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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

Bonnefoi, H.; Litiere, S.; Piccart, M.; MacGrogan, G.; Fumoleau, P.; Brain, E.; Petit, T.; Rouanet, P.; Jassem, J. and Moldovan, C., et al. (2014) In Annals of Oncology 25(6). p.1128-1136
Abstract
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 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... (More)
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 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. 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). pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis. (Less)
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published
subject
keywords
breast cancer, neoadjuvant chemotherapy, TP53, landmark analysis, pathological complete response
in
Annals of Oncology
volume
25
issue
6
pages
1128 - 1136
publisher
Oxford University Press
external identifiers
  • wos:000337028100008
  • scopus:84903277747
ISSN
1569-8041
DOI
10.1093/annonc/mdu118
language
English
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yes
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0375add3-30bb-4a65-a0f3-3af80d413f40 (old id 4549120)
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2014-08-01 07:37:56
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2017-11-05 04:04:14
@article{0375add3-30bb-4a65-a0f3-3af80d413f40,
  abstract     = {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 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. 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 &lt; 0.001 in favour of pCR], DMFS (HR = 0.32, P &lt; 0.001) and OS (HR = 0.32, P &lt; 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). pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis.},
  author       = {Bonnefoi, H. and Litiere, S. and Piccart, M. and MacGrogan, G. and Fumoleau, P. and Brain, E. and Petit, T. and Rouanet, P. and Jassem, J. and Moldovan, C. and Bodmer, A. and Zaman, K. and Cufer, T. and Campone, M. and Luporsi, E. and Malmström, Per and Werutsky, G. and Bogaerts, J. and Bergh, J. and Cameron, D. A.},
  issn         = {1569-8041},
  keyword      = {breast cancer,neoadjuvant chemotherapy,TP53,landmark analysis,pathological complete response},
  language     = {eng},
  number       = {6},
  pages        = {1128--1136},
  publisher    = {Oxford University Press},
  series       = {Annals of Oncology},
  title        = {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},
  url          = {http://dx.doi.org/10.1093/annonc/mdu118},
  volume       = {25},
  year         = {2014},
}