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Part of the book series: Practical Guides in Radiation Oncology ((PGRO))

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Abstract

Breast cancer is the most common malignancy of females in the United States with an estimated incidence of >230,000 in 2015 [1]. Radiation therapy plays an important role in prevention of locoregional and distant recurrence which can translate into improvements in overall survival with long-term follow-up [2–4]. Proton radiotherapy offers the potential ability to spare critical strutures and thus potential toxicity while maximizing target coverage. Here we review the data for proton radiation in breast cancer and techniques for its delivery in various clinical settings.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29. https://doi.org/10.3322/caac.21254.

    Article  PubMed  Google Scholar 

  2. Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong J-H, Wolmark N. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347:1233–41. https://doi.org/10.1056/NEJMoa022152.

    Article  PubMed  Google Scholar 

  3. Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, Godwin J, Gray R, Hicks C, James S, Mac Kinnon E, Mc Gale P, Mc Hugh T, Peto R, Taylor C, Wang Y, Early Breast Cancer Trialists' Collaborative Group (EBCTCG). 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. 2005;366:2087–106. https://doi.org/10.1016/S0140-6736(05)67887-7.

    Article  CAS  PubMed  Google Scholar 

  4. EBCTCG (Early Breast Cancer Trialists' Collaborative Group), Mc Gale P, Taylor C, Correa C, Cutter D, Duane F, Ewertz M, Gray R, Mannu G, Peto R, Whelan T, Wang Y, Wang Z, Darby S. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014;383:2127–35. https://doi.org/10.1016/S0140-6736(14)60488-8.

    Article  Google Scholar 

  5. Whelan TJ, Olivotto IA, Parulekar WR, Ackerman I, Chua BH, Nabid A, Vallis KA, White JR, Rousseau P, Fortin A, Pierce LJ, Manchul L, Chafe S, Nolan MC, Craighead P, Bowen J, Mc Cready DR, Pritchard KI, Gelmon K, Murray Y, Chapman J-AW, Chen BE, Levine MN, MA.20 Study Investigators. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373:307–16. https://doi.org/10.1056/NEJMoa1415340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Poortmans PM, Collette S, Kirkove C, Van Limbergen E, Budach V, Struikmans H, Collette L, Fourquet A, Maingon P, Valli M, De Winter K, Marnitz S, Barillot I, Scandolaro L, Vonk E, Rodenhuis C, Marsiglia H, Weidner N, van Tienhoven G, Glanzmann C, Kuten A, Arriagada R, Bartelink H, Van den Bogaert W, EORTC Radiation Oncology and Breast Cancer Groups. Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med. 2015;373:317–27. https://doi.org/10.1056/NEJMoa1415369.

    Article  CAS  PubMed  Google Scholar 

  7. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, Correa C, Cutter D, Gagliardi G, Gigante B, Jensen M-B, Nisbet A, Peto R, Rahimi K, Taylor C, Hall P. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013;368:987–98. https://doi.org/10.1056/NEJMoa1209825.

    Article  CAS  PubMed  Google Scholar 

  8. Liljegren G, Holmberg L, Bergh J, Lindgren A, Tabár L, Nordgren H, Adami HO. 10-year results after sector resection with or without postoperative radiotherapy for stage I breast cancer: a randomized trial. J Clin Oncol. 1999;17:2326–33.

    Article  CAS  PubMed  Google Scholar 

  9. Veronesi U, Marubini E, Mariani L, Galimberti V, Luini A, Veronesi P, Salvadori B, Zucali R. Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term results of a randomized trial. Ann Oncol. 2001;12:997–1003.

    Article  CAS  PubMed  Google Scholar 

  10. Strnad V, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, Lyczek J, Guinot JL, Dunst J, Gutierrez Miguelez C, Slampa P, Allgäuer M, Lössl K, Polat B, Kovács G, Fischedick A-R, Wendt TG, Fietkau R, Hindemith M, Resch A, Kulik A, Arribas L, Niehoff P, Guedea F, Schlamann A, Pötter R, Gall C, Malzer M, Uter W, Polgár C, Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial. Lancet. 2016;387:229–38. https://doi.org/10.1016/S0140-6736(15)00471-7.

    Article  PubMed  Google Scholar 

  11. Smith BD, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH, Julian TB, Marks LB, Todor DA, Vicini FA, Whelan TJ, White J, Wo JY, Harris JR. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Int J Radiat Oncol Biol Phys. 2009;74(4):987–1001.

    Article  PubMed  Google Scholar 

  12. Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Keshtgar M, Flyger HL, Massarut S, Alvarado M, Saunders C, Eiermann W, Metaxas M, Sperk E, Sütterlin M, Brown D, Esserman L, Roncadin M, Thompson A, Dewar JA, Holtveg HMR, Pigorsch S, Falzon M, Harris E, Matthews A, Brew-Graves C, Potyka I, Corica T, Williams NR, Baum M, TARGIT trialists' group. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet. 2014;383:603–13. https://doi.org/10.1016/S0140-6736(13)61950-9.

    Article  PubMed  Google Scholar 

  13. Olivotto IA, Whelan TJ, Parpia S, Kim D-H, Berrang T, Truong PT, Kong I, Cochrane B, Nichol A, Roy I, Germain I, Akra M, Reed M, Fyles A, Trotter T, Perera F, Beckham W, Levine MN, Julian JA. Interim cosmetic and toxicity results from RAPID: a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J Clin Oncol. 2013;31:4038–45. https://doi.org/10.1200/JCO.2013.50.5511.

    Article  PubMed  Google Scholar 

  14. Liss AL, Ben-David MA, Jagsi R, Hayman JA, Griffith KA, Moran JM, Marsh RB, Pierce LJ. Decline of cosmetic outcomes following accelerated partial breast irradiation using intensity modulated radiation therapy: results of a single-institution prospective clinical trial. Int J Radiat Oncol Biol Phys. 2014;89:96–102. https://doi.org/10.1016/j.ijrobp.2014.01.005.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Hepel JT, Tokita M, MacAusland SG, Evans SB, Hiatt JR, Price LL, DiPetrillo T, Wazer DE. Toxicity of three-dimensional conformal radiotherapy for accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys. 2009;75:1290–6. https://doi.org/10.1016/j.ijrobp.2009.01.009.

    Article  PubMed  Google Scholar 

  16. Leonard KL, Hepel JT, Hiatt JR, Dipetrillo TA, Price LL, Wazer DE. The effect of dose-volume parameters and interfraction interval on cosmetic outcome and toxicity after 3-dimensional conformal accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys. 2013;85:623–9. https://doi.org/10.1016/j.ijrobp.2012.06.052.

    Article  PubMed  Google Scholar 

  17. Peterson D, Truong PT, Parpia S, Olivotto IA, Berrang T, Kim D-H, Kong I, Germain I, Nichol A, Akra M, Roy I, Reed M, Fyles A, Trotter T, Perera F, Balkwill S, Lavertu S, Elliott E, Julian JA, Levine MN, Whelan TJ, RAPID trial investigators. Predictors of adverse cosmetic outcome in the RAPID trial: an exploratory analysis. Int J Radiat Oncol Biol Phys. 2015;91:968–76. https://doi.org/10.1016/j.ijrobp.2014.12.040.

    Article  PubMed  Google Scholar 

  18. Livi L, Meattini I, Marrazzo L, Simontacchi G, Pallotta S, Saieva C, Paiar F, Scotti V, De Luca CC, Bastiani P, Orzalesi L, Casella D, Sanchez L, Nori J, Fambrini M, Bianchi S. Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer. 2015;51:451–63. https://doi.org/10.1016/j.ejca.2014.12.013.

    Article  PubMed  Google Scholar 

  19. Formenti SC, Hsu H, Fenton-Kerimian M, Roses D, Guth A, Jozsef G, Goldberg JD, Dewyngaert JK. Prone accelerated partial breast irradiation after breast-conserving surgery: five-year results of 100 patients. Int J Radiat Oncol Biol Phys. 2012;84:606–11. https://doi.org/10.1016/j.ijrobp.2012.01.039.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Taghian AG, Kozak KR, Katz A, Adams J, Lu H-M, Powell SN, Delaney TF. Accelerated partial breast irradiation using proton beams: initial dosimetric experience. Int J Radiat Oncol Biol Phys. 2006;65:1404–10. https://doi.org/10.1016/j.ijrobp.2006.03.017.

    Article  PubMed  Google Scholar 

  21. Moon SH, Shin KH, Kim TH, Yoon M, Park S, Lee D-H, Kim JW, Kim DW, Park SY, Cho KH. Dosimetric comparison of four different external beam partial breast irradiation techniques: three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, helical tomotherapy, and proton beam therapy. Radiother Oncol. 2009;90:66–73. https://doi.org/10.1016/j.radonc.2008.09.027.

    Article  PubMed  Google Scholar 

  22. Galland-Girodet S, Pashtan I, MacDonald SM, Ancukiewicz M, Hirsch AE, Kachnic LA, Specht M, Gadd M, Smith BL, Powell SN, Recht A, Taghian AG. Long-term cosmetic outcomes and toxicities of proton beam therapy compared with photon-based 3-dimensional conformal accelerated partial-breast irradiation: a phase 1 trial. Int J Radiat Oncol Biol Phys. 2014;90:493–500. https://doi.org/10.1016/j.ijrobp.2014.04.008.

    Article  PubMed  Google Scholar 

  23. Chang JH, Lee NK, Kim JY, Kim Y-J, Moon SH, Kim TH, Kim J-Y, Kim DY, Cho KH, Shin KH. Phase II trial of proton beam accelerated partial breast irradiation in breast cancer. Radiother Oncol. 2013;108:209–14. https://doi.org/10.1016/j.radonc.2013.06.008.

    Article  CAS  PubMed  Google Scholar 

  24. Bush DA, Slater JD, Garberoglio C, Do S, Lum S, Slater JM. Partial breast irradiation delivered with proton beam: results of a phase II trial. Clin Breast Cancer. 2011;11:241–5. https://doi.org/10.1016/j.clbc.2011.03.023.

    Article  PubMed  Google Scholar 

  25. Bush DA, Do S, Lum S, Garberoglio C, Mirshahidi H, Patyal B, Grove R, Slater JD. Partial breast radiation therapy with proton beam: 5-year results with cosmetic outcomes. Int J Radiat Oncol Biol Phys. 2014;90:501–5. https://doi.org/10.1016/j.ijrobp.2014.05.1308.

    Article  PubMed  Google Scholar 

  26. Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, Kamby C, Kjaer M, Gadeberg CC, Rasmussen BB, Blichert-Toft M, Mouridsen HT. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish breast cancer cooperative group DBCG 82c randomised trial. Lancet. 1999;353:1641–8. https://doi.org/10.1016/S0140-6736(98)09201-0.

    Article  CAS  PubMed  Google Scholar 

  27. Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen MB, Zedeler K. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish breast cancer cooperative group 82b trial. N Engl J Med. 1997;337:949–55. https://doi.org/10.1056/NEJM199710023371401.

    Article  CAS  PubMed  Google Scholar 

  28. Thorsen LBJ, Offersen BV, Danø H, Berg M, Jensen I, Pedersen AN, Zimmermann SJ, Brodersen H-J, Overgaard M, Overgaard J. DBCG-IMN: a population-based cohort study on the effect of internal mammary node irradiation in early node-positive breast cancer. J Clin Oncol. 2016;34:314–20. https://doi.org/10.1200/JCO.2015.63.6456.

    Article  PubMed  Google Scholar 

  29. Ares C, Khan S, Macartain AM, Heuberger J, Goitein G, Gruber G, Lutters G, Hug EB, Bodis S, Lomax AJ. Postoperative proton radiotherapy for localized and locoregional breast cancer: potential for clinically relevant improvements? Int J Radiat Oncol Biol Phys. 2010;76:685–97. https://doi.org/10.1016/j.ijrobp.2009.02.062.

    Article  PubMed  Google Scholar 

  30. MacDonald SM, Jimenez R, Paetzold P, Adams J, Beatty J, Delaney TF, Kooy H, Taghian AG, Lu H-M. Proton radiotherapy for chest wall and regional lymphatic radiation; dose comparisons and treatment delivery. Radiat Oncol. 2013;8:71. https://doi.org/10.1186/1748-717X-8-71.

    Article  PubMed  PubMed Central  Google Scholar 

  31. MacDonald SM, Patel SA, Hickey S, Specht M, Isakoff SJ, Gadd M, Smith BL, Yeap BY, Adams J, Delaney TF, Kooy H, Lu H-M, Taghian AG. Proton therapy for breast cancer after mastectomy: early outcomes of a prospective clinical trial. Int J Radiat Oncol Biol Phys. 2013;86:484–90. https://doi.org/10.1016/j.ijrobp.2013.01.038.

    Article  PubMed  Google Scholar 

  32. Mast ME, Vredeveld EJ, Credoe HM, van Egmond J, Heijenbrok MW, Hug EB, Kalk P, van Kempen-Harteveld LML, Korevaar EW, van der Laan HP, Langendijk JA, Rozema HJE, Petoukhova AL, Schippers JM, Struikmans H, Maduro JH. Whole breast proton irradiation for maximal reduction of heart dose in breast cancer patients. Breast Cancer Res Treat. 2014;148:33–9. https://doi.org/10.1007/s10549-014-3149-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Xu N, Ho MW, Li Z, Morris CG, Mendenhall NP. Can proton therapy improve the therapeutic ratio in breast cancer patients at risk for nodal disease? Am J Clin Oncol. 2014;37:568–74. https://doi.org/10.1097/COC.0b013e318280d614.

    Article  PubMed  Google Scholar 

  34. Bradley JA, Dagan R, Ho MW, Rutenberg M, Morris CG, Li Z, Mendenhall NP. Initial report of a prospective Dosimetric and clinical feasibility trial demonstrates the potential of protons to increase the therapeutic ratio in breast cancer compared with photons. Int J Radiat Oncol Biol Phys. 2016;95:411–21. https://doi.org/10.1016/j.ijrobp.2015.09.018.

    Article  PubMed  Google Scholar 

  35. Lin LL, Vennarini S, Dimofte A, Ravanelli D, Shillington K, Batra S, Tochner Z, Both S, Freedman G. Proton beam versus photon beam dose to the heart and left anterior descending artery for left-sided breast cancer. Acta Oncol. 2015;54:1032–9. https://doi.org/10.3109/0284186X.2015.1011756.

    Article  CAS  PubMed  Google Scholar 

  36. Taylor CW, Wang Z, Macaulay E, Jagsi R, Duane F, Darby SC. Exposure of the heart in breast cancer radiation therapy: a systematic review of heart doses published during 2003 to 2013. Int J Radiat Oncol Biol Phys. 2015;93:845–53. https://doi.org/10.1016/j.ijrobp.2015.07.2292.

    Article  PubMed  Google Scholar 

  37. Cuaron JJ, Chon B, Tsai H, Goenka A, DeBlois D, Ho A, Powell S, Hug E, Cahlon O. Early toxicity in patients treated with postoperative proton therapy for locally advanced breast cancer. Int J Radiat Oncol Biol Phys. 2015;92:284–91. https://doi.org/10.1016/j.ijrobp.2015.01.005.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Fagundes MA, Pankuch M, Hartsell W, Ward C, Fang LC, Cahlon O, McNeeley S, Mao L, Lavilla M, Hug E. Cardiac-sparing Postmastectomy proton radiation therapy for women with stage III, loco-regional, breast cancer: a Dosimetric comparison study. Int J Radiat Oncol Biol Phys. 2013;87:S245. https://doi.org/10.1016/j.ijrobp.2013.06.637.

    Article  Google Scholar 

  39. Brown LC, Diehn FE, Boughey JC, Childs SK, Park SS, Yan ES, Petersen IA, Mutter RW. Delineation of supraclavicular target volumes in breast cancer radiation therapy. Int J Radiat Oncol Biol Phys. 2015;92:642–9. https://doi.org/10.1016/j.ijrobp.2015.02.022.

    Article  PubMed  Google Scholar 

  40. White BM, Vennarini S, Lin L, Freedman G, Santhanam A, Low DA, Both S. Accuracy of routine treatment planning 4-dimensional and deep-inspiration breath-hold computed tomography delineation of the left anterior descending artery in radiation therapy. Int J Radiat Oncol Biol Phys. 2015;91:825–31. https://doi.org/10.1016/j.ijrobp.2014.11.036.

    Article  PubMed  Google Scholar 

  41. Vargo JA, Beriwal S. RTOG Chest Wall contouring guidelines for post-mastectomy radiation therapy: is it evidence-based? Int J Radiat Oncol Biol Phys. 2015;93:266–7. https://doi.org/10.1016/j.ijrobp.2015.03.001.

    Article  PubMed  Google Scholar 

  42. Depauw N, Batin E, Daartz J, Rosenfeld A, Adams J, Kooy H, MacDonald S, Lu H-M. A novel approach to postmastectomy radiation therapy using scanned proton beams. Int J Radiat Oncol Biol Phys. 2015;91:427–34. https://doi.org/10.1016/j.ijrobp.2014.10.039.

    Article  PubMed  Google Scholar 

  43. Moyers MF, Mah D, Boyer SP, Chang C, Pankuch M. Use of proton beams with breast prostheses and tissue expanders. Med Dosim. 2014;39:98–101. https://doi.org/10.1016/j.meddos.2013.10.006.

    Article  PubMed  Google Scholar 

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Correspondence to Oren Cahlon .

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Samstein, R., DeBlois, D., Mutter, R.W., Cahlon, O. (2018). Breast Cancer. In: Lee, N., et al. Target Volume Delineation and Treatment Planning for Particle Therapy. Practical Guides in Radiation Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-42478-1_17

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