Bone metabolism and quality-of-life of postmenopausal women with invasive breast cancer receiving neoadjuvant hormonal therapy: Sub-analyses from celecoxib anti-aromatase neoadjuvant (CAAN) trial

Journal of Steroid Biochemistry and Molecular Biology

Volumn 125, Issue 1-2, 2011, Pages 112-119

  Chow, Louis W C ^a,b,c   Yip, Adrian Y S ^b   Chu, W P ^b   Loo, Wings T Y ^b,c   Toi, Masakazu ^b,d  

^a UNIVERSITY OF HONG KONG   (Hong Kong)

^b Organisation for Oncology and Translational Research   (Hong Kong)

^c UNIMED Medical Institute   (Hong Kong)

^d KYOTO UNIVERSITY   (Japan)

Author keywords

Aromatase inhibitor; Bone metabolism; Breast cancer; Cyclooxygenase 2 inhibitors; Neoadjuvant; Quality of life

Indexed keywords

ALKALINE PHOSPHATASE BONE ISOENZYME; CARBOXY TERMINAL TELOPEPTIDE; CELECOXIB; EXEMESTANE; LETROZOLE;

ARTICLE; BONE DENSITY; BONE METABOLISM; BONE TURNOVER; BREAST CANCER; BREAST CANCER SUBSCALE SCORE; CANCER HORMONE THERAPY; CANCER INVASION; CLINICAL ASSESSMENT TOOL; CONTROLLED STUDY; FEMALE; FUNCTIONAL ASSESSMENT OF CANCER THERAPY CORE QUESTIONNAIRE; HISTOPATHOLOGY; HUMAN; POSTMENOPAUSE; QUALITY OF LIFE; QUESTIONNAIRE; RANDOMIZED CONTROLLED TRIAL;

ANDROSTADIENES; ANIMALS; ANTINEOPLASTIC AGENTS; AROMATASE INHIBITORS; BIOLOGICAL MARKERS; BONE AND BONES; BONE DENSITY; BREAST NEOPLASMS; CYCLOOXYGENASE 2 INHIBITORS; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; NEOADJUVANT THERAPY; POSTMENOPAUSE; PYRAZOLES; QUALITY OF LIFE; QUESTIONNAIRES; SULFONAMIDES; TREATMENT OUTCOME;

ANIMALIA;

EID: 79957678145     PISSN: 09600760     EISSN: 18791220     Source Type: Journal    
DOI: 10.1016/j.jsbmb.2010.12.018     Document Type: Article

References (96)

1. D.M. Parkin, F. Bray, and J. Ferlay Global cancer statistics, 2002, CA Cancer J. Clin. 55 2005 74 108 (Pubitemid 40372904)
2. A. Jemal, R. Siegel, E. Ward, T. Murray, J. Xu, C. Smigal, and M.J. Thun Cancer Stat. 56 2006 106 130
3. A.P. Forrest Beatson: hormones and the management of breast cancer J. R. Coll. Surg. Edinb. 27 1982 253 263 (Pubitemid 13252125)
4. M. Lambe Parity, age at first and last birth, and risk of breast cancer: a population-based study in Sweden Breast Cancer Res. Treat. 38 1996 305 311 (Pubitemid 26126665)
5. J. Staszewski Age at menarche and breast cancer J. Natl. Cancer Inst. 47 1971 935 940
6. D. Trichopoulos Menopause and breast cancer risk J. Natl. Cancer Inst. 48 1972 605 613
7. S.M. Cohen, and L.B. Ellwein Genetic errors, cell proliferation, and carcinogenesis Cancer Res. 51 1991 6493 6505
8. L.W.C. Chow, and P. Ho Hormonal receptor determination of 1052 Chinese breast cancers J. Surg. Oncol. 75 2002 172 175
9. E. di Salle, G. Ornati, and D. Giudici Exemestane (FCE 24304), a new steroidal aromatase inhibitor J. Steroid Biochem. Mol. Biol. 43 1992 137 143
10. S.R. Johnston, and M. Dowsett Aromatase inhibitors for breast cancer: lessons from the laboratory Nat. Rev. Cancer 3 2003 821 831 (Pubitemid 37376980)
11. R.W. Brueggemeier, J.C. Hackett, and E.S. Diaz-Cruz Aromatase inhibitors in the treatment of breast cancer Endocr. Rev. 26 2005 331 345 (Pubitemid 40686647)
12. V.H.T. James, J.M. McNeill, L.C. Lai, C.J. Newton, H. Braunsberg, M. Ghilchik, and M.J. Reed Aromatase activity in normal breast and breast tumor tissues: in vivo and in vitro studies Steroids 50 1987 269 279
13. W.R. Miller, P. Mullen, P. Sourdaine, C. Watson, J.M. Dixon, and J. Telford Regulation of aromatase activity within the breast J. Steroid Biochem. Mol. Biol. 61 1997 193 202 (Pubitemid 27455678)
14. M.J. Reed The role of aromatase in breast tumors Breast Cancer Res. Treat. 30 1994 7 17 (Pubitemid 24250755)
15. E.R. Simpson Sources of estrogen and their importance J. Steroid Biochem. Mol. Biol. 86 2003 225 230 (Pubitemid 37412561)
16. E.A. Thompson Jr., and P.K. Siiteri Utilization of oxygen and reduced nicotinamide adeninedinucleotide phosphate by human placental microsomes during aromatization of androstenedione J. Biol. Chem. 249 1974 5364 5372
17. M.P. Cohen, and P.P. Foa Aminoglutethimide inhibition of adrenal deso lase activity Proc. Soc. Exp. Biol. Med. 727 1969 1086 1090
18. S.W.M. Hughes, and D.M. Burley Aminoglutethimide. A "side- effect" turned to therapeutic advantage Postgrad. Med. J. 46 1970 409 416
19. P.E. Lonning Pharmacology of new aromatase inhibitors Breast 5 1996 202 208 (Pubitemid 26234111)
20. J. Geisler, N. King, and G. Anker In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients Clin. Cancer Res. 4 1998 2089 2093 (Pubitemid 28415652)
21. Y. Hong, B. Yu, and M. Sherman Molecular basis for the aromatization reaction and exemestane-mediated irreversible inhibition of human aromatase Mol. Endocrinol. 21 2007 401 414 (Pubitemid 46184893)
22. Y.C. Kao, L.L. Cam, C.A. Laughton, D. Zhou, and S. Chen Binding characteristics of seven inhibitors of human aromatase: a site-directed mutagenesis study Cancer Res. 56 1996 3451 3460 (Pubitemid 26251636)
23. P.A. Cole, and C.H. Robinson Mechanism and inhibition of cytochrome P-450 aromatase J. Med. Chem. 33 1990 2933 2942 (Pubitemid 20349513)
24. A. Buzdar, and A. Howell Advances in aromatase inhibition: clinical efficacy and tolerability in the treatment of breast cancer Cancer Lett. 140 2001 27-25
25. P.E. Goss, and K. Strasser Aromatase inhibitors J. Clin. Oncol. 19 2001 881 894
26. Y. Zhao, V. Agarwal, C. Mendelson, and E. Simpson Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene Endocrinology 137 1996 5739 5742 (Pubitemid 26423150)
27. A. Bennett, E.M. Charlier, A.M. McDonald, J.S. Simpson, I.F. Stamford, and T. Zebro Prostaglandins and breast cancer Lancet 2 1977 624 626 (Pubitemid 8183109)
28. D.M.A. Watson, R.W. Kelly, R.A. Hawkins, and W.R. Miller Prostaglandins in human mammary cancer Br. J. Cancer 49 1984 459 464 (Pubitemid 14125254)
29. A. Singhakowinta, H.G. Potter, T.R. Buroker, B. Samal, S.C. Brooks, and V.K. Vaitkevicius Estrogen receptor and natural course of breast cancer Ann. Surg. 183 1976 84
30. C. Costa, R. Soares, J.S. Reis-Filho, D. Leitão, I. Amendoeira, and F.C. Schmitt Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer J. Clin. Pathol. 55 6 2002 429 434 (Pubitemid 34620779)
31. R.E. Harris, K.K. Namboodiri, and W.B. Farrar Epidemiologic study of non-steroidal anti-inflammatory drugs and breast cancer Oncol. Rep. 2 1995 591 592
32. R.E. Harris, K.K. Namboodiri, and W.B. Farrar Nonsteroidal antiinflammatory drugs and breast cancer Epidemiology 7 1996 203 205 (Pubitemid 26068056)
33. R.E. Harris, S. Kasbari, and W.B. Farrar Prospective study of nonsteroidal drugs and breast cancer Oncol. Rep. 6 1999 71 73
34. A.M. Fulton In vivo effects of indomethacin on the growth of murine mammary tumors Cancer Res. 44 1984 2416 2420 (Pubitemid 14110660)
35. D.L. McCormick, and R.C. Moon Inhibition of mammary carcinogenesis by flurbiprofen, a non-steroidal anti-inflammatory agent Br. J. Cancer 48 1983 859 861 (Pubitemid 14210830)
36. P.P. Lee, and M.M. Ip Regulation of proliferation of rat mammary tumor cells by inhibitors of cyclooxygenase and lipoxygenase Prostag. Leukotr. Essent. Fatty Acids 45 1992 21 31
37. D.L. McCormick, M.J. Madigan, and R.C. Moon Modulation of rat mammary carcinogenesis by indomethacin Cancer Res. 45 1985 1803 1808 (Pubitemid 15079141)
38. L.W. Chow, A.Y. Yip, W.T. Loo, C.K. Lam, and M. Toi Celecoxib anti-aromatase neoadjuvant (CAAN) trial for locally advanced breast cancer J. Steroid Biochem. Mol. Biol. 111 1-2 2008 13 17
39. H.F. Kang, X.J. Wang, X.X. Liu, Z.J. Dai, F.J. Xue, and X.H. Xue Chemopreventive effect of tamoxifen combined with celecoxib on DMBA-induced breast cancer in rats Ai Zheng 25 11 2006 1346 1350
40. S. Woditschka, J.D. Haag, B. Mau, R.A. Lubet, and M.N. Gould Chemopreventive effects of celecoxib are limited to hormonally responsive mammary carcinomas in the neu-induced retroviral rat model Breast Cancer Res. 10 1 2008 R18
41. P.A. Canney, M.A. Machin, and J. Curto A feasibility study of the efficacy and tolerability of the combination of exemestane with the COX-2 inhibitor celecoxib in postmenopausal patients with advanced breast cancer Eur. J. Cancer 41 2006 2751 2756 (Pubitemid 44584673)
42. L.Y. Dirix, J. Ignacio, and S. Nag Treatment of advanced hormone-sensitive breast cancer in postmenopausal women with exemestane alone or in combination with celecoxib J. Clin. Oncol. 26 2008 1253 1259
43. C. Osborne, and D. Tripathy Aromatase inhibitors: rationale and use in breast cancer Annu. Rev. Med. 56 2005 103 116 (Pubitemid 40299776)
44. B.A. Mincey, and E.A. Perez Aromatase inhibitors and bone health ASCO 2005 Education Book 41st Annual Meeting, Orlando, FL 2005 pp. 27-34
45. J. Pfeilschifter, and I.J. Diel Osteoporosis due to cancer treatment: pathogenesis and management J. Clin. Oncol. 18 2000 1570 1593 (Pubitemid 30205404)
46. B.A. Mincey Osteoporosis in women with breast cancer Curr. Oncol. Rep. 5 2003 53 57 (Pubitemid 38898766)
47. J.R. Mackey, and A.A. Joy Skeletal health in postmenopausal survivors of early breast cancer Int. J. Cancer 114 2005 1010 1015
48. J. Lester, D. Dodwell, and E. McCloskey The causes and treatment of bone loss associated with carcinoma of the breast Cancer Treat. Rev. 31 2005 115 142 (Pubitemid 40542890)
49. R. Eastell, R.A. Hannon, and J. Cuzick Effect of anastrozole on bone density and bone turnover: Results of the 'Arimidex' (anastrozole), Tamoxifen, Alone or in Combination (ATAC) Study (abstract 1170) J. Bone Miner. Res. 17 Suppl. 1 2002 S165
50. J.A. Kanis Pathogenesis of Osteoporosis and Fracture, Osteoporosis 1996 Blackwell Healthcare Communications London pp. 22-55
51. M.S. Aapro Long-term implications of bone loss in breast cancer Breast 13 Suppl. 1 2004 S29 S37
52. M. Candelaria, R. Hurtado-Monroy, P. Vargas-Viveros, S. Carrillo-Muñnoz, and A. Duenas-Gonzalez Tamoxifen-associated vasculitis in a breast cancer patient World J. Surg. Oncol. 5 2007 9
53. Early Breast Cancer Trialists' Collaborative Group Tamoxifen for early breast cancer: an overview of the randomised trials Lancet 351 1998 1451 1467
54. B. Fisher, J. Dignam, and J. Bryant Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial J. Natl. Cancer Inst. 93 2001 684 690 (Pubitemid 32492809)
55. S. Demissie, R.A. Silliman, and T.L. Lash Adjuvant tamoxifen: predictors of use, side effects, and discontinuation in older woman J. Clin. Oncol. 19 2001 322 328 (Pubitemid 32112842)
56. B. Fisher, J.P. Costantino, and D.L. Wickerham Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study J. Natl. Cancer Inst. 90 1998 1371 1388 (Pubitemid 28439961)
57. A. Howell, J. Cuzick, and M. Baum Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years adjuvant treatment for breast cancer Lancet 365 2005 60 62
58. J. Cuzick, T. Powles, and U. Veronesi Overview of the main outcomes in breast-cancer prevention trials Lancet 361 2003 296 300 (Pubitemid 36126189)
59. S. Duffy Gynecological adverse events including hysterectomy occur less frequently with anastrozole than with tamoxifen: data from the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial J. Clin. Oncol. 23 16 Suppl. 2005 721a
60. B. Ettinger Reduction of Vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene JAMA 287 7 1999 637 645 (Pubitemid 29384151)
61. S.R. Cummings The effect of raloxifene on risk of breast cancer in postmenopausal women JAMA 281 23 1999 2189 2197
62. H.U. Bryant, P.K. Wilson, M.D. Adrian, H.W. Cole, D.L. Phillips, J.A. Doge, T.A. Grese, J.P. Sluka, and A.L. Glasebrook J. Soc. Gynecol. Invest. 3 1996 152
63. L.J. Black, M. Sato, E.R. Rowley, D.E. Magee, A. Bekele, D.C. Williams, G.J. Cullinan, R. Bendele, R.F. Kauffman, W.R. Bensch, C.A. Frolik, J.D. Termine, and H.U. Bryant Raloxifene (LY139481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats J. Clin. Invest. 93 1994 63 69 (Pubitemid 24030821)
64. M.W. Draper, D.E. Flowers, W.J. Huster, J.A. Neild, K.D. Harper, and C. Arnaud A controlled trial of raloxifene (LY139481) HCl: impact on bone turnover and serum lipid profile in healthy postmenopausal women J. Bone Miner. Res. 11 1996 835 842 (Pubitemid 26172808)
65. J.A. Cauley, F.L. Lucas, L.H. Kuller, M.T. Vogt, W.S. Browner, and S.R. Cummings Bone mineral density and risk of breast cancer in older women: the study of osteoporotic fractures JAMA 276 17 1996 1404 1408 (Pubitemid 26365846)
66. J. Geisler, P.E. Lonning, and L.E. Krag Estrogens and bone metabolism in postmenopausal women with early breast cancer at low risk treated with exemestane: a randomized placebo-controlled study J. Clin. Oncol. 22 14 Suppl. 2004 531a
67. S.E. Jones, J. Cantrell, and S. Vukelja The effect of tamoxifen (T) or exemestane (E) on bone mineral density (BMD) after 1 year of adjuvant treatment of postmenopausal women with early breast cancer J. Clin. Oncol. 23 Suppl. 16 2005 610a
68. E.A. Perez, R.G. Josse, and K.I. Pritchard Effect of letrozole versus placebo on bone mineral density in women completing 5 years of adjuvant tamoxifen: NCIC CTG MA.17b Breast Cancer Res. Treat. 88 Suppl. 1 2004 404a
69. M. Clemons, S. Danson, and A. Howell Tamoxifen ('Nolvadex'): a review Cancer Treat. Rev. 28 2002 165 180 (Pubitemid 35244125)
70. L.B. Michaud Adjuvant use of aromatase inhibitors in postmenopausal women with breast cancer Am. J. Health Syst. Pharm. 62 2005 266 273 (Pubitemid 40403541)
71. A.U. Buzdar, J.F. Robertson, W. Eiermann, and J.M. Nabholtz An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane Cancer 95 2002 2006 2016 (Pubitemid 35222182)
72. J. Geisler, P.E. Lønning, L.E. Krag, E. Løkkevik, T. Risberg, A.I. Hagen, E. Schlichting, E.A. Lien, E.S. Ofjord, G.E. Eide, A. Polli, E. di Salle, and J. Paolini Changes in bone and lipid metabolism in postmenopausal women with early breast cancer after terminating 2-year treatment with exemestane: a randomised, placebo-controlled study Eur. J. Cancer. 42 17 2006 2968 2975 (Pubitemid 44667475)
73. P.E. Goss, S. Qi, A.M. Cheung, H. Hu, M. Mendes, and K.P. Pritzker Effects of the steroidal aromatase inhibitor exemestane and the nonsteroidal aromatase inhibitor letrozole on bone and lipid metabolism in ovariectomized rats Clin. Cancer Res. 10 17 2004 5717 5723 (Pubitemid 39180947)
74. R.E. Coleman, L.M. Banks, S.I. Girgis, L.S. Kilburn, E. Vrdoljak, and J. Fox Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study Lancet Oncol. 8 2007 119 127 (Pubitemid 46158372)
75. A. Martinetti, N. Zilembo, L. Ferrari, G. Massimini, A. Polli, I. La Torre, R. Giovanazzi, P. Pozzi, P. Bidoli, D. De Candis, E. Seregni, E. Bombardieri, and E. Bajetta Bone turnover markers and insulin-like growth factor components in metastatic breast cancer: results from a randomised trial of exemestane vs megestrol acetate Anticancer Res. 23 2003 3485 3491 (Pubitemid 36975454)
76. M. Subar, P. Goss, and T. Thomsen Effects of steroidal and nonsteroidal aromatase inhibitors (Ais) on markers of bone turnover and lipid metabolism in healthy volunteers Am. Soc. Clin. Oncol. 23 2004 734
77. P. Goss, T. Thompsen, and J. Banke-Bochita A randomized, placebo-controlled, explorative study to investigate the effect of low estrogen plasma levels on markers of bone turnover in healthy postmenopausal women during the 12-week treatment with exemestane or letrozole Breast Cancer Res. Treat. 76 Suppl 1 2002 S76 (abstract 267)
78. P.E. Goss, J.N. Ingle, S. Martino, N.J. Robert, H.B. Muss, and M.J. Piccart A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer New. Engl. J. Med. 349 2003 1793 1802 (Pubitemid 37362955)
79. E.A. Perez, R.G. Josse, K.I. Pritchard, J.N. Ingle, S. Martino, B.P. Findlay, T.N. Shenkier, R.G. Tozer, M.J. Palmer, and L.E. Shepherd Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: a companion study to NCIC CTG MA.17 J. Clin. Oncol. 24 2006 3629 3635 (Pubitemid 46630537)
80. R.E. Coleman, L.M. Banks, E. Hall, D. Price, S. Girgis, J.M. Bliss, and R.C. Coombes Intergroup exemestane study: 1 year results of the bone sub-protocol [abstract 401] Breast Cancer Res. Treat. 88 2004 S35
81. E. McCloskey, R. Hannon, G. Lakner, G. Clack, A. Miyamoto, and R. Eastell The letrozole (L), exemestane (E), and anastrozole (A) pharmacodynamics (LEAP) trial: a direct comparison of bone biochemical measurements between aromatase inhibitors (AIs) in healthy postmenopausal women J. Clin. Oncol. 24 2006 555
82. E. McCloskey Effects of third-generation aromatase inhibitors on bone Eur. J. Cancer. 42 2006 1044 1051
83. J.E. Compston Sex steroids and bone Physiol. Rev. 81 2001 419 447 (Pubitemid 32096180)
84. B.L. Riggs, S. Khosla, and L.J. Melton 3rd Sex steroids and the construction and conservation of the adult skeleton Endocr. Rev. 23 3 2002 279 302 (Pubitemid 34651948)
85. L.C. Hofbauer, and M. Schoppet Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases JAMA 292 4 2004 490 495 (Pubitemid 38988958)
86. J. Pfeilschifter Role of cytokines in postmenopausal bone loss Curr. Osteoporosis Rep. 1 2003 53 58
87. M.K. Lindberg, L. Vandenput, S. Moverare Skrtic, D. Vandrschueren, S. Boonen, and R. Bouillon Androgens and the skeleton Minerva Endocrinol. 30 2005 15 25
88. D.C. Johannessen, T. Engan, E. Di Salle, M.G. Zurio, J. Paolini, G. Ornati, G. Piscitelli, S. Kvinnsland, and P.E. Lonning Endocrine and clinical effects of exemestane (PNU 155971), a novel steroidal aromatase inhibitor, in postmenopausal breast cancer patients: a phase I study Clin. Cancer Res. 3 1997 1101 1108 (Pubitemid 27319756)
89. P.E. Goss, S. Qi, R.G. Josse, K.P. Pritzker, M. Mendes, and H. Hu The steroidal aromatase inhibitors exemestane prevents bone loss in ovariectomized rats Bone 34 2004 384 392 (Pubitemid 38314903)
90. C.L. Shapiro Aromatase inhibitors and bone loss: risks in perspective J. Clin. Oncol. 23 22 2005 4847 4849 (Pubitemid 46223987)
91. P.A. Canney A phase II study of the efficacy and tolerability of the combination of exemestane with the cyclooxygenase-2 inhibitor celecoxib in postmenopausal patients with advanced breast cancer Proc. Am. Soc. Clin. Oncol. 22 2003 40 (abstract 158)
92. L.Y. Dirix, J. Ignacio, and S. Nag Final results from an open-label, multicenter, controlled study of exemestane +/- celecoxib in postmenopausal women with advanced breast cancer (ABC) progressed on tamoxifen (T) Proc. Am. Soc. Clin. Oncol. 22 2003 20 (abstract 77)
93. E. Pesenti, J.L. Masferrer, and E. di Salle Effect of exemestane and celecoxib alone or in combination on DMBA-induced mammary carcinoma in rats Breast Cancer Res. 69 2001 288 (abstract 445) (Pubitemid 33789160)
94. N. Majkic-Singh, M. Ilic, S. Ignjatovic, and G. Aleksandra Postic Assessment of four biochemical markers of bone metabolism in post-menopausal osteoporosis Clin. Lab. 48 2002 407 413 (Pubitemid 34823574)
95. D.L. Wickerham, J.P. Costantino, V.G. Vogel, W.M. Cronin, R.S. Cecchini, L.G. Ford, and N. Wolmark The use of tamoxifen and raloxifene for the prevention of breast cancer Recent Results Cancer Res. 181 2009 113 119
96. V.G. Vogel, J.P. Costantino, and D.L. Wickerham Update of the national surgical adjuvant breast and bowel project Study of Tamoxifen and Raloxifene (STAR) P-2 trial: preventing breast cancer Cancer Prev. Res. 3 2010 696 706