Do patients whose tumor achieved a pathological response relapse at specific sites? A substudy of the EORTC 10994/BIG-1-00 trial
- 103 Downloads
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.
KeywordsBreast 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).
- 4.van der Hage JA, van de Velde CJ, Julien JP et al (2001) Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol 19:4224–4237. https://doi.org/10.1200/jco.2001.19.22.4224 CrossRefPubMedGoogle Scholar
- 7.Bonnefoi H, Litiere S, Piccart M et al (2014) Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial. Ann Oncol 25:1128–1136. https://doi.org/10.1093/annonc/mdu118 CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Lindström LS, Karlsson E, Wilking UM et al (2012) Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol 30:2601–2608. https://doi.org/10.1200/jco.2011.37.2482 CrossRefPubMedGoogle Scholar
- 12.Bonnefoi HR, Piccart-Gebhart MJ, Bogaerts J et al (2011) TP53 status for prediction of sensitivity to taxane versus non-taxane neoadjuvant chemotherapy in breast cancer (EORTC 10994/BIG 1-00): a randomised phase 3 trial. Lancet Oncol 12:527–539. https://doi.org/10.1016/s1470-2045(11)70094-8 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Goldhirsch A, Wood WC, Coates AS et al (2011) Strategies for subtypes-dealing with the diversity of breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol 22:1736–1747. https://doi.org/10.1093/annonc/mdr304 CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Metzger-Filho O, Sun Z, Viale G et al (2013) Patterns of recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international breast cancer study group trials VIII and IX. J Clin Oncol 31:3083–3090. https://doi.org/10.1200/jco.2012.46.1574 CrossRefPubMedPubMedCentralGoogle Scholar