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Clinical Trial
. 2014 Jun;25(6):1128-36.
doi: 10.1093/annonc/mdu118. Epub 2014 Mar 11.

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

H Bonnefoi  1 , S Litière  2 , M Piccart  3 , G MacGrogan  4 , P Fumoleau  5 , E Brain  6 , T Petit  7 , P Rouanet  8 , J Jassem  9 , C Moldovan  10 , A Bodmer  11 , K Zaman  12 , T Cufer  13 , M Campone  14 , E Luporsi  15 , P Malmström  16 , G Werutsky  2 , J Bogaerts  2 , J Bergh  17 , D A Cameron  18 ; EORTC 10994/BIG 1-00 Study investigators
Affiliations
Clinical Trial

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

H Bonnefoi et al. Ann Oncol. 2014 Jun.

Abstract

Background: Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes.

Patients and methods: Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses.

Results: Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P < 0.001 in favour of pCR], DMFS (HR = 0.32, P < 0.001) and OS (HR = 0.32, P < 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1).

Conclusions: pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis.

Clinicaltrialsgov: EORTC 10994/BIG 1-00 Trial registration number NCT00017095.

Keywords: TP53; breast cancer; landmark analysis; neoadjuvant chemotherapy; pathological complete response.

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Figures

Figure 1.
Figure 1.
Effect of pCR on EFS by intrinsic subtype (N = 1212 eligible and assessable patients). pCR, pathological complete response; EFS, event-free survival.
Figure 1.
Figure 1.
Effect of pCR on EFS by intrinsic subtype (N = 1212 eligible and assessable patients). pCR, pathological complete response; EFS, event-free survival.
Figure 1.
Figure 1.
Effect of pCR on EFS by intrinsic subtype (N = 1212 eligible and assessable patients). pCR, pathological complete response; EFS, event-free survival.
Figure 2.
Figure 2.
Effect of pCR on EFS by intrinsic subtype: univariate Cox regression models (N = 1212 eligible and assessable patients). pCR, pathological complete response; EFS, event-free survival; HR, hazard ratio; CI, confidence interval; HER2, human epidermal growth factor 2; df, degrees of freedom.
Figure 3.
Figure 3.
Effect of pCR on event-free survival by intrinsic subtype and TP53 status: univariate Cox regression models (N = 1212 eligible and assessable patients)a. pCR, pathological complete response; HR, hazard ratio; CI, confidence interval; HER2, human epidermal growth factor 2; df, degrees of freedom. aTwo hundred and thirty-seven patients with p53 status missing were not considered in this graph.
See this image and copyright information in PMC

References

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