Individualization of post-mastectomy radiotherapy and regional nodal irradiation based on treatment response after neoadjuvant chemotherapy for breast cancer

A systematic review
  • David Krug
  • René Baumann
  • Wilfried Budach
  • Jürgen Dunst
  • Petra Feyer
  • Rainer Fietkau
  • Wulf Haase
  • Wolfgang Harms
  • Thomas Hehr
  • Marc D. Piroth
  • Felix Sedlmayer
  • Rainer Souchon
  • Frederik Wenz
  • Rolf Sauer
Review Article

Abstract

Purpose

To review the evidence regarding post-mastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NACT) for breast cancer, with a special focus on individualization of adjuvant radiotherapy based on treatment response.

Methods

A systematic literature search using the PubMed/Medline database was performed. We included prospective and retrospective reports with a minimum of 10 patients that had been published since 1st January 2000, and provided clinical outcome data analyzed by treatment response and radiotherapy.

Results

Out of 763 articles identified via PubMed/Medline and hand search, 68 full text-articles were assessed for eligibility after screening of title and abstract. 13 studies were included in the systematic review, 9 for PMRT and 5 for RNI. All included studies were retrospective reports.

Conclusions

There is a considerable lack of evidence regarding the role of adjuvant radiotherapy and its individualization based on treatment response after NACT. Results of prospective randomized trials such as NSABP B‑51/RTOG 1304 and Alliance A11202 are eagerly awaited.

Keywords

Local recurrence Neoadjuvant therapy Breast neoplasms Radiotherapy 

Individualisierung von Post-Mastektomie-Radiotherapie und regionärer Lymphknotenbestrahlung anhand des Therapieansprechens nach neoadjuvanter Chemotherapie bei Brustkrebs

Ein systematischer Review

Zusammenfassung

Zielsetzung

Überblick über die Datenlage zur Post-Mastektomie-Radiotherapie (PMRT) und Bestrahlung der Lymphabflusswege (RNI) nach neoadjuvanter Chemotherapie (NACT) bei Patientinnen mit Mammakarzinom mit besonderem Schwerpunkt auf der Individualisierung der adjuvanten Radiotherapie anhand des Therapieansprechens.

Methoden

Es wurde eine systematische Literaturrecherche mit der PubMed/Medline-Datenbank durchgeführt. Eingeschlossen wurden prospektive und retrospektive Studien mit mindestens 10 Patientinnen, die klinische Rezidiv- und Überlebensdaten mit Subgruppenanalysen bezüglich verabreichter Bestrahlung und Therapieansprechen lieferten und seit 1. Januar 2000 veröffentlicht wurden.

Ergebnisse

Von 763 Artikeln, die durch die Datenbankabfrage und eine ergänzende händische Suche identifiziert wurden, wurden nach Prüfung von Titel und Zusammenfassung 68 einer Volltextprüfung unterzogen. Schlussendlich wurden 13 retrospektive Arbeiten in den systematischen Review eingeschlossen, hiervon 9 mit PMRT und 5 mit RNI.

Schlussfolgerung

Es besteht eine deutliche Evidenzlücke bezüglich der Rolle der adjuvanten Radiotherapie nach NACT sowie deren Individualisierung anhand des Therapieansprechens bei Patientinnen mit Mammakarzinom. Prospektive Daten aus randomisiert kontrollierten Studien wie NSABP B-51/RTOG 1304 und Alliance A11202 werden dringend erwartet.

Schlüsselwörter

Lokalrezidiv Neoadjuvante Therapie Brustkrebs Strahlentherapie 

Notes

Compliance with ethical guidelines

Conflict of interest

D. Krug, R. Baumann, W. Budach, J. Dunst, P. Feyer, R. Fietkau, W. Haase, W. Harms, T. Hehr, M.D. Piroth, F. Sedlmayer, R. Souchon, F. Wenz, and R. Sauer declare that they have no competing interests.

Ethical standards

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Kaufmann M, von Minckwitz G, Smith R et al (2003) International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations. J Clin Oncol 21:2600–2608.  https://doi.org/10.1200/JCO.2003.01.136 CrossRefPubMedGoogle Scholar
  2. 2.
    Cortazar P, Zhang L, Untch M et al (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384:164–172.  https://doi.org/10.1016/S0140-6736(13)62422-8 CrossRefPubMedGoogle Scholar
  3. 3.
    Mougalian SS, Soulos PR, Killelea BK et al (2015) Use of neoadjuvant chemotherapy for patients with stage I to III breast cancer in the United States. Cancer 121:2544–2552.  https://doi.org/10.1002/cncr.29348 CrossRefPubMedGoogle Scholar
  4. 4.
    Hennigs A, Riedel F, Marmé F et al (2016) Changes in chemotherapy usage and outcome of early breast cancer patients in the last decade. Breast Cancer Res Treat 160:491–499.  https://doi.org/10.1007/s10549-016-4016-4 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Mamounas EP, Anderson SJ, Dignam JJ et al (2012) Predictors oflLocoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of national surgical adjuvant breast and bowel project B‑18 and B‑27. J Clin Oncol 30:3960–3966.  https://doi.org/10.1200/JCO.2011.40.8369 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Recht A, Comen EA, Fine RE et al (2016) Postmastectomy radiotherapy: an American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology focused guideline update. J Clin Oncol 34:4431–4442.  https://doi.org/10.1200/JCO.2016.69.1188 CrossRefPubMedGoogle Scholar
  7. 7.
    Sautter-Bihl ML, Sedlmayer F, Budach W et al (2014) DEGRO practical guidelines: radiotherapy of breast cancer III—radiotherapy of the lymphatic pathways. Strahlenther Onkol 190:342–351.  https://doi.org/10.1007/s00066-013-0543-7 CrossRefPubMedGoogle Scholar
  8. 8.
    Wenz F, Sperk E, Budach W et al (2014) DEGRO practical guidelines for radiotherapy of breast cancer IV: radiotherapy following mastectomy for invasive breast cancer. Strahlenther Onkol 190:705–714.  https://doi.org/10.1007/s00066-014-0687-0 CrossRefPubMedGoogle Scholar
  9. 9.
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2014) 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 383:2127–2135.  https://doi.org/10.1016/S0140-6736(14)60488-8 CrossRefGoogle Scholar
  10. 10.
    Poortmans PM, Collette S, Kirkove C et al (2015) Internal mammary and medial supraclavicular irradiation in breast cancer. N Engl J Med 373:317–327.  https://doi.org/10.1056/NEJMoa1415369 CrossRefPubMedGoogle Scholar
  11. 11.
    Whelan TJ, Olivotto IA, Parulekar WR et al (2015) Regional nodal irradiation in early-stage breast cancer. N Engl J Med 373:307–316.  https://doi.org/10.1056/NEJMoa1415340 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Burstein HJ, Morrow M (2015) Nodal irradiation after breast-cancer surgery in the era of effective adjuvant therapy. N Engl J Med 373:379–381.  https://doi.org/10.1056/NEJMe1503608 CrossRefPubMedGoogle Scholar
  13. 13.
    Marks LB, Kaidar-Person O, Poortmans P (2017) Regarding current recommendations for postmastectomy radiation therapy in patients with one to three positive axillary lymph nodes. J Clin Oncol 35:1256–1258.  https://doi.org/10.1200/JCO.2016.71.0764 CrossRefPubMedGoogle Scholar
  14. 14.
    Poortmans P (2014) Postmastectomy radiation in breast cancer with one to three involved lymph nodes: ending the debate. Lancet 383:2104–2106.  https://doi.org/10.1016/S0140-6736(14)60192-6 CrossRefPubMedGoogle Scholar
  15. 15.
    Cassidy RJ, Liu Y, Kahn ST et al (2017) The role of postmastectomy radiotherapy in women with pathologic T3N0M0 breast cancer. Cancer 123:2829–2839.  https://doi.org/10.1002/cncr.30675 CrossRefPubMedGoogle Scholar
  16. 16.
    Floyd SR, Buchholz TA, Haffty BG et al (2006) Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger. Int J Radiat Oncol Biol Phys 66:358–364.  https://doi.org/10.1016/j.ijrobp.2006.05.001 CrossRefPubMedGoogle Scholar
  17. 17.
    Johnson ME, Handorf EA, Martin JM, Hayes SB (2014) Postmastectomy radiation therapy for T3N0: A SEER analysis. Cancer 120:3569–3574.  https://doi.org/10.1002/cncr.28865 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Taghian AG, Jeong J‑H, Mamounas EP et al (2006) Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol 24:3927–3932.  https://doi.org/10.1200/JCO.2006.06.9054 CrossRefPubMedGoogle Scholar
  19. 19.
    Fowble BL, Einck JP, Kim DN et al (2012) Role of postmastectomy radiation after neoadjuvant chemotherapy in stage II–III breast cancer. Int J Radiat Oncol Biol Phys 83:494–503.  https://doi.org/10.1016/j.ijrobp.2012.01.068 CrossRefPubMedGoogle Scholar
  20. 20.
    White J, Mamounas E (2014) Locoregional radiotherapy in patients with breast cancer responding to neoadjuvant chemotherapy: a paradigm for treatment individualization. J Clin Oncol 32:494–495.  https://doi.org/10.1200/JCO.2013.53.4974 CrossRefPubMedGoogle Scholar
  21. 21.
    Rusthoven CG, Rabinovitch RA, Jones BL et al (2016) The impact of postmastectomy and regional nodal radiation after neoadjuvant chemotherapy for clinically lymph node-positive breast cancer: a National Cancer Database (NCDB) analysis. Ann Oncol 27:818–827.  https://doi.org/10.1093/annonc/mdw046 CrossRefPubMedGoogle Scholar
  22. 22.
    Daveau C, Stevens D, Brain E et al (2010) Is regional lymph node irradiation necessary in stage II to III breast cancer patients with negative pathologic node status after neoadjuvant chemotherapy? Int J Radiat Oncol Biol Phys 78:337–342.  https://doi.org/10.1016/j.ijrobp.2009.08.053 CrossRefPubMedGoogle Scholar
  23. 23.
    Bae SH, Park W, Huh SJ et al (2012) Radiation treatment in pathologic N0-N1 patients treated with neoadjuvant chemotherapy followed by surgery for locally advanced breast cancer. J Breast Cancer 15:329–328.  https://doi.org/10.4048/jbc.2012.15.3.329 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Noh JM, Park W, Suh C‑O et al (2014) Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II–III breast cancer? A multicentre retrospective study (KROG 12-05). Br J Cancer 110:1420–1426.  https://doi.org/10.1038/bjc.2014.26 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kim KH, Noh JM, Kim YB et al (2015) Does internal mammary node irradiation affect treatment outcome in clinical stage II–III breast cancer patients receiving neoadjuvant chemotherapy? Breast Cancer Res Treat 152:589–599.  https://doi.org/10.1007/s10549-015-3505-1 CrossRefPubMedGoogle Scholar
  26. 26.
    McGuire SE, Gonzalez-Angulo AM, Huang EH et al (2007) Postmastectomy radiation improves the outcome of patients with locally advanced breast cancer who achieve a pathologic complete response to neoadjuvant chemotherapy. Int J Radiat Oncol Biol Phys 68:1004–1009.  https://doi.org/10.1016/j.ijrobp.2007.01.023 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Nagar H, Mittendorf EA, Strom EA et al (2011) Local-regional recurrence with and without radiation therapy after neoadjuvant chemotherapy and mastectomy for clinically staged T3N0 breast cancer. Int J Radiat Oncol Biol Phys 81:782–787.  https://doi.org/10.1016/j.ijrobp.2010.06.027 CrossRefPubMedGoogle Scholar
  28. 28.
    Le Scodan R, Selz J, Stevens D et al (2012) Radiotherapy for stage II and stage III breast cancer patients with negative lymph nodes after preoperative chemotherapy and mastectomy. Int J Radiat Oncol Biol Phys 82:e1–e7.  https://doi.org/10.1016/j.ijrobp.2010.12.054 CrossRefPubMedGoogle Scholar
  29. 29.
    Shim SJ, Park W, Huh SJ et al (2014) The role of postmastectomy radiation therapy after neoadjuvant chemotherapy in clinical stage II–III breast cancer patients with pN0: a multicenter, retrospective study (KROG 12-05). Int J Radiat Oncol Biol Phys 88:65–72.  https://doi.org/10.1016/j.ijrobp.2013.09.021 CrossRefPubMedGoogle Scholar
  30. 30.
    Xin F, Yu Y, Yang Z‑J et al (2016) Number of negative lymph nodes as a prognostic factor for ypN0-N1 breast cancer patients undergoing neoadjuvant chemotherapy. Tumor Biol 37:1–10.  https://doi.org/10.1007/s13277-015-4640-3 Google Scholar
  31. 31.
    Meattini I, Cecchini S, Di Cataldo V et al (2014) Postmastectomy radiotherapy for locally advanced breast cancer receiving neoadjuvant chemotherapy. Biomed Res Int 2014:1–12.  https://doi.org/10.1155/2014/719175 CrossRefGoogle Scholar
  32. 32.
    Liu J, Mao K, Jiang S et al (2016) The role of postmastectomy radiotherapy in clinically node-positive, stage II–III breast cancer patients with pathological negative nodes after neoadjuvant chemotherapy: an analysis from the NCDB. Oncotarget 7:24848–24859.  https://doi.org/10.18632/oncotarget.6664 PubMedGoogle Scholar
  33. 33.
    Kantor O, Pesce C, Singh P et al (2017) Post-mastectomy radiation therapy and overall survival after neoadjuvant chemotherapy. J Surg Oncol 28:2396–2399.  https://doi.org/10.1002/jso.24551 Google Scholar
  34. 34.
    Mamounas EP, Cortazar P, Zhang L et al (2014) Locoregional recurrence (LRR) after neoadjuvant chemotherapy (NAC): pooled-analysis results from the Collaborative Trials in Neoadjuvant Breast Cancer (CTNeoBC). J Clin Oncol 32:61–61.  https://doi.org/10.1200/jco.2014.32.26_suppl.61 CrossRefGoogle Scholar
  35. 35.
    Marks LB, Prosnitz LR (2014) Reducing local therapy in patients responding to preoperative systemic therapy: are we outsmarting ourselves? J Clin Oncol 32:491–493.  https://doi.org/10.1200/JCO.2013.51.3523 CrossRefPubMedGoogle Scholar
  36. 36.
    Poortmans PMP, Arenas M, Livi L (2017) Over-irradiation. Breast 31:295–302.  https://doi.org/10.1016/j.breast.2016.07.022 CrossRefPubMedGoogle Scholar
  37. 37.
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2018) Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol 19:27–39.  https://doi.org/10.1016/S1470-2045(17)30777-5 CrossRefGoogle Scholar
  38. 38.
    Mieog JSD, van der Hage JA, van de Velde CJH (2007) Neoadjuvant chemotherapy for operable breast cancer. Br J Surg 94:1189–1200.  https://doi.org/10.1002/bjs.5894 CrossRefPubMedGoogle Scholar
  39. 39.
    Mauri D, Pavlidis N, Ioannidis JPA (2005) Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst 97:188–194.  https://doi.org/10.1093/jnci/dji021 CrossRefPubMedGoogle Scholar
  40. 40.
    Budach W, Bölke E, Kammers K et al (2015) Adjuvant radiation therapy of regional lymph nodes in breast cancer—a meta-analysis of randomized trials—an update. Radiat Oncol 10:1–7.  https://doi.org/10.1186/s13014-015-0568-4 CrossRefGoogle Scholar
  41. 41.
    McGale P, Cutter D, Darby SC et al (2016) Can observational data replace randomized trials? J Clin Oncol 34:3355–3357.  https://doi.org/10.1200/JCO.2016.68.8879 CrossRefPubMedGoogle Scholar
  42. 42.
    Gianni L, Pienkowski T, Im Y‑H et al (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13:25–32.  https://doi.org/10.1016/S1470-2045(11)70336-9 CrossRefPubMedGoogle Scholar
  43. 43.
    Schneeweiss A, Chia S, Hickish T et al (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24:2278–2284.  https://doi.org/10.1093/annonc/mdt182 CrossRefPubMedGoogle Scholar
  44. 44.
    Dawood S, Merajver SD, Viens P et al (2011) International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Ann Oncol 22:515–523.  https://doi.org/10.1093/annonc/mdq345 CrossRefPubMedGoogle Scholar
  45. 45.
    Rea D, Francis A, Hanby AM et al (2015) Inflammatory breast cancer: time to standardise diagnosis assessment and management, and for the joining of forces to facilitate effective research. Br J Cancer 112:1613–1615.  https://doi.org/10.1038/bjc.2015.115 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Plos Med 6:e1000097.  https://doi.org/10.1371/journal.pmed.1000097 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • David Krug
    • 1
    • 2
  • René Baumann
    • 3
  • Wilfried Budach
    • 4
  • Jürgen Dunst
    • 3
  • Petra Feyer
    • 5
  • Rainer Fietkau
    • 6
  • Wulf Haase
    • 7
  • Wolfgang Harms
    • 8
  • Thomas Hehr
    • 9
  • Marc D. Piroth
    • 10
  • Felix Sedlmayer
    • 11
  • Rainer Souchon
    • 12
  • Frederik Wenz
    • 13
  • Rolf Sauer
    • 6
  1. 1.Department of Radiation OncologyUniversity Hospital HeidelbergHeidelbergGermany
  2. 2.Heidelberg Institute for Radiation Oncology (HIRO)National Center for Radiation Research in Oncology (NCRO)HeidelbergGermany
  3. 3.University Hospital Schleswig-HolsteinKielGermany
  4. 4.Heinrich-Heine-UniversityDuesseldorfGermany
  5. 5.Vivantes Hospital NeukoellnBerlinGermany
  6. 6.University Hospital ErlangenErlangenGermany
  7. 7.Formerly St.-Vincentius-HospitalKarlsruheGermany
  8. 8.St. ClaraspitalBaselSwitzerland
  9. 9.Department of Radiation OncologyMarienhospital StuttgartStuttgartGermany
  10. 10.HELIOS-Hospital WuppertalWitten/Herdecke UniversityWuppertalGermany
  11. 11.Paracelsus Medical University HospitalSalzburgAustria
  12. 12.Formerly University Hospital TuebingenTuebingenGermany
  13. 13.Universitätsmedizin Mannheim, Medizinische Fakultät MannheimUniversität HeidelbergMannheimGermany

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