title: Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome.
abstract: The aim of this study was to provide a better insight into breast cancer response to chemotherapy. Chemotherapy improves outcome in breast cancer patients. The effect of cytotoxic treatment cannot be predicted for individual patients. Therefore, the identification of tumour characteristics associated with tumour response and outcome is of great clinical interest. We studied 97 patients, who received anthracycline-based neoadjuvant chemotherapy. Tumour samples were taken prior to and after chemotherapy. We quantified the response to chemotherapy clinically and pathologically and determined histological and molecular tumour characteristics. We assessed changes in the expression of Bcl-2, ER, P53 HER2 and Ki-67. Association with response and outcome was tested for all parameters. The experimental results showed 15 clinical (17%) and three (3%) pathological complete remissions. There were 18 (20%) clinical vs 29 (33%) pathological nonresponders. The expression of most markers was similar before and after chemotherapy. Only Ki-67 was significantly decreased after chemotherapy. Factors correlated with response were: large tumour size, ER negativity, high Ki-67 count and positive P53 status. Tumour response and marker expression did not predict disease-free or overall survival. In conclusion, clinical and pathological response assessments are poorly associated. Proliferation decreases significantly after chemotherapy. ER negativity and a high proliferation index are associated with better response. HER2 status does not predict response, and outcome is not related to tumour response.
authors.affiliation: Department of Pathology, The Netherlands Cancer Institute, Amsterdam.
authors.forename: I F
authors.initials: IF
authors.lastname: Faneyte
authors.forename: J G
authors.initials: JG
authors.lastname: Schrama
authors.forename: J L
authors.initials: JL
authors.lastname: Peterse
authors.forename: P L
authors.initials: PL
authors.lastname: Remijnse
authors.forename: S
authors.initials: S
authors.lastname: Rodenhuis
authors.forename: M J
authors.initials: MJ
authors.lastname: van de Vijver
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016019:Survival Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D000903:Antibiotics, Antineoplastic; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53