title: Treatment response to preoperative anthracycline-based chemotherapy in locally advanced breast cancer: the relevance of proliferation and apoptosis rates.
abstract: Objectives were to evaluate the relevance of proliferating fraction (Ki-67) along with apoptotic index (AI) which denoted growth index (Ki-67/AI ratio, GI) to predict pathological response to preoperative chemotherapy, and the pattern of their modifications following chemotherapy in women with locally advanced breast cancer. Archival material of diagnostic biopsies and surgical specimens from 106 patients were examined. Response rate to chemotherapy in this group was 95 %, eight (8 %) patients achieved a pathological complete remission (pCR) and five (5 %) had a progressive/stable disease (PD/SD). The expression of Ki-67 and AI were assessed using immunohistochemistry and in situ DNA nick labeling assay respectively. Higher baseline level of Ki-67 and GI were associated with an improved pathological response (p = 0.0001 and p = 0.008), but the degree of correlation with GI was no greater than that with Ki-67 alone. Ki-67 below 1 % highly indicated a lack of tumor response. High AI which characterized the opposite chemo-sensitive tumors, pCR vs. PD/SD (p = 0.72) implied that treatment response was not influenced by the "presence" or "absence" of apoptosis. A significant decrease in Ki-67 (p < 0.001), AI (p = 0.035) and GI (p = 0.008) was found following chemotherapy, but percentage change in biomarker values revealed an increase in a number of cases. Higher initial Ki-67 and AI was associated with profound reduction of GI and raising value of GI after treatment, respectively. Such a variance of a given parameter elicited by chemotherapy may have various impact on disease outcome.
authors.affiliation: Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, Belgrade, Serbia. ksenijakanjer@gmail.com
authors.forename: Ksenija
authors.initials: K
authors.lastname: Kanjer
authors.forename: Svetislav
authors.initials: S
authors.lastname: Tatić
authors.forename: Zora
authors.initials: Z
authors.lastname: Nešković-Konstantinović
authors.forename: Zaki
authors.initials: Z
authors.lastname: Abu Rabi
authors.forename: Dragica
authors.initials: D
authors.lastname: Nikolić-Vukosavljević
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D057234:Preoperative Period; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil