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Influence of XRCC4 expression by breast cancer cells on ipsilateral recurrence after breast-conserving therapy

  • Mio Kitagawa
  • Masanori Someya
  • Tomokazu Hasegawa
  • Toshihiko Mikami
  • Kazuaki Asaishi
  • Tadashi Hasegawa
  • Yoshihisa Matsumoto
  • Goro Kutomi
  • Ichiro Takemasa
  • Koh-ichi SakataEmail author
Original Article
  • 66 Downloads

Abstract

Background

We examined the expression of nonhomologous end-joining (NHEJ) proteins by breast cancer cells in patients with or without ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy. We also investigated whether there was a difference of NHEJ-related protein expression by tumor cells between two types of IBTR, i.e., true recurrence (TR) with regrowth from the tumor bed or development of a new primary tumor (NP).

Patients and methods

The original cohort comprised 560 breast cancer patients who received breast-conserving therapy between February 1995 and March 2006, including 520 patients without IBTR and 40 patients with IBTR. Propensity score matching was employed to select 40 trios (120 patients) consisting of 1 patient with IBTR and 2 patients without IBTR. Immunohistochemical examination of proteins related to NHEJ was performed in surgical specimens.

Results

The 40 patients with IBTR included 22 patients who developed TR and 18 who had NP. The 15-year overall survival rate was 85.9% for patients with NP and 95.5% for those with TR, while it was 96.5% for patients without IBTR. Patients with high XRCC4 expression in tumor cells had significantly higher IBTR rates than those with low XRCC4 expression (P < 0.001). The frequency of TR was significantly higher in patients with high expression of XRCC4 than in those with low XRCC4 expression (p < 0.001). XRCC4 expression by tumor cells was not significantly related to development of NP.

Conclusion

IBTR due to TR may be related to low radiosensitivity of tumor cells, possibly related to high XRCC4 expression.

Keywords

Radiotherapy Nonhomologous end-joining (NHEJ) proteins DNA repair New primary tumor True recurrence 

Einfluss der XRCC4-Expression von Brustkrebszellen auf ipsilaterale Rezidive nach brusterhaltender Therapie

Zusammenfassung

Hintergrund

Wir untersuchten die Tumorexpression von nichthomologen endverknüpften Proteinen (NHEJ) in Patienten mit oder ohne ipsilateralen Brustkrebszrezidiven (IBTR) nach brusterhaltenden Therapieverfahren. Weiterhin untersuchten wir, ob die Expression NHEJ-verwandter Proteine bei den beiden IBTR-Typen, d. h. echte Rezidive mit Nachwachsen vom Tumorbett oder Entwicklung neuer Primärtumore, unterschiedlich ist.

Patienten und Methoden

Die ursprüngliche Gruppe umfasste 560 zwischen Februar 1995 und März 2006 mit brusterhaltenden Therapieverfahren behandelte Brustkrebspatienten, einschließlich 520 Patienten ohne IBTR und 40 Patienten mit IBTR. „Propensity score matching“ wurde eingesetzt, um 40 Trios (120 Patienten) aus 1 Patient mit IBTR und 2 Patienten ohne IBTR auszuwählen. Immunhistochemische Untersuchungen der NHEJ-verwandten Proteine wurden an Biopsieproben durchgeführt.

Ergebnisse

Die 40 Patienten mit IBTR umfassten 22 Patienten mit echten Rezidiven und 18, die einen neuen Primärtumor entwickelten. Die 15-Jahres-Gesamtüberlebensrate betrug 85,9 % für Patienten mit einem neuen Primärtumor und 95,5 % für Patienten mit echten Rezidiven, während sie für Patienten ohne IBTR 96,5 % war. Patienten mit einer starken XRCC4-Expression durch die Tumorzellen hatten eine signifikant höhere IBTR-Rate als diejenigen mit geringer XRCC4-Expression (p < 0,001). Die Häufigkeit echter Rezidive war bei Patienten mit erhöhter XRCC4-Expression höher als bei Patienten mit geringer XRCC4-Expression (21/64 Patienten versus 1/56 Patienten). Demgegenüber hatte die XRCC4-Expression keine wesentliche Beziehung zur Entwicklung eines neuen Primärtumors.

Schlussfolgerung

Durch echte Rezidive hervorgerufene IBTR könnte mit der geringen Strahlenempfindlichkeit der Tumorzellen und möglicherweise der hohen XRCC4-Expression in Verbindung stehen.

Schlüsselwörter

Strahlentherapie Nichthomologen endverknüpfte Proteine DNA-Reparatur Neuer primärer Tumor Echtes Rezidiv 

Notes

Funding

This work was supported by a grants-in-aid of Ono Cancer Research Fund and JSPS KAKENHI grant number 15K10000.

Conflict of interest

M. Kitagawa, M. Someya, T. Hasegawa, T. Mikami, K. Asaishi, T. Hasegawa, Y. Matsumoto, G. Kutomi, I. Takemasa, and K.-i. Sakata declare that they have no competing interests.

Supplementary material

66_2019_1468_MOESM1_ESM.tiff (56 kb)
Supplementary Fig. 1 XRCC4 expression according to ER
66_2019_1468_MOESM2_ESM.docx (60 kb)
Supplementary Table 1

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Mio Kitagawa
    • 1
  • Masanori Someya
    • 1
  • Tomokazu Hasegawa
    • 1
  • Toshihiko Mikami
    • 2
  • Kazuaki Asaishi
    • 2
  • Tadashi Hasegawa
    • 3
  • Yoshihisa Matsumoto
    • 4
  • Goro Kutomi
    • 5
  • Ichiro Takemasa
    • 5
  • Koh-ichi Sakata
    • 1
    Email author
  1. 1.Department of RadiologySapporo Medical University School of MedicineChuo-ku, SapporoJapan
  2. 2.Sapporo-Kotoni Breast ClinicNishi-ku, SapporoJapan
  3. 3.Department of Surgical PathologySapporo Medical University School of MedicineChuo-ku, SapporoJapan
  4. 4.Institute of Innovative Research Laboratory for Advanced Nuclear EnergyTokyo Institute of TechnologyTokyoJapan
  5. 5.Department of Surgery, Surgical Oncology and ScienceSapporo Medical University School of MedicineChuo-ku, SapporoJapan

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