Top

Published in:

01-02-2016 | Clinical Trial

Randomized, blinded trial of vitamin D₃ for treating aromatase inhibitor-associated musculoskeletal symptoms (AIMSS)

Authors: Alice C. Shapiro, Susan A. Adlis, Kim Robien, Mark N. Kirstein, Shuang Liang, Sara A. Richter, Rachel E. Lerner

Published in: Breast Cancer Research and Treatment | Issue 3/2016

Abstract

The purpose of the study was to evaluate the efficacy and safety of vitamin D₃ at 4000 IU/day as a treatment option for aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) when compared with the usual care dose of 600 IU D₃. We conducted a single site randomized, double-blind, phase 3 clinical trial in women with AIMSS comparing change in symptoms, reproductive hormones and AI pharmacokinetics. Postmenopausal women ≥18 years with stages I–IIIA breast cancer, taking AI and experiencing AIMSS [breast cancer prevention trial symptom scale-musculoskeletal (BCPT-MS) subscale ≥1.5] were admitted. Following randomization, 116 patients had a run-in period of 1 month on 600 IU D₃, then began the randomized assignment to either 600 IU D₃ (n = 56) or 4000 IU D₃ (n = 57) daily for 6 months. The primary endpoint was a change in AIMSS from baseline (after 1 month run-in) on the BCPT-MS (general MS pain, joint pain, muscle stiffness, range for each question: 0 = not at all to 4 = extremely). Groups had no statistically significant differences demographically or clinically. There were no discernable differences between the randomly allocated treatment groups at 6 months in measures of AIMSS, pharmacokinetics of anastrozole and letrozole, serum levels of reproductive hormones, or adverse events. We found no significant changes in AIMSS measures between women who took 4000 IU D₃ daily compared with 600 IU D₃. The 4000 IU D₃ did not adversely affect reproductive hormone levels or the steady state pharmacokinetics of anastrozole or letrozole. In both groups, serum 25(OH)D remained in the recommended range for bone health (≥30 ng/mL) and safety (<50 ng/mL).

Khan QJ, Kimler BF, Reddy PS, Sharma P, Klemp JR, Fabian CJ (2012) Randomized trial of vitamin D₃ to prevent worsening of musculoskeletal symptoms and fatigue in women with breast cancer starting adjuvant letrozole: the VITAL trial. ASCO Meet Abstr 30(15_Suppl):9000

Rastelli AL, Taylor ME, Gao F, Armamento-Villareal R, Jamalabadi-Majidi S, Napoli N, Ellis MJ (2011) Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Res Treat 129(1):107–116. doi:10.1007/s10549-011-1644-6 CrossRefPubMed

Prieto-Alhambra D, Javaid MK, Servitja S, Arden NK, Martinez-Garcia M, Diez-Perez A, Albanell J, Tusquets I, Nogues X (2011) Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study. Breast Cancer Res Treat 125(3):869–878. doi:10.1007/s10549-010-1075-9 CrossRefPubMed

Singer O, Cigler T, Moore AB, Levine AB, Do HT, Mandl LA (2014) Hypovitaminosis D is a predictor of aromatase inhibitor musculoskeletal symptoms. Breast J 20(2):174–179. doi:10.1111/tbj.12227 CrossRefPubMed

Khan QJ, Reddy PS, Kimler BF, Sharma P, Baxa SE, O’Dea AP, Klemp JR, Fabian CJ (2010) Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer. Breast Cancer Res Treat 119(1):111–118. doi:10.1007/s10549-009-0495-x CrossRefPubMedPubMedCentral

Waltman NL, Ott CD, Twiss JJ, Gross GJ, Lindsey AM (2009) Vitamin D insufficiency and musculoskeletal symptoms in breast cancer survivors on aromatase inhibitor therapy. Cancer Nurs 32(2):143–150. doi:10.1097/01.NCC.0000339262.44560.92 CrossRefPubMedPubMedCentral

Lintermans A, Laenen A, Van Calster B, Van Hoydonck M, Pans S, Verhaeghe J, Westhovens R, Henry NL, Wildiers H, Paridaens R, Dieudonne AS, Leunen K, Morales L, Verschueren K, Timmerman D, De Smet L, Vergote I, Christiaens MR, Neven P (2013) Prospective study to assess fluid accumulation and tenosynovial changes in the aromatase inhibitor-induced musculoskeletal syndrome: 2-year follow-up data. Ann Oncol Off J Eur Soc Med Oncol 24(2):350–355. doi:10.1093/annonc/mds290 CrossRef

Niravath P (2013) Aromatase inhibitor-induced arthralgia: a review. Ann Oncol Off J Eur Soc Med Oncol 24(6):1443–1449. doi:10.1093/annonc/mdt037 CrossRef

Mao JJ, Stricker C, Bruner D, Xie S, Bowman MA, Farrar JT, Greene BT, DeMichele A (2009) Patterns and risk factors associated with aromatase inhibitor-related arthralgia among breast cancer survivors. Cancer 115(16):3631–3639. doi:10.1002/cncr.24419 CrossRefPubMedPubMedCentral

10.

Henry NL, Giles JT, Stearns V (2008) Aromatase inhibitor-associated musculoskeletal symptoms: etiology and strategies for management. Oncology (Williston Park) 22(12):1401–1408

11.

Crew KD, Greenlee H, Capodice J, Raptis G, Brafman L, Fuentes D, Sierra A, Hershman DL (2007) Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol Off J Am Soc Clin Oncol 25(25):3877–3883. doi:10.1200/JCO.2007.10.7573 CrossRef

12.

Morales L, Pans S, Verschueren K, Van Calster B, Paridaens R, Westhovens R, Timmerman D, De Smet L, Vergote I, Christiaens MR, Neven P (2008) Prospective study to assess short-term intra-articular and tenosynovial changes in the aromatase inhibitor-associated arthralgia syndrome. J Clin Oncol Off J Am Soc Clin Oncol 26(19):3147–3152. doi:10.1200/JCO.2007.15.4005 CrossRef

13.

Fusi C, Materazzi S, Benemei S, Coppi E, Trevisan G, Marone IM, Minocci D, De Logu F, Tuccinardi T, Di Tommaso MR, Susini T, Moneti G, Pieraccini G, Geppetti P, Nassini R (2014) Steroidal and non-steroidal third-generation aromatase inhibitors induce pain-like symptoms via TRPA1. Nat Commun 5:5736. doi:10.1038/ncomms6736 CrossRefPubMedPubMedCentral

14.

Holick MF (2006) High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 81(3):353–373. doi:10.4065/81.3.353 CrossRefPubMed

15.

Glerup H, Mikkelsen K, Poulsen L, Hass E, Overbeck S, Andersen H, Charles P, Eriksen EF (2000) Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement. Calcif Tissue Int 66(6):419–424CrossRefPubMed

16.

Holick MF (2007) Vitamin D deficiency. N Engl J Med 357(3):266–281. doi:10.1056/NEJMra070553 CrossRefPubMed

17.

Felson DT, Cummings SR (2005) Aromatase inhibitors and the syndrome of arthralgias with estrogen deprivation. Arthritis Rheum 52(9):2594–2598. doi:10.1002/art.21364 CrossRefPubMed

18.

Ceglia L (2008) Vitamin D and skeletal muscle tissue and function. Mol Asp Med 29(6):407–414. doi:10.1016/j.mam.2008.07.002 CrossRef

19.

Boonen S, Bischoff-Ferrari HA, Cooper C, Lips P, Ljunggren O, Meunier PJ, Reginster JY (2006) Addressing the musculoskeletal components of fracture risk with calcium and vitamin D: a review of the evidence. Calcif Tissue Int 78(5):257–270. doi:10.1007/s00223-005-0009-8 CrossRefPubMed

20.

National Research Council (2011) Dietary reference intakes for calcium and vitamin D. The National Academies Press, Washington, DC

21.

Gralow JR, Biermann JS, Farooki A, Fornier MN, Gagel RF, Kumar R, Litsas G, McKay R, Podoloff DA, Srinivas S, Van Poznak CH (2013) NCCN Task Force report: bone health in cancer care. J Natl Compr Cancer Netw 11(Suppl 3):S-1–S-50

22.

Kristal AR, Darke AK, Morris JS, Tangen CM, Goodman PJ, Thompson IM, Meyskens FL Jr, Goodman GE, Minasian LM, Parnes HL, Lippman SM, Klein EA (2014) Baseline selenium status and effects of selenium and vitamin E supplementation on prostate cancer risk. J Natl Cancer Inst 106(3):djt456. doi:10.1093/jnci/djt456 CrossRefPubMedPubMedCentral

23.

Greenwald P, Anderson D, Nelson SA, Taylor PR (2007) Clinical trials of vitamin and mineral supplements for cancer prevention. Am J Clin Nutr 85(1):314S–317SPubMed

24.

Goodwin PJ, Ennis M, Pritchard KI, Koo J, Hood N (2009) Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer. J Clin Oncol Off J Am Soc Clin Oncol 27(23):3757–3763. doi:10.1200/JCO.2008.20.0725 CrossRef

25.

Kristal AR, Till C, Song X, Tangen CM, Goodman PJ, Neuhauser ML, Schenk JM, Thompson IM, Meyskens FL Jr, Goodman GE, Minasian LM, Parnes HL, Klein EA (2014) Plasma vitamin D and prostate cancer risk: results from the Selenium and Vitamin E Cancer Prevention Trial. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cospons Am Soc Prev Oncol 23(8):1494–1504. doi:10.1158/1055-9965.EPI-14-0115 CrossRef

26.

Manson JE, Bassuk SS (2015) Vitamin D research and clinical practice: at a crossroads. JAMA 313(13):1311–1312. doi:10.1001/jama.2015.1353 CrossRefPubMed

27.

Swenson KK, Nissen MJ, Henly SJ, Maybon L, Pupkes J, Zwicky K, Tsai ML, Shapiro AC (2013) Identification of tools to measure changes in musculoskeletal symptoms and physical functioning in women with breast cancer receiving aromatase inhibitors. Oncol Nurs Forum 40(6):549–557. doi:10.1188/13.ONF.549-557 CrossRefPubMed

28.

World Health Organization FRAX^® WHO fracture risk assessment tool. World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield. http://www.sheffield.ac.uk/FRAX/. Accessed 13 Oct 2015

29.

Bellamy N, Sothern RB, Campbell J, Buchanan WW (2002) Rhythmic variations in pain, stiffness, and manual dexterity in hand osteoarthritis. Ann Rheum Dis 61(12):1075–1080CrossRefPubMedPubMedCentral

30.

Allen KD, DeVellis RF, Renner JB, Kraus VB, Jordan JM (2007) Validity and factor structure of the AUSCAN Osteoarthritis Hand Index in a community-based sample. Osteoarthr Cartil/Osteoarthr Res Soc 15(7):830–836. doi:10.1016/j.joca.2007.01.012 CrossRef

31.

Bellamy N (2005) The WOMAC Knee and Hip Osteoarthritis Indices: development, validation, globalization and influence on the development of the AUSCAN Hand Osteoarthritis Indices. Clin Exp Rheumatol 23(5 Suppl 39):S148–S153PubMed

32.

Stanton AL, Bernaards CA, Ganz PA (2005) The BCPT symptom scales: a measure of physical symptoms for women diagnosed with or at risk for breast cancer. J Natl Cancer Inst 97(6):448–456. doi:10.1093/jnci/dji069 CrossRefPubMed

33.

Fries JF, Cella D, Rose M, Krishnan E, Bruce B (2009) Progress in assessing physical function in arthritis: PROMIS short forms and computerized adaptive testing. J Rheumatol 36(9):2061–2066. doi:10.3899/jrheum.090358 CrossRefPubMed

34.

Mathiowetz V, Kashman N, Volland G, Weber K, Dowe M, Rogers S (1985) Grip and pinch strength: normative data for adults. Arch Phys Med Rehabil 66(2):69–74PubMed

35.

Apostolou C, Dotsikas Y, Kousoulos C, Loukas YL (2008) Development and validation of an improved high-throughput method for the determination of anastrozole in human plasma by LC–MS/MS and atmospheric pressure chemical ionization. J Pharm Biomed Anal 48(3):853–859. doi:10.1016/j.jpba.2008.06.006 CrossRefPubMed

36.

Goebelsmann U, Bernstein GS, Gale JA, Kletzky OA, Nakamure RM, Coulson AH, Korelitz JJ (1979) Serum gonadotropin, testosterone, estradiol and estrone levels prior to and following bilateral vasectomy. In: Lepow IH, Crozier R (eds) Vasectomy: immunologic and pathophysiologic effects in animals and man. Academic Press, New York, pp 165–181

37.

Probst-Hensch NM, Ingles SA, Diep AT, Haile RW, Stanczyk FZ, Kolonel LN, Henderson BE (1999) Aromatase and breast cancer susceptibility. Endocr Relat Cancer 6(2):165–173CrossRefPubMed

38.

Rinaldi S, Geay A, Dechaud H, Biessy C, Zeleniuch-Jacquotte A, Akhmedkhanov A, Shore RE, Riboli E, Toniolo P, Kaaks R (2002) Validity of free testosterone and free estradiol determinations in serum samples from postmenopausal women by theoretical calculations. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cospons Am Soc Prev Oncol 11(10 Pt 1):1065–1071

39.

Sodergard R, Backstrom T, Shanbhag V, Carstensen H (1982) Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J Steroid Biochem 16(6):801–810CrossRefPubMed

40.

Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84(10):3666–3672. doi:10.1210/jcem.84.10.6079 CrossRefPubMed

41.

Glanz K, Yaroch AL, Dancel M, Saraiya M, Crane LA, Buller DB, Manne S, O’Riordan DL, Heckman CJ, Hay J, Robinson JK (2008) Measures of sun exposure and sun protection practices for behavioral and epidemiologic research. Arch Dermatol 144(2):217–222. doi:10.1001/archdermatol.2007.46 CrossRefPubMed

42.

Ainsworth BE, Haskell WL, Leon AS, Jacobs DR Jr, Montoye HJ, Sallis JF, Paffenbarger RS Jr (1993) Compendium of physical activities: classification of energy costs of human physical activities. Med Sci Sports Exerc 25(1):71–80CrossRefPubMed

43.

Rowland M, Tozer TN, Rowland M (2011) Clinical pharmacokinetics and pharmacodynamics: concepts and applications, 4th edn. Wolters Kluwer Health/Lippincott William and Wilkins, Philadelphia

44.

Helzlsouer KJ, Gallicchio L, MacDonald R, Wood B, Rushovich E (2012) A prospective study of aromatase inhibitor therapy, vitamin D, C-reactive protein and musculoskeletal symptoms. Breast Cancer Res Treat 131(1):277–285. doi:10.1007/s10549-011-1729-2 CrossRefPubMed

45.

Singh S, Cuzick J, Mesher D, Richmond B, Howell A (2012) Effect of baseline serum vitamin D levels on aromatase inhibitors induced musculoskeletal symptoms: results from the IBIS-II, chemoprevention study using anastrozole. Breast Cancer Res Treat 132(2):625–629. doi:10.1007/s10549-011-1911-6 CrossRefPubMed

46.

Lintermans A, Van Asten K, Wildiers H, Laenen A, Paridaens R, Weltens C, Verhaeghe J, Vanderschueren D, Smeets A, Van Limbergen E, Leunen K, Christiaens MR, Neven P (2014) A prospective assessment of musculoskeletal toxicity and loss of grip strength in breast cancer patients receiving adjuvant aromatase inhibitors and tamoxifen, and relation with BMI. Breast Cancer Res Treat 146(1):109–116. doi:10.1007/s10549-014-2986-7 CrossRefPubMed

47.

Visser M, Deeg DJ, Lips P (2003) Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab 88(12):5766–5772. doi:10.1210/jc.2003-030604 CrossRefPubMed

48.

Enjuanes A, Garcia-Giralt N, Supervia A, Nogues X, Mellibovsky L, Carbonell J, Grinberg D, Balcells S, Diez-Perez A (2003) Regulation of CYP19 gene expression in primary human osteoblasts: effects of vitamin D and other treatments. Eur J Endocrinol/Eur Fed Endocr Soc 148(5):519–526CrossRef

49.

Enjuanes A, Garcia-Giralt N, Supervia A, Nogues X, Ruiz-Gaspa S, Bustamante M, Mellibovsky L, Grinberg D, Balcells S, Diez-Perez A (2005) Functional analysis of the I.3, I.6, pII and I.4 promoters of CYP19 (aromatase) gene in human osteoblasts and their role in vitamin D and dexamethasone stimulation. Eur J Endocrinol/Eur Fed Endocr Soc 153(6):981–988. doi:10.1530/eje.1.02032 CrossRef

50.

Lou YR, Murtola T, Tuohimaa P (2005) Regulation of aromatase and 5alpha-reductase by 25-hydroxyvitamin D(3), 1alpha,25-dihydroxyvitamin D(3), dexamethasone and progesterone in prostate cancer cells. J Steroid Biochem Mol Biol 94(1–3):151–157. doi:10.1016/j.jsbmb.2005.01.024 CrossRefPubMed

51.

Pino AM, Rodriguez JM, Rios S, Astudillo P, Leiva L, Seitz G, Fernandez M, Rodriguez JP (2006) Aromatase activity of human mesenchymal stem cells is stimulated by early differentiation, vitamin D and leptin. J Endocrinol 191(3):715–725. doi:10.1677/joe.1.07026 CrossRefPubMed

52.

Barrera D, Avila E, Hernandez G, Halhali A, Biruete B, Larrea F, Diaz L (2007) Estradiol and progesterone synthesis in human placenta is stimulated by calcitriol. J Steroid Biochem Mol Biol 103(3–5):529–532. doi:10.1016/j.jsbmb.2006.12.097 CrossRefPubMed

53.

Yague JG, Garcia-Segura LM, Azcoitia I (2009) Selective transcriptional regulation of aromatase gene by vitamin D, dexamethasone, and mifepristone in human glioma cells. Endocrine 35(2):252–261. doi:10.1007/s12020-008-9134-2 CrossRefPubMed

54.

Cescon DW, Ennis M, Ganz PA, Beddows S, Stanczyk FZ, Sridhar SS, Goodwin PJ (2011) An analysis of vitamin D (Vit D) and serum estrogens in postmenopausal (PM) breast cancer (BC) patients receiving aromatase inhibitors (AIs). ASCO Meet Abstr 29(15_Suppl):596

55.

Irwin ML, Cartmel B, Gross CP, Ercolano E, Li F, Yao X, Fiellin M, Capozza S, Rothbard M, Zhou Y, Harrigan M, Sanft T, Schmitz K, Neogi T, Hershman D, Ligibel J (2015) Randomized exercise trial of aromatase inhibitor-induced arthralgia in breast cancer survivors. J Clin Oncol Off J Am Soc Clin Oncol 33(10):1104–1111. doi:10.1200/JCO.2014.57.1547 CrossRef

56.

Galantino ML, Callens ML, Cardena GJ, Piela NL, Mao JJ (2013) Tai chi for well-being of breast cancer survivors with aromatase inhibitor-associated arthralgias: a feasibility study. Altern Ther Health Med 19(6):38–44PubMed

57.

Galantino ML, Desai K, Greene L, Demichele A, Stricker CT, Mao JJ (2012) Impact of yoga on functional outcomes in breast cancer survivors with aromatase inhibitor-associated arthralgias. Integr Cancer Ther 11(4):313–320. doi:10.1177/1534735411413270 CrossRefPubMed

58.

Greenlee H, Crew KD, Shao T, Kranwinkel G, Kalinsky K, Maurer M, Brafman L, Insel B, Tsai WY, Hershman DL (2013) Phase II study of glucosamine with chondroitin on aromatase inhibitor-associated joint symptoms in women with breast cancer. Support Care Cancer 21(4):1077–1087. doi:10.1007/s00520-012-1628-z CrossRefPubMed

59.

Crew KD, Capodice JL, Greenlee H, Brafman L, Fuentes D, Awad D, Yann Tsai W, Hershman DL (2010) Randomized, blinded, sham-controlled trial of acupuncture for the management of aromatase inhibitor-associated joint symptoms in women with early-stage breast cancer. J Clin Oncol Off J Am Soc Clin Oncol 28(7):1154–1160. doi:10.1200/JCO.2009.23.4708 CrossRef

60.

Bao T, Cai L, Giles JT, Gould J, Tarpinian K, Betts K, Medeiros M, Jeter S, Tait N, Chumsri S, Armstrong DK, Tan M, Folkerd E, Dowsett M, Singh H, Tkaczuk K, Stearns V (2013) A dual-center randomized controlled double blind trial assessing the effect of acupuncture in reducing musculoskeletal symptoms in breast cancer patients taking aromatase inhibitors. Breast Cancer Res Treat 138(1):167–174. doi:10.1007/s10549-013-2427-z CrossRefPubMedPubMedCentral

61.

Chien TJ, Liu CY, Chang YF, Fang CJ, Hsu CH (2015) Acupuncture for treating aromatase inhibitor-related arthralgia in breast cancer: a systematic review and meta-analysis. J Altern Complement Med 21(5):251–260. doi:10.1089/acm.2014.0083 CrossRefPubMedPubMedCentral

62.

Hershman DL, Unger JM, Crew KD, Awad D, Dakhil SR, Gralow J, Greenlee H, Lew DL, Minasian LM, Till C, Wade JL III, Meyskens FL, Moinpour CM (2015) Randomized multicenter placebo-controlled trial of omega-3 fatty acids for the control of aromatase inhibitor-induced musculoskeletal pain: SWOG S0927. J Clin Oncol Off J Am Soc Clin Oncol 33(17):1910–1917. doi:10.1200/JCO.2014.59.5595 CrossRef

63.

Briot K, Tubiana-Hulin M, Bastit L, Kloos I, Roux C (2010) Effect of a switch of aromatase inhibitors on musculoskeletal symptoms in postmenopausal women with hormone-receptor-positive breast cancer: the ATOLL (articular tolerance of letrozole) study. Breast Cancer Res Treat 120(1):127–134. doi:10.1007/s10549-009-0692-7 CrossRefPubMed

64.

Desai K, Mao JJ, Su I, Demichele A, Li Q, Xie SX, Gehrman PR (2013) Prevalence and risk factors for insomnia among breast cancer patients on aromatase inhibitors. Support Care Cancer 21(1):43–51. doi:10.1007/s00520-012-1490-z CrossRefPubMedPubMedCentral

65.

Lopez C, Charles C, Rouby P, Boinon D, Laurent S, Rey A, Spielmann M, Dauchy S (2015) Relations between arthralgia and fear of recurrence: results of a cross-sectional study of breast cancer patients treated with adjuvant aromatase inhibitors therapy. Support Care Cancer 23(12):3581–3588. doi:10.1007/s00520-015-2722-9 CrossRefPubMed

66.

Peng N, Zhang Y, Ma C, Yu MW, Yang GW, Fu Q, Xu WR, Wang XM (2014) Effects of the traditional Chinese medicine Yi Shen Jian Gu granules on aromatase inhibitor-associated musculoskeletal symptoms: a study protocol for a multicenter, randomized, controlled clinical trial. Trials 15:171. doi:10.1186/1745-6215-15-171 CrossRefPubMedPubMedCentral

67.

Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, Tamez H, Zhang D, Bhan I, Karumanchi SA, Powe NR, Thadhani R (2013) Vitamin D-binding protein and vitamin D status of Black Americans and White Americans. N Engl J Med 369(21):1991–2000. doi:10.1056/NEJMoa1306357 CrossRefPubMedPubMedCentral

68.

Bischoff-Ferrari HA, Willett WC, Orav EJ, Lips P, Meunier PJ, Lyons RA, Flicker L, Wark J, Jackson RD, Cauley JA, Meyer HE, Pfeifer M, Sanders KM, Stahelin HB, Theiler R, Dawson-Hughes B (2012) A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med 367(1):40–49. doi:10.1056/NEJMoa1109617 CrossRefPubMed

69.

Cescon DW, Ganz PA, Beddows S, Ennis M, Mills BK, Goodwin PJ (2012) Feasibility of a randomized controlled trial of vitamin D vs. placebo in women with recently diagnosed breast cancer. Breast Cancer Res Treat 134(2):759–767. doi:10.1007/s10549-012-2120-7 CrossRefPubMed

70.

Neuhouser ML, Sorensen B, Hollis BW, Ambs A, Ulrich CM, McTiernan A, Bernstein L, Wayne S, Gilliland F, Baumgartner K, Baumgartner R, Ballard-Barbash R (2008) Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors. Am J Clin Nutr 88(1):133–139PubMedPubMedCentral

71.

Crew KD, Shane E, Cremers S, McMahon DJ, Irani D, Hershman DL (2009) High prevalence of vitamin D deficiency despite supplementation in premenopausal women with breast cancer undergoing adjuvant chemotherapy. J Clin Oncol Off J Am Soc Clin Oncol 27(13):2151–2156. doi:10.1200/JCO.2008.19.6162 CrossRef

72.

Durup D, Jorgensen HL, Christensen J, Tjonneland A, Olsen A, Halkjaer J, Lind B, Heegaard AM, Schwarz P (2015) A reverse J-shaped association between serum 25-hydroxyvitamin D and cardiovascular disease mortality: the CopD study. J Clin Endocrinol Metab 100(6):2339–2346. doi:10.1210/jc.2014-4551 CrossRefPubMed

Title: Randomized, blinded trial of vitamin D3 for treating aromatase inhibitor-associated musculoskeletal symptoms (AIMSS)
Authors: Alice C. Shapiro
Susan A. Adlis
Kim Robien
Mark N. Kirstein
Shuang Liang
Sara A. Richter
Rachel E. Lerner
Publication date: 01-02-2016
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2016
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-016-3710-6

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

ACC 2024 Congress

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2016

Characteristics of second breast events among women treated with breast-conserving surgery for DCIS in the community

Erratum to: Vaccination with ErbB-2 peptides prevents cancer stem cell expansion and suppresses the development of spontaneous tumors in MMTV-PyMT transgenic mice

Clinical predictors of long-term survival in HER2-positive metastatic breast cancer

Comparison of intra-operative specimen mammography to standard specimen mammography for excision of non-palpable breast lesions: a randomized trial

Healthy dietary patterns and risk of breast cancer by molecular subtype

Erratum to: CXCL13–CXCR5 co-expression regulates epithelial to mesenchymal transition of breast cancer cells during lymph node metastasis

Keynote webinar | Spotlight on antibody–drug conjugates in cancer