Breast Cancer Research and Treatment

, Volume 144, Issue 3, pp 673–681 | Cite as

Early treatment discontinuation and switching in first-line metastatic breast cancer: the role of patient-reported symptom burden

  • Mark S. WalkerEmail author
  • Anthony S. Masaquel
  • Jiandong Kerr
  • Deepa Lalla
  • Oyewale Abidoye
  • Arthur C. Houts
  • Lee S. Schwartzberg


Treatment options for metastatic breast cancer (MBC) are complex, and some patients experience early discontinuation or switching of treatment (ETDS). We examined the relationship between ETDS and patient-reported symptom burden among patients receiving first-line treatment of MBC in community oncology settings. This retrospective observational study used the ACORN Data Warehouse, a comprehensive community oncology repository of medical records and patient-reported outcomes. Patients with first-line treatment for MBC who had Patient Care Monitor (PCM) surveys were eligible. ETDS was defined as: record stating ETDS, treatment duration < planned, and planned therapy <6 weeks. Symptom burden was measured by two PCM composite scores [continuous (0–22) and categorical (absent, mild, moderate, and severe)] computed from 22 PCM items with varying cut points to assess symptom burden over time. Cox regression with time-varying covariates was used to assess risk for ETDS controlling for patient characteristics and treatment type: chemo (chemotherapy without targeted therapy (±hormone therapy); targeted (chemotherapy plus targeted therapy (±hormone therapy); and hormone (hormone therapy only). Overall, 197 (24.7 %) of a total sample of 797 patients had an ETDS event, of which 109 (55.3 %) were switches rather than early discontinuation. ETDS rate was nominally lower in the hormone group (11.1 %) versus chemo (27.6 %) or targeted (26.1 %). PCM continuous composite score predicted ETDS, controlling for other variables (HR = 1.132, p < 0.0001). ETDS was predicted by moderate and severe levels of PCM categorical composite score (HR = 4.135, and HR = 5.287 vs. absent, respectively, both p < 0.0001), with the pattern suggesting a threshold effect. Moderate or severe levels of a wide range of patient-reported symptoms and the accumulation of symptoms over time significantly predicted ETDS. Providers may better maintain patients on planned therapy if they attend to overall symptom burden patients experience over time.


Metastatic breast cancer Symptom burden Treatment discontinuation Treatment switching Community oncology 



This study was funded by Genentech, Inc.

Conflict of interest

AM and OA are employed by and own stock in Genentech, Inc. DL was employed at Genentech, Inc. at the time of the study, and is currently affiliated with Palo Alto Outcomes Research, Inc., Palo Alto, CA. DL and LS serve in a consultant/advisory role to Genentech, Inc. For the remaining authors, no conflicts of interest were declared.

Ethical Standards

The conduct of this research complies with the current laws of the United States. This research was reviewed and approved by the Institutional Review Board of IntegReview, Austin, TX, USA.


  1. 1.
    Saad ED, Katz A, Buyse M (2010) Overall survival and post-progression survival in advanced breast cancer: a review of recent randomized clinical trials. J Clin Oncol 28(11):1958–1962. doi: 10.1200/JCO.2009.25.5414 PubMedCrossRefGoogle Scholar
  2. 2.
    American Cancer Society (2011) Breast Cancer Facts and Figures 2011–2012. American Cancer Society. Accessed 4 Dec 2011
  3. 3.
    National Comprehensive Cancer Network (NCCN) (2014) NCCN Clinical Practice Guidelines in Oncology: Breast CancerGoogle Scholar
  4. 4.
    Gray R, Bhattacharya S, Bowden C, Miller K, Comis RL (2009) Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. J Clin Oncol 27(30):4966–4972. doi: 10.1200/JCO.2008.21.6630 PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357(26):2666–2676. doi: 10.1056/NEJMoa072113 PubMedCrossRefGoogle Scholar
  6. 6.
    Robert NJ, Dieras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O’Shaughnessy J (2011) RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol 29(10):1252–1260. doi: 10.1200/JCO.2010.28.0982 PubMedCrossRefGoogle Scholar
  7. 7.
    Schwartzberg LS, Franco SX, Florance A, O’Rourke L, Maltzman J, Johnston S (2010) Lapatinib plus letrozole as first-line therapy for HER-2+ hormone receptor-positive metastatic breast cancer. Oncologist 15(2):122–129. doi: 10.1634/theoncologist.2009-0240 PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Di Leo A, Gomez HL, Aziz Z, Zvirbule Z, Bines J, Arbushites MC, Guerrera SF, Koehler M, Oliva C, Stein SH, Williams LS, Dering J, Finn RS, Press MF (2008) Phase III, double-blind, randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for metastatic breast cancer. J Clin Oncol 26(34):5544–5552. doi: 10.1200/JCO.2008.16.2578 PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Baselga J, Costa F, Gomez H, Hudis CA, Rapoport B, Roche H, Schwartzberg LS, Petrenciuc O, Shan M, Gradishar WJ (2013) A phase 3 tRial comparing capecitabinE in combination with SorafenIb or pLacebo for treatment of locally advanced or metastatIc HER2-Negative breast CancEr (the RESILIENCE study): study protocol for a randomized controlled trial. Trials 14:228. doi: 10.1186/1745-6215-14-228 PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Baselga J, Segalla JG, Roche H, Del Giglio A, Pinczowski H, Ciruelos EM, Filho SC, Gomez P, Van Eyll B, Bermejo B, Llombart A, Garicochea B, Duran MA, Hoff PM, Espie M, de Moraes AA, Ribeiro RA, Mathias C, Gil Gil M, Ojeda B, Morales J, Kwon Ro S, Li S, Costa F (2012) Sorafenib in combination with capecitabine: an oral regimen for patients with HER2-negative locally advanced or metastatic breast cancer. J Clin Oncol 30(13):1484–1491. doi: 10.1200/JCO.2011.36.7771 PubMedCrossRefGoogle Scholar
  11. 11.
    Bergh J, Bondarenko IM, Lichinitser MR, Liljegren A, Greil R, Voytko NL, Makhson AN, Cortes J, Lortholary A, Bischoff J, Chan A, Delaloge S, Huang X, Kern KA, Giorgetti C (2012) First-line treatment of advanced breast cancer with sunitinib in combination with docetaxel versus docetaxel alone: results of a prospective, randomized phase III study. J Clin Oncol 30(9):921–929. doi: 10.1200/JCO.2011.35.7376 PubMedCrossRefGoogle Scholar
  12. 12.
    Robert NJ, Saleh MN, Paul D, Generali D, Gressot L, Copur MS, Brufsky AM, Minton SE, Giguere JK, Smith JW 2nd, Richards PD, Gernhardt D, Huang X, Liau KF, Kern KA, Davis J (2011) Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: a phase III, randomized, open-label trial. Clin Breast Cancer 11(2):82–92. doi: 10.1016/j.clbc.2011.03.005 PubMedCrossRefGoogle Scholar
  13. 13.
    O’Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley C (2011) Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med 364(3):205–214. doi: 10.1056/NEJMoa1011418 PubMedCrossRefGoogle Scholar
  14. 14.
    O’Shaughnessy J, Schwartzberg LS, Danso MA, Rugo HS, Miller K, Yardley DA, Carlson RW, Finn RS, Charpentier E, Freese M, Gupta S, Blackwood-Chirchir A, Winer EP (2011) A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). ASCO Meeting Abstracts 29 (15_suppl):1007Google Scholar
  15. 15.
    Burstein HJ (2011) Bevacizumab for advanced breast cancer: all tied up with a RIBBON? J Clin Oncol 29(10):1232–1235. doi: 10.1200/JCO.2010.33.2684 PubMedCrossRefGoogle Scholar
  16. 16.
    Lyman GH, Burstein HJ, Buzdar AU, D’Agostino R, Ellis PA (2012) Making genuine progress against metastatic breast cancer. J Clin Oncol 30(28):3448–3451. doi: 10.1200/JCO.2012.43.6931 PubMedCrossRefGoogle Scholar
  17. 17.
    Mayer EL, Dhakil S, Patel T, Sundaram S, Fabian C, Kozloff M, Qamar R, Volterra F, Parmar H, Samant M, Burstein HJ (2010) SABRE-B: an evaluation of paclitaxel and bevacizumab with or without sunitinib as first-line treatment of metastatic breast cancer. Ann Oncol 21(12):2370–2376. doi: 10.1093/annonc/mdq260 PubMedCrossRefGoogle Scholar
  18. 18.
    Marino P, Roche H, Biron P, Janvier M, Spaeth D, Fabbro M, Linassier C, Delozier T, Martin AL, Santin G, Moatti JP (2008) Deterioration of quality of life of high-risk breast cancer patients treated with high-dose chemotherapy: the PEGASE 01 Quality of Life Study. Value Health 11(4):709–718. doi: 10.1111/j.1524-4733.2007.00306.x PubMedCrossRefGoogle Scholar
  19. 19.
    Genre D, Protiere C, Macquart-Moulin G, Gravis G, Camerlo J, Alzieu C, Maraninchi D, Moatti JP, Viens P (2002) Quality of life of breast cancer patients receiving high-dose-intensity chemotherapy: impact of length of cycles. Support Care Cancer 10(3):222–230. doi: 10.1007/s00520-001-0322-3 PubMedCrossRefGoogle Scholar
  20. 20.
    Osoba D, Slamon DJ, Burchmore M, Murphy M (2002) Effects on quality of life of combined trastuzumab and chemotherapy in women with metastatic breast cancer. J Clin Oncol 20(14):3106–3113PubMedCrossRefGoogle Scholar
  21. 21.
    Sherrill B, Amonkar MM, Sherif B, Maltzman J, O’Rourke L, Johnston S (2010) Quality of life in hormone receptor-positive HER-2+ metastatic breast cancer patients during treatment with letrozole alone or in combination with lapatinib. Oncologist 15(9):944–953. doi: 10.1634/theoncologist.2010-0012 PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Richardson LC, Wang W, Hartzema AG, Wagner S (2007) The role of health-related quality of life in early discontinuation of chemotherapy for breast cancer. Breast J 13(6):581–587. doi: 10.1111/j.1524-4741.2007.00512.x PubMedCrossRefGoogle Scholar
  23. 23.
    Pettengell R, Schwenkglenks M, Leonard R, Bosly A, Paridaens R, Constenla M, Szucs TD, Jackisch C, Impact of Neutropenia in Chemotherapy-European Study Group (2008) Neutropenia occurrence and predictors of reduced chemotherapy delivery: results from the INC-EU prospective observational European neutropenia study. Support Care Cancer 16(11):1299–1309. doi: 10.1007/s00520-008-0430-4 PubMedCrossRefGoogle Scholar
  24. 24.
    Mayer EL, Burstein HJ (2007) Chemotherapy for metastatic breast cancer. Hematol Oncol Clin North Am 21(2):257–272. doi: 10.1016/j.hoc.2007.03.001 PubMedCrossRefGoogle Scholar
  25. 25.
    Reed E, Simmonds P, Haviland J, Corner J (2012) Quality of life and experience of care in women with metastatic breast cancer: a cross-sectional survey. J Pain Symptom Manage 43(4):747–758. doi: 10.1016/j.jpainsymman.2011.05.005 PubMedCrossRefGoogle Scholar
  26. 26.
    Abernethy AP, Zafar SY, Uronis H, Wheeler JL, Coan A, Rowe K, Shelby RA, Fowler R, Herndon JE 2nd (2010) Validation of the patient care monitor (Version 2.0): a review of system assessment instrument for cancer patients. J Pain Symptom Manage 40(4):545–558. doi: 10.1016/j.jpainsymman.2010.01.017 Google Scholar
  27. 27.
    Houts AC, Lipinski D, Olsen JP, Baldwin S, Hasan M (2010) Use of the Patient Care Monitor to screen for depression in adult cancer patients interviewed with the structured clinical interview for DSM-IV. Psychooncology 19(4):399–407. doi: 10.1002/pon.1583 PubMedCrossRefGoogle Scholar
  28. 28.
    Stepanski EJ, Walker MS, Schwartzberg LS, Blakely LJ, Ong JC, Houts AC (2009) The relation of trouble sleeping, depressed mood, pain, and fatigue in patients with cancer. J Clin Sleep Med 5(2):132–136PubMedCentralPubMedGoogle Scholar
  29. 29.
    Walker MS, Hasan M, Yim YM, Yu E, Stepanski EJ, Schwartzberg LS (2011) Retrospective study of the effect of disease progression on patient reported outcomes in HER-2 negative metastatic breast cancer patients. Health Qual Life Outcomes 9:46. doi: 10.1186/1477-7525-9-46 PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Walker MS, Miller PJ, Namjoshi M, Houts AC, Stepanski EJ, Schwartzberg LS (2013) Relationship between incidence of fracture and health-related quality-of-life in metastatic breast cancer patients with bone metastases. J Med Econ 16(1):179–189. doi: 10.3111/13696998.2012.737883 PubMedCrossRefGoogle Scholar
  31. 31.
    Walker MS, Schwartzberg LS, Stepanski EJ, Fortner BV (2009) A retrospective study of quality of life in a community sample of patients with early stage breast cancer. Breast Cancer Res Treat 115(2):415–422. doi: 10.1007/s10549-009-0387-0 PubMedCrossRefGoogle Scholar
  32. 32.
    Schwartzberg LS, Cobb P, Walker MS, Stepanski EJ, Houts AC (2009) Patient and practice impact of capecitabine compared to taxanes in first/second line chemotherapy for metastatic breast cancer. Support Care Cancer 8:1081–1099CrossRefGoogle Scholar
  33. 33.
    Fortner B, Okon T, Schwartzberg L, Tauer K, Houts AC (2003) The Cancer Care Monitor: psychometric content evaluation and pilot testing of a computer administered system for symptom screening and quality of life in adult cancer patients. J Pain Symptom Manage 26(6):1077–1092PubMedCrossRefGoogle Scholar
  34. 34.
    Fortner B, Baldwin S, Schwartzberg L, Houts AC (2006) Validation of the Cancer Care Monitor items for physical symptoms and treatment side effects using expert oncology nurse evaluation. J Pain Symptom Manage 31(3):207–214. doi: 10.1016/j.jpainsymman.2005.07.009 PubMedCrossRefGoogle Scholar
  35. 35.
    Sharma PP, Sail K, Delea TE, Patt DA (2013) Treatment patterns in HER2+/HR+ postmenopausal women with metastatic breast cancer initiating first-line treatment in a community oncology setting. Community Oncol 10:74–81Google Scholar
  36. 36.
    Tripathy D, Kaufman PA, Brufsky AM, Mayer M, Yood MU, Yoo B, Quah C, Yardley D, Rugo HS (2013) First-line treatment patterns and clinical outcomes in patients with HER2-positive and hormone receptor-positive metastatic breast cancer from registHER. Oncologist 18(5):501–510. doi: 10.1634/theoncologist.2012-0414 PubMedCrossRefGoogle Scholar
  37. 37.
    Flygare JA, Pillow TH, Aristoff P (2013) Antibody-drug conjugates for the treatment of cancer. Chem Biol Drug Des 81(1):113–121. doi: 10.1111/cbdd.12085 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Mark S. Walker
    • 1
    Email author
  • Anthony S. Masaquel
    • 2
  • Jiandong Kerr
    • 1
  • Deepa Lalla
    • 2
  • Oyewale Abidoye
    • 2
  • Arthur C. Houts
    • 1
  • Lee S. Schwartzberg
    • 3
  1. 1.ACORN Research, LLCMemphisUSA
  2. 2.Genentech, Inc.South San FranciscoUSA
  3. 3.The West ClinicMemphisUSA

Personalised recommendations