PRECLINICAL STUDY Pathological non-response to chemotherapy in a neoadjuvant setting of breast cancer: an inter-institutional study

To identify markers of non-response to neoadjuvant chemotherapy (NAC) that could be used in the adjuvant setting. Sixteen pathologists of the European Working Group for Breast Screening Pathology reviewed the core biopsies of breast cancers treated with NAC and recorded the clinico-pathological findings (histological type and grade; estrogen, progesterone receptors, and HER2 status; Ki67; mitotic count; tumor-infiltrating lymphocytes; necrosis) and data regarding the pathological response in corresponding surgical resection specimens. Analyses were carried out in a cohort of 490 cases by comparing the groups of patients showing pathological complete response (pCR) and partial response (pPR) with the group of non-responders (pathological non-response: pNR). Among other parameters, the lobular histotype and the absence of inflammation were significantly more common in pNR (p \ 0.001). By ROC curve analyses, cutoff values of 9 mitosis/2 mm and 18 % of Ki67-positive cells best discriminated the pNR and pCR ? pPR categories (p = 0.018 and \ 0.001, respectively). By multivariable analysis, only the cut-off value of 9 mitosis discriminated the different response categories (p = 0.036) in the entire cohort. In the Luminal B/HER2subgroup, a mitotic count \9, although not statistically significant, showed an OR of 2.7 of pNR. A lobular histotype and the absence of inflammation were independent predictors of pNR (p = 0.024 and \0.001, respectively). Classical morphological parameters, such as lobular histotype and Electronic supplementary material The online version of this article (doi:10.1007/s10549-014-3192-3) contains supplementary material, which is available to authorized users. D. Balmativola C. Marchiò L. Chiusa L. Annaratone F. Maletta A. Sapino (&) Division of Pathology, Department of Medical Sciences, University of Turin, via Santena 7, Turin, Italy e-mail: [email protected] M. Maule Cancer Epidemiology Unit, CeRMS and CPO-Piemonte, Department of Medical Sciences, University of Turin, Turin, Italy F. Montemurro Unit of Investigative Clinical Oncology (INCO), Institute for Cancer Research and Treatment (IRCCs), Candiolo, Italy J. Kulka 2nd Department of Pathology, Semmelweis University, 1091 Budapest, Hungary P. Figueiredo Laboratorio De Histopatologica, Centro Regional De Oncologia De Coimbra, Coimbra, Portugal Z. Varga Institute of Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland I. Liepniece-Karele State Pathology Center, Riga East Clinical University Hospital, Riga, Latvia G. Cserni Department of Pathology, Bács-Kiskun County Teaching Hospital, Nyiri ut 38, 6000 Kecskemet, Hungary E. Arkoumani Michael Letcher Department of Cellular Pathology, The Princess Alexandra Hospital, Harlow, Essex, UK I. Amendoeira Instituto de Patologia e Imunologia Molecular da Universidade do Porto e Serviço de Anatomia Patologica, Hospital S Joao, 4200 Porto, Portugal 123 Breast Cancer Res Treat (2014) 148:511–523 DOI 10.1007/s10549-014-3192-3