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Strahlentherapie und Onkologie

, Volume 195, Issue 4, pp 297–305 | Cite as

Impact of postmastectomy radiotherapy on the outcomes of breast cancer patients with T1–2 N1 disease

An individual patient data analysis of three clinical trials
  • Omar Abdel-RahmanEmail author
Original Article

Abstract

Purpose

To assess the impact of postmastectomy radiotherapy (PMRT) on overall survival and relapse-free survival among breast cancer patients with T1–T2 N1 disease who received standard adjuvant systemic therapy.

Methods

This is an individual patient data pooled analysis of 1053 breast cancer patients referred for adjuvant therapy in three clinical trials (BIG 02/98, BCIRG001, and BCIRG005). Overall survival was assessed according to whether or not patients received adjuvant radiotherapy through Kaplan–Meier analysis. Univariate and multivariate analyses of predictors of overall and relapse-free survival were conducted through Cox regression analysis.

Results

Locoregional relapse rates (after a median follow up of 116 months) were 5.6% among patients who received adjuvant radiotherapy vs. 6.6% among patients who did not receive adjuvant radiotherapy. Actuarial 5‑ and 10-year locoregional relapse-free survival rates were 94 and 93%, respectively, among patients who did not receive adjuvant radiotherapy versus 95 and 92% among patients who received adjuvant radiotherapy. The following factors were associated with worse overall survival in multivariate Cox regression analysis: age < 40 years (P < 0.0001), T2 stage (P = 0.004), higher lymph node ratio (P < 0.0001), and negative hormone receptor status (P < 0.0001). Likewise, the following factors were predictive of shorter locoregional relapse-free survival: age ≤ 40 (P < 0.0001), no PMRT (P = 0.034), fluorouracil/adriamycin/cyclophosphamide (FAC) chemotherapy (P = 0.001), and higher T stage (P = 0.002).

Conclusion

The current analysis does not show a beneficial impact of PMRT on overall or relapse-free survival among patients with T1–T2 N1 disease who received standard adjuvant systemic therapy. There is, however, evidence of improvement in locoregional relapse-free survival with PMRT. These findings need to be prospectively validated.

Keywords

Locoregional control Survival Prognosis Evidence-based medicine Relapse 

Auswirkungen der Strahlentherapie nach Mastektomie auf die Ergebnisse von Mammakarzinompatientinnen im Stadium T1–2 N1

Eine individuelle Patientendatenanalyse aus 3 klinischen Studien

Zusammenfassung

Ziel

Untersuchung der Auswirkungen der Postmastektomie-Strahlentherapie (PMRT) auf das Gesamtüberleben und das rezidivfreie Überleben von Mammakarzinompatientinnen im Stadium T1–2 N1, die anschließend eine systemische adjuvante Standardtherapie erhielten.

Methoden

Gepoolte individuelle Patientendatenanalyse von 1053 Mammakarzinompatientinnen mit einer adjuvanten Systemtherapie im Rahmen von drei klinischen Studien (BIG 02/98; BCIRG001, BCIRG005). Das Gesamtüberleben von Patientinnen mit und ohne adjuvante Strahlentherapie wurde mittels Kaplan-Meier-Analyse verglichen. Zur univariaten und multivariaten Analyse von unabhängigen Prädiktoren für das Gesamt- und rezidivfreie Überleben wurde eine Cox-Regression durchgeführt.

Ergebnisse

In einem medianen Follow-up-Zeitraum von 116 Monaten kam es in 5,1 % aller Patientinnen mit adjuvanter Strahlentherapie zum lokoregionären Rezidiv im Vergleich zu 6,4 % der nichtbestrahlten Patientinnen. Die rezidivfreien 5‑Jahres- und 10-Jahres-Überlebensraten betrugen 94 und 93 % bei Patientinnen ohne bzw. 95 und 92 % mit adjuvanter Strahlentherapie. Die folgenden Faktoren waren mit einem schlechteren Gesamtüberleben in der multivariaten Cox-Regression assoziiert: Alter < 40 Jahre (P < 0,0001), T2-Stadium (P = 0,004), höheres Lymphknotenverhältnis (P < 0,0001) und negativer Hormonrezeptorstatus (P < 0,0001). Zudem waren die folgenden Faktoren prädiktiv für ein kürzeres lokoregionäres rezidivfreies Überleben: Alter < 40 (P < 0,0001), kein PMRT (P = 0,034), „Fluorouracil/Adriamycin/Cyclophosphamide“(FAC)-Chemotherapie (P = 0,001) und höheres T‑Stadium (P = 0,002).

Fazit

Die aktuelle Analyse zeigt keinen positiven Einfluss der PMRT auf das Gesamt- oder rezidivfreie Überleben bei Patientinnen mit Mammakarzinom im Stadium T1–2 N1, die eine standardmäßige adjuvante Systemtherapie erhielten. Es gibt aber Hinweise auf eine Verbesserung des lokoregionalen rezidivfreien Überlebens mit PMRT. Diese Ergebnisse bedürfen jedoch einer prospektiven Evaluierung.

Schlüsselwörter

Locoregionale Kontrolle Überleben Prognose Rückfälle Medizin basierend auf Fakten 

Notes

Acknowledgements

This publication is based on research using information obtained from www.projectdatasphere.org, which is maintained by Project Data Sphere, LLC. Neither Project Data Sphere, LLC, nor the owner(s) of any information from the website have contributed to, approved, or are in any way responsible for the contents of this publication. The datasets were downloaded from the project data sphere platform after obtaining all appropriate relevant approvals.

Compliance with ethical guidelines

Conflict of interest

O. Abdel-Rahman declares that he has 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.
    Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E et al (2015) Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 26(Suppl 5):v8–v30CrossRefPubMedGoogle Scholar
  2. 2.
    Salerno KE (2017) NCCN guidelines update: evolving radiation therapy recommendations for breast cancer. J Natl Compr Canc Netw 15(5s):682–684CrossRefPubMedGoogle Scholar
  3. 3.
    Gradishar W, Salerno KE (2016) NCCN guidelines update: breast cancer. J Natl Compr Canc Netw 14(5 Suppl):641–644CrossRefPubMedGoogle Scholar
  4. 4.
    Wenz F, Sperk E, Budach W, Dunst J, Feyer P, Fietkau R et al (2014) DEGRO practical guidelines for radiotherapy of breast cancer IV: radiotherapy following mastectomy for invasive breast cancer. Strahlenther Onkol 190(8):705–714CrossRefPubMedGoogle Scholar
  5. 5.
    Ragaz J, Jackson SM, Le N, Plenderleith IH, Spinelli JJ, Basco VE et al (1997) Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 337(14):956–962CrossRefPubMedGoogle Scholar
  6. 6.
    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(9935):2127–2135CrossRefGoogle Scholar
  7. 7.
    CEO Life Sciences Consortium (2014) Project Data Sphere. https://www.projectdatasphere.org/projectdatasphere/html/home. Accessed 7 Oct 2017Google Scholar
  8. 8.
    Fernandez-Cuesta L, Oakman C, Falagan-Lotsch P, Smoth KS, Quinaux E, Buyse M et al (2012) Prognostic and predictive value of TP53 mutations in node-positive breast cancer patients treated with anthracycline- or anthracycline/taxane-based adjuvant therapy: results from the BIG 02-98 phase III trial. Breast Cancer Res 14(3):R70CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Mackey JR, Martin M, Pienkowski T, Rolski J, Guastalla JP, Sami A et al (2013) Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol 14(1):72–80CrossRefPubMedGoogle Scholar
  10. 10.
    Eiermann W, Pienkowski T, Crown J, Sadeghi S, Martin M, Chan A et al (2011) Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2‑normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol 29(29):3877–3884CrossRefPubMedGoogle Scholar
  11. 11.
    Alberto A, Imbens GW (2006) Large sample properties of matching estimators for average treatment effects. Econometrica 74(1):235–267CrossRefGoogle Scholar
  12. 12.
    Korah MP, Sener SF, Tripathy D (2013) The impact of postmastectomy radiation therapy in intermediate-risk breast cancer patients with limited axillary disease. Int J Radiat Oncol Biol Phys 87(2):S230CrossRefGoogle Scholar
  13. 13.
    Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F et al (1997) Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. N Engl J Med 337(14):949–955CrossRefPubMedGoogle Scholar
  14. 14.
    Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M et al (1999) Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 353(9165):1641–1648CrossRefPubMedGoogle Scholar
  15. 15.
    Overgaard M, Nielsen HM, Overgaard J (2007) Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b&c randomized trials. Radiother Oncol 82(3):247–253CrossRefPubMedGoogle Scholar
  16. 16.
    Su Y‑L, Li S‑H, Chen Y‑Y, Chen H‑C, Tang Y, Huang C‑H et al (2014) Post-mastectomy radiotherapy benefits subgroups of breast cancer patients with T1–2 tumor and 1–3 axillary lymph node(s) metastasis. Radiol Oncol 48(3):314–322CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Abdel-Rahman O, Cheung WY (2018) Impact of smoking history on the outcomes of women with early-stage breast cancer: a secondary analysis of a randomized study. Med Oncol 35(5):68CrossRefPubMedGoogle Scholar
  18. 18.
    Truong PT, Olivotto IA, Kader HA, Panades M, Speers CH, Berthelet E (2005) Selecting breast cancer patients with T1–T2 tumors and one to three positive axillary nodes at high postmastectomy locoregional recurrence risk for adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 61(5):1337–1347CrossRefPubMedGoogle Scholar
  19. 19.
    Cheng JC, Chen CM, Liu MC, Tsou MH, Yang PS, Jian JJ et al (2002) Locoregional failure of postmastectomy patients with 1–3 positive axillary lymph nodes without adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 52(4):980–988CrossRefPubMedGoogle Scholar
  20. 20.
    Zeidan YH, Habib JG, Ameye L, Paesmans M, de Azambuja E, Gelber RD et al (2018) Postmastectomy Radiation Therapy in Women with T1–T2 Tumors and 1 to 3 Positive Lymph Nodes: Analysis of the Breast International Group 02-98 Trial. Int J Radiat Oncol Biol Phys 101(2):316–324CrossRefPubMedGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Clinical Oncology Department, Faculty of MedicineAin Shams UniversityCairoEgypt
  2. 2.Department of Oncology, Tom Baker Cancer CentreUniversity of CalgaryCalgaryCanada

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