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Pneumonitis and pulmonary fibrosis associated with breast cancer treatments

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Abstract

To review the available published data regarding the incidence, mechanisms of pathogenesis, clinical presentations and management of pneumonitis caused by anti-cancer treatments (radiotherapy (RT) and systemic agents) that are included in the guidelines of the treatment of breast cancer (BC) and address the issues on the current grading classification of pneumonitis. A literature search was performed between July and October 2013 using PubMed for papers published from January 1989 to October 2013. Any clinical trial, case report, case series, meta-analysis or systematic review that reported on pulmonary toxicity of any BC therapeutic modality was included (only papers published in English). Most of anticancer treatments currently used in the management of BC may induce some degree of pneumonitis that is estimated to have an incidence of 1–3 %. There is an obvious distinction between chemotherapy- and targeted treatment-related lung toxicity. Moreover, the current classification of pneumonitis needs to be modified as there is a clear diversity in grade 2. As pneumonitis is relatively common and reported as side effect of new anticancer agents, physicians need to be aware of the clinical and radiological manifestations of drug- and RT-induced toxicities in patients with BC. A key recommendation is the subdivision of grade 2 cases to two subgroups. We provide an algorithm, along with real life cases as managed in the breast Unit of Royal Marsden Hospital, with the aim to guide physicians in managing all possible eventualities that may come across in clinical practise.

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References

  1. Senkus E, Kyriakides S, Penault-Llorca F, Poortmans P, Thompson A, Zackrisson S, Cardoso F (2013) Primary breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. doi:10.1093/annonc/mdt284

    PubMed  Google Scholar 

  2. Camus P, Kudoh S, Ebina M (2004) Interstitial lung disease associated with drug therapy. Br J Cancer 91(Suppl 2):S18–S23. doi:10.1038/sj.bjc.6602063

    CAS  PubMed Central  PubMed  Google Scholar 

  3. de Castro G Jr, Awada A (2006) Side effects of anti-cancer molecular-targeted therapies (not monoclonal antibodies). Curr Opin Oncol 18(4):307–315. doi:10.1097/01.cco.0000228733.55132.ea

    PubMed  Google Scholar 

  4. Vahid B, Marik PE (2008) Pulmonary complications of novel antineoplastic agents for solid tumors. Chest 133(2):528–538. doi:10.1378/chest.07-0851

    CAS  PubMed  Google Scholar 

  5. Camus PH, Foucher P, Bonniaud PH, Ask K (2001) Drug-induced infiltrative lung disease. Eur Respir J Suppl 32:93s–100s

    CAS  PubMed  Google Scholar 

  6. Rosenow EC III, Limper AH (1995) Drug-induced pulmonary disease. Semin Respir Infect 10(2):86–95

    PubMed  Google Scholar 

  7. Ellard SL, Clemons M, Gelmon KA, Norris B, Kennecke H, Chia S, Pritchard K, Eisen A, Vandenberg T, Taylor M, Sauerbrei E, Mishaeli M, Huntsman D, Walsh W, Olivo M, McIntosh L, Seymour L (2009) Randomized phase II study comparing two schedules of everolimus in patients with recurrent/metastatic breast cancer: NCIC Clinical Trials Group IND. 163. J Clin Oncol 27(27):4536–4541. doi:10.1200/JCO.2008.21.3033

    CAS  PubMed  Google Scholar 

  8. Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN (2012) Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 366(6):520–529. doi:10.1056/NEJMoa1109653

    CAS  PubMed  Google Scholar 

  9. Baselga J, Semiglazov V, van Dam P, Manikhas A, Bellet M, Mayordomo J, Campone M, Kubista E, Greil R, Bianchi G, Steinseifer J, Molloy B, Tokaji E, Gardner H, Phillips P, Stumm M, Lane HA, Dixon JM, Jonat W, Rugo HS (2009) Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer. J Clin Oncol 27(16):2630–2637. doi:10.1200/JCO.2008.18.8391

    CAS  PubMed  Google Scholar 

  10. Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, Abadie-Lacourtoisie S, Eymard JC, Debled M, Spaeth D, Legouffe E, Allouache D, El Kouri C, Pujade-Lauraine E (2012) Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol 30(22):2718–2724. doi:10.1200/JCO.2011.39.0708

    CAS  PubMed  Google Scholar 

  11. Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R (2011) Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet 378(9804):1707–1716. doi:10.1016/S0140-6736(11)61629-2

    CAS  PubMed  Google Scholar 

  12. Buchanan CL, Dorn PL, Fey J, Giron G, Naik A, Mendez J, Murphy C, Sclafani LM (2006) Locoregional recurrence after mastectomy: incidence and outcomes. J Am Coll Surg 203(4):469–474. doi:10.1016/j.jamcollsurg.2006.06.015

    PubMed  Google Scholar 

  13. Oie Y, Saito Y, Kato M, Ito F, Hattori H, Toyama H, Kobayashi H, Katada K (2013) Relationship between radiation pneumonitis and organizing pneumonia after radiotherapy for breast cancer. Radiat Oncol 8:56. doi:10.1186/1748-717X-8-56

    PubMed Central  PubMed  Google Scholar 

  14. Vogelius IR, Bentzen SM (2012) A literature-based meta-analysis of clinical risk factors for development of radiation induced pneumonitis. Acta Oncol 51(8):975–983. doi:10.3109/0284186X.2012.718093

    PubMed Central  PubMed  Google Scholar 

  15. White DA, Camus P, Endo M, Escudier B, Calvo E, Akaza H, Uemura H, Kpamegan E, Kay A, Robson M, Ravaud A, Motzer RJ (2010) Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med 182(3):396–403. doi:10.1164/rccm.200911-1720OC

    PubMed  Google Scholar 

  16. Limper AH (2004) Chemotherapy-induced lung disease. Clin Chest Med 25(1):53–64. doi:10.1016/S0272-5231(03)00123-0

    PubMed  Google Scholar 

  17. Cleverley JR, Screaton NJ, Hiorns MP, Flint JD, Muller NL (2002) Drug-induced lung disease: high-resolution CT and histological findings. Clin Radiol 57(4):292–299. doi:10.1053/crad.2001.0792

    PubMed  Google Scholar 

  18. Torrisi JM, Schwartz LH, Gollub MJ, Ginsberg MS, Bosl GJ, Hricak H (2011) CT findings of chemotherapy-induced toxicity: what radiologists need to know about the clinical and radiologic manifestations of chemotherapy toxicity. Radiology 258(1):41–56. doi:10.1148/radiol.10092129

    PubMed  Google Scholar 

  19. von Rohr L, Klaeser B, Joerger M, Kluckert T, Cerny T, Gillessen S (2007) Increased pulmonary FDG uptake in bleomycin-associated pneumonitis. Onkologie 30(6):320–323. doi:10.1159/0000101517

    Google Scholar 

  20. Post MC, Grutters JC, Verzijlbergen JF, Biesma DH (2007) PET scintigraphy of etoposide-induced pulmonary toxicity. Clin Nucl Med 32(9):683–684. doi:10.1097/RLU.0b013e318123f78d

    PubMed  Google Scholar 

  21. Kalkanis D, Stefanovic A, Paes F, Escalon MP, Serafini A, Lossos IS (2009) [18F]-fluorodeoxyglucose positron emission tomography combined with computed tomography detection of asymptomatic late pulmonary toxicity in patients with non-Hodgkin lymphoma treated with rituximab-containing chemotherapy. Leuk Lymphoma 50(6):904–911. doi:10.1080/10428190902919200

    CAS  PubMed  Google Scholar 

  22. Yerushalmi R, Kramer MR, Rizel S, Sulkes A, Gelmon K, Granot T, Neiman V, Stemmer SM (2009) Decline in pulmonary function in patients with breast cancer receiving dose-dense chemotherapy: a prospective study. Ann Oncol 20(3):437–440. doi:10.1093/annonc/mdn652

    CAS  PubMed  Google Scholar 

  23. Wardley AM, Hiller L, Howard HC, Dunn JA, Bowman A, Coleman RE, Fernando IN, Ritchie DM, Earl HM, Poole CJ (2008) tAnGo: a randomised phase III trial of gemcitabine in paclitaxel-containing, epirubicin/cyclophosphamide-based, adjuvant chemotherapy for early breast cancer: a prospective pulmonary, cardiac and hepatic function evaluation. Br J Cancer 99(4):597–603. doi:10.1038/sj.bjc.6604538

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Dimopoulou I, Galani H, Dafni U, Samakovii A, Roussos C, Dimopoulos MA (2002) A prospective study of pulmonary function in patients treated with paclitaxel and carboplatin. Cancer 94(2):452–458. doi:10.1002/cncr.10182

    CAS  PubMed  Google Scholar 

  25. Bossi G, Cerveri I, Volpini E, Corsico A, Baio A, Corbella F, Klersy C, Arico M (1997) Long-term pulmonary sequelae after treatment of childhood Hodgkin’s disease. Ann Oncol 8(Suppl 1):19–24

    PubMed  Google Scholar 

  26. Camus P, Bonniaud P, Fanton A, Camus C, Baudaun N, Foucher P (2004) Drug-induced and iatrogenic infiltrative lung disease. Clin Chest Med 25(3):479–519. doi:10.1016/j.ccm.2004.05.006

    PubMed  Google Scholar 

  27. Takano T, Ohe Y, Kusumoto M, Tateishi U, Yamamoto S, Nokihara H, Yamamoto N, Sekine I, Kunitoh H, Tamura T, Kodama T, Saijo N (2004) Risk factors for interstitial lung disease and predictive factors for tumor response in patients with advanced non-small cell lung cancer treated with gefitinib. Lung Cancer 45(1):93–104. doi:10.1016/j.lungcan.2004.01.010

    PubMed  Google Scholar 

  28. Ochoa R, Bejarano PA, Gluck S, Montero AJ (2012) Pneumonitis and pulmonary fibrosis in a patient receiving adjuvant docetaxel and cyclophosphamide for stage 3 breast cancer: a case report and literature review. J Med Case Rep 6(1):413. doi:10.1186/1752-1947-6-413

    PubMed Central  PubMed  Google Scholar 

  29. Yu TK, Whitman GJ, Thames HD, Buzdar AU, Strom EA, Perkins GH, Schechter NR, McNeese MD, Kau SW, Thomas ES, Hortobagyi GN, Buchholz TA (2004) Clinically relevant pneumonitis after sequential paclitaxel-based chemotherapy and radiotherapy in breast cancer patients. J Natl Cancer Inst 96(22):1676–1681. doi:10.1093/jnci/djh315

    CAS  PubMed  Google Scholar 

  30. McDonald S, Rubin P, Phillips TL, Marks LB (1995) Injury to the lung from cancer therapy: clinical syndromes, measurable endpoints, and potential scoring systems. Int J Radiat Oncol Biol Phys 31(5):1187–1203. doi:10.1016/0360-3016(94)00429-O

    CAS  PubMed  Google Scholar 

  31. Lind PA, Marks LB, Hardenbergh PH, Clough R, Fan M, Hollis D, Hernando ML, Lucas D, Piepgrass A, Prosnitz LR (2002) Technical factors associated with radiation pneumonitis after local ± regional radiation therapy for breast cancer. Int J Radiat Oncol Biol Phys 52(1):137–143

    PubMed  Google Scholar 

  32. Blom-Goldman U, Svane G, Wennberg B, Lidestahl A, Lind PA (2007) Quantitative assessment of lung density changes after 3-D radiotherapy for breast cancer. Acta Oncol 46(2):187–193. doi:10.1080/02841860600949586

    PubMed  Google Scholar 

  33. Deantonio L, Gambaro G, Beldi D, Masini L, Tunesi S, Magnani C, Krengli M (2010) Hypofractionated radiotherapy after conservative surgery for breast cancer: analysis of acute and late toxicity. Radiat Oncol 5:112. doi:10.1186/1748-717X-5-112

    PubMed Central  PubMed  Google Scholar 

  34. Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bliss JM, Brown J, Dewar JA, Dobbs HJ, Haviland JS, Hoskin PJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Morgan DA, Owen JR, Simmons S, Sumo G, Sydenham MA, Venables K, Yarnold JR (2008) The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol 9(4):331–341. doi:10.1016/S1470-2045(08)70077-9

    CAS  PubMed  Google Scholar 

  35. Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bliss JM, Brown J, Dewar JA, Dobbs HJ, Haviland JS, Hoskin PJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Morgan DA, Owen JR, Simmons S, Sumo G, Sydenham MA, Venables K, Yarnold JR (2008) The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet 371(9618):1098–1107. doi:10.1016/S0140-6736(08)60348-7

    CAS  PubMed  Google Scholar 

  36. Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L, Lada B, Lukka H, Perera F, Fyles A, Laukkanen E, Gulavita S, Benk V, Szechtman B (2002) Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst 94(15):1143–1150

    PubMed  Google Scholar 

  37. Fragkandrea I, Kouloulias V, Mavridis P, Zettos A, Betsou S, Georgolopoulou P, Sotiropoulou A, Gouliamos A, Kouvaris I (2013) Radiation induced pneumonitis following whole breast radiotherapy treatment in early breast cancer patients treated with breast conserving surgery: a single institution study. Hippokratia 17(3):233–238

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, Dobbs HJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Simmons S, Sydenham MA, Venables K, Bliss JM, Yarnold JR (2013) The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol 14(11):1086–1094. doi:10.1016/S1470-2045(13)70386-3

    PubMed  Google Scholar 

  39. Taghian AG, Assaad SI, Niemierko A, Kuter I, Younger J, Schoenthaler R, Roche M, Powell SN (2001) Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel. J Natl Cancer Inst 93(23):1806–1811

    CAS  PubMed  Google Scholar 

  40. Hanna YM, Baglan KL, Stromberg JS, Vicini FA, Decker AD (2002) Acute and subacute toxicity associated with concurrent adjuvant radiation therapy and paclitaxel in primary breast cancer therapy. Breast J 8(3):149–153

    CAS  PubMed  Google Scholar 

  41. Varga Z, Cserhati A, Kelemen G, Boda K, Thurzo L, Kahan Z (2011) Role of systemic therapy in the development of lung sequelae after conformal radiotherapy in breast cancer patients. Int J Radiat Oncol Biol Phys 80(4):1109–1116. doi:10.1016/j.ijrobp.2010.03.044

    PubMed  Google Scholar 

  42. Pierce LJ, Hutchins LF, Green SR, Lew DL, Gralow JR, Livingston RB, Osborne CK, Albain KS (2005) Sequencing of tamoxifen and radiotherapy after breast-conserving surgery in early-stage breast cancer. J Clin Oncol 23(1):24–29. doi:10.1200/JCO.2005.01.198

    CAS  PubMed  Google Scholar 

  43. Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans E, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366(9503):2087–2106. doi:10.1016/S0140-6736(05)67887-7

    CAS  PubMed  Google Scholar 

  44. Epperly M, Bray J, Kraeger S, Zwacka R, Engelhardt J, Travis E, Greenberger J (1998) Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy. Gene Ther 5(2):196–208. doi:10.1038/sj.gt.3300580

    CAS  PubMed  Google Scholar 

  45. Anscher MS, Kong FM, Andrews K, Clough R, Marks LB, Bentel G, Jirtle RL (1998) Plasma transforming growth factor beta1 as a predictor of radiation pneumonitis. Int J Radiat Oncol Biol Phys 41(5):1029–1035

    CAS  PubMed  Google Scholar 

  46. Anscher MS, Marks LB, Shafman TD, Clough R, Huang H, Tisch A, Munley M, Herndon JE, Garst J, Crawford J, Jirtle RL (2003) Risk of long-term complications after TFG-beta1-guided very-high-dose thoracic radiotherapy. Int J Radiat Oncol Biol Phys 56(4):988–995

    PubMed  Google Scholar 

  47. Chen Y, Williams J, Ding I, Hernady E, Liu W, Smudzin T, Finkelstein JN, Rubin P, Okunieff P (2002) Radiation pneumonitis and early circulatory cytokine markers. Semin Radiat Oncol 12(1 Suppl 1):26–33

    PubMed  Google Scholar 

  48. Nozaki M, Kagami Y, Mitsumori M, Hiraoka M (2012) A multicenter investigation of late adverse events in Japanese women treated with breast-conserving surgery plus conventional fractionated whole-breast radiation therapy. Jpn J Clin Oncol 42(6):522–527. doi:10.1093/jjco/hys050

    PubMed  Google Scholar 

  49. Katayama N, Sato S, Katsui K, Takemoto M, Tsuda T, Yoshida A, Morito T, Nakagawa T, Mizuta A, Waki T, Niiya H, Kanazawa S (2009) Analysis of factors associated with radiation-induced bronchiolitis obliterans organizing pneumonia syndrome after breast-conserving therapy. Int J Radiat Oncol Biol Phys 73(4):1049–1054. doi:10.1016/j.ijrobp.2008.05.050

    PubMed  Google Scholar 

  50. Kubo A, Osaki K, Kawanaka T, Furutani S, Ikushima H, Nishitani H (2009) Risk factors for radiation pneumonitis caused by whole breast irradiation following breast-conserving surgery. J Med Invest 56(3–4):99–110

    PubMed  Google Scholar 

  51. Kano A, Ujita M, Kobayashi M, Sunakawa Y, Shirahama J, Harada T, Kanehira C, Fukuda K (2012) Radiographic and CT features of radiation-induced organizing pneumonia syndrome after breast-conserving therapy. Jpn J Radiol 30(2):128–136. doi:10.1007/s11604-011-0024-9

    PubMed  Google Scholar 

  52. Ma LD, Taylor GA, Wharam MD, Wiley JM (1993) “Recall” pneumonitis: adriamycin potentiation of radiation pneumonitis in two children. Radiology 187(2):465–467

    CAS  PubMed  Google Scholar 

  53. Schwarte S, Wagner K, Karstens JH, Bremer M (2007) Radiation recall pneumonitis induced by gemcitabine. Strahlenther Onkol 183(4):215–217. doi:10.1007/s00066-007-1688-z

    PubMed  Google Scholar 

  54. Schweitzer VG, Juillard GJ, Bajada CL, Parker RG (1995) Radiation recall dermatitis and pneumonitis in a patient treated with paclitaxel. Cancer 76(6):1069–1072

    CAS  PubMed  Google Scholar 

  55. Bourgier C, Massard C, Moldovan C, Soria JC, Deutsch E (2011) Total recall of radiotherapy with mTOR inhibitors: a novel and potentially frequent side-effect? Ann Oncol 22(2):485–486. doi:10.1093/annonc/mdq741

    CAS  PubMed  Google Scholar 

  56. Vahid B, Marik PE (2008) Infiltrative lung diseases: complications of novel antineoplastic agents in patients with hematological malignancies. Can Respir J 15(4):211–216

    PubMed Central  PubMed  Google Scholar 

  57. Sleijfer S (2001) Bleomycin-induced pneumonitis. Chest 120(2):617–624

    CAS  PubMed  Google Scholar 

  58. Semb KA, Aamdal S, Oian P (1998) Capillary protein leak syndrome appears to explain fluid retention in cancer patients who receive docetaxel treatment. J Clin Oncol 16(10):3426–3432

    CAS  PubMed  Google Scholar 

  59. Briasoulis E, Pavlidis N (2001) Noncardiogenic pulmonary edema: an unusual and serious complication of anticancer therapy. Oncologist 6(2):153–161

    CAS  PubMed  Google Scholar 

  60. Wang GS, Yang KY, Perng RP (2001) Life-threatening hypersensitivity pneumonitis induced by docetaxel (taxotere). Br J Cancer 85(9):1247–1250. doi:10.1054/bjoc.2001.2071

    CAS  PubMed Central  PubMed  Google Scholar 

  61. Malik SW, Myers JL, DeRemee RA, Specks U (1996) Lung toxicity associated with cyclophosphamide use. Two distinct patterns. Am J Respir Crit Care Med 154(6 Pt 1):1851–1856. doi:10.1164/ajrccm.154.6.8970380

    CAS  PubMed  Google Scholar 

  62. Shaib W, Lansigan F, Cornfeld D, Syrigos K, Saif MW (2008) Gemcitabine-induced pulmonary toxicity during adjuvant therapy in a patient with pancreatic cancer. JOP 9(6):708–714

    PubMed  Google Scholar 

  63. Miettinen PJ, Warburton D, Bu D, Zhao JS, Berger JE, Minoo P, Koivisto T, Allen L, Dobbs L, Werb Z, Derynck R (1997) Impaired lung branching morphogenesis in the absence of functional EGF receptor. Dev Biol 186(2):224–236. doi:10.1006/dbio.1997.8593

    CAS  PubMed  Google Scholar 

  64. Dillman RO (1999) Infusion reactions associated with the therapeutic use of monoclonal antibodies in the treatment of malignancy. Cancer Metastasis Rev 18(4):465–471

    CAS  PubMed  Google Scholar 

  65. Pham PT, Pham PC, Danovitch GM, Ross DJ, Gritsch HA, Kendrick EA, Singer J, Shah T, Wilkinson AH (2004) Sirolimus-associated pulmonary toxicity. Transplantation 77(8):1215–1220

    CAS  PubMed  Google Scholar 

  66. Morelon E, Stern M, Israel-Biet D, Correas JM, Danel C, Mamzer-Bruneel MF, Peraldi MN, Kreis H (2001) Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients. Transplantation 72(5):787–790

    CAS  PubMed  Google Scholar 

  67. Albiges L, Chamming’s F, Duclos B, Stern M, Motzer RJ, Ravaud A, Camus P (2012) Incidence and management of mTOR inhibitor-associated pneumonitis in patients with metastatic renal cell carcinoma. Ann Oncol 23(8):1943–1953. doi:10.1093/annonc/mds115

    CAS  PubMed  Google Scholar 

  68. Chilosi M, Pea M, Martignoni G, Brunelli M, Gobbo S, Poletti V, Bonetti F (2009) Cathepsin-k expression in pulmonary lymphangioleiomyomatosis. Mod Pathol 22(2):161–166. doi:10.1038/modpathol.2008.189

    CAS  PubMed  Google Scholar 

  69. Hamada K, Nagai S, Kitaichi M, Jin G, Shigematsu M, Nagao T, Sato A, Mishima M (2003) Cyclophosphamide-induced late-onset lung disease. Intern Med 42(1):82–87

    PubMed  Google Scholar 

  70. Segura A, Yuste A, Cercos A, Lopez-Tendero P, Girones R, Perez-Fidalgo JA, Herranz C (2001) Pulmonary fibrosis induced by cyclophosphamide. Ann Pharmacother 35(7–8):894–897

    CAS  PubMed  Google Scholar 

  71. Hoyt DG, Lazo JS (1989) Early increases in pulmonary mRNA encoding procollagens and transforming growth factor-beta in mice sensitive to cyclophosphamide-induced pulmonary fibrosis. J Pharmacol Exp Ther 249(1):38–43

    CAS  PubMed  Google Scholar 

  72. Stentoft J (1987) Progressive pulmonary fibrosis complicating cyclophosphamide therapy. Acta Med Scand 221(4):403–407

    CAS  PubMed  Google Scholar 

  73. Mendez M, Barriga F, Garcia C, Holmgren NL, Gonzalez S, Sanchez I (2000) Bronchiolitis obliterans with organizing pneumonia secondary to chemotherapy in a child with primary pericardial sarcoma. Rev Med Chil 128(6):633–640

    CAS  PubMed  Google Scholar 

  74. Jacobs C, Slade M, Lavery B (2002) Doxorubicin and BOOP. A possible near fatal association. Clin Oncol (R Coll Radiol) 14(3):262

    CAS  Google Scholar 

  75. Dang CT, D’Andrea GM, Moynahan ME, Dickler MN, Seidman AD, Fornier M, Robson ME, Theodoulou M, Lake D, Currie VE, Hurria A, Panageas KS, Norton L, Hudis CA (2004) Phase II study of feasibility of dose-dense FEC followed by alternating weekly taxanes in high-risk, four or more node-positive breast cancer. Clin Cancer Res 10(17):5754–5761. doi:10.1158/1078-0432.CCR-04-0634

    CAS  PubMed  Google Scholar 

  76. Therasse P, Mauriac L, Welnicka-Jaskiewicz M, Bruning P, Cufer T, Bonnefoi H, Tomiak E, Pritchard KI, Hamilton A, Piccart MJ (2003) Final results of a randomized phase III trial comparing cyclophosphamide, epirubicin, and fluorouracil with a dose-intensified epirubicin and cyclophosphamide + filgrastim as neoadjuvant treatment in locally advanced breast cancer: an EORTC-NCIC-SAKK multicenter study. J Clin Oncol 21(5):843–850

    CAS  PubMed  Google Scholar 

  77. Burnell M, Levine MN, Chapman JA, Bramwell V, Gelmon K, Walley B, Vandenberg T, Chalchal H, Albain KS, Perez EA, Rugo H, Pritchard K, O’Brien P, Shepherd LE (2010) Cyclophosphamide, epirubicin, and fluorouracil versus dose-dense epirubicin and cyclophosphamide followed by paclitaxel versus doxorubicin and cyclophosphamide followed by paclitaxel in node-positive or high-risk node-negative breast cancer. J Clin Oncol 28(1):77–82. doi:10.1200/JCO.2009.22.1077

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Couderc LJ, Stelianides S, Frachon I, Stern M, Epardeau B, Baumelou E, Caubarrere I, Hermine O (1999) Pulmonary toxicity of chemotherapy and G/GM-CSF: a report of five cases. Respir Med 93(1):65–68

    CAS  PubMed  Google Scholar 

  79. Ostoros G, Pretz A, Fillinger J, Soltesz I, Dome B (2006) Fatal pulmonary fibrosis induced by paclitaxel: a case report and review of the literature. Int J Gynecol Cancer 16(Suppl 1):391–393. doi:10.1111/j.1525-1438.2006.00222.x

    PubMed  Google Scholar 

  80. Harvey V, Mouridsen H, Semiglazov V, Jakobsen E, Voznyi E, Robinson BA, Groult V, Murawsky M, Cold S (2006) Phase III trial comparing three doses of docetaxel for second-line treatment of advanced breast cancer. J Clin Oncol 24(31):4963–4970. doi:10.1200/JCO.2005.05.0294

    CAS  PubMed  Google Scholar 

  81. Mauer AM, Masters GA, Haraf DJ, Hoffman PC, Watson SM, Golomb HM, Vokes EE (1998) Phase I study of docetaxel with concomitant thoracic radiation therapy. J Clin Oncol 16(1):159–164

    CAS  PubMed  Google Scholar 

  82. Dimopoulou I, Bamias A, Lyberopoulos P, Dimopoulos MA (2006) Pulmonary toxicity from novel antineoplastic agents. Ann Oncol 17(3):372–379. doi:10.1093/annonc/mdj057

    CAS  PubMed  Google Scholar 

  83. Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C (2008) Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 non overexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol 26(10):1642–1649. doi:10.1200/JCO.2007.11.6699

    CAS  PubMed  Google Scholar 

  84. Furuse K, Kubota K, Kawahara M, Ogawara M, Kinuwaki E, Motomiya M, Nishiwaki Y, Niitani H, Sakuma A (1994) A phase II study of vinorelbine, a new derivative of vinca alkaloid, for previously untreated advanced non-small cell lung cancer. Japan Vinorelbine Lung Cancer Study Group. Lung Cancer 11(5–6):385–391

    CAS  PubMed  Google Scholar 

  85. Igishi T, Shigeoka Y, Yasuda K, Suyama H, Katayama S, Sugitani A, Matsumoto S, Yamamoto M, Ueda Y, Takeda K, Sumikawa T, Sako T, Kodani M, Hitsuda Y, Shimizu E (2009) UFT plus vinorelbine in advanced non-small cell lung cancer: a phase I and an elderly patient-directed phase II study. J Thorac Oncol 4(3):376–382. doi:10.1097/JTO.0b013e3181989dfc

    PubMed  Google Scholar 

  86. Yanagitani N, Shimizu Y, Kaira K, Tatsuno S, Sunaga N, Ishizuka T, Mori M (2008) Pulmonary toxicity associated with vinorelbine-based chemotherapy in breast cancer. Gan To Kagaku Ryoho 35(9):1619–1621

    PubMed  Google Scholar 

  87. Radzikowska E, Szczepulska E, Chabowski M, Bestry I (2003) Organising pneumonia caused by transtuzumab (herceptin) therapy for breast cancer. Eur Respir J 21(3):552–555

    CAS  PubMed  Google Scholar 

  88. Vahid B, Mehrotra A (2006) Trastuzumab (herceptin)-associated lung injury. Respirology 11(5):655–658. doi:10.1111/j.1440-1843.2006.00907.x

    PubMed  Google Scholar 

  89. Bettini AC, Tondini C, Poletti P, Caremoli ER, Guerra U, Labianca R (2008) A case of interstitial pneumonitis associated with Guillain-Barre syndrome during administration of adjuvant trastuzumab. Tumori 94(5):737–741

    PubMed  Google Scholar 

  90. Pepels MJ, Boomars KA, van Kimmenade R, Hupperets PS (2009) Life-threatening interstitial lung disease associated with trastuzumab: case report. Breast Cancer Res Treat 113(3):609–612. doi:10.1007/s10549-008-9966-8

    CAS  PubMed  Google Scholar 

  91. Cortes J, O’Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, Chollet P, Manikas A, Dieras V, Delozier T, Vladimirov V, Cardoso F, Koh H, Bougnoux P, Dutcus CE, Seegobin S, Mir D, Meneses N, Wanders J, Twelves C (2011) Eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet 377(9769):914–923. doi:10.1016/S0140-6736(11)60070-6

    CAS  PubMed  Google Scholar 

  92. Swami U, Chaudhary I, Ghalib MH, Goel S (2012) Eribulin—a review of preclinical and clinical studies. Crit Rev Oncol Hematol 81(2):163–184. doi:10.1016/j.critrevonc.2011.03.002

    PubMed Central  PubMed  Google Scholar 

  93. Aogi K, Iwata H, Masuda N, Mukai H, Yoshida M, Rai Y, Taguchi K, Sasaki Y, Takashima S (2012) A phase II study of eribulin in Japanese patients with heavily pretreated metastatic breast cancer. Ann Oncol 23(6):1441–1448. doi:10.1093/annonc/mdr444

    CAS  PubMed  Google Scholar 

  94. O’Donnell PH, Dolan ME (2009) Cancer pharmacoethnicity: ethnic differences in susceptibility to the effects of chemotherapy. Clin Cancer Res 15(15):4806–4814. doi:10.1158/1078-0432.CCR-09-0344

    PubMed Central  PubMed  Google Scholar 

  95. Mack PC, Gandara DR, Lara PN Jr (2012) Efficacy and toxicity differences in lung cancer populations in the era of clinical trials globalization: the ‘common arm’ approach. Expert Rev Anticancer Ther 12(12):1591–1596. doi:10.1586/era.12.135

    CAS  PubMed  Google Scholar 

  96. Nakagawa M, Nishimura T, Teramukai S, Tada H, Tanaka F, Yanagihara K, Furuse K, Wada H, Fukushima M (2009) Interstitial lung disease in gefitinib-treated Japanese patients with non-small cell lung cancer - a retrospective analysis: JMTO LC03-02. BMC Res Notes 2:157. doi:10.1186/1756-0500-2-157

    PubMed Central  PubMed  Google Scholar 

  97. Kim S, Tannock I, Sridhar S, Seki J, Bordeleau L (2012) Chemotherapy-induced infiltrative pneumonitis cases in breast cancer patients. J Oncol Pharm Pract 18(2):311–315. doi:10.1177/1078155211429384

    PubMed  Google Scholar 

  98. Cook-Bruns N (2001) Retrospective analysis of the safety of herceptin immunotherapy in metastatic breast cancer. Oncology 61(Suppl 2):58–66

    CAS  PubMed  Google Scholar 

  99. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353(16):1673–1684. doi:10.1056/NEJMoa052122

    CAS  PubMed  Google Scholar 

  100. Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Dieras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K (2012) Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 367(19):1783–1791. doi:10.1056/NEJMoa1209124

    CAS  PubMed  Google Scholar 

  101. Krop IE, LoRusso P, Miller KD, Modi S, Yardley D, Rodriguez G, Guardino E, Lu M, Zheng M, Girish S, Amler L, Winer EP, Rugo HS (2012) A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. J Clin Oncol 30(26):3234–3241. doi:10.1200/JCO.2011.40.5902

    CAS  PubMed  Google Scholar 

  102. Burris HA III, Rugo HS, Vukelja SJ, Vogel CL, Borson RA, Limentani S, Tan-Chiu E, Krop IE, Michaelson RA, Girish S, Amler L, Zheng M, Chu YW, Klencke B, O’Shaughnessy JA (2011) Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol 29(4):398–405. doi:10.1200/JCO.2010.29.5865

    CAS  PubMed  Google Scholar 

  103. Yip AY, Tse LA, Ong EY, Chow LW (2010) Survival benefits from lapatinib therapy in women with HER2-overexpressing breast cancer: a systematic review. Anticancer Drugs 21(5):487–493. doi:10.1097/CAD.0b013e3283388eaf

    CAS  PubMed  Google Scholar 

  104. Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O’Rourke L, Oliva C, Stein S, Pegram M (2009) Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol 27(33):5538–5546. doi:10.1200/JCO.2009.23.3734

    CAS  PubMed  Google Scholar 

  105. Capri G, Chang J, Chen SC, Conte P, Cwiertka K, Jerusalem G, Jiang Z, Johnston S, Kaufman B, Link J, Ro J, Schutte J, Oliva C, Parikh R, Preston A, Rosenlund J, Selzer M, Zembryki D, De Placido S (2010) An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer. Ann Oncol 21(3):474–480. doi:10.1093/annonc/mdp373

    CAS  PubMed  Google Scholar 

  106. Peterson ME (2013) Management of adverse events in patients with hormone receptor-positive breast cancer treated with everolimus: observations from a phase III clinical trial. Support Care Cancer 21(8):2341–2349. doi:10.1007/s00520-013-1826-3

    PubMed Central  PubMed  Google Scholar 

  107. Iacovelli R, Palazzo A, Mezi S, Morano F, Naso G, Cortesi E (2012) Incidence and risk of pulmonary toxicity in patients treated with mTOR inhibitors for malignancy. A meta-analysis of published trials. Acta Oncol 51(7):873–879. doi:10.3109/0284186X.2012.705019

    CAS  PubMed  Google Scholar 

  108. Jerusalem G, Fasolo A, Dieras V, Cardoso F, Bergh J, Vittori L, Zhang Y, Massacesi C, Sahmoud T, Gianni L (2011) Phase I trial of oral mTOR inhibitor everolimus in combination with trastuzumab and vinorelbine in pre-treated patients with HER2-overexpressing metastatic breast cancer. Breast Cancer Res Treat 125(2):447–455. doi:10.1007/s10549-010-1260-x

    CAS  PubMed  Google Scholar 

  109. Schwarzlose-Schwarck S, Scholz CW, Regierer AC, Martus P, Neumann C, Habbel P, Liu H, Zang C, Schefe JH, Schulz CO, Possinger K, Eucker J (2012) The mTOR inhibitor everolimus in combination with carboplatin in metastatic breast cancer—a phase I trial. Anticancer Res 32(8):3435–3441

    CAS  PubMed  Google Scholar 

  110. Moulder S, Gladish G, Ensor J, Gonzalez-Angulo AM, Cristofanilli M, Murray JL, Booser D, Giordano SH, Brewster A, Moore J, Rivera E, Hortobagyi GN, Tran HT (2012) A phase 1 study of weekly everolimus (RAD001) in combination with docetaxel in patients with metastatic breast cancer. Cancer 118(9):2378–2384. doi:10.1002/cncr.26571

    CAS  PubMed Central  PubMed  Google Scholar 

  111. Morrow PK, Wulf GM, Ensor J, Booser DJ, Moore JA, Flores PR, Xiong Y, Zhang S, Krop IE, Winer EP, Kindelberger DW, Coviello J, Sahin AA, Nunez R, Hortobagyi GN, Yu D, Esteva FJ (2011) Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. J Clin Oncol 29(23):3126–3132. doi:10.1200/JCO.2010.32.2321

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Andre F, Campone M, O’Regan R, Manlius C, Massacesi C, Sahmoud T, Mukhopadhyay P, Soria JC, Naughton M, Hurvitz SA (2010) Phase I study of everolimus plus weekly paclitaxel and trastuzumab in patients with metastatic breast cancer pretreated with trastuzumab. J Clin Oncol 28(34):5110–5115. doi:10.1200/JCO.2009.27.8549

    CAS  PubMed  Google Scholar 

  113. Dabydeen DA, Jagannathan JP, Ramaiya N, Krajewski K, Schutz FA, Cho DC, Pedrosa I, Choueiri TK (2012) Pneumonitis associated with mTOR inhibitors therapy in patients with metastatic renal cell carcinoma: incidence, radiographic findings and correlation with clinical outcome. Eur J Cancer 48(10):1519–1524. doi:10.1016/j.ejca.2012.03.012

    CAS  PubMed  Google Scholar 

  114. Soria JC, Shepherd FA, Douillard JY, Wolf J, Giaccone G, Crino L, Cappuzzo F, Sharma S, Gross SH, Dimitrijevic S, Di Scala L, Gardner H, Nogova L, Papadimitrakopoulou V (2009) Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors. Ann Oncol 20(10):1674–1681. doi:10.1093/annonc/mdp060

    PubMed  Google Scholar 

  115. White DA, Schwartz LH, Dimitrijevic S, Scala LD, Hayes W, Gross SH (2009) Characterization of pneumonitis in patients with advanced non-small cell lung cancer treated with everolimus (RAD001). J Thorac Oncol 4(11):1357–1363. doi:10.1097/JTO.0b013e3181ba20b1

    PubMed  Google Scholar 

  116. Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Oberg K (2011) Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 364(6):514–523. doi:10.1056/NEJMoa1009290

    CAS  PubMed  Google Scholar 

  117. Yao JC, Lombard-Bohas C, Baudin E, Kvols LK, Rougier P, Ruszniewski P, Hoosen S, St Peter J, Haas T, Lebwohl D, Van Cutsem E, Kulke MH, Hobday TJ, O’Dorisio TM, Shah MH, Cadiot G, Luppi G, Posey JA, Wiedenmann B (2010) Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol 28(1):69–76. doi:10.1200/JCO.2009.24.2669

    CAS  PubMed  Google Scholar 

  118. Pavel ME, Hainsworth JD, Baudin E, Peeters M, Horsch D, Winkler RE, Klimovsky J, Lebwohl D, Jehl V, Wolin EM, Oberg K, Van Cutsem E, Yao JC (2011) Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet 378(9808):2005–2012. doi:10.1016/S0140-6736(11)61742-X

    CAS  PubMed  Google Scholar 

  119. Ito Y, Noguchi S, Deleu I, Baselga J, Hortobagyi GN, Bachelot TD, Masuda N, Pistilli B, Pritchard KI, Iwata H, Gnant M, Eakle JF, Csõszi T, Srimuninnimit V, Puttawibul P, Roila F, Panneerselvam A, Taran T, Sahmoud T, Rugo HS (2013) Incidence, management, and resolution of noninfectious pneumonitis in BOLERO-2. J Clin Oncol 31, 2013 (suppl; abstr 561)

  120. Common Terminology Criteria for Adverse Events (CTCAE) (2009) http://www.acrin.org/Portals/0/Administration/Regulatory/CTCAE_4.02_2009-09-15_QuickReference_5x7.pdf

  121. Yazbeck VY, Villaruz L, Haley M, Socinski MA (2013) Management of normal tissue toxicity associated with chemoradiation (primary skin, esophagus, and lung). Cancer J 19(3):231–237. doi:10.1097/PPO.0b013e31829453fb

    CAS  PubMed  Google Scholar 

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Omarini, C., Thanopoulou, E. & Johnston, S.R.D. Pneumonitis and pulmonary fibrosis associated with breast cancer treatments. Breast Cancer Res Treat 146, 245–258 (2014). https://doi.org/10.1007/s10549-014-3016-5

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