Low Levels of Omega-3 Long-Chain Polyunsaturated Fatty Acids Are Associated with Bone Metastasis Formation in Premenopausal Women with Breast Cancer: A Retrospective Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Samples Collection
2.3. Lipid Analysis
2.4. Statistics
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pulido, C.; Vendrell, I.; Ferreira, A.R.; Casimiro, S.; Mansinho, A.; Alho, I.; Costa, L. Bone metastasis risk factors in breast cancer. Ecancermedicalscience 2017, 11, 715. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Diessner, J.; Wischnewsky, M.; Stüber, T.; Stein, R.; Krockenberger, M.; Häusler, S.; Janni, W.; Kreienberg, R.; Blettner, M.; Schwentner, L.; et al. Evaluation of clinical parameters influencing the development of bone metastasis in breast cancer. BMC Cancer 2016, 16, 307. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Braun, S.; Vogl, F.D.; Naume, B.; Janni, W.; Osborne, M.P.; Coombes, R.C.; Schlimok, G.; Diel, I.J.; Gerber, B.; Gebauer, G.; et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N. Engl. J. Med. 2005, 353, 793–802. [Google Scholar] [CrossRef] [PubMed]
- Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) Adjuvant bisphosphonate treatment in early breast cancer: Meta-analyses of individual patient data from randomised trials. Lancet 2015, 386, 1353–1361. [CrossRef] [Green Version]
- Coleman, R.E.; Gregory, W.; Marshall, H.; Wilson, C.; Holen, I. The metastatic microenvironment of breast cancer: Clinical implications. Breast 2013, 22, S50–S56. [Google Scholar] [CrossRef] [PubMed]
- Gdowski, A.S.; Ranjan, A.; Vishwanatha, J.K. Current concepts in bone metastasis, contemporary therapeutic strategies and ongoing clinical trials. J. Exp. Clin. Cancer Res. 2017, 36, 108. [Google Scholar] [CrossRef] [Green Version]
- Croucher, P.I.; McDonald, M.M.; Martin, T.J. Bone metastasis: The importance of the neighbourhood. Nat. Rev. Cancer 2016, 16, 373–386. [Google Scholar] [CrossRef]
- Roodman, G.D. Mechanisms of Bone Metastasis. N. Engl. J. Med. 2004, 350, 1655–1664. [Google Scholar] [CrossRef]
- Paget, S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 1989, 8, 98–101. [Google Scholar]
- Talmadge, J.E.; Fidler, I.J. AACR centennial series: The biology of cancer metastasis: Historical perspective. Cancer Res. 2010, 70, 5649–5669. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, H.-M.; Chen, F.-P.; Yang, K.-C.; Yuan, S.-S. Association of Bone Metastasis With Early-Stage Breast Cancer in Women With and Without Precancer Osteoporosis According to Osteoporosis Therapy Status. JAMA Netw. Open 2019, 2, e190429. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zheng, J.-S.; Hu, X.-J.; Zhao, Y.-M.; Yang, J.; Li, D. Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: Meta-analysis of data from 21 independent prospective cohort studies. BMJ 2013, 346, f3706. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fasano, E.; Serini, S.; Cittadini, A.; Calviello, G. Long-chain n-3 PUFA against breast and prostate cancer: Which are the appropriate doses for intervention studies in animals and humans? Crit. Rev. Food Sci. Nutr. 2017, 57, 2245–2262. [Google Scholar] [CrossRef]
- Makarem, N.; Chandran, U.; Bandera, E.V.; Parekh, N. Dietary fat in breast cancer survival. Annu. Rev. Nutr. 2013, 33, 319–348. [Google Scholar] [CrossRef] [Green Version]
- Hodson, L.; Skeaff, C.M.; Fielding, B.A. Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog. Lipid Res. 2008, 47, 348–380. [Google Scholar] [CrossRef]
- Strawford, A.; Antelo, F.; Christiansen, M.; Hellerstein, M.K. Adipose tissue triglyceride turnover, de novo lipogenesis, and cell proliferation in humans measured with 2H2O. Am. J. Physiol. Endocrinol. Metab. 2004, 286, E577–E588. [Google Scholar] [CrossRef] [Green Version]
- Beynen, A.C.; Hermus, R.J.; Hautvast, J.G. A mathematical relationship between the fatty acid composition of the diet and that of the adipose tissue in man. Am. J. Clin. Nutr. 1980, 33, 81–85. [Google Scholar] [CrossRef]
- Baylin, A.; Campos, H. The use of fatty acid biomarkers to reflect dietary intake. Curr. Opin. Lipidol. 2006, 17, 22–27. [Google Scholar] [CrossRef]
- Yee, L.D.; Lester, J.L.; Cole, R.M.; Richardson, J.R.; Hsu, J.C.; Li, Y.; Lehman, A.; Belury, M.A.; Clinton, S.K. Omega-3 fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition. Am. J. Clin. Nutr. 2010, 91, 1185–1194. [Google Scholar] [CrossRef] [Green Version]
- Khadge, S.; Thiele, G.M.; Sharp, J.G.; McGuire, T.R.; Klassen, L.W.; Black, P.N.; DiRusso, C.C.; Cook, L.; Talmadge, J.E. Long-chain omega-3 polyunsaturated fatty acids decrease mammary tumor growth, multiorgan metastasis and enhance survival. Clin. Exp. Metastasis 2018, 35, 797–818. [Google Scholar] [CrossRef] [PubMed]
- Mandal, C.C.; Ghosh-Choudhury, T.; Yoneda, T.; Choudhury, G.G.; Ghosh-Choudhury, N. Fish oil prevents breast cancer cell metastasis to bone. Biochem. Biophys. Res. Commun. 2010, 402, 602–607. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, Q.; Luo, Q.; Halim, A.; Song, G. Targeting lipid metabolism of cancer cells: A promising therapeutic strategy for cancer. Cancer Lett. 2017, 401, 39–45. [Google Scholar] [CrossRef] [PubMed]
- Mika, A.; Kobiela, J.; Czumaj, A.; Chmielewski, M.; Stepnowski, P.; Sledzinski, T. Hyper-Elongation in Colorectal Cancer Tissue—Cerotic Acid is a Potential Novel Serum Metabolic Marker of Colorectal Malignancies. Cell. Physiol. Biochem. 2017, 41, 722–730. [Google Scholar] [CrossRef] [PubMed]
- Yam, D.; Ben-Hur, H.; Dgani, R.; Fink, A.; Shani, A.; Berry, E.M. Subcutaneous, omentum and tumor fatty acid composition, and serum insulin status in patients with benign or cancerous ovarian or endometrial tumors. Do tumors preferentially utilize polyunsaturated fatty acids? Cancer Lett. 1997, 111, 179–185. [Google Scholar] [CrossRef]
- Mika, A.; Kobiela, J.; Pakiet, A.; Czumaj, A.; Sokołowska, E.; Makarewicz, W.; Chmielewski, M.; Stepnowski, P.; Marino-Gammazza, A.; Sledzinski, T. Preferential uptake of polyunsaturated fatty acids by colorectal cancer cells. Sci. Rep. 2020, 10, 1954. [Google Scholar] [CrossRef]
- Raclot, T.; Oudart, H. Selectivity of fatty acids on lipid metabolism and gene expression. Proc. Nutr. Soc. 1999, 58, 633–646. [Google Scholar] [CrossRef] [Green Version]
- Koundouros, N.; Poulogiannis, G. Reprogramming of fatty acid metabolism in cancer. Br. J. Cancer 2020, 122, 4–22. [Google Scholar] [CrossRef] [Green Version]
- Hanhoff, T.; Lücke, C.; Spener, F. Insights into binding of fatty acids by fatty acid binding proteins. Mol. Cell Biochem. 2002, 239, 45–54. [Google Scholar] [CrossRef]
- Zhong Xu, L.; Sánchez, R.; Sali, A.; Heintz, N. Ligand Specificity of Brain Lipid-binding Protein. J. Biol. Chem. 1996, 271, 24711–24719. [Google Scholar] [CrossRef] [Green Version]
- Zanoaga, O.; Jurj, A.; Raduly, L.; Cojocneanu-Petric, R.; Fuentes-Mattei, E.; Wu, O.; Braicu, C.; Gherman, C.; Berindan-Neagoe, I. Implications of dietary ω-3 and ω-6 polyunsaturated fatty acids in breast cancer (Review). Exp. Ther. Med. 2017, 15, 1167–1176. [Google Scholar] [CrossRef]
- Liu, J.; Ma, D. The Role of n-3 Polyunsaturated Fatty Acids in the Prevention and Treatment of Breast Cancer. Nutrients 2014, 6, 5184–5223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Camargo, A.; Meneses, M.E.; Pérez-Martínez, P.; Delgado-Lista, J.; Rangel-Zúñiga, O.A.; Marín, C.; Almadén, Y.; Yubero-Serrano, E.M.; González-Guardia, L.; Fuentes, F.; et al. Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome patients. Genes Nutr. 2014, 9, 409. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Georgiadi, A.; Kersten, S. Mechanisms of Gene Regulation by Fatty Acids. Adv. Nutr. 2012, 3, 127–134. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, W.; Zhu, J.; Lyu, F.; Panigrahy, D.; Ferrara, K.W.; Hammock, B.; Zhang, G. ω-3 Polyunsaturated fatty acids-derived lipid metabolites on angiogenesis, inflammation and cancer. Prostaglandins Other Lipid Mediat. 2014, 113–115, 13–20. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Burdge, G.C.; Calder, P.C. α-Linolenic acid metabolism in adult humans: The effects of gender and age on conversion to longer-chain polyunsaturated fatty acids. Eur. J. Lipid Sci. Technol. 2005, 107, 426–439. [Google Scholar] [CrossRef]
- Kang, Y.; Siegel, P.M.; Shu, W.; Drobnjak, M.; Kakonen, S.M.; Cordón-Cardo, C.; Guise, T.A.; Massagué, J. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003, 3, 537–549. [Google Scholar] [CrossRef] [Green Version]
- Bidwell, B.N.; Slaney, C.Y.; Withana, N.P.; Forster, S.; Cao, Y.; Loi, S.; Andrews, D.; Mikeska, T.; Mangan, N.E.; Samarajiwa, S.A.; et al. Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape. Nat. Med. 2012, 18, 1224–1231. [Google Scholar] [CrossRef]
- Santini, D.; Schiavon, G.; Vincenzi, B.; Gaeta, L.; Pantano, F.; Russo, A.; Ortega, C.; Porta, C.; Galluzzo, S.; Armento, G.; et al. Receptor Activator of NF-kB (RANK) Expression in Primary Tumors Associates with Bone Metastasis Occurrence in Breast Cancer Patients. PLoS ONE 2011, 6, e19234. [Google Scholar] [CrossRef] [Green Version]
- Kang, Y.; Pantel, K. Tumor cell dissemination: Emerging biological insights from animal models and cancer patients. Cancer Cell 2013, 23, 573–581. [Google Scholar] [CrossRef] [Green Version]
- Massagué, J.; Obenauf, A.C. Metastatic colonization by circulating tumour cells. Nature 2016, 529, 298–306. [Google Scholar] [CrossRef] [PubMed]
- Ottewell, P.D.; Wang, N.; Brown, H.K.; Reeves, K.J.; Fowles, C.A.; Croucher, P.I.; Eaton, C.L.; Holen, I. Zoledronic Acid Has Differential Antitumor Activity in the Pre- and Postmenopausal Bone Microenvironment In Vivo. Clin. Cancer Res. 2014, 20, 2922–2932. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ottewell, P.D.; Wang, N.; Brown, H.K.; Fowles, C.A.; Croucher, P.I.; Eaton, C.L.; Holen, I. OPG-Fc inhibits ovariectomy-induced growth of disseminated breast cancer cells in bone: OPG-Fc inhibits breast cancer bone metastasis. Int. J. Cancer 2015, 137, 968–977. [Google Scholar] [CrossRef] [PubMed]
- Mandal, C.C.; Ghosh-Choudhury, T.; Dey, N.; Choudhury, G.G.; Ghosh-Choudhury, N. miR-21 is targeted by omega-3 polyunsaturated fatty acid to regulate breast tumor CSF-1 expression. Carcinogenesis 2012, 33, 1897–1908. [Google Scholar] [CrossRef] [Green Version]
- Cao, W.; Ma, Z.; Rasenick, M.M.; Yeh, S.; Yu, J. N-3 poly-unsaturated fatty acids shift estrogen signaling to inhibit human breast cancer cell growth. PLoS ONE 2012, 7, e52838. [Google Scholar] [CrossRef] [Green Version]
- Rahman, M.M.; Veigas, J.M.; Williams, P.J.; Fernandes, G. DHA is a more potent inhibitor of breast cancer metastasis to bone and related osteolysis than EPA. Breast Cancer Res. Treat. 2013, 141, 341–352. [Google Scholar] [CrossRef] [Green Version]
- Altenburg, J.D.; Siddiqui, R.A. Omega-3 polyunsaturated fatty acids down-modulate CXCR4 expression and function in MDA-MB-231 breast cancer cells. Mol. Cancer Res. 2009, 7, 1013–1020. [Google Scholar] [CrossRef] [Green Version]
- Li, Y.; Greiner, R.S.; Salem, N.; Watkins, B.A. Impact of dietary n-3 FA deficiency on rat bone tissue FA composition. Lipids 2003, 38, 683–686. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Seifert, M.F.; Lim, S.-Y.; Salem, N.; Watkins, B.A. Bone mineral content is positively correlated to n-3 fatty acids in the femur of growing rats. Br. J. Nutr. 2010, 104, 674–685. [Google Scholar] [CrossRef] [Green Version]
- Kruger, M.C.; Coetzee, M.; Haag, M.; Weiler, H. Long-chain polyunsaturated fatty acids: Selected mechanisms of action on bone. Prog. Lipid Res. 2010, 49, 438–449. [Google Scholar] [CrossRef] [Green Version]
- Levental, K.R.; Surma, M.A.; Skinkle, A.D.; Lorent, J.H.; Zhou, Y.; Klose, C.; Chang, J.T.; Hancock, J.F.; Levental, I. ω-3 polyunsaturated fatty acids direct differentiation of the membrane phenotype in mesenchymal stem cells to potentiate osteogenesis. Sci. Adv. 2017, 3, eaao1193. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kasonga, A.E.; Deepak, V.; Kruger, M.C.; Coetzee, M. Arachidonic acid and docosahexaenoic acid suppress osteoclast formation and activity in human CD14+ monocytes, in vitro. PLoS ONE 2015, 10, e0125145. [Google Scholar] [CrossRef] [PubMed]
- Kasonga, A.; Kruger, M.C.; Coetzee, M. Activation of PPARs Modulates Signalling Pathways and Expression of Regulatory Genes in Osteoclasts Derived from Human CD14+ Monocytes. Int. J. Mol. Sci. 2019, 20, 1798. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kishikawa, A.; Kitaura, H.; Kimura, K.; Ogawa, S.; Qi, J.; Shen, W.-R.; Ohori, F.; Noguchi, T.; Marahleh, A.; Nara, Y.; et al. Docosahexaenoic Acid Inhibits Inflammation-Induced Osteoclast Formation and Bone Resorption in vivo Through GPR120 by Inhibiting TNF-α Production in Macrophages and Directly Inhibiting Osteoclast Formation. Front. Endocrinol. 2019, 10, 157. [Google Scholar] [CrossRef] [PubMed]
- Boeyens, J.C.A.; Deepak, V.; Chua, W.-H.; Kruger, M.C.; Joubert, A.M.; Coetzee, M. Effects of ω3- and ω6-polyunsaturated fatty acids on RANKL-induced osteoclast differentiation of RAW264.7 cells: A comparative in vitro study. Nutrients 2014, 6, 2584–2601. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Longo, A.B.; Ward, W.E. PUFAs, Bone Mineral Density, and Fragility Fracture: Findings from Human Studies. Adv. Nutr. 2016, 7, 299–312. [Google Scholar] [CrossRef] [Green Version]
- Lage, S.; Bueno, M.; Andrade, F.; Prieto, J.A.; Delgado, C.; Legarda, M.; Sanjurjo, P.; Aldámiz-Echevarría, L.J. Fatty acid profile in patients with phenylketonuria and its relationship with bone mineral density. J. Inherit. Metab. Dis. 2010, 33 (Suppl. 3), S363–S371. [Google Scholar] [CrossRef]
- Monaco, M.E. Fatty acid metabolism in breast cancer subtypes. Oncotarget 2017, 8, 29487–29500. [Google Scholar] [CrossRef] [Green Version]
- Bolton-Smith, C.; Woodward, M.; Tavendale, R. Evidence for age-related differences in the fatty acid composition of human adipose tissue, independent of diet. Eur. J. Clin. Nutr. 1997, 51, 619–624. [Google Scholar] [CrossRef] [Green Version]
- Plourde, M.; Chouinard-Watkins, R.; Vandal, M.; Zhang, Y.; Lawrence, P.; Brenna, J.T.; Cunnane, S.C. Plasma incorporation, apparent retroconversion and β-oxidation of 13C-docosahexaenoic acid in the elderly. Nutr. Metab. 2011, 8, 5. [Google Scholar] [CrossRef] [Green Version]
- Drouin, G.; Rioux, V.; Legrand, P. The n-3 docosapentaenoic acid (DPA): A new player in the n-3 long chain polyunsaturated fatty acid family. Biochimie 2019, 159, 36–48. [Google Scholar] [CrossRef]
- Wilson, C.; Brown, H.; Holen, I. The endocrine influence on the bone microenvironment in early breast cancer. Endocr. Relat. Cancer 2016, 23, R567–R576. [Google Scholar] [CrossRef] [Green Version]
- Wang, C.; Meng, H.; Wang, X.; Zhao, C.; Peng, J.; Wang, Y. Differentiation of Bone Marrow Mesenchymal Stem Cells in Osteoblasts and Adipocytes and its Role in Treatment of Osteoporosis. Med. Sci. Monit. 2016, 22, 226–233. [Google Scholar] [CrossRef] [PubMed]
- Chas, M.; Goupille, C.; Arbion, F.; Bougnoux, P.; Pinault, M.; Jourdan, M.L.; Chevalier, S.; Ouldamer, L. Low eicosapentaenoic acid and gamma-linolenic acid levels in breast adipose tissue are associated with inflammatory breast cancer. Breast 2019, 45, 113–117. [Google Scholar] [CrossRef] [PubMed]
- Alsharari, Z.D.; Leander, K.; Sjögren, P.; Carlsson, A.; Cederholm, T.; de Faire, U.; Hellenius, M.-L.; Marklund, M.; Risérus, U. Association between carbohydrate intake and fatty acids in the de novo lipogenic pathway in serum phospholipids and adipose tissue in a population of Swedish men. Eur. J. Nutr. 2020, 59, 2089–2097. [Google Scholar] [CrossRef] [PubMed] [Green Version]
No Bone Metastasis n = 208 | Bone Metastasis n = 53 | Statistics | |||
---|---|---|---|---|---|
Mean or n (%) | Range | Mean or n (%) | Range | p | |
Age (years) | 57.0 | 28–89 | 55.9 | 33–84 | 0.49 |
Premenopausal | 78 (37.5%) | 21 (39.6%) | 0.95 | ||
Postmenopausal | 127 (61.1%) | 32 (60.4%) | |||
UK menopausal status | 3 (1.4%) | 0 | |||
HRT | 33 (25.9%) | 7 (21.9%) | 1 | ||
BMI (Kg/m2) | 25.2 | 16–40 | 25.5 | 13–41 | 0.78 |
Histological size (mm) | 26.6 | 3–210 | 29.3 | 5–70 | 0.35 |
Molecular phenotype | 0.45 | ||||
Luminal A | 67 (32.7%) | 21 (39.6%) | |||
Luminal B | 56 (27.3%) | 16 (30.3%) | |||
Triple negative | 51 (24.9%) | 12 (22.6%) | |||
HER2 | 31 (15.1%) | 4 (7.5%) | |||
Grade | 0.01 | ||||
-Grade 1 | 23 (11.0%) | 0 (0%) | |||
-Grade 2 | 88 (42.3%) | 30 (56.6%) | |||
-Grade 3 | 95 (45.7%) | 21 (39.6%) | |||
-Unknown | 2 (1%) | 2 (3.8%) | |||
Lymphovascular invasion | 58 (27.9%) | 16 (30.2%) | 0.53 | ||
Axillary positive LN | 81 (38.9%) | 29 (54.7%) | 0.01 | ||
Multifocality | 52 (25%) | 8 (15.1%) | 0.19 |
Fatty Acids * | No Bone Metastasis n = 78 | Bone Metastasis n = 21 | Statistics | |||
---|---|---|---|---|---|---|
Mean | Range | Mean | Range | p | ||
Saturated | ||||||
Myristic acid | 14:0 | 3.47 | 1.65–4.90 | 3.56 | 2.47–4.72 | 0.14 |
Palmitic acid | 16:0 | 23.61 | 19.63–28.8 | 23.9 | 21.01–26.63 | 0.52 |
Stearic acid | 18:0 | 6.02 | 3.20–8.33 | 5.96 | 3.03–8.57 | 0.86 |
Total SFA | 34.11 | 25.97–40.62 | 34.37 | 29.85–40.12 | 0.68 | |
Monounsaturated | ||||||
Myristoleic acid | 14:1 | 0.27 | 0.01–0.56 | 0.30 | 0.14–0.60 | 0.38 |
Palmitoleic acid | 16:1 | 3.34 | 1.09–8.45 | 3.56 | 1.80–6.89 | 0.54 |
Oleic acid | 18:1n-9c | 43.23 | 38.01–47.65 | 43.17 | 38.13–48.11 | 0.91 |
Vaccenic acid | 18:1n-7c | 1.79 | 1.25–2.86 | 1.81 | 1.39–2.56 | 0.81 |
Total MUFA | 49.94 | 42.48–56.19 | 50.15 | 45.92–55.71 | 0.77 | |
Polyunsaturated | ||||||
Linoleic acid | 18:2n-6c | 10.63 | 6.43–21.0 | 10.37 | 7.39–15.05 | 0.59 |
Gamma linolenic acid | 18:3n-6 | 0.04 | 0.02–0.09 | 0.04 | 0.02–0.06 | 0.31 |
Arachidonic acid | 20:4n-6 | 0.29 | 0.15–0.63 | 0.30 | 0.16–0.60 | 0.92 |
LC PUFA n-6 | 0.91 | 0.45–2.06 | 0.88 | 0.50-1.55 | 0.71 | |
Total n-6 | 11.61 | 6.94–22.68 | 11.33 | 8.30–16.22 | 0.57 | |
Alpha linolenic acid | 18:3n-3 | 0.60 | 0.29–1.04 | 0.58 | 0.37–0.98 | 0.62 |
Eicosapentaenoic acid | 20:5n-3 | 0.07 | 0.02–0.16 | 0.06 | 0.03–0.11 | 0.15 |
Docosapentaenoic acid | 22:5n-3 | 0.19 | 0.05–0.51 | 0.16 | 0.07–0.24 | 0.03 |
Docosahexaenoic acid | 22:6n-3 | 0.16 | 0.03–0.35 | 0.13 | 0.05–0.21 | 0.06 |
LC PUFA n-3 | 0.42 | 0.12–0.97 | 0.36 | 0.16–0.49 | 0.02 | |
Total n-3 | 1.05 | 0.63–1.52 | 0.97 | 0.60–1.43 | 0.11 | |
n-6/n-3 ratio | n-6/n-3 | 11.41 | 7.26–26.91 | 11.98 | 7.69–20.07 | 0.44 |
Fatty Acid * | No Bone Metastasis n = 127 | Bone Metastasis n = 32 | Statistics | |||
---|---|---|---|---|---|---|
Mean | Range | Mean | Range | p | ||
Saturated | ||||||
Myristic acid | 14:0 | 3.00 | 1.65–5.25 | 3.04 | 1.83–4.63 | 0.76 |
Palmitic acid | 16:0 | 22.42 | 16.71–28.13 | 23.27 | 18.23–27.58 | 0.07 |
Stearic acid | 18:0 | 5.07 | 1.99–7.82 | 5.06 | 2.79–7.66 | 0.98 |
Total SFA | 31.36 | 23.42–40.32 | 32.25 | 23.74–37.27 | 0.22 | |
Monounsaturated | ||||||
Myristoleic acid | 14:1 | 0.27 | 0.05–0.51 | 0.24 | 0.08–0.48 | 0.20 |
Palmitoleic acid | 16:1 | 3.90 | 1.41–7.49 | 3.64 | 1.65–7.97 | 0.38 |
Oleic acid | 18:1n-9c | 43.61 | 36.59–50.57 | 43.49 | 38.73–49.16 | 0.81 |
Vaccenic acid | 18:1n-7c | 2.03 | 1.40–3.50 | 1.99 | 1.47–3.75 | 0.67 |
Total MUFA | 51.14 | 42.02–60.9 | 50.63 | 45.26–58.81 | 0.51 | |
Polyunsaturated | ||||||
Linoleic acid | 18:2n-6c | 11.45 | 6.27–18.76 | 11.23 | 5.97–21.49 | 0.68 |
Gamma linolenic acid | 18:3n-6 | 0.05 | 0.02–0.10 | 0.04 | 0.02–0.16 | 0.56 |
Arachidonic acid | 20:4n-6 | 0.44 | 0.20–1.01 | 0.45 | 0.23–0.88 | 0.72 |
LC-PUFA n-6 | 1.29 | 0.55–3.76 | 1.34 | 0.71–2.24 | 0.60 | |
Total n-6 | 12.82 | 7.35–20.06 | 12.64 | 7.21–22.74 | 0.75 | |
Alpha linolenic acid | 18:3n-3 | 0.60 | 0.20–1.30 | 0.60 | 0.28–1.32 | 0.96 |
Eicosapentaenoic acid | 20:5n-3 | 0.10 | 0.02–0.31 | 0.09 | 0.03–0.33 | 0.39 |
Docosapentaenoic acid | 22:5n-3 | 0.30 | 0.09–0.61 | 0.43 | 0.16–0.88 | 0.17 |
Docosahexaenoic acid | 22:6n-3 | 0.25 | 0.04–0.54 | 0.27 | 0.08–0.87 | 0.43 |
LC-PUFA n-3 | 0.65 | 0.19–1.20 | 0.70 | 0.28–2.08 | 0.43 | |
Total n-3 | 1.30 | 0.69–2.15 | 1.34 | 0.65–2.79 | 0.54 | |
n-6/n-3 ratio | 10.46 | 5.49–27.08 | 9.96 | 3.42–17.87 | 0.41 |
Premenopausal Women with BM n = 21 | Postmenopausal Women with BM n = 32 | Statistics | |||
---|---|---|---|---|---|
Mean or n (%) | Range | Mean or n (%) | Range | p | |
Age (years) | 41.8 | 33–53 | 64.4 | 45–84 | <0.0001 |
BMI (kg/m2) | 24.8 | 13–41 | 25.9 | 17–40 | 0.55 |
Histological size (mm) | 36.2 | 5–70 | 25.8 | 5–70 | 0.05 |
Molecular phenotype | |||||
Luminal A | 8 (36.8%) | 13 (40.6%) | 0.33 | ||
Luminal B | 4 (21.0%) | 12 (37.5%) | |||
Triple negative | 7 (31.6%) | 5 (15.6%) | |||
HER2 | 2 (10.5%) | 2 (6.2%) | |||
Other metastatic sites | |||||
-Visceral | 11 (63.1%) | 21 (65.6%) | 1 | ||
-Brain | 7 (31.6%) | 8 (25.0%) | 0.72 | ||
Lymphovascular invasion | 6 (31.6%) | 10 (31.2%) | 0.97 | ||
Positive axillary LN | 12 (63.1%) | 16 (50.0%) | 1 | ||
Multifocality | 5 (26.3%) | 3 (9.3%) | 0.28 | ||
Inflammatory Breast cancer | 7 (36.8%) | 5 (15.6%) | 0.20 |
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Goupille, C.; Frank, P.G.; Arbion, F.; Jourdan, M.-L.; Guimaraes, C.; Pinault, M.; Body, G.; Chevalier, S.; Bougnoux, P.; Ouldamer, L. Low Levels of Omega-3 Long-Chain Polyunsaturated Fatty Acids Are Associated with Bone Metastasis Formation in Premenopausal Women with Breast Cancer: A Retrospective Study. Nutrients 2020, 12, 3832. https://doi.org/10.3390/nu12123832
Goupille C, Frank PG, Arbion F, Jourdan M-L, Guimaraes C, Pinault M, Body G, Chevalier S, Bougnoux P, Ouldamer L. Low Levels of Omega-3 Long-Chain Polyunsaturated Fatty Acids Are Associated with Bone Metastasis Formation in Premenopausal Women with Breast Cancer: A Retrospective Study. Nutrients. 2020; 12(12):3832. https://doi.org/10.3390/nu12123832
Chicago/Turabian StyleGoupille, Caroline, Philippe G. Frank, Flavie Arbion, Marie-Lise Jourdan, Cyrille Guimaraes, Michelle Pinault, Gilles Body, Stephan Chevalier, Philippe Bougnoux, and Lobna Ouldamer. 2020. "Low Levels of Omega-3 Long-Chain Polyunsaturated Fatty Acids Are Associated with Bone Metastasis Formation in Premenopausal Women with Breast Cancer: A Retrospective Study" Nutrients 12, no. 12: 3832. https://doi.org/10.3390/nu12123832