearman's coefficient r = 0.2721, p = 0.0006; r = 0.1916, p = 0.002; and r = -0.179, p = 0.03, respectively). Nearly all included patients suffered from vitamin D insufficiency by the end of the neoadjuvant chemotherapy with changes in the calcium/RANKL/OPG axis that are evocative of deregulation of a functional regulatory mechanism. Further studies are needed to determine how drugs modulate this regulatory mechanism to preserve bone homeostasis in patients with breast cancer.
authors.affiliation: Département d'Oncologie Médicale, CRLC Val d'Aurelle-Paul Lamarque, 208, rue des Apothicaires, 34298 Montpellier, France.
authors.forename: William
authors.initials: W
authors.lastname: Jacot
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pouderoux
authors.forename: Simon
authors.initials: S
authors.lastname: Thezenas
authors.forename: Angélique
authors.initials: A
authors.lastname: Chapelle
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bleuse
authors.forename: Gilles
authors.initials: G
authors.lastname: Romieu
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Lamy
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D002118:Calcium / Q000097:blood; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D017024:Chemotherapy, Adjuvant; D003094:Collagen / Q000097:blood; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D000077143:Docetaxel; D015251:Epirubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D007527:Isoenzymes / Q000097:blood; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D053244:Osteoprotegerin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D015995:Prevalence; D053245:RANK Ligand / Q000097:blood; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood; D000071681:Tartrate-Resistant Acid Phosphatase; D043823:Taxoids / Q000008:administration & dosage; D014807:Vitamin D / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology
chemical_list: D015415:Biomarkers; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D053244:Osteoprotegerin; D010446:Peptide Fragments; D053245:RANK Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C506030:TNFRSF11B protein, human; C505653:TNFSF10 protein, human; C505688:TNFSF11 protein, human; D043823:Taxoids; C110762:glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine; D014807:Vitamin D; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide; D003094:Collagen; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002118:Calcium; D005472:Fluorouracil