Gene Expression Profile of Breast Cancer Samples After Vitamin D Supplementation

Influence of Vitamin D on Gene Expression Profile of Breast Cancer Samples From Post-menopausal Patients

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.

Study Overview

• Status: Unknown
• Conditions: Breast Neoplasms; Postmenopausal Disorder
• Intervention / Treatment: Drug: calcitriol; Drug: Calcitriol

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • SP
    • São Paulo, SP, Brazil, 03102-002
      • Instituto Brasileiro de Controle do Cancer - ibcc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: calcitriol; calcitriol supplementation (0.25 mcg 2x/d)	Drug: calcitriol; Post menopausal patients will receive Calcitriol 0.50 mcg PO per day for 1 month.; Other Names: Rocaltrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Tumor dimension and proliferation evaluated by ultrasound and Ki67 expression; Tumor gene expression profile	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Follow-up for 5 years	5 years

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: Instituto Brasileiro de Controle do Cancer
• Investigators: Study Chair: Maria Aparecida A Koike Folgueira, MD,PhD, Faculdade de Medicina - Universidade de São Paulo; Principal Investigator: Eduardo Carneiro de Lyra, MD, PhD, Instituto Brasileiro de Controle do Cancer; Principal Investigator: Yuri N Urata, MSc, Faculdade de Medicina da Universidade de Sao Paulo; Principal Investigator: Maria Lucia H Katayama, PhD, Faculdade de Medicina da Universidade de Sao Paulo

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (ANTICIPATED): June 1, 2013
• Study Completion (ANTICIPATED): December 1, 2013

Study Registration Dates

• First Submitted: June 19, 2009
• First Submitted That Met QC Criteria: June 22, 2009
• First Posted (ESTIMATE): June 23, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): November 1, 2012
• Last Update Submitted That Met QC Criteria: October 31, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Cell Proliferation; Breast Neoplasms; Postmenopausal; Gene Expression Profiling; Calcitriol
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vasoconstrictor Agents; Calcium Channel Agonists; Calcitriol
• Other Study ID Numbers: FMUSPIBCCVD2009; CAPPesq 626/06 (REGISTRY: Comissão Ética para Análise Projetos Pesquisa HCFMUSP 626/06); FAPESP 07/04799-2 (OTHER_GRANT: Fundação de Amparo à Pesquisa Estado de São Paulo 07/04799-2); IBCC 108/2006/07 (REGISTRY: Comitê de Ética em Pesquisa IBCC 108/2006/07); CAPPesq 0018/09 (REGISTRY: Comissão Ética para Análise Projetos Pesquisa HCFMUSP)