Supportive Care in Cancer

, Volume 24, Issue 2, pp 683–689 | Cite as

Joint symptoms and health-related quality of life in postmenopausal women with breast cancer who completed 5 years of anastrozole

  • Hiroshi YagataEmail author
  • Hiroshi Ohtsu
  • Yoshifumi Komoike
  • Shigehira Saji
  • Hiroyuki Takei
  • Toshitaka Nakamura
  • Yasuo Ohashi
  • Takuya Iwase
  • Kojiro Shimozuma
Original Article



To assess the joint symptoms and the impact on patients’ health-related quality of life (HRQOL) due to 5 years of anastrozole from the baseline data in the N-SAS BC 05 trial, a randomized clinical trial was designed to assess the efficacy of 5 additional years of anastrozole among women with breast cancer.


Joint symptoms and HRQOL were evaluated using an original questionnaire for joint symptoms, the Short Form 36-item Health Survey (SF-36), the EuroQol EQ-5D-3L, and a subscale of the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES).


Baseline joint symptom and HRQOL data were collected from 330 patients between November 2007 and March 2010. Joint pain and joint stiffness were reported by 61.6 and 59.1 % of patients, respectively, although these symptoms did not affect the activities of daily living in 96.0 and 97.9 % of patients, respectively. Joint pain was reported in the knee by 61.0 % of patients and in the hand by 36.0 % of patients. Joint stiffness mainly affected the hand (67.9 %), especially the proximal interphalangeal joint, and typically occurred upon waking up or in the morning. Most SF-36 domains had good average scores, although slight decreases in physical functioning and role-physical were observed (compared to the national standard scores). The mean EQ-5D utility score was 0.86, and the total FACT-ES subscale score was 62.2/76.


After 5 years of anastrozole, many of the patients reported joint pain and stiffness in mainly the hand and knee with mild symptoms and good HRQOL.


Breast cancer Anastrozole Joint pain and stiffness Quality of life 



This study was supported by the Comprehensive Support Project for Oncology Research (CSP-OR) and the Comprehensive Support Project for Health Outcomes Research (CSP-HOR) of the Public Health Research Foundation. The corporate and individual sponsors of this study are listed on the CSP-OR website ( The pharmaceutical manufacturer/distributor played no role in this study, except in providing information regarding the proper use of the study drugs. All decisions concerning the planning, implementation, and publication of this study were made exclusively by the executive committee. We would like to thank Editage ( for the English language editing.


The authors declare that they have no competing interests.

Supplementary material

520_2015_2830_MOESM1_ESM.doc (2.4 mb)
ESM 1 (DOC 2.44 mb)


  1. 1.
    Coombes RC, Hall E, Gibson LJ, et al (2004) A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 350:1081–1092PubMedCrossRefGoogle Scholar
  2. 2.
    Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group, Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M (2008) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 9:45–53CrossRefGoogle Scholar
  3. 3.
    Regan MM, Neven P, Giobbie-Hurder A, et al (2011) Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol 12:1101–1108PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Mouridsen HT (2006) Incidence and management of side effects associated with aromatase inhibitors in the adjuvant treatment of breast cancer in postmenopausal women. Curr Med Res Opin 22:1609–1621PubMedCrossRefGoogle Scholar
  5. 5.
    Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS, ATAC Trialists’ Group (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365:60–62PubMedCrossRefGoogle Scholar
  6. 6.
    Arimidex, Tamoxifen, Alone or in Combination Trialists’ Group, Buzdar A, Howell A, et al (2006) Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Lancet Oncol 7:633–643PubMedCrossRefGoogle Scholar
  7. 7.
    Crew KD, Greenlee H, Capodice J, et al (2007) Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol 25:3877–3883PubMedCrossRefGoogle Scholar
  8. 8.
    Henry NL, Azzouz F, Desta Z, et al (2012) Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer. J Clin Oncol 30:936–942PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Chim K, Xie SX, Stricker CT, et al (2013) Joint pain severity predicts premature discontinuation of aromatase inhibitors in breast cancer survivors. BMC Cancer 13:401PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collab Group Lancet 351:1451–1467Google Scholar
  11. 11.
    Ohsumi S, Shimozuma K (2013) Current status and future perspectives of patient-reported outcome research in clinical trials for patients with breast cancer in Japan. Breast Cancer 20:296–301PubMedCrossRefGoogle Scholar
  12. 12.
    Ware JE, Jr SF-36 Health Survey Update. http://www.sf-36org/tools/sf36s.html.
  13. 13.
    McHorney CA, Ware Jr JE, Raczek AE (1993) The MOS 36-Item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care 31:247–263PubMedCrossRefGoogle Scholar
  14. 14.
    Fukuhara S, Ware Jr JE, Kosinski M, Wada S, Gandek B (1998) Psychometric and clinical tests of validity of the Japanese SF-36 Health Survey. J Clin Epidemiol 51:1045–1053PubMedCrossRefGoogle Scholar
  15. 15.
    Fukuhara S, Bito S, Green J, Hsiao A, Kurokawa K (1998) Translation, adaptation, and validation of the SF-36 Health Survey for use in Japan. J Clin Epidemiol 51:1037–1044PubMedCrossRefGoogle Scholar
  16. 16.
  17. 17.
    EuroQol Group (1990) EuroQol—a new facility for the measurement of health-related quality of life. Health Policy 16:199–208CrossRefGoogle Scholar
  18. 18.
    Tsuchiya A, Ikeda S, Ikegami N, et al (2002) Estimating an EQ-5D population value set: the case of Japan. Health Econ 11:341–353PubMedCrossRefGoogle Scholar
  19. 19.
    Fallowfield LJ, Leaity SK, Howell A, Benson S, Cella D (1999) Assessment of quality of life in women undergoing hormonal therapy for breast cancer: validation of an endocrine symptom subscale for the FACT-B. Breast Cancer Res Treat 55:189–199PubMedCrossRefGoogle Scholar
  20. 20.
    Aaronson NK, Ahmedzai S, Bergman B, et al (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85:365–376PubMedCrossRefGoogle Scholar
  21. 21.
    Cella DF, Tulsky DS, Gray G, et al (1993) The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol 11:570–579PubMedGoogle Scholar
  22. 22.
    Kurihara M, Shimizu H, Tsuboi K, et al (1999) Development of quality of life questionnaire in Japan: quality of life assessment of cancer patients receiving chemotherapy. Psychooncology 8:355–563PubMedCrossRefGoogle Scholar
  23. 23.
    Shimozuma K, Ohashi Y, Takeuchi A, et al (2009) Feasibility and validity of the Patient Neurotoxicity Questionnaire during taxane chemotherapy in a phase III randomized trial in patients with breast cancer: N-SAS BC 02. Support Care Cancer 17:1483–1491PubMedCrossRefGoogle Scholar
  24. 24.
    Shiroiwa T, Fukuda T, Shimozuma K, et al (2011) Comparison of EQ-5D scores among anthracycline-containing regimens followed by taxane and taxane-only regimens for node-positive breast cancer patients after surgery: the N-SAS BC 02 trial. Value Health 14:746–751PubMedCrossRefGoogle Scholar
  25. 25.
    Velikova G, Wright P, Smith AB, et al (2001) Self-reported quality of life of individual cancer patients: concordance of results with disease course and medical records. J Clin Oncol 19:2064–2073PubMedGoogle Scholar
  26. 26.
    Fromme EK, Eilers KM, Mori M, Hsieh YC, Beer TM (2004) How accurate is clinician reporting of chemotherapy adverse effects? A comparison with patient-reported symptoms from the Quality-of-Life Questionnaire C30. J Clin Oncol 22:3485–3490PubMedCrossRefGoogle Scholar
  27. 27.
    Ruhstaller T, von Moos R, Rufibach K, et al (2009) Breast cancer patients on endocrine therapy reveal more symptoms when self-reporting than in pivotal trials: an outcome research study. Oncology 76:142–148PubMedCrossRefGoogle Scholar
  28. 28.
    Mao JJ, Stricker C, Bruner D, et al (2009) Patterns and risk factors associated with aromatase inhibitor-related arthralgia among breast cancer survivors. Cancer 115:3631–3639PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Pickard AS, Wilke CT, Lin HW, Lloyd A (2007) Health utilities using the EQ-5D in studies of cancer. PharmacoEconomics 25:365–384PubMedCrossRefGoogle Scholar
  30. 30.
    Cella D, Fallowfield L, Barker P, Cuzick J, Locker G, Howell A (2006) Quality of life of postmenopausal women in the ATAC (“Arimidex”, tamoxifen, alone or in combination) trial after completion of 5 years’ adjuvant treatment for early breast cancer. Breast Cancer Res Treat 100:273–284PubMedCrossRefGoogle Scholar
  31. 31.
    Whelan TJ, Goss PE, Ingle JN, et al (2005) Assessment of quality of life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women. J Clin Oncol 23:6931–6940PubMedCrossRefGoogle Scholar
  32. 32.
    Muss HB, Tu D, Ingle JN, et al (2008) Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG Intergroup Trial MA.17. J Clin Oncol 26:1956–1964PubMedCrossRefGoogle Scholar
  33. 33.
    Davies C, Pan H, Godwin J, et al (2013) Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 381:805–816PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Higgins MJ, Liedke PE, Goss PE (2013) Extended adjuvant endocrine therapy in hormone dependent breast cancer: the paradigm of the NCIC-CTG MA.17/BIG 1-97 trial. Crit Rev Oncol Hematol 86:23–32PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Hiroshi Yagata
    • 1
    Email author
  • Hiroshi Ohtsu
    • 2
  • Yoshifumi Komoike
    • 3
  • Shigehira Saji
    • 4
  • Hiroyuki Takei
    • 5
  • Toshitaka Nakamura
    • 6
  • Yasuo Ohashi
    • 7
  • Takuya Iwase
    • 8
  • Kojiro Shimozuma
    • 9
  1. 1.Department of Breast Care, Saitama Medical CenterSaitama Medical UniversityKawagoe-shiJapan
  2. 2.Leading Center for the Development and Research of Cancer MedicineJuntendo University Graduate School of MedicineBunkyo-KuJapan
  3. 3.Department of SurgeryKinki University Faculty of MedicineOsaka-SayamaJapan
  4. 4.Department of Medical OncologyFukushima Medical UniversityFukushimaJapan
  5. 5.Department of Breast OncologyNippon Medical School HospitalBunkyou-kuJapan
  6. 6.National Center for Global Health and Medicine Center HospitalShinjuku-kuJapan
  7. 7.Department of Integrated Science and Engineering for Sustainable SocietyChuo UniversityBunkyo-kuJapan
  8. 8.Department of Breast SurgeryCancer Institute HospitalKotoJapan
  9. 9.Department of Biomedical Sciences, College of Life SciencesRitsumeikan UniversityKusatsuJapan

Personalised recommendations