Skip to main content
SpringerLink
Log in

Concomitant Radiation and Systemic Therapy in the Adjuvant and Metastatic Setting

  • Chapter
  • First Online:
Breast Cancer Radiation Therapy

  • 606 Accesses

Abstract

More than 80% of patients affected by breast cancer are expected to require radiation therapy (RT) at some time during their disease course. Data regarding concurrent administration of the RT and systemic agents in terms of timing (concurrent, sequential), efficacy, and safety are still scarce. Old fashioned anticancer drugs such as anthracyclines and taxanes, but also fluoropyrimidines, still represent the mainstream for the systemic treatment of high-risk patients with breast cancer both in the preoperative and adjuvant setting, although combining RT with such agents remains controversial, and appears to hit the plateau with respect to efficacy and safety, mainly because of concerns on potential increase in skin and hematological toxicity. Novel (targeted) drugs and immunotherapy are increasingly being integrated into standards of care in patients with breast cancer and new drug-RT combinations are being explored. Technical improvements, including 3D-based adjuvant RT for breast cancer, the use of IMRT/VMAT for more complex target volumes, SBRT/SRS for metastasis and the use of IGRT, allow to deliver RT with a high anatomical precision, and reduce the doses to non-target volumes. Therefore, potentially lead to improvement of the therapeutic index in case of RT combined with systemic therapy. In this chapter, a summary of the current available literature regarding safety and efficacy of the concurrent administration of chemotherapy, novel drugs, immunotherapy, and endocrine therapy with RT is reported, aiming to analyze all the potential critical points and to provide important information for clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. NCI Dictionary of Cancer Terms. https://www.cancer.gov/publications/dictionaries/cancer-terms.

  2. Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, Kuroi K, Im SA, Park BW, Kim SB, Yanagita Y, Ohno S, Takao S, Aogi K, Iwata H, Jeong J, Kim A, Park KH, Sasano H, Ohashi Y, Toi M. Adjuvant Capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017;376:2147–59. https://doi.org/10.1056/NEJMoa1612645.

    Article  CAS  PubMed  Google Scholar 

  3. NCCN breast cancer guidelines, v4.2020. https://www.nccn.org/guidelines/category_1.

  4. Sherry AD, Mayer IA, Ayala-Peacock DN, Abramson VG, Rexer BN, Chakravarthy AB. Combining adjuvant radiotherapy with Capecitabine in chemotherapy-resistant breast cancer: feasibility, safety, and toxicity. Clin Breast Cancer. 2020 Aug;20(4):344–52. https://doi.org/10.1016/j.clbc.2020.02.010.

    Article  CAS  PubMed  Google Scholar 

  5. Liu YL, Chin C, Catanese B, Lee SM, Zhan S, Kalinsky K, Connolly EP. Concurrent use of capecitabine with radiation therapy and survival in breast cancer (BC) after neoadjuvant chemotherapy. Clin Transl Oncol. 2018;20(10):1280–8. https://doi.org/10.1007/s12094-018-1859-7.

    Article  CAS  PubMed  Google Scholar 

  6. Bollet MA, Sigal-Zafrani B, Gambotti L, Extra JM, Meunier M, Nos C, Dendale R, Campana F, Kirova YM, Diéras V, Fourquet A, on behalf of the Institut Curie Breast Cancer Study Group. Pathological response to preoperative concurrent chemo-radiotherapy for breast cancer: results of a phase II study. Eur J Cancer. 2006;42:2286–95.

    Article  CAS  Google Scholar 

  7. Kosma L, Koukourakis M, Skarlatos J, Zambatis C, Ardavanis A, Beroukas K, Yannakakis D. Hypofractionated radiotherapy with 5-fluorouracil radiosensitization for locally “far advanced” breast cancer. Am J Clin Oncol. 1997;20:562–6. https://doi.org/10.1097/00000421-199712000-00005.

    Article  CAS  PubMed  Google Scholar 

  8. Woodward WA, Fang P, Arriaga L, Gao H, Cohen EN, Reuben JM, Valero V, Le-Petross H, Middleton LP, Babiera GV, Strom EA, Tereffe W, Hoffman K, Smith BD, Buchholz TA, Perkins GH. A phase II study of preoperative Capecitabine and concomitant radiation in women with advanced breast cancer. Int J Radiat Oncol Biol Phys. 2017;99(4):777–83. https://doi.org/10.1016/j.ijrobp.2017.04.030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ismaili N, Elmajjaoui S, Lalya I, Lamia Boulaamane L, Belbaraka R, Abahssain H, Aassab R, Benjaafar N, El Guddari BEK, El Mesbahi O, Sbitti Y, Ismaili M, Errihani H. Anthracycline and concurrent radiotherapy as adjuvant treatment of operable breast cancer: a retrospective cohort study in a single institution. BMC Res Notes. 2010;3:247. https://doi.org/10.1186/1756-0500-3-247.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Leonardi MC, Morra A, Santoro L, Balduzzi A, Ivaldi GB, Vischioni B, Ferrari A, Fodor C, Dell'Acqua V, Cardinale DM, Cipolla C, Luini A, Colleoni M, Jereczek-Fossa BA, Orecchia R. Nonrandomized comparison between concomitant and sequential chemoradiotherapy with anthracyclines in breast cancer. Tumori. 2015;101(1):64–71. https://doi.org/10.5301/tj.5000218.

    Article  CAS  PubMed  Google Scholar 

  11. Kim DY, Youn JC, Park MS, Lee S, Choi SW, Ryu KH, Kim LS, Shim MS, Lee JJ, Han S. Cardiovascular outcome of breast cancer patients with concomitant radiotherapy and chemotherapy: a 10-year multicenter cohort study. J Cardiol. 2019 Aug;74(2):175–81. https://doi.org/10.1016/j.jjcc.2019.02.001.

    Article  PubMed  Google Scholar 

  12. Fernando IN, Bowden SJ, Herring K, et al. Synchronous versus sequential chemo-radiotherapy in patients with early stage breast cancer (SECRAB): a randomised, phase III, trial. Radiother Oncol. 2020;142:52–61. https://doi.org/10.1016/j.radonc.2019.10.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lange OF, Scheef W, Haase KD, Heckmann M, Leyendecker R, Urban G, Zegners G. Palliative chemo-radiotherapy with ifosfamide and epirubicin as first-line treatment for high-risk metastatic breast cancer. Results of a prospective multicenter trial. Cancer Chemother Pharmacol. 1990;26(Suppl):S74–7. https://doi.org/10.1007/BF00685427.

    Article  PubMed  Google Scholar 

  14. Elmongy M, Stolier A, Linares L, Seiler M. Concurrent use of paclitaxel and radiation therapy for the adjuvant treatment of cancer of the breast [abstract]. Breast Cancer Res Treat. 1999;57:57.

    Google Scholar 

  15. Bellon JR, Lindsley KL, Ellis GK, Gralow JR, Livingston RB, Austin Seymour MM. Concurrent radiation therapy and paclitaxel or docetaxel chemotherapy in high-risk breast cancer. Int J Radiat Oncol Biol Phys. 2000;48:393–7. https://doi.org/10.1016/S0360-3016(00)00636-2.

    Article  CAS  PubMed  Google Scholar 

  16. Taghian AG, Assaad SI, Niemierko A, et al. Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel. J Natl Cancer Inst. 2001;93:1806–11. https://doi.org/10.1093/jnci/93.23.1806.

    Article  CAS  PubMed  Google Scholar 

  17. Hanna YM, Baglan KL, Stromberg JS, Vicini FA, Decker A, D. Acute and subacute toxicity associated with concurrent adjuvant radiation therapy and paclitaxel in primary breast cancer therapy. Breast J. 2002;8:149–53. https://doi.org/10.1046/j.1524-4741.2002.08306.x.

    Article  CAS  PubMed  Google Scholar 

  18. Formenti SC, Volm M, Skinner KA, et al. Preoperative twice-weekly paclitaxel with concurrent radiation therapy followed by surgery and postoperative doxorubicin-based chemotherapy in locally advanced breast cancer: a phase i/ii trial. J Clin Oncol. 2003;21:864–70. https://doi.org/10.1200/JCO.2003.06.132.

    Article  CAS  PubMed  Google Scholar 

  19. Kao J, Conzen SD, Jaskowiak NT, et al. Concomitant radiation therapy and paclitaxel for unresectable locally advanced breast cancer: results from two consecutive phase i/ii trials. Int J Radiat Oncol Biol Phys. 2005;61:1045–53. https://doi.org/10.1016/j.ijrobp.2004.07.714.

    Article  CAS  PubMed  Google Scholar 

  20. Burstein HJ, Bellon JR, Galper S, et al. Prospective evaluation of concurrent paclitaxel and radiation therapy after adjuvant doxorubicin and cyclophosphamide chemotherapy for stage ii or iii breast cancer. Int J Radiat Oncol Biol Phys. 2006;64:496–504. https://doi.org/10.1016/j.ijrobp.2005.07.975.

    Article  CAS  PubMed  Google Scholar 

  21. Chakravarthy AB, Kelley MC, McLaren B, et al. Neoadjuvant concurrent paclitaxel and radiation in stage ii/iii breast cancer. Clin Cancer Res. 2006;12:1570–6. https://doi.org/10.1158/1078-0432.CCR-05-2304.

    Article  CAS  PubMed  Google Scholar 

  22. Chen WC, Kim J, Kim E, et al. A phase ii study of radiotherapy and concurrent paclitaxel chemotherapy in breast-conserving treatment for node-positive breast cancer. Int J Radiat Oncol Biol Phys. 2012;82:14–20. https://doi.org/10.1016/j.ijrobp.2010.08.051.

    Article  CAS  PubMed  Google Scholar 

  23. Ellerbroek N, Martino S, Mautner B, Tao ML, Rose C, Botnick L. Breast-conserving therapy with adjuvant paclitaxel and radiation therapy: feasibility of concurrent treatment. Breast J. 2003;9:74–8. https://doi.org/10.1046/j.1524-4741.2003.09203.x.

    Article  PubMed  Google Scholar 

  24. Cai G, Cao L, Kirova YM, Feng Y, Chen JY. Prospective results of concurrent radiation therapy and weekly paclitaxel as salvage therapy for unre sectable locoregionally recurrent breast cancer. Radiat Oncol. 2019;14:115. https://doi.org/10.1186/s13014-019-1321-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Semrau S, Gerber B, Reimer T, Klautke G, Fietkau R. Concurrent radiotherapy and Taxane chemotherapy in patients with Locoregional recurrence of breast cancer. Strahlenther Onkol. 2006;182(10)):596–603. https://doi.org/10.1007/s00066-006-1549-1.

    Article  PubMed  Google Scholar 

  26. Kokufu I, Tanei T, Taniguchi H, Kimura F, Fukuda K, Yamamoto M, Yano T, Yamada K, Tamaoka K, Hosono M. Two cases of effective weekly paclitaxel administration and concurrent radiation for metastatic breast cancer. Gan To Kagaku Ryoho. 2003 Jan;30(1):111–4.

    PubMed  Google Scholar 

  27. Cardoso F, Paluch-Shimon S, Senkus E, Curigliano G, Aapro MS, André F, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5)†. Ann Oncol. 2020;31(12):1623–49. https://doi.org/10.1016/j.annonc.2020.09.010.

    Article  CAS  PubMed  Google Scholar 

  28. Xu H, Yu S, Liu Q, Yuan X, Mani S, Pestell RG, et al. Recent advances of highly selective CDK4/6 inhibitors in breast cancer. J Hematol Oncol. 2017;10 https://doi.org/10.1186/s13045-017-0467-2.

  29. Bernhard EJ, Maity A, Muschel RJ, McKenna WG. Effects of ionizing radiation on cell cycle progression - a review. Radiat Environ Biophys. 1995;34:79–83. https://doi.org/10.1007/BF01275210.

    Article  CAS  PubMed  Google Scholar 

  30. Sharda N, Yang C-R, Kinsella T, Boothman D. Radiation Resistance. Encycl Cancer. 2002:1–11. https://doi.org/10.1016/b0-12-227555-1/00519-0.

  31. Hashizume R, Zhang A, Mueller S, Prados MD, Lulla RR, Goldman S, et al. Inhibition of DNA damage repair by the CDK4/6 inhibitor palbociclib delays irradiated intracranial atypical teratoid rhabdoid tumor and glioblastoma xenograft regrowth. Neuro-Oncology. 2016;18:1519–28. https://doi.org/10.1093/neuonc/now106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Beddok A, Xu HP, Henry AA, Porte B, Fourquet A, Cottu P, et al. Concurrent use of palbociclib and radiation therapy: single-Centre experience and review of the literature. Br J Cancer. 2020;123:905–8. https://doi.org/10.1038/s41416-020-0957-9.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Messer JA, Ekinci E, Patel TA, Teh BS. Enhanced dermatologic toxicity following concurrent treatment with palbociclib and radiation therapy: a case report. Reports Pract Oncol Radiother. 2019;24:276–80. https://doi.org/10.1016/j.rpor.2019.03.001.

    Article  Google Scholar 

  34. Nasir UM, Mozeika AM, Sayan M, Jan I, Kowal N, Haffty B, et al. Severe gastrointestinal mucositis following concurrent palbociclib and palliative radiation therapy. Anticancer Res. 2020;40:5291–4. https://doi.org/10.21873/anticanres.14534.

    Article  PubMed  Google Scholar 

  35. Kawamoto T, Shikama N, Sasai K. Severe acute radiation-induced enterocolitis after combined palbociclib and palliative radiotherapy treatment. Radiother Oncol. 2019;131:240–1. https://doi.org/10.1016/j.radonc.2018.09.020.

    Article  PubMed  Google Scholar 

  36. Dasgupta A, Sahgal A, Warner E, Czarnota GJ. Safety of palbociclib concurrent with palliative pelvic radiotherapy: discussion of a case of increased toxicity and brief review of literature. J Med Radiat Sci. 2020:1–7. https://doi.org/10.1002/jmrs.435.

  37. Kalash R, Iarrobino NA, Beriwal S, Sun M, Glaser SM, Champ CE. Palbociclib enhances pulmonary fibrosis in patients undergoing thoracic radiation therapy: a case series and review of the literature. Int J Radiat Oncol. 2018;102:e610. https://doi.org/10.1016/j.ijrobp.2018.07.1673.

    Article  Google Scholar 

  38. Hans S, Cottu P, Kirova YM. Preliminary results of the association of Palbociclib and radiotherapy in metastatic breast cancer patients. Radiother Oncol. 2018;126:181. https://doi.org/10.1016/j.radonc.2017.09.010.

    Article  PubMed  Google Scholar 

  39. Meattini I, Desideri I, Scotti V, Simontacchi G, Livi L. Ribociclib plus letrozole and concomitant palliative radiotherapy for metastatic breast cancer. Breast. 2018;42:1–2. https://doi.org/10.1016/j.breast.2018.08.096.

    Article  PubMed  Google Scholar 

  40. Figura NB, Potluri TK, Mohammadi H, Oliver DE, Arrington JA, Robinson TJ, et al. CDK 4/6 inhibitors and stereotactic radiation in the management of hormone receptor positive breast cancer brain metastases. J Neuro-Oncol. 2019;144:583–9. https://doi.org/10.1007/s11060-019-03260-6.

    Article  CAS  Google Scholar 

  41. Ippolito E, Greco C, Silipigni S, Dell’Aquila E, Petrianni GM, Tonini G, et al. Concurrent radiotherapy with palbociclib or ribociclib for metastatic breast cancer patients: preliminary assessment of toxicity. Breast. 2019;46:70–4. https://doi.org/10.1016/j.breast.2019.05.001.

    Article  PubMed  Google Scholar 

  42. Chowdhary M, Sen N, Chowdhary A, Usha L, Cobleigh MA, Wang D, et al. Safety and efficacy of Palbociclib and radiation therapy in patients with metastatic breast cancer: initial results of a novel combination. Adv Radiat Oncol. 2019;4:453–7. https://doi.org/10.1016/j.adro.2019.03.011.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Guerini AE, Pedretti S, Salah E, Simoncini EL, Maddalo M, Pegurri L, et al. A single-center retrospective safety analysis of cyclin-dependent kinase 4/6 inhibitors concurrent with radiation therapy in metastatic breast cancer patients. Sci Rep. 2020;10 https://doi.org/10.1038/s41598-020-70430-2.

  44. Ratosa I, Orazem M, Scoccimarro E, Steinacher M, Dominici L, Aquilano M, et al. Cyclin-dependent kinase 4/6 inhibitors combined with radiotherapy for patients with metastatic breast cancer. Clin Breast Cancer. 2020; https://doi.org/10.1016/j.clbc.2020.05.013.

  45. Moja L, Tagliabue L, Balduzzi S, Parmelli E, Pistotti V, Guarneri V, D'Amico R. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev. 2012;4:CD006243. https://doi.org/10.1002/14651858.

    Article  CAS  Google Scholar 

  46. Denduluri N, Chavez-MacGregor M, Telli ML, Eisen A, Graff SL, Hassett MJ, et al. Selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer: ASCO clinical practice guideline focused update. J Clin Oncol. 2018;36(23):2433–43. https://doi.org/10.1200/JCO.2018.78.8604.

    Article  CAS  PubMed  Google Scholar 

  47. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Herceptin adjuvant (HERA) trial study team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659–72. https://doi.org/10.1056/NEJMoa052306.

    Article  CAS  PubMed  Google Scholar 

  48. Mignot F, Ajgal Z, Xu H, Geraud A, Chen JY, Mégnin-Chanet F, Kirova Y. Concurrent administration of anti-HER2 therapy and radiotherapy: systematic review. Radiother Oncol. 2017;124(2):190–9. https://doi.org/10.1016/j.radonc.2017.07.006.

    Article  CAS  PubMed  Google Scholar 

  49. Segovia-Mendoza M, González-González ME, Barrera D, Díaz L, García-Becerra R. Efficacy and mechanism of action of the tyrosine kinase inhibitors gefitinib, lapatinib and neratinib in the treatment of HER2-positive breast cancer: preclinical and clinical evidence. Am J Cancer Res. 2015;5(9):2531–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Kroeze SG, Fritz C, Hoyer M, Lo SS, Ricardi U, Sahgal A, et al. Toxicity of concurrent stereotactic radiotherapy and targeted therapy or immunotherapy: a systematic review. Cancer Treat Rev. 2017;53:25–37. https://doi.org/10.1016/j.ctrv.2016.11.013.

    Article  PubMed  Google Scholar 

  51. Yu T, Cho BJ, Choi EJ, Park JM, Kim DH, Kim IA. Radiosensitizing effect of lapatinib in human epidermal growth factor receptor 2-positive breast cancer cells. Oncotarget. 2016;7(48):79089–100. https://doi.org/10.18632/oncotarget.12597.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Parsai S, Miller JA, Juloori A, Chao ST, Kotecha R, Mohammadi AM, et al. Stereotactic radiosurgery with concurrent lapatinib is associated with improved local control for HER2-positive breast cancer brain metastases. J Neurosurg. 2019;132(2):503–11. https://doi.org/10.3171/2018.10.JNS182340.

    Article  PubMed  Google Scholar 

  53. Kim JM, Miller JA, Kotecha R, Chao ST, Ahluwalia MS, Peereboom DM, et al. Stereotactic radiosurgery with concurrent HER2-directed therapy is associated with improved objective response for breast cancer brain metastasis. Neuro-Oncology. 2019;21(5):659–68. https://doi.org/10.1093/neuonc/noz006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 2008;68:9280–90. https://doi.org/10.1158/0008-5472.CAN-08-1776.

    Article  CAS  PubMed  Google Scholar 

  55. von Minckwitz G, Huang C-S, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab Emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380:617–28. https://doi.org/10.1056/nejmoa1814017.

    Article  CAS  Google Scholar 

  56. Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18:732–42. https://doi.org/10.1016/S1470-2045(17)30312-1.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Stumpf PK, DiM C, Robin TP, Carlson JA, Stuhr KA, Contreras-Zarate MJ, et al. Combination of trastuzumab emtansine and stereotactic radiosurgery results in high rates of clinically significant radionecrosis and dysregulation of aquaporin-4. Clin Cancer Res. 2019;25:3946–53. https://doi.org/10.1158/1078-0432.CCR-18-2851.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Carlson JA, Nooruddin Z, Rusthoven C, Elias A, Borges VF, Diamond JR, et al. Trastuzumab emtansine and stereotactic radiosurgery: an unexpected increase in clinically significant brain edema. Neuro-Oncology. 2014;16:1006–9. https://doi.org/10.1093/neuonc/not329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Geraud A, Xu HP, Beuzeboc P, Kirova YM. Preliminary experience of the concurrent use of radiosurgery and T-DM1 for brain metastases in HER2-positive metastatic breast cancer. J Neuro-Oncol. 2017;131:69–72. https://doi.org/10.1007/s11060-016-2265-z.

    Article  CAS  Google Scholar 

  60. Géraud A, Xu HP, Beuzeboc P, Kirova YM. Preliminary results of the concurrent use of radiotherapy for bone metastases and trastuzumab emtansine in patients with HER2-positive metastatic breast cancer. Cancer/Radiotherapie. 2016;20:312–3. https://doi.org/10.1016/j.canrad.2016.03.010.

    Article  Google Scholar 

  61. Dulaney C, Marcrom S, Stanley J, Yang ES. Poly(ADP-ribose) polymerase activity and inhibition in cancer. Semin Cell Dev Biol. 2017;63:144–53. https://doi.org/10.1016/j.semcdb.2017.01.007.

    Article  CAS  PubMed  Google Scholar 

  62. Césaire M, Thariat J, Candéias SM, Stefan D, Saintigny Y, Chevalier F. Combining PARP inhibition, radiation, and immunotherapy: a possible strategy to improve the treatment of cancer? Int J Mol Sci. 2018;19 https://doi.org/10.3390/ijms19123793.

  63. Loap P, Loirat D, Berger F, Ricci F, Vincent-Salomon A, Ezzili C, et al. Combination of Olaparib and radiation therapy for triple negative breast cancer: preliminary results of the RADIOPARP phase 1 trial. Int J Radiat Oncol Biol Phys. 2021;109(2):436–40. https://doi.org/10.1016/j.ijrobp.2020.09.032.

    Article  PubMed  Google Scholar 

  64. Jagsi R, Griffith KA, Bellon JR, Woodward WA, Horton JK, Ho A, et al. Concurrent veliparib with chest wall and nodal radiotherapy in patients with inflammatory or locoregionally recurrent breast cancer: the TBCRC 024 phase I multicenter study. J Clin Oncol. 2018;36:1317–22. https://doi.org/10.1200/JCO.2017.77.2665.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Manegold PC, Paringer C, Kulka U, Krimmel K, Eichhorn ME, Wilkowski R, et al. Antiangiogenic therapy with mammalian target of rapamycin inhibitor RAD001 (Everolimus) increases radiosensitivity in solid cancer. Clin Cancer Res. 2008;14(3):892–900. https://doi.org/10.1158/1078-0432.CCR-07-0955.

    Article  CAS  PubMed  Google Scholar 

  66. Deutsch E, Le Péchoux C, Faivre L, Rivera S, Tao Y, Pignon JP, et al. Phase I trial of everolimus in combination with thoracic radiotherapy in non-small-cell lung cancer. Ann Oncol. 2015;26(6):1223–9. https://doi.org/10.1093/annonc/mdv105.

    Article  CAS  PubMed  Google Scholar 

  67. Willemsen AE, Grutters JC, Gerritsen WR, van Erp NP, van Herpen CM, Tol J. mTOR inhibitor-induced interstitial lung disease in cancer patients: comprehensive review and a practical management algorithm. Int J Cancer. 2016;138(10):2312–21. https://doi.org/10.1002/ijc.29887.

    Article  CAS  PubMed  Google Scholar 

  68. Bourgier C, Massard C, Moldovan C, Soria JC, Deutsch E. Total recall of radiotherapy with mTOR inhibitors: a novel and potentially frequent side-effect? Ann Oncol. 2011;22(2):485–6. https://doi.org/10.1093/annonc/mdq741.

    Article  CAS  PubMed  Google Scholar 

  69. Ioannidis G, Gkogkou P, Charalampous P, Diamandi M, Ioannou R. Radiation-recall dermatitis with the everolimus/exemestane combination ten years after adjuvant whole-breast radiotherapy. Radiother Oncol. 2014;112(3):449–50. https://doi.org/10.1016/j.radonc.2014.08.030.

    Article  PubMed  Google Scholar 

  70. André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, et al. SOLAR-1 study group. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019;380(20):1929–40. https://doi.org/10.1056/NEJMoa1813904.

    Article  PubMed  Google Scholar 

  71. Rugo HS, André F, Yamashita T, Cerda H, Toledano I, Stemmer SM, et al. Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. Ann Oncol. 2020;31(8):1001–10. https://doi.org/10.1016/j.annonc.2020.05.001.

    Article  CAS  PubMed  Google Scholar 

  72. Day D, Prawira A, Spreafico A, Waldron J, Karithanam R, Giuliani M, et al. Phase I trial of alpelisib in combination with concurrent cisplatin-based chemoradiotherapy in patients with locoregionally advanced squamous cell carcinoma of the head and neck. Oral Oncol. 2020;108:104753. https://doi.org/10.1016/j.oraloncology.2020.104753.

    Article  CAS  PubMed  Google Scholar 

  73. Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, et al. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015;33(6):594–601. https://doi.org/10.1200/JCO.2013.52.4892.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Meattini I, Desideri I, Di Cataldo V, Francolini G, De Luca CC, Scotti V, et al. Safety of eribulin mesylate and concomitant radiotherapy for metastatic breast cancer: a single-center experience. Future Oncol. 2016;12(9):1117–24. https://doi.org/10.2217/fon-2015-0059.

    Article  CAS  PubMed  Google Scholar 

  75. de Bono JS, Molife LR, Sonpavde G, Maroto JP, Calvo E, Cartwright TH, et al. Phase II study of eribulin mesylate (E7389) in patients with metastatic castration-resistant prostate cancer stratified by prior taxane therapy. Ann Oncol. 2012;23(5):1241–9. https://doi.org/10.1093/annonc/mdr380.

    Article  PubMed  Google Scholar 

  76. Chargari C, Levy A, Paoletti X, Soria JC, Massard C, Weichselbaum RR, et al. Methodological development of combination drug and radiotherapy in basic and clinical research. Clin Cancer Res. 2020;26(18):4723–36. https://doi.org/10.1158/1078-0432.CCR-19-4155.

    Article  CAS  PubMed  Google Scholar 

  77. Deutsch E, Chargari C, Galluzzi L, Kroemer G. Optimising efficacy and reducing toxicity of anticancer radioimmunotherapy. Lancet Oncol. 2019;20(8):e452–63. https://doi.org/10.1016/S1470-2045(19)30171-8.

    Article  CAS  PubMed  Google Scholar 

  78. Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, et al. KEYNOTE-522 investigators. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382(9):810–21. https://doi.org/10.1056/NEJMoa1910549.

    Article  CAS  PubMed  Google Scholar 

  79. Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H. IMpassion130 trial investigators. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108–21. https://doi.org/10.1056/NEJMoa1809615.

    Article  CAS  PubMed  Google Scholar 

  80. Schmid P, Rugo HS, Adams S, Schneeweiss A, Barrios CH, Iwata H. IMpassion130 investigators. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21(1):44–59. https://doi.org/10.1016/S1470-2045(19)30689-8.

    Article  CAS  PubMed  Google Scholar 

  81. Ho AY, Barker CA, Arnold BB, Powell SN, Hu ZI, Gucalp A, et al. A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple-negative breast cancer. Cancer. 2020;126(4):850–60. https://doi.org/10.1002/cncr.32599.

    Article  CAS  PubMed  Google Scholar 

  82. Lehrer EJ, Peterson J, Brown PD, Sheehan JP, Quiñones-Hinojosa A, Zaorsky NG, et al. Treatment of brain metastases with stereotactic radiosurgery and immune checkpoint inhibitors: an international meta-analysis of individual patient data. Radiother Oncol. 2019;130:104–12. https://doi.org/10.1016/j.radonc.2018.08.025.

    Article  PubMed  Google Scholar 

  83. Chargari C, Toillon RA, Macdermed D, Castadot P, Magné N. Concurrent hormone and radiation therapy in patients with breast cancer: what is the rationale? Lancet Oncol. 2009;10(1):53–60. https://doi.org/10.1016/S1470-2045(08)70333-4.

    Article  CAS  PubMed  Google Scholar 

  84. McGee SF, Mazzarello S, Caudrelier JM, Lima MAG, Hutton B, Sienkiewicz M, et al. Optimal sequence of adjuvant endocrine and radiation therapy in early-stage breast cancer - a systematic review. Cancer Treat Rev. 2018;69:132–42. https://doi.org/10.1016/j.ctrv.2018.06.015.

    Article  CAS  PubMed  Google Scholar 

  85. Harris EE, Christensen VJ, Hwang WT, Fox K, Solin LJ. Impact of concurrent versus sequential tamoxifen with radiation therapy in early-stage breast cancer patients undergoing breast conservation treatment. J Clin Oncol. 2005;23(1):11–6. https://doi.org/10.1200/JCO.2005.09.056.

    Article  CAS  PubMed  Google Scholar 

  86. Pierce LJ, Hutchins LF, Green SR, Lew DL, Gralow JR, Livingston RB, et al. Sequencing of tamoxifen and radiotherapy after breast-conserving surgery in early-stage breast cancer. J Clin Oncol. 2005;23(1):24–9. https://doi.org/10.1200/JCO.2005.01.198.

    Article  CAS  PubMed  Google Scholar 

  87. Ding J, Guo Y, Jiang X, Li K, Fu W, Cao Y. Concomitant fulvestrant with reirradiation for unresectable locoregional recurrent estrogen receptor positive (ER+) breast cancer: a case report and narrative review. Medicine (Baltimore). 2020;99(30):e21344. https://doi.org/10.1097/MD.0000000000021344.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia

    Ivica Ratosa

  2. Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

    Ivica Ratosa

  3. Radiotherapy Unit, Oncology Department Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy

    Luca Visani

Authors
  1. Ivica Ratosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luca Visani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ivica Ratosa .

Editor information

Editors and Affiliations

  1. Radiation Oncology Unit, Sheba Medical Center, Ramat Gan, Israel

    Orit Kaidar-Person

  2. Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

    Icro Meattini

  3. Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium

    Philip Poortmans

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ratosa, I., Visani, L. (2022). Concomitant Radiation and Systemic Therapy in the Adjuvant and Metastatic Setting. In: Kaidar-Person, O., Meattini, I., Poortmans, P. (eds) Breast Cancer Radiation Therapy. Springer, Cham. https://doi.org/10.1007/978-3-030-91170-6_53

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-91170-6_53

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-91169-0

  • Online ISBN: 978-3-030-91170-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation