Clinical trial NCT00926315: Gene Expression Profile of Breast Cancer Samples After Vitamin D Supplementation
Official title: Influence of Vitamin D on Gene Expression Profile of Breast Cancer Samples From Post-menopausal Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Neoplasms
Postmenopausal Disorder
Keywords: Breast Neoplasms
Calcitriol
Postmenopausal
Cell Proliferation
Gene Expression Profiling
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
Collaborators: name: Instituto Brasileiro de Controle do Cancer
First posted: 2009-06-23
Enrollment: 60
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: The purpose of this study is to evaluate whether calcitriol supplementation may reduce tumor cell proliferation and influence gene expression profile of breast cancer samples from post-menopausal patients.

Detailed description: Women affected by breast cancer present lower 1,25(OH)2D3 or 25(OH)D3 serum levels than unaffected ones. Calcitriol supplementation may be indicated to post-menopausal women to reduce bone loss. Vitamin D has antiproliferative effects in breast cancer cell lines and breast cancer xenografts.

Post-menopausal breast cancer patients will be prescribed calcitriol supplementation, in doses indicated to prevent osteoporosis, while they are submitted to biopsy, staging exams and have their breast surgery scheduled (approximately one month). Tumor dimension and proliferation rate (as determined by Ki67 expression), 25(OH)D3 and/or 1,25(OH)2D3 serum concentration, will be evaluated before and after calcitriol supplementation. Tumor gene expression will be evaluated in samples collected before and after supplementation to analyze the differential profile.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal women
* Invasive breast carcinoma
* Clinical conditions for breast surgery
* No previous neoadjuvant treatment for breast cancer
* Agreement to take part in the study and sign the informed consent

Exclusion Criteria:

* History of hypercalcemia or nephrolithiasis
* Current use of corticosteroids, vitamin D supplementation, HRT
* Previous chemotherapy, hormonotherapy or radiotherapy
* Parathyroid disease
* Absence of clinical condition to receive supplementation

Primary outcomes:
measure: Tumor dimension and proliferation evaluated by ultrasound and Ki67 expression; Tumor gene expression profile
timeFrame: 30 days
Secondary outcomes:
measure: Follow-up for 5 years
timeFrame: 5 years
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Instituto Brasileiro de Controle do Câncer - IBCC
state: SP
Study officials:
affiliation: Faculdade de Medicina - Universidade de São Paulo
name: Maria Aparecida A Koike Folgueira, MD,PhD
role: STUDY_CHAIR
affiliation: Instituto Brasileiro de Controle do Cancer
name: Eduardo Carneiro de Lyra, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Faculdade de Medicina da Universidade de São Paulo
name: Yuri N Urata, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Faculdade de Medicina da Universidade de São Paulo
name: Maria Lucia H Katayama, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Lyra EC, da Silva IA, Katayama ML, Brentani MM, Nonogaki S, Goes JC, Folgueira MA. 25(OH)D3 and 1,25(OH)2D3 serum concentration and breast tissue expression of 1alpha-hydroxylase, 24-hydroxylase and Vitamin D receptor in women with and without breast cancer. J Steroid Biochem Mol Biol. 2006 Aug;100(4-5):184-92. doi: 10.1016/j.jsbmb.2006.04.009. Epub 2006 Jul 7.
citation: Rozenchan PB, Folgueira MA, Katayama ML, Snitcovsky IM, Brentani MM. Ras activation is associated with vitamin D receptor mRNA instability in HC11 mammary cells. J Steroid Biochem Mol Biol. 2004 Sep;92(1-2):89-95. doi: 10.1016/j.jsbmb.2004.05.007.
citation: Katayama ML, Pasini FS, Folgueira MA, Snitcovsky IM, Brentani MM. Molecular targets of 1,25(OH)2D3 in HC11 normal mouse mammary cell line. J Steroid Biochem Mol Biol. 2003 Jan;84(1):57-69. doi: 10.1016/s0960-0760(03)00004-9.
citation: Bortman P, Folgueira MA, Katayama ML, Snitcovsky IM, Brentani MM. Antiproliferative effects of 1,25-dihydroxyvitamin D3 on breast cells: a mini review. Braz J Med Biol Res. 2002 Jan;35(1):1-9. doi: 10.1590/s0100-879x2002000100001.
citation: Folgueira MA, Federico MH, Katayama ML, Silva MR, Brentani MM. Expression of vitamin D receptor (VDR) in HL-60 cells is differentially regulated during the process of differentiation induced by phorbol ester, retinoic acid or interferon-gamma. J Steroid Biochem Mol Biol. 1998 Aug;66(4):193-201. doi: 10.1016/s0960-0760(98)00041-7.
citation: Janjoppi L, Katayama MH, Scorza FA, Folgueira MA, Brentani M, Pansani AP, Cavalheiro EA, Arida RM. Expression of vitamin D receptor mRNA in the hippocampal formation of rats submitted to a model of temporal lobe epilepsy induced by pilocarpine. Brain Res Bull. 2008 Jul 30;76(5):480-4. doi: 10.1016/j.brainresbull.2008.01.002. Epub 2008 Feb 5.
citation: Folgueira MA, Carraro DM, Brentani H, Patrao DF, Barbosa EM, Netto MM, Caldeira JR, Katayama ML, Soares FA, Oliveira CT, Reis LF, Kaiano JH, Camargo LP, Vencio RZ, Snitcovsky IM, Makdissi FB, e Silva PJ, Goes JC, Brentani MM. Gene expression profile associated with response to doxorubicin-based therapy in breast cancer. Clin Cancer Res. 2005 Oct 15;11(20):7434-43. doi: 10.1158/1078-0432.CCR-04-0548.