Abstract P1-08-19: Changes in circulating vitamin D levels as a predictor for pathological response to neoadjuvant chemotherapy (NAC) in breast cancer (BC): A Dutch breast cancer trialists group (BOOG) side-study
Authors: Charehbili A , Hamdy NAT , Smit VTHBM , Liefers G-J , Putter H , Meershoek-Klein Kranenbarg E , Heijns JB , van Warmerdam LJ , Kessels LW , Dercksen W , Pepels MJ , Maartense E , van Laarhoven HWM , Vriens B , van Leeuwen-Stok E , van de Velde CJH , Nortier HWR , Kroep JR 
Published: August 2014

Abstract
Background:
Vitamin D (vit D) status is suggested to be of prognostic value for treatment outcome in women with breast cancer. However, there are no data of the predictive value of vit D status and changes of vit D levels for response to neoadjuvant chemotherapy (NAC).
Methods:
A subset of patients (pts) from the NEOZOTAC trial in whom vit D data were available was evaluated. NEOZOTAC is a randomized phase III study comparing the efficacy of NCT with or without zoledronic acid (ZA) in pts with stage II/III, measurable, HER2-negative BC. Vit D deficiency and severe deficiency were defined as vit D levels of ≤ 50 and ≤25 nmol/L, respectively. Baseline vit D levels were available for correlation to pathological response of 165 pts (83 ZA-arm), while 67 pts (35 ZA arm) could be evaluated for changes in vit D levels between baseline and cycle 6. Pts who were allocated to the ZA arm should by protocol receive daily supplements of calcium/vit D 500/400 IU. Pathological response was assessed using the Miller and Payne scoring system; pathological complete response (pCR) was defined as absence of tumor cells in the tumor bed and good response was defined as ≥90% decrease of tumor cellularity.
Results:
Vit D was measured in 168 pts and was done in 75% of pre/perimenopausal pts and 51.3% of postmenopausal pts. There was no significant relation between baseline vit D deficiency (&lt; 50 nmol/L) and pCR (pCR 25.8% for deficient pts vs. 14.1% for non-deficient pts, P = 0.06). Pts with severe vit D deficiency (&lt;25 nmol/L) tended to respond less (pCR 10.5 vs 19.9%, p = 0.53). At the end of chemotherapy, good pathological responders seemed to have a slight increase in vit D levels compared to non-responders who rather showed a decrease (mean 1.11 vs. -9.71, P = 0.08). After multivariate analysis correcting for menopausal status and treatment arm, this result was significant (P = 0.03, 95% C.I. 1.004-1.055). When pts in the ZA arm were analyzed separately, again, good response was rather associated with an increase than a decrease (mean = 9.8 vs. -1.6, P = 0.12). From 17 out of 35 ZA treated pts who were vit D deficient at baseline, only 5 (29.4%) reached levels &gt;50 nmol/L at the end of treatment.
Conclusions:
Baseline vit D status was not predictive for pCR. However, increase in vit D levels during therapy tended to be associated with better pathological response. Therefore, achieving higher vit D levels can be important. Daily suppletion with calcium/ vitamin D 500/400 might be inadequate for achieving sufficient levels after NAC.
Contact information:
Dr. J.R. Kroep, M.D., Ph.D., Department of Medical Oncology, email:j.r.kroep@lumc.nl or A. Charehbili, BSc. Department of Surgery and Medical Oncology, email: a.charehbili@lumc.nl or LUMC datacenter, Department of Surgery, phone +31(0)71-5263500, fax +31(0)71-5266744, email: datacenter@lumc.nl, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-19.