Skip to main content
Top
Published in: Breast Cancer Research and Treatment 1/2014

01-07-2014 | Clinical Trial

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

Authors: A. Lintermans, K. Van Asten, H. Wildiers, A. Laenen, R. Paridaens, C. Weltens, J. Verhaeghe, D. Vanderschueren, A. Smeets, E. Van Limbergen, K. Leunen, M. R. Christiaens, P. Neven

Published in: Breast Cancer Research and Treatment | Issue 1/2014

Login to get access

Abstract

Aromatase inhibitor (AI) therapy for estrogen receptor-positive breast cancer is known to induce or enhance musculoskeletal problems. We have previously reported that loss of grip strength is more pronounced in AI-users with extremes in BMI. We here report results from a larger prospective study. Postmenopausal early breast cancer patients scheduled to start AI or tamoxifen therapy were recruited. A functional assessment grip strength test was performed at baseline, 3, 6, and 12 months of therapy. BMI was assessed, and a rheumatologic questionnaire was completed at each visit. 188 patients on an AI and 104 patients on tamoxifen were enrolled. 74 % of AI-users reported new/worsened musculoskeletal complaints compared with 37 % in the tamoxifen group. This was translated in a larger grip strength decrease in patients experiencing AI-induced pain opposed to patients without new/worsened complaints (p = 0.0002). 15 % of AI-users discontinued therapy due to musculoskeletal symptoms, who were characterized by a larger grip strength reduction versus adherent patients (p = 0.0107). Young age (p = 0.0135), taxane-based chemotherapy (p = 0.0223), and baseline VAS score >4 (p = 0.0155) were predictors for AI-related musculoskeletal pain. In addition, a quadratic trend of BMI with grip strength change (p = 0.0090) and probability of discontinuation was observed (p = 0.0424). Musculoskeletal events were a substantial problem in AI-treated patients and an important reason for treatment discontinuation. The decrease in grip strength was larger in AI- than in tamoxifen-users, with a more pronounced change in symptomatic patients. The inverse relationship between BMI extremes and grip strength change was confirmed in this large group of AI-patients.
Literature
1.
go back to reference Petit T, Dufour P, Tannock I (2011) A critical evaluation of the role of aromatase inhibitors as adjuvant therapy for postmenopausal women with breast cancer. Endocr Relat Cancer 18(3):R79–R89PubMedCrossRef Petit T, Dufour P, Tannock I (2011) A critical evaluation of the role of aromatase inhibitors as adjuvant therapy for postmenopausal women with breast cancer. Endocr Relat Cancer 18(3):R79–R89PubMedCrossRef
2.
go back to reference Thürlimann B, Keshaviah A, Coates A, Mouridsen H, Mauriac L, Forbes J, Paridaens R, Castiglione-Gertsch M, Gelber R, Rabaglio M et al (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353(26):2747–2757PubMedCrossRef Thürlimann B, Keshaviah A, Coates A, Mouridsen H, Mauriac L, Forbes J, Paridaens R, Castiglione-Gertsch M, Gelber R, Rabaglio M et al (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353(26):2747–2757PubMedCrossRef
3.
go back to reference Crew K, Greenlee H, Capodice J, Raptis G, Brafman L, Fuentes D, Sierra A, Hershman D (2007) Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol 25(25):3877–3883PubMedCrossRef Crew K, Greenlee H, Capodice J, Raptis G, Brafman L, Fuentes D, Sierra A, Hershman D (2007) Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol 25(25):3877–3883PubMedCrossRef
4.
go back to reference Henry N, Giles J, Ang D, Mohan M, Dadabhoy D, Robarge J, Hayden J, Lemler S, Shahverdi K, Powers P et al (2008) Prospective characterization of musculoskeletal symptoms in early stage breast cancer patients treated with aromatase inhibitors. Breast Cancer Res Treat 111(2):365–372PubMedCentralPubMedCrossRef Henry N, Giles J, Ang D, Mohan M, Dadabhoy D, Robarge J, Hayden J, Lemler S, Shahverdi K, Powers P et al (2008) Prospective characterization of musculoskeletal symptoms in early stage breast cancer patients treated with aromatase inhibitors. Breast Cancer Res Treat 111(2):365–372PubMedCentralPubMedCrossRef
5.
go back to reference Coleman R, Bolten W, Lansdown M, Dale S, Jackisch C, Merkel D, Maass N, Hadji P (2008) Aromatase inhibitor-induced arthralgia: clinical experience and treatment recommendations. Cancer Treat Rev 34(3):275–282PubMedCrossRef Coleman R, Bolten W, Lansdown M, Dale S, Jackisch C, Merkel D, Maass N, Hadji P (2008) Aromatase inhibitor-induced arthralgia: clinical experience and treatment recommendations. Cancer Treat Rev 34(3):275–282PubMedCrossRef
6.
go back to reference Morales L, Pans S, Verschueren K, Van Calster B, Paridaens R, Westhovens R, Timmerman D, De Smet L, Vergote I, Christiaens M et al (2008) Prospective study to assess short-term intra-articular and tenosynovial changes in the aromatase inhibitor-associated arthralgia syndrome. J Clin Oncol 26(19):3147–3152PubMedCrossRef Morales L, Pans S, Verschueren K, Van Calster B, Paridaens R, Westhovens R, Timmerman D, De Smet L, Vergote I, Christiaens M et al (2008) Prospective study to assess short-term intra-articular and tenosynovial changes in the aromatase inhibitor-associated arthralgia syndrome. J Clin Oncol 26(19):3147–3152PubMedCrossRef
7.
go back to reference Lintermans A, Van Calster B, Van Hoydonck M, Pans S, Verhaeghe J (2011) Aromatase inhibitor-induced loss of grip strength is body mass index dependent: hypothesis generating findings for its pathogenesis. Ann Oncol 22(8):1763–1769PubMedCrossRef Lintermans A, Van Calster B, Van Hoydonck M, Pans S, Verhaeghe J (2011) Aromatase inhibitor-induced loss of grip strength is body mass index dependent: hypothesis generating findings for its pathogenesis. Ann Oncol 22(8):1763–1769PubMedCrossRef
8.
go back to reference Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, Senn HJ, members P (2013) Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 24(9):2206–2223PubMedCentralPubMedCrossRef Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, Senn HJ, members P (2013) Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 24(9):2206–2223PubMedCentralPubMedCrossRef
9.
go back to reference Grunfeld EA, Hunter MS, Sikka P, Mittal S (2005) Adherence beliefs among breast cancer patients taking tamoxifen. Patient Educ Couns 59(1):97–102PubMedCrossRef Grunfeld EA, Hunter MS, Sikka P, Mittal S (2005) Adherence beliefs among breast cancer patients taking tamoxifen. Patient Educ Couns 59(1):97–102PubMedCrossRef
10.
go back to reference von Blanckenburg P, Schuricht F, Albert US, Rief W, Nestoriuc Y (2013) Optimizing expectations to prevent side effects and enhance quality of life in breast cancer patients undergoing endocrine therapy: study protocol of a randomized controlled trial. BMC Cancer 13:426CrossRef von Blanckenburg P, Schuricht F, Albert US, Rief W, Nestoriuc Y (2013) Optimizing expectations to prevent side effects and enhance quality of life in breast cancer patients undergoing endocrine therapy: study protocol of a randomized controlled trial. BMC Cancer 13:426CrossRef
11.
go back to reference 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):549–557PubMedCrossRef 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):549–557PubMedCrossRef
12.
go back to reference Singer O, Cigler T, Moore AB, Levine AB, Hentel K, Belfi L, Do HT, Mandl LA (2012) Defining the aromatase inhibitor musculoskeletal syndrome: a prospective study. Arthritis Care Res (Hoboken) 64(12):1910–1918CrossRef Singer O, Cigler T, Moore AB, Levine AB, Hentel K, Belfi L, Do HT, Mandl LA (2012) Defining the aromatase inhibitor musculoskeletal syndrome: a prospective study. Arthritis Care Res (Hoboken) 64(12):1910–1918CrossRef
13.
go back to reference Basch E, Jia X, Heller G, Barz A, Sit L, Fruscione M, Appawu M, Iasonos A, Atkinson T, Goldfarb S et al (2009) Adverse symptom event reporting by patients vs clinicians: relationships with clinical outcomes. J Natl Cancer Inst 101(23):1624–1632PubMedCentralPubMedCrossRef Basch E, Jia X, Heller G, Barz A, Sit L, Fruscione M, Appawu M, Iasonos A, Atkinson T, Goldfarb S et al (2009) Adverse symptom event reporting by patients vs clinicians: relationships with clinical outcomes. J Natl Cancer Inst 101(23):1624–1632PubMedCentralPubMedCrossRef
14.
go back to reference Irwin ML, Cartmel B, Gross C (2013) Randomized trial of exercise vs. usual care on aromatase inhibitor-associated arthralgias in women with breast cancer: the hormones and physical exercise (HOPE) study. In: San Antonio Breast Cancer Symposium: 2013, San Antonio, 2013 Irwin ML, Cartmel B, Gross C (2013) Randomized trial of exercise vs. usual care on aromatase inhibitor-associated arthralgias in women with breast cancer: the hormones and physical exercise (HOPE) study. In: San Antonio Breast Cancer Symposium: 2013, San Antonio, 2013
15.
go back to reference 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. In: ASCO: 2012, Chicago, 2012 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. In: ASCO: 2012, Chicago, 2012
16.
go back to reference Henry NL, Banerjee M, Wicha M, Van Poznak C, Smerage JB, Schott AF, Griggs JJ, Hayes DF (2011) Pilot study of duloxetine for treatment of aromatase inhibitor-associated musculoskeletal symptoms. Cancer 117(24):5469–5475PubMedCrossRef Henry NL, Banerjee M, Wicha M, Van Poznak C, Smerage JB, Schott AF, Griggs JJ, Hayes DF (2011) Pilot study of duloxetine for treatment of aromatase inhibitor-associated musculoskeletal symptoms. Cancer 117(24):5469–5475PubMedCrossRef
17.
go back to reference Mao JJ, Xie SX, Farrar JT, Stricker CT, Bowman MA, Bruner D, DeMichele A (2014) A randomised trial of electro-acupuncture for arthralgia related to aromatase inhibitor use. Eur J Cancer 50(2):267–276PubMedCrossRef Mao JJ, Xie SX, Farrar JT, Stricker CT, Bowman MA, Bruner D, DeMichele A (2014) A randomised trial of electro-acupuncture for arthralgia related to aromatase inhibitor use. Eur J Cancer 50(2):267–276PubMedCrossRef
18.
go back to reference 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):1077–1087PubMedCrossRef 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):1077–1087PubMedCrossRef
19.
go back to reference Kubo M, Onishi H, Kuroki S, Okido M, Shimada K, Yokohata K, Umeda S, Ogawa T, Tanaka M, Katano M (2012) Short-term and low-dose prednisolone administration reduces aromatase inhibitor-induced arthralgia in patients with breast cancer. Anticancer Res 32(6):2331–2336PubMed Kubo M, Onishi H, Kuroki S, Okido M, Shimada K, Yokohata K, Umeda S, Ogawa T, Tanaka M, Katano M (2012) Short-term and low-dose prednisolone administration reduces aromatase inhibitor-induced arthralgia in patients with breast cancer. Anticancer Res 32(6):2331–2336PubMed
20.
go back to reference Henry NL, Azzouz F, Desta Z, Li L, Nguyen AT, Lemler S, Hayden J, Tarpinian K, Yakim E, Flockhart DA et al (2012) Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer. J Clin Oncol 30(9):936–942PubMedCentralPubMedCrossRef Henry NL, Azzouz F, Desta Z, Li L, Nguyen AT, Lemler S, Hayden J, Tarpinian K, Yakim E, Flockhart DA et al (2012) Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer. J Clin Oncol 30(9):936–942PubMedCentralPubMedCrossRef
21.
go back to reference Shi Q, Giordano SH, Lu H, Saleeba AK, Malveaux D, Cleeland CS (2013) Anastrozole-associated joint pain and other symptoms in patients with breast cancer. J Pain 14(3):290–296PubMedCentralPubMedCrossRef Shi Q, Giordano SH, Lu H, Saleeba AK, Malveaux D, Cleeland CS (2013) Anastrozole-associated joint pain and other symptoms in patients with breast cancer. J Pain 14(3):290–296PubMedCentralPubMedCrossRef
22.
go back to reference Park JY, Lee SK, Bae SY, Kim J, Kim MK, Kil WH, Lee JE, Nam SJ (2013) Aromatase inhibitor-associated musculoskeletal symptoms: incidence and associated factors. J Korean Surg Soc 85(5):205–211PubMedCentralPubMedCrossRef Park JY, Lee SK, Bae SY, Kim J, Kim MK, Kil WH, Lee JE, Nam SJ (2013) Aromatase inhibitor-associated musculoskeletal symptoms: incidence and associated factors. J Korean Surg Soc 85(5):205–211PubMedCentralPubMedCrossRef
23.
go back to reference Chim K, Xie SX, Stricker CT, Li QS, Gross R, Farrar JT, DeMichele A, Mao JJ (2013) Joint pain severity predicts premature discontinuation of aromatase inhibitors in breast cancer survivors. BMC Cancer 13:401PubMedCentralPubMedCrossRef Chim K, Xie SX, Stricker CT, Li QS, Gross R, Farrar JT, DeMichele A, Mao JJ (2013) Joint pain severity predicts premature discontinuation of aromatase inhibitors in breast cancer survivors. BMC Cancer 13:401PubMedCentralPubMedCrossRef
24.
go back to reference Sestak I, Cuzick J, Sapunar F, Eastell R, Forbes J, Bianco A, Buzdar A, Group AT (2008) Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis. Lancet Oncol 9(9):866–872PubMedCrossRef Sestak I, Cuzick J, Sapunar F, Eastell R, Forbes J, Bianco A, Buzdar A, Group AT (2008) Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis. Lancet Oncol 9(9):866–872PubMedCrossRef
25.
go back to reference Hirokaga K, Egawa C, Takao S (2013) Chemotherapy, but not body mass index has impact on joint symptoms in postmenopausal Japanese breast cancer patients treated with anastrozole: a prospective multicenter cohort study of patient-reported outcomes. In: San Antonio Breast Cancer Symposium: 2013, San Antonio, 2013 Hirokaga K, Egawa C, Takao S (2013) Chemotherapy, but not body mass index has impact on joint symptoms in postmenopausal Japanese breast cancer patients treated with anastrozole: a prospective multicenter cohort study of patient-reported outcomes. In: San Antonio Breast Cancer Symposium: 2013, San Antonio, 2013
26.
go back to reference Muslimani A, Spiro T, Chaudhry A, Taylor H, Jaiyesimi I, Daw H (2009) Aromatase inhibitor-related musculoskeletal symptoms: is preventing osteoporosis the key to eliminating these symptoms? Clin Breast Cancer 9(1):34–38PubMedCrossRef Muslimani A, Spiro T, Chaudhry A, Taylor H, Jaiyesimi I, Daw H (2009) Aromatase inhibitor-related musculoskeletal symptoms: is preventing osteoporosis the key to eliminating these symptoms? Clin Breast Cancer 9(1):34–38PubMedCrossRef
27.
go back to reference 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):3631–3639PubMedCentralPubMedCrossRef 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):3631–3639PubMedCentralPubMedCrossRef
28.
go back to reference Kanematsu M, Morimoto M, Honda J, Nagao T, Nakagawa M, Takahashi M, Tangoku A, Sasa M (2011) The time since last menstrual period is important as a clinical predictor for non-steroidal aromatase inhibitor-related arthralgia. BMC Cancer 11:436PubMedCentralPubMedCrossRef Kanematsu M, Morimoto M, Honda J, Nagao T, Nakagawa M, Takahashi M, Tangoku A, Sasa M (2011) The time since last menstrual period is important as a clinical predictor for non-steroidal aromatase inhibitor-related arthralgia. BMC Cancer 11:436PubMedCentralPubMedCrossRef
29.
go back to reference Laroche F, Coste J, Medkour T, Cottu PH, Pierga JY, Lotz JP, Beerblock K, Tournigand C, Declèves X, de Cremoux P et al (2014) Classification of and risk factors for estrogen deprivation pain syndromes related to aromatase inhibitor treatments in women with breast cancer: a prospective multicenter cohort study. J Pain 15(3):293–303PubMedCrossRef Laroche F, Coste J, Medkour T, Cottu PH, Pierga JY, Lotz JP, Beerblock K, Tournigand C, Declèves X, de Cremoux P et al (2014) Classification of and risk factors for estrogen deprivation pain syndromes related to aromatase inhibitor treatments in women with breast cancer: a prospective multicenter cohort study. J Pain 15(3):293–303PubMedCrossRef
30.
go back to reference Chlebowski RT, Kim JS, Haque R (2014) Adherence to endocrine therapy in breast cancer adjuvant and prevention settings. Cancer Prev Res (Phila) 7(4):378–387 Chlebowski RT, Kim JS, Haque R (2014) Adherence to endocrine therapy in breast cancer adjuvant and prevention settings. Cancer Prev Res (Phila) 7(4):378–387
Metadata
Title
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
Authors
A. Lintermans
K. Van Asten
H. Wildiers
A. Laenen
R. Paridaens
C. Weltens
J. Verhaeghe
D. Vanderschueren
A. Smeets
E. Van Limbergen
K. Leunen
M. R. Christiaens
P. Neven
Publication date
01-07-2014
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2014
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-014-2986-7

Other articles of this Issue 1/2014

Breast Cancer Research and Treatment 1/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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