Breast Cancer Research and Treatment

, Volume 169, Issue 3, pp 497–505 | Cite as

Do patients whose tumor achieved a pathological response relapse at specific sites? A substudy of the EORTC 10994/BIG-1-00 trial

  • Kim C. Aalders
  • Nathan Touati
  • Konstantinos Tryfonidis
  • Mylène Annonay
  • Saskia Litiere
  • Jonas Bergh
  • Alexandre Bodmer
  • David A. Cameron
  • Hervé R. Bonnefoi
  • on behalf of the EORTC 10994/BIG 1-00 Study Investigators
Clinical trial



To determine the sites of first distant relapse in patients with or without pCR following neoadjuvant chemotherapy in breast cancer patients enrolled in the EORTC 10994/BIG-1-00 trial.


We included patients enrolled in the EORTC 10994/BIG-1-00 trial who received at least one chemotherapy cycle before surgery and who had been diagnosed with a distant relapse. pCR was defined as no evidence of residual invasive cancer in the primary tumor and axillary lymph nodes with or without residual ductal carcinoma in situ. Site of first distant relapse was categorized as ‘soft tissue,’ ‘visceral,’ ‘skeletal,’ ‘central nervous system (CNS),’ and ‘other.’ The association between relapse site and achievement of pCR was assessed using multivariate logistic regression models for molecular subtypes classification and preceding locoregional recurrence.


The study included 383 (21%) eligible patients out of the 1856 randomized, of whom 28 (7%) had achieved pCR. Median follow-up was 5.4 years. Achievement of pCR was associated with a trend towards a decreased presentation of skeletal metastases [21% (pCR) vs. 50% (non-pCR), OR 0.32, adjusted p value = 0.071] and an increase in the proportion of patients with CNS metastases as first distant relapse site (21% vs. 9%, OR 2.39, adjusted p value = 0.183). Patients with pCR were more likely to present with only one relapse location category when compared to non-pCR (86% vs. 69%).


Patients that achieved a pCR appeared less likely to present with skeletal metastases and more frequently presented with CNS metastases as first site of distant relapse, even after adjustment for molecular subtypes.


Breast cancer Pathological complete response Neoadjuvant chemotherapy Relapse Metastases Patterns 



We thank the patients, doctors, and nurses involved in the EORTC 10994/BIG 1-00 study for their generous participation. We also thank the data managers from the EORTC, the Anglo-Celtic Cooperative Oncology Group (ACCOG) at the Information and Statistics Division of the Scottish NHS, the Swedish Breast Cancer Group (SweBCG) and the Swiss Group for Clinical Cancer Research (SAKK). We thank SIRIC BRIO (Site de Recherche Intégrée sur le Cancer – Bordeaux Recherche Intégrée Oncologie) for financial support [Grant INCa-DGOS-Inserm 6046]. This publication was supported by the EORTC Cancer Research Fund (Grant No. ID0EGDAE10737).

Supplementary material

10549_2018_4698_MOESM1_ESM.docx (38 kb)
Supplementary material 1 (DOCX 38 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Kim C. Aalders
    • 1
  • Nathan Touati
    • 2
  • Konstantinos Tryfonidis
    • 1
  • Mylène Annonay
    • 3
  • Saskia Litiere
    • 2
  • Jonas Bergh
    • 4
    • 5
  • Alexandre Bodmer
    • 6
    • 7
  • David A. Cameron
    • 8
  • Hervé R. Bonnefoi
    • 3
  • on behalf of the EORTC 10994/BIG 1-00 Study Investigators
  1. 1.Medical DepartmentEuropean Organisation for Research and Treatment of Cancer (EORTC)BrusselsBelgium
  2. 2.Department of StatisticsEuropean Organisation for Research and Treatment of CancerBrusselsBelgium
  3. 3.Department of Medical Oncology, Institut Bergonié UnicancerUniversité de Bordeaux, INSERM U1218, INSERM CIC1401BordeauxFrance
  4. 4.Swedish Breast Cancer Group (SweBCG)StockholmSweden
  5. 5.Department of Oncology and PathologyKarolinska InstitutetStockholmSweden
  6. 6.Swiss Group for Clinical Cancer Research (SAKK)BernSwitzerland
  7. 7.Department of OncologyGeneva University HospitalGenevaSwitzerland
  8. 8.Edinburgh Cancer CentreUniversity of EdinburghEdinburghUK

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