Skip to main content
Top
Published in: Breast Cancer Research and Treatment 2/2022

17-09-2022 | Sarcopenia | Clinical trial

Association of sarcopenia with endocrine therapy toxicity in patients with early breast cancer

Authors: Gabriel Francisco Pereira Aleixo, Stephanie A. Valente, Wei Wei, Halle C. F. Moore

Published in: Breast Cancer Research and Treatment | Issue 2/2022

Login to get access

Abstract

Background

Endocrine therapy reduces recurrence risk and improves survival in women with hormone receptor-positive breast cancer; however, side effects can decrease quality of life, leading to reduced treatment adherence. Sarcopenia is the loss of skeletal muscle mass that happens with age; it is associated with worse survival and reduced chemotherapy adherence in patients with breast cancer. The impact of sarcopenia on endocrine therapy tolerance has not been investigated. The current study evaluates the associations of sarcopenia with endocrine therapy toxicity and treatment tolerance.

Methods

Skeletal muscle mass was measured by bioelectrical impedance spectrometry. Skeletal muscle index (SMI) was calculated to assess for sarcopenia: SMI = (SMM kg)/(patient height, m2). Patients with SMI ≤ 6.75 kg/m2 were considered sarcopenic. A chart review was performed to obtain patient characteristics, endocrine therapy toxicity, and early treatment change or termination. Fisher's exact test was performed to associate patient characteristics and outcomes with sarcopenia status.

Results

Four hundred eighty-two patients with stage I–III breast cancer were prescribed endocrine therapy and had undergone sarcopenia evaluation. The median age was 61 years (29–88 years). Sarcopenia was identified in 35% of patients. Twelve percent of patients experienced grade 3–4 endocrine-related toxicities. On multivariable logistic analysis, sarcopenia was associated with increased odds of experiencing endocrine-related side effects (p = 0.006). In addition, patients with sarcopenia stopped or changed their medication due to side effects more often than those without sarcopenia (p = 0.03).

Conclusion

The presence of sarcopenia in patients with EBC represents a potentially modifiable risk factor for more significant endocrine therapy side effects and reduced treatment tolerance.
Appendix
Available only for authorised users
Literature
1.
go back to reference Mohsin SK, Weiss H, Havighurst T, Clark GM, Berardo M, le Roanh D et al (2004) Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study. Mod Pathol 17(12):1545–1554CrossRef Mohsin SK, Weiss H, Havighurst T, Clark GM, Berardo M, le Roanh D et al (2004) Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study. Mod Pathol 17(12):1545–1554CrossRef
2.
go back to reference Anderson WF, Chatterjee N, Ershler WB, Brawley OW (2002) Estrogen receptor breast cancer phenotypes in the Surveillance, Epidemiology, and End Results database. Breast Cancer Res Treat 76(1):27–36CrossRef Anderson WF, Chatterjee N, Ershler WB, Brawley OW (2002) Estrogen receptor breast cancer phenotypes in the Surveillance, Epidemiology, and End Results database. Breast Cancer Res Treat 76(1):27–36CrossRef
3.
go back to reference Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365(9472):1687–1717 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365(9472):1687–1717
4.
go back to reference Cella D, Fallowfield LJ (2008) Recognition and management of treatment-related side effects for breast cancer patients receiving adjuvant endocrine therapy. Breast Cancer Res Treat 107(2):167–180CrossRef Cella D, Fallowfield LJ (2008) Recognition and management of treatment-related side effects for breast cancer patients receiving adjuvant endocrine therapy. Breast Cancer Res Treat 107(2):167–180CrossRef
5.
go back to reference Eastell R, Adams JE, Coleman RE, Howell A, Hannon RA, Cuzick J et al (2008) Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol 26(7):1051–1057CrossRef Eastell R, Adams JE, Coleman RE, Howell A, Hannon RA, Cuzick J et al (2008) Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol 26(7):1051–1057CrossRef
6.
go back to reference Mohanty SS, Mohanty PK (2021) Obesity as potential breast cancer risk factor for postmenopausal women. Genes Dis 8(2):117–123CrossRef Mohanty SS, Mohanty PK (2021) Obesity as potential breast cancer risk factor for postmenopausal women. Genes Dis 8(2):117–123CrossRef
7.
go back to reference Santa-Maria CA, Yan J, Xie XJ, Euhus DM (2015) Aggressive estrogen-receptor-positive breast cancer arising in patients with elevated body mass index. Int J Clin Oncol 20(2):317–323CrossRef Santa-Maria CA, Yan J, Xie XJ, Euhus DM (2015) Aggressive estrogen-receptor-positive breast cancer arising in patients with elevated body mass index. Int J Clin Oncol 20(2):317–323CrossRef
8.
go back to reference Chan DS, Norat T (2015) Obesity and breast cancer: not only a risk factor of the disease. Curr Treat Options Oncol 16(5):22CrossRef Chan DS, Norat T (2015) Obesity and breast cancer: not only a risk factor of the disease. Curr Treat Options Oncol 16(5):22CrossRef
9.
go back to reference Gerard C, Brown KA (2018) Obesity and breast cancer - Role of estrogens and the molecular underpinnings of aromatase regulation in breast adipose tissue. Mol Cell Endocrinol 466:15–30CrossRef Gerard C, Brown KA (2018) Obesity and breast cancer - Role of estrogens and the molecular underpinnings of aromatase regulation in breast adipose tissue. Mol Cell Endocrinol 466:15–30CrossRef
10.
go back to reference Kwan ML, Chen WY, Kroenke CH, Weltzien EK, Beasley JM, Nechuta SJ et al (2012) Pre-diagnosis body mass index and survival after breast cancer in the After Breast Cancer Pooling Project. Breast Cancer Res Treat 132(2):729–739CrossRef Kwan ML, Chen WY, Kroenke CH, Weltzien EK, Beasley JM, Nechuta SJ et al (2012) Pre-diagnosis body mass index and survival after breast cancer in the After Breast Cancer Pooling Project. Breast Cancer Res Treat 132(2):729–739CrossRef
11.
go back to reference Greenlee H, Unger JM, LeBlanc M, Ramsey S, Hershman DL (2017) Association between body mass index and cancer survival in a pooled analysis of 22 clinical trials. Cancer Epidemiol Biomarkers Prev 26(1):21–29CrossRef Greenlee H, Unger JM, LeBlanc M, Ramsey S, Hershman DL (2017) Association between body mass index and cancer survival in a pooled analysis of 22 clinical trials. Cancer Epidemiol Biomarkers Prev 26(1):21–29CrossRef
12.
go back to reference Goodwin PJ (2013) Obesity and endocrine therapy: host factors and breast cancer outcome. Breast 22(Suppl 2):S44–S47CrossRef Goodwin PJ (2013) Obesity and endocrine therapy: host factors and breast cancer outcome. Breast 22(Suppl 2):S44–S47CrossRef
13.
go back to reference Rosenberg IH (1997) Sarcopenia: origins and clinical relevance. J Nutr 127(5 Suppl):990S-S991CrossRef Rosenberg IH (1997) Sarcopenia: origins and clinical relevance. J Nutr 127(5 Suppl):990S-S991CrossRef
14.
go back to reference Rolland Y, Czerwinski S, Abellan Van Kan G, Morley JE, Cesari M, Onder G et al (2008) Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives. J Nutr Health Aging 12(7):433–50CrossRef Rolland Y, Czerwinski S, Abellan Van Kan G, Morley JE, Cesari M, Onder G et al (2008) Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives. J Nutr Health Aging 12(7):433–50CrossRef
15.
go back to reference Aleixo GFP, Shachar SS, Nyrop KA, Muss HB, Battaglini CL, Williams GR (2020) Bioelectrical Impedance Analysis for the Assessment of Sarcopenia in Patients with Cancer: A Systematic Review. Oncologist 25(2):170–182CrossRef Aleixo GFP, Shachar SS, Nyrop KA, Muss HB, Battaglini CL, Williams GR (2020) Bioelectrical Impedance Analysis for the Assessment of Sarcopenia in Patients with Cancer: A Systematic Review. Oncologist 25(2):170–182CrossRef
16.
go back to reference Shachar SS, Deal AM, Weinberg M, Williams GR, Nyrop KA, Popuri K et al (2017) Body composition as a predictor of toxicity in patients receiving anthracycline and taxane-based chemotherapy for early-stage breast cancer. Clin Cancer Res 23(14):3537–3543CrossRef Shachar SS, Deal AM, Weinberg M, Williams GR, Nyrop KA, Popuri K et al (2017) Body composition as a predictor of toxicity in patients receiving anthracycline and taxane-based chemotherapy for early-stage breast cancer. Clin Cancer Res 23(14):3537–3543CrossRef
17.
go back to reference Shachar SS, Deal AM, Weinberg M, Nyrop KA, Williams GR, Nishijima TF et al (2017) Skeletal muscle measures as predictors of toxicity, hospitalization, and survival in patients with metastatic breast cancer receiving taxane-based chemotherapy. Clin Cancer Res 23(3):658–665CrossRef Shachar SS, Deal AM, Weinberg M, Nyrop KA, Williams GR, Nishijima TF et al (2017) Skeletal muscle measures as predictors of toxicity, hospitalization, and survival in patients with metastatic breast cancer receiving taxane-based chemotherapy. Clin Cancer Res 23(3):658–665CrossRef
18.
go back to reference Shachar SS, Williams GR, Muss HB, Nishijima TF (2016) Prognostic value of sarcopenia in adults with solid tumours: a meta-analysis and systematic review. Eur J Cancer 57:58–67CrossRef Shachar SS, Williams GR, Muss HB, Nishijima TF (2016) Prognostic value of sarcopenia in adults with solid tumours: a meta-analysis and systematic review. Eur J Cancer 57:58–67CrossRef
19.
go back to reference Otten L, Stobaus N, Franz K, Genton L, Muller-Werdan U, Wirth R et al (2019) Impact of sarcopenia on 1-year mortality in older patients with cancer. Age Ageing 48(3):413–418CrossRef Otten L, Stobaus N, Franz K, Genton L, Muller-Werdan U, Wirth R et al (2019) Impact of sarcopenia on 1-year mortality in older patients with cancer. Age Ageing 48(3):413–418CrossRef
20.
go back to reference Zhu Y, Cohen SM, Rosenzweig MQ, Bender CM (2019) Symptom map of endocrine therapy for breast cancer: a scoping review. Cancer Nurs 42(5):E19–E30CrossRef Zhu Y, Cohen SM, Rosenzweig MQ, Bender CM (2019) Symptom map of endocrine therapy for breast cancer: a scoping review. Cancer Nurs 42(5):E19–E30CrossRef
21.
go back to reference Trotti A, Colevas AD, Setser A, Basch E (2007) Patient-reported outcomes and the evolution of adverse event reporting in oncology. J Clin Oncol 25(32):5121–5127CrossRef Trotti A, Colevas AD, Setser A, Basch E (2007) Patient-reported outcomes and the evolution of adverse event reporting in oncology. J Clin Oncol 25(32):5121–5127CrossRef
22.
go back to reference Kidwell KM, Harte SE, Hayes DF, Storniolo AM, Carpenter J, Flockhart DA et al (2014) Patient-reported symptoms and discontinuation of adjuvant aromatase inhibitor therapy. Cancer 120(16):2403–2411CrossRef Kidwell KM, Harte SE, Hayes DF, Storniolo AM, Carpenter J, Flockhart DA et al (2014) Patient-reported symptoms and discontinuation of adjuvant aromatase inhibitor therapy. Cancer 120(16):2403–2411CrossRef
23.
go back to reference Kadakia KC, Snyder CF, Kidwell KM, Seewald NJ, Flockhart DA, Skaar TC et al (2016) Patient-reported outcomes and early discontinuation in aromatase inhibitor-treated postmenopausal women with early stage breast cancer. Oncologist 21(5):539–546CrossRef Kadakia KC, Snyder CF, Kidwell KM, Seewald NJ, Flockhart DA, Skaar TC et al (2016) Patient-reported outcomes and early discontinuation in aromatase inhibitor-treated postmenopausal women with early stage breast cancer. Oncologist 21(5):539–546CrossRef
24.
go back to reference Wagner LI, Zhao F, Goss PE, Chapman JW, Shepherd LE, Whelan TJ et al (2018) Patient-reported predictors of early treatment discontinuation: treatment-related symptoms and health-related quality of life among postmenopausal women with primary breast cancer randomized to anastrozole or exemestane on NCIC Clinical Trials Group (CCTG) MA.27 (E1Z03). Breast Cancer Res Treat 169(3):537–548CrossRef Wagner LI, Zhao F, Goss PE, Chapman JW, Shepherd LE, Whelan TJ et al (2018) Patient-reported predictors of early treatment discontinuation: treatment-related symptoms and health-related quality of life among postmenopausal women with primary breast cancer randomized to anastrozole or exemestane on NCIC Clinical Trials Group (CCTG) MA.27 (E1Z03). Breast Cancer Res Treat 169(3):537–548CrossRef
25.
26.
go back to reference Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW (2012) Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat 134(2):459–478CrossRef Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW (2012) Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat 134(2):459–478CrossRef
27.
go back to reference Cao A, Ferrucci LM, Caan BJ, Irwin ML (2022) Effect of exercise on sarcopenia among cancer survivors: a systematic review. Cancers (Basel) 14(3):786CrossRef Cao A, Ferrucci LM, Caan BJ, Irwin ML (2022) Effect of exercise on sarcopenia among cancer survivors: a systematic review. Cancers (Basel) 14(3):786CrossRef
28.
go back to reference Irwin ML, Cartmel B, Gross CP, Ercolano E, Li F, Yao X et al (2015) Randomized exercise trial of aromatase inhibitor-induced arthralgia in breast cancer survivors. J Clin Oncol 33(10):1104–1111CrossRef Irwin ML, Cartmel B, Gross CP, Ercolano E, Li F, Yao X et al (2015) Randomized exercise trial of aromatase inhibitor-induced arthralgia in breast cancer survivors. J Clin Oncol 33(10):1104–1111CrossRef
29.
go back to reference Bartlett DB, Hanson ED, Lee JT, Wagoner CW, Harrell EP, Sullivan SA et al (2021) The effects of 16 weeks of exercise training on neutrophil functions in breast cancer survivors. Front Immunol 12:733101CrossRef Bartlett DB, Hanson ED, Lee JT, Wagoner CW, Harrell EP, Sullivan SA et al (2021) The effects of 16 weeks of exercise training on neutrophil functions in breast cancer survivors. Front Immunol 12:733101CrossRef
30.
go back to reference Li C, Zhou C, Li R (2016) Can exercise ameliorate aromatase inhibitor-induced cognitive decline in breast cancer patients? Mol Neurobiol 53(6):4238–4246CrossRef Li C, Zhou C, Li R (2016) Can exercise ameliorate aromatase inhibitor-induced cognitive decline in breast cancer patients? Mol Neurobiol 53(6):4238–4246CrossRef
31.
go back to reference Thomas GA, Cartmel B, Harrigan M, Fiellin M, Capozza S, Zhou Y et al (2017) The effect of exercise on body composition and bone mineral density in breast cancer survivors taking aromatase inhibitors. Obesity (Silver Spring) 25(2):346–351CrossRef Thomas GA, Cartmel B, Harrigan M, Fiellin M, Capozza S, Zhou Y et al (2017) The effect of exercise on body composition and bone mineral density in breast cancer survivors taking aromatase inhibitors. Obesity (Silver Spring) 25(2):346–351CrossRef
32.
go back to reference Adams SC, Segal RJ, McKenzie DC, Vallerand JR, Morielli AR, Mackey JR et al (2016) Impact of resistance and aerobic exercise on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. Breast Cancer Res Treat 158(3):497–507CrossRef Adams SC, Segal RJ, McKenzie DC, Vallerand JR, Morielli AR, Mackey JR et al (2016) Impact of resistance and aerobic exercise on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. Breast Cancer Res Treat 158(3):497–507CrossRef
33.
go back to reference Villasenor A, Ballard-Barbash R, Baumgartner K, Baumgartner R, Bernstein L, McTiernan A et al (2012) Prevalence and prognostic effect of sarcopenia in breast cancer survivors: the HEAL Study. J Cancer Surviv 6(4):398–406CrossRef Villasenor A, Ballard-Barbash R, Baumgartner K, Baumgartner R, Bernstein L, McTiernan A et al (2012) Prevalence and prognostic effect of sarcopenia in breast cancer survivors: the HEAL Study. J Cancer Surviv 6(4):398–406CrossRef
34.
go back to reference Arango-Lopera VE, Arroyo P, Gutierrez-Robledo LM, Perez-Zepeda MU, Cesari M (2013) Mortality as an adverse outcome of sarcopenia. J Nutr Health Aging 17(3):259–262CrossRef Arango-Lopera VE, Arroyo P, Gutierrez-Robledo LM, Perez-Zepeda MU, Cesari M (2013) Mortality as an adverse outcome of sarcopenia. J Nutr Health Aging 17(3):259–262CrossRef
35.
go back to reference Batsis JA, Mackenzie TA, Jones JD, Lopez-Jimenez F, Bartels SJ (2016) Sarcopenia, sarcopenic obesity and inflammation: results from the 1999–2004 National Health and Nutrition Examination Survey. Clin Nutr 35(6):1472–1483CrossRef Batsis JA, Mackenzie TA, Jones JD, Lopez-Jimenez F, Bartels SJ (2016) Sarcopenia, sarcopenic obesity and inflammation: results from the 1999–2004 National Health and Nutrition Examination Survey. Clin Nutr 35(6):1472–1483CrossRef
36.
go back to reference Caan BJ, Cespedes Feliciano EM, Prado CM, Alexeeff S, Kroenke CH, Bradshaw P et al (2018) Association of muscle and adiposity measured by computed tomography with survival in patients with nonmetastatic breast cancer. JAMA Oncol 4(6):798–804CrossRef Caan BJ, Cespedes Feliciano EM, Prado CM, Alexeeff S, Kroenke CH, Bradshaw P et al (2018) Association of muscle and adiposity measured by computed tomography with survival in patients with nonmetastatic breast cancer. JAMA Oncol 4(6):798–804CrossRef
37.
go back to reference Williams GR, Dunne RF, Giri S, Shachar SS, Caan BJ (2021) Sarcopenia in the older adult with cancer. J Clin Oncol 39(19):2068–2078CrossRef Williams GR, Dunne RF, Giri S, Shachar SS, Caan BJ (2021) Sarcopenia in the older adult with cancer. J Clin Oncol 39(19):2068–2078CrossRef
Metadata
Title
Association of sarcopenia with endocrine therapy toxicity in patients with early breast cancer
Authors
Gabriel Francisco Pereira Aleixo
Stephanie A. Valente
Wei Wei
Halle C. F. Moore
Publication date
17-09-2022
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2022
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-022-06741-x

Other articles of this Issue 2/2022

Breast Cancer Research and Treatment 2/2022 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