Skip to main content
Top
Published in: Annals of Surgical Oncology 8/2012

01-08-2012 | Breast Oncology

The Association Between Breast Cancer Prognostic Indicators and Serum 25-OH Vitamin D Levels

Authors: Luke J. Peppone, PhD, MPH, Aaron S. Rickles, MD, Michelle C. Janelsins, PhD, Michael R. Insalaco, AS, Kristin A. Skinner, MD

Published in: Annals of Surgical Oncology | Issue 8/2012

Login to get access

Abstract

Background

Studies show that women with low vitamin D levels have an increased risk of breast cancer (BC) incidence and mortality, but there is a lack of research examining vitamin D levels and prognostic variables in BC patients. The aim of this study is to examine 25-OH vitamin D levels between BC cases and controls and by prognostic indicators among BC cases.

Methods

25-OH vitamin D levels were collected from 194 women who underwent BC surgery and 194 cancer-free (CF) controls at the University of Rochester between January 2009 and October 2010. Mean 25-OH vitamin D levels and odds ratios (OR) were calculated by case/control status for the overall cohort and by prognostic indicators (invasiveness, ER status, triple-negative status, Oncotype DX score, molecular phenotype) for BC cases.

Results

BC cases had significantly lower 25-OH vitamin D levels than CF controls (BC: 32.7 ng/mL vs. CF: 37.4 ng/mL; P = .02). In case-series analyses, women with suboptimal 25-OH vitamin D concentrations (<32 ng/mL) had significantly higher odds of having ER− (OR = 2.59, 95% confidence interval [95% CI] = 1.08–6.23) and triple-negative cancer (OR = 3.15, 95% CI = 1.05–9.49) than those with optimal 25-OH D concentrations. Women with basal-like phenotype had lower 25-OH vitamin D levels than women luminal A phenotype (basal-like: 24.2 ng/mL vs. luminal A: 32.8 ng/mL; P = 0.04).

Conclusions

BC patients with a more aggressive molecular phenotype (basal-like) and worse prognostic indicators (ER− and triple-negative) had lower mean 25-OH vitamin D levels. Further research is needed to elucidate the biological relationship between vitamin D and BC progression.
Literature
1.
go back to reference Townsend K, Banwell CM, Guy M, Colston KW, Mansi JL, Stewart PM, et al. Autocrine metabolism of vitamin D in normal and malignant breast tissue. Clin Cancer Res. 2005;11:3579–86.PubMedCrossRef Townsend K, Banwell CM, Guy M, Colston KW, Mansi JL, Stewart PM, et al. Autocrine metabolism of vitamin D in normal and malignant breast tissue. Clin Cancer Res. 2005;11:3579–86.PubMedCrossRef
2.
go back to reference Goodwin PJ, Ennis M, Pritchard KI, Koo J, Hood N. Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer. J Clin Oncol. 2009;27:3757–63.PubMedCrossRef Goodwin PJ, Ennis M, Pritchard KI, Koo J, Hood N. Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer. J Clin Oncol. 2009;27:3757–63.PubMedCrossRef
3.
go back to reference Gissel T, Rejnmark L, Mosekilde L, Vestergaard P. Intake of vitamin D and risk of breast cancer—a meta-analysis. J Steroid Biochem Mol Biol. 2008;111:195–9.PubMedCrossRef Gissel T, Rejnmark L, Mosekilde L, Vestergaard P. Intake of vitamin D and risk of breast cancer—a meta-analysis. J Steroid Biochem Mol Biol. 2008;111:195–9.PubMedCrossRef
4.
go back to reference Bertone-Johnson ER, Chen WY, Holick MF, Hollis BW, Colditz GA, Willett WC, et al. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:1991–7.PubMedCrossRef Bertone-Johnson ER, Chen WY, Holick MF, Hollis BW, Colditz GA, Willett WC, et al. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:1991–7.PubMedCrossRef
5.
go back to reference Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med. 2007;167:1050–9.PubMedCrossRef Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med. 2007;167:1050–9.PubMedCrossRef
6.
go back to reference Neuhouser ML, Sorensen B, Hollis BW, Ambs A, Ulrich CM, McTiernan A, et al. Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors. Am J Clin Nutr. 2008;88:133–9.PubMed Neuhouser ML, Sorensen B, Hollis BW, Ambs A, Ulrich CM, McTiernan A, et al. Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors. Am J Clin Nutr. 2008;88:133–9.PubMed
7.
go back to reference Yao S, Sucheston LE, Millen AE, Johnson CS, Trump DL, Nesline MK, et al. Pretreatment serum concentrations of 25-hydroxyvitamin d and breast cancer prognostic characteristics: a case-control and a case-series study. PLoS One. 2011;6:e17251. Yao S, Sucheston LE, Millen AE, Johnson CS, Trump DL, Nesline MK, et al. Pretreatment serum concentrations of 25-hydroxyvitamin d and breast cancer prognostic characteristics: a case-control and a case-series study. PLoS One. 2011;6:e17251.
8.
go back to reference Palmieri C, MacGregor T, Girgis S, Vigushin D. Serum 25-hydroxyvitamin D levels in early and advanced breast cancer. J Clin Pathol. 2006;59:1334–6.PubMedCrossRef Palmieri C, MacGregor T, Girgis S, Vigushin D. Serum 25-hydroxyvitamin D levels in early and advanced breast cancer. J Clin Pathol. 2006;59:1334–6.PubMedCrossRef
9.
go back to reference Abbas S, Linseisen J, Slanger T, Kropp S, Mutschelknauss EJ, Flesch-Janys D, et al. Serum 25-hydroxyvitamin D and risk of post-menopausal breast cancer–results of a large case-control study. Carcinogenesis. 2008;29:93–9.PubMedCrossRef Abbas S, Linseisen J, Slanger T, Kropp S, Mutschelknauss EJ, Flesch-Janys D, et al. Serum 25-hydroxyvitamin D and risk of post-menopausal breast cancer–results of a large case-control study. Carcinogenesis. 2008;29:93–9.PubMedCrossRef
10.
go back to reference Lowe LC, Guy M, Mansi JL, Peckitt C, Bliss J, Wilson RG, et al. Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population. Eur J Cancer. 2005;41:1164–9.PubMedCrossRef Lowe LC, Guy M, Mansi JL, Peckitt C, Bliss J, Wilson RG, et al. Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population. Eur J Cancer. 2005;41:1164–9.PubMedCrossRef
11.
go back to reference Chen P, Hu P, Xie D, Qin Y, Wang F, Wang H. Meta-analysis of vitamin D, calcium and the prevention of breast cancer. Breast Cancer Res Treat. 2010;121:469–77.PubMedCrossRef Chen P, Hu P, Xie D, Qin Y, Wang F, Wang H. Meta-analysis of vitamin D, calcium and the prevention of breast cancer. Breast Cancer Res Treat. 2010;121:469–77.PubMedCrossRef
12.
go back to reference Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, et al. Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol. 2007;103:708–11.PubMedCrossRef Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, et al. Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol. 2007;103:708–11.PubMedCrossRef
13.
go back to reference Peppone LJ, Huston AJ, Reid ME, Rosier RN, Zakharia Y, Trump DL, et al. The effect of various vitamin D supplementation regimens in breast cancer patients. Breast Cancer Res Treat. 2011;127:171–7.PubMedCrossRef Peppone LJ, Huston AJ, Reid ME, Rosier RN, Zakharia Y, Trump DL, et al. The effect of various vitamin D supplementation regimens in breast cancer patients. Breast Cancer Res Treat. 2011;127:171–7.PubMedCrossRef
14.
go back to reference Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31:48–54.PubMedCrossRef Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31:48–54.PubMedCrossRef
15.
go back to reference Deshpande AD, Jeffe DB, Gnerlich J, Iqbal AZ, Thummalakunta A, Margenthaler JA. Racial disparities in breast cancer survival: an analysis by age and stage. J Surg Res. 2009;153:105–13.PubMedCrossRef Deshpande AD, Jeffe DB, Gnerlich J, Iqbal AZ, Thummalakunta A, Margenthaler JA. Racial disparities in breast cancer survival: an analysis by age and stage. J Surg Res. 2009;153:105–13.PubMedCrossRef
16.
go back to reference Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med. 2009;360:790–800.PubMedCrossRef Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med. 2009;360:790–800.PubMedCrossRef
17.
go back to reference Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26.PubMedCrossRef Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26.PubMedCrossRef
18.
go back to reference Cui Y, Rohan TE. Vitamin D, calcium, and breast cancer risk: a review. Cancer Epidemiol Biomarkers Prev. 2006;15:1427–37.PubMedCrossRef Cui Y, Rohan TE. Vitamin D, calcium, and breast cancer risk: a review. Cancer Epidemiol Biomarkers Prev. 2006;15:1427–37.PubMedCrossRef
19.
go back to reference Abbas S, Chang-Claude J, Linseisen J. Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study. Int J Cancer. 2009;124:250–5.PubMedCrossRef Abbas S, Chang-Claude J, Linseisen J. Plasma 25-hydroxyvitamin D and premenopausal breast cancer risk in a German case-control study. Int J Cancer. 2009;124:250–5.PubMedCrossRef
20.
go back to reference Grant WB, Peiris AN. Possible role of serum 25-hydroxyvitamin D in black–white health disparities in the United States. J Am Med Dir Assoc. 2010;11:617–28.PubMedCrossRef Grant WB, Peiris AN. Possible role of serum 25-hydroxyvitamin D in black–white health disparities in the United States. J Am Med Dir Assoc. 2010;11:617–28.PubMedCrossRef
21.
go back to reference Crowe JP, Jr., Gordon NH, Hubay CA, Shenk RR, Zollinger RM, Brumberg DJ, et al. Estrogen receptor determination and long term survival of patients with carcinoma of the breast. Surg Gynecol Obstet. 1991;173:273–8.PubMed Crowe JP, Jr., Gordon NH, Hubay CA, Shenk RR, Zollinger RM, Brumberg DJ, et al. Estrogen receptor determination and long term survival of patients with carcinoma of the breast. Surg Gynecol Obstet. 1991;173:273–8.PubMed
22.
go back to reference Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007;109:1721–8.PubMedCrossRef Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007;109:1721–8.PubMedCrossRef
23.
go back to reference Colston KW, Hansen CM. Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer. Endocr Relat Cancer. 2002;9:45–59.PubMedCrossRef Colston KW, Hansen CM. Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer. Endocr Relat Cancer. 2002;9:45–59.PubMedCrossRef
24.
go back to reference Lowe L, Hansen CM, Senaratne S, Colston KW. Mechanisms implicated in the growth regulatory effects of vitamin D compounds in breast cancer cells. Recent Results Cancer Res. 2003;164:99–110.PubMed Lowe L, Hansen CM, Senaratne S, Colston KW. Mechanisms implicated in the growth regulatory effects of vitamin D compounds in breast cancer cells. Recent Results Cancer Res. 2003;164:99–110.PubMed
25.
go back to reference Welsh J, Wietzke JA, Zinser GM, Smyczek S, Romu S, Tribble E, et al. Impact of the Vitamin D3 receptor on growth-regulatory pathways in mammary gland and breast cancer. J Steroid Biochem Mol Biol. 2002;83:85–92.PubMedCrossRef Welsh J, Wietzke JA, Zinser GM, Smyczek S, Romu S, Tribble E, et al. Impact of the Vitamin D3 receptor on growth-regulatory pathways in mammary gland and breast cancer. J Steroid Biochem Mol Biol. 2002;83:85–92.PubMedCrossRef
26.
go back to reference Kemmis CM, Salvador SM, Smith KM, Welsh J. Human mammary epithelial cells express CYP27B1 and are growth inhibited by 25-hydroxyvitamin D-3, the major circulating form of vitamin D-3. J Nutr. 2006;136:887–92.PubMed Kemmis CM, Salvador SM, Smith KM, Welsh J. Human mammary epithelial cells express CYP27B1 and are growth inhibited by 25-hydroxyvitamin D-3, the major circulating form of vitamin D-3. J Nutr. 2006;136:887–92.PubMed
27.
go back to reference Lazzaro G, Agadir A, Qing W, Poria M, Mehta RR, Moriarty RM, et al. Induction of differentiation by 1alpha-hydroxyvitamin D(5) in T47D human breast cancer cells and its interaction with vitamin D receptors. Eur J Cancer. 2000;36:780–6.PubMedCrossRef Lazzaro G, Agadir A, Qing W, Poria M, Mehta RR, Moriarty RM, et al. Induction of differentiation by 1alpha-hydroxyvitamin D(5) in T47D human breast cancer cells and its interaction with vitamin D receptors. Eur J Cancer. 2000;36:780–6.PubMedCrossRef
28.
go back to reference Simboli-Campbell M, Narvaez CJ, Tenniswood M, Welsh J. 1,25-Dihydroxyvitamin D3 induces morphological and biochemical markers of apoptosis in MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 1996;58:367–76.PubMedCrossRef Simboli-Campbell M, Narvaez CJ, Tenniswood M, Welsh J. 1,25-Dihydroxyvitamin D3 induces morphological and biochemical markers of apoptosis in MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 1996;58:367–76.PubMedCrossRef
29.
go back to reference Mantell DJ, Owens PE, Bundred NJ, Mawer EB, Canfield AE. 1 alpha,25-dihydroxyvitamin D(3) inhibits angiogenesis in vitro and in vivo. Circ Res. 2000;87:214–20.PubMedCrossRef Mantell DJ, Owens PE, Bundred NJ, Mawer EB, Canfield AE. 1 alpha,25-dihydroxyvitamin D(3) inhibits angiogenesis in vitro and in vivo. Circ Res. 2000;87:214–20.PubMedCrossRef
30.
go back to reference Pendas-Franco N, Gonzalez-Sancho JM, Suarez Y, Aguilera O, Steinmeyer A, Gamallo C, et al. Vitamin D regulates the phenotype of human breast cancer cells. Differentiation. 2007;75:193–207.PubMedCrossRef Pendas-Franco N, Gonzalez-Sancho JM, Suarez Y, Aguilera O, Steinmeyer A, Gamallo C, et al. Vitamin D regulates the phenotype of human breast cancer cells. Differentiation. 2007;75:193–207.PubMedCrossRef
31.
go back to reference Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79:362–71.PubMed Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79:362–71.PubMed
32.
go back to reference Lagunova Z, Porojnicu AC, Lindberg F, Hexeberg S, Moan J. The dependency of vitamin D status on body mass index, gender, age and season. Anticancer Res. 2009;29:3713–20.PubMed Lagunova Z, Porojnicu AC, Lindberg F, Hexeberg S, Moan J. The dependency of vitamin D status on body mass index, gender, age and season. Anticancer Res. 2009;29:3713–20.PubMed
Metadata
Title
The Association Between Breast Cancer Prognostic Indicators and Serum 25-OH Vitamin D Levels
Authors
Luke J. Peppone, PhD, MPH
Aaron S. Rickles, MD
Michelle C. Janelsins, PhD
Michael R. Insalaco, AS
Kristin A. Skinner, MD
Publication date
01-08-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 8/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2297-3

Other articles of this Issue 8/2012

Annals of Surgical Oncology 8/2012 Go to the issue