P3-14-14: Increased Prevalence of Low Vitamin D Level in Breast Cancer Patients during Neoadjuvant Chemotherapy.
Authors: Jacot W , Pouderoux S , Thezenas S , Chapelle A , Romieu G , Lamy P-J 
Published: June 2012

Purpose: Patients with early-stage breast cancer treated with neoadjuvant chemotherapy (NCT) are at risk of bone metabolism changes, resulting in loss of bone mass. Cancer treatment-induced bone loss (CTIBL) increases the risk for skeletal morbidity. An understanding of CTIBL is critical for determining the risk, identifying which patients may benefit from preventive therapy, and for screening patients for early intervention with therapies such as bisphosphonates or anti-RANKL therapies. In addition, considering the bone metabolism profile in early breast cancer patients, only a minority of women had vitamin D levels in the range considered sufficient for optimal health. This vitamin D deficiency may be associated with poor outcomes in breast cancer. In order to study the variation of the bone metabolism markers during NCT, we evaluated 78 early breast cancer patients homogeneously treated in our centre.

Patients and methods: We studied the serum level of a panel of bone metabolism biomarkers (calcium, vitamin D, TRAIL, RANK-Ligand, Osteoprotegerin (OPG), serum bone trap, serum crosslap and DKK1), in a population of 78 early breast cancer patients treated by the association of 3 cycles of FEC100 then 4 taxane cycles between March 2007 and August 2008. Serum samples were withdrawn before the first CT cycle and before surgery. Time course and correlations between these biomarkers levels were evaluated. All computations were carried out using Stata. Two-sided P-values below 0.05 were considered to be statistically significant.

Results: The clinicopathological characteristics of the population were classical of a neoadjuvant setting. 23% of the patients achieved a pCR. At baseline, 79.5% of the patients presented with vitamin D insufficiency (&lt; 30 ng/ml). This proportion increased to nearly all the patients before surgery (97.4%, p &lt; 0.0001). The same significant decrease in serum levels was found for calcium and RANK-ligand, while a significant increase in serum OPG level was noted, resulting in an increase of the OPG/RANK-Ligand ratio. Serum calcium and vitamin D levels were significantly correlated (Spearman's coefficient = 0.023), while there was a trend (Spearman's coefficient = 0.1) for correlation between serum calcium and RANK-Ligand levels.

Conclusion: To our knowledge, this is the first clinical study comprehensively evaluating the changes in bone metabolism during early stage breast cancer NCT. In our study, nearly all the patients suffered from vitamin D insufficiency by the end of NCT. This insufficiency was associated with changes in the calcium / Rank-Ligand / OPG axis, evocative of a functional regulatory mechanism. These results require further analyses in order to define the role of pharmacologic modulation of this regulatory mechanism in the bone wellbeing of early breast cancer patients. A study evaluating the best medical intervention to correct this highly prevalent vitamin D insufficiency in this population is ongoing.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-14.