Cargando…

Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer

INTRODUCTION: Biological markers that reliably predict clinical or pathological response to primary systemic therapy early during a course of chemotherapy may have considerable clinical potential. This study evaluated changes in Ki-67 labeling index and apoptotic index (AI) before, during, and after...

Descripción completa

Detalles Bibliográficos
Autores principales: Burcombe, Russell, Wilson, George D, Dowsett, Mitch, Khan, Ifty, Richman, Paul I, Daley, Frances, Detre, Simone, Makris, Andreas
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1557736/
https://www.ncbi.nlm.nih.gov/pubmed/16790076
http://dx.doi.org/10.1186/bcr1508
_version_ 1782129400662196224
author Burcombe, Russell
Wilson, George D
Dowsett, Mitch
Khan, Ifty
Richman, Paul I
Daley, Frances
Detre, Simone
Makris, Andreas
author_facet Burcombe, Russell
Wilson, George D
Dowsett, Mitch
Khan, Ifty
Richman, Paul I
Daley, Frances
Detre, Simone
Makris, Andreas
author_sort Burcombe, Russell
collection PubMed
description INTRODUCTION: Biological markers that reliably predict clinical or pathological response to primary systemic therapy early during a course of chemotherapy may have considerable clinical potential. This study evaluated changes in Ki-67 labeling index and apoptotic index (AI) before, during, and after neoadjuvant anthracycline chemotherapy. METHODS: Twenty-seven patients receiving neoadjuvant FEC (5-fluorouracil, epirubicin, and cyclophosphamide) chemotherapy for operable breast cancer underwent repeat core biopsy after 21 days of treatment. Tissue from pre-treatment biopsy, day 21 and surgery was analysed for Ki-67 index and AI. RESULTS: The objective clinical response rate was 56%. Eight patients (31%) achieved a pathological response by histological criteria; two patients had a near-complete pathological response. A reduction in Ki-67 index was observed in 68% of patients at day 21 and 72% at surgery; Ki-67 index increased between day 21 and surgery in 54%. AI decreased in 50% of tumours by day 21, increased in 45% and was unchanged in one patient; 56% demonstrated rebound increases in AI by the time of surgery. Neither pre-treatment nor post-chemotherapy median Ki-67 index nor median AI at all three time points or relative changes at day 21 and surgery differed significantly between clinical or pathological responders and non-responders. Clinical responders had lower median Ki-67 indices at day 21 (11.4% versus 27.0%, p = 0.02) and significantly greater percentage reductions in Ki-67 at day 21 than did non-responders (-50.6% versus -5.3%, p = 0.04). The median day-21 Ki-67 was higher in pathological responders (30.3% versus 14.1%, p = 0.046). A trend toward increased AI at day 21 in pathological responders was observed (5.30 versus 1.68, p = 0.12). Increased day-21 AI was a statistically significant predictor of pathological response (p = 0.049). A strong trend for predicting pathological response was seen with higher Ki-67 indices at day 21 and AI at surgery (p = 0.06 and 0.06, respectively). CONCLUSION: The clinical utility of early changes in biological marker expression during chemotherapy remains unclear. Until further prospectively validated evidence confirming the reliability of predictive markers is available, clinical decision-making should not be based upon individual biological tumour marker profiles.
format Text
id pubmed-1557736
institution National Center for Biotechnology Information
language English
publishDate 2006
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-15577362006-09-01 Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer Burcombe, Russell Wilson, George D Dowsett, Mitch Khan, Ifty Richman, Paul I Daley, Frances Detre, Simone Makris, Andreas Breast Cancer Res Research Article INTRODUCTION: Biological markers that reliably predict clinical or pathological response to primary systemic therapy early during a course of chemotherapy may have considerable clinical potential. This study evaluated changes in Ki-67 labeling index and apoptotic index (AI) before, during, and after neoadjuvant anthracycline chemotherapy. METHODS: Twenty-seven patients receiving neoadjuvant FEC (5-fluorouracil, epirubicin, and cyclophosphamide) chemotherapy for operable breast cancer underwent repeat core biopsy after 21 days of treatment. Tissue from pre-treatment biopsy, day 21 and surgery was analysed for Ki-67 index and AI. RESULTS: The objective clinical response rate was 56%. Eight patients (31%) achieved a pathological response by histological criteria; two patients had a near-complete pathological response. A reduction in Ki-67 index was observed in 68% of patients at day 21 and 72% at surgery; Ki-67 index increased between day 21 and surgery in 54%. AI decreased in 50% of tumours by day 21, increased in 45% and was unchanged in one patient; 56% demonstrated rebound increases in AI by the time of surgery. Neither pre-treatment nor post-chemotherapy median Ki-67 index nor median AI at all three time points or relative changes at day 21 and surgery differed significantly between clinical or pathological responders and non-responders. Clinical responders had lower median Ki-67 indices at day 21 (11.4% versus 27.0%, p = 0.02) and significantly greater percentage reductions in Ki-67 at day 21 than did non-responders (-50.6% versus -5.3%, p = 0.04). The median day-21 Ki-67 was higher in pathological responders (30.3% versus 14.1%, p = 0.046). A trend toward increased AI at day 21 in pathological responders was observed (5.30 versus 1.68, p = 0.12). Increased day-21 AI was a statistically significant predictor of pathological response (p = 0.049). A strong trend for predicting pathological response was seen with higher Ki-67 indices at day 21 and AI at surgery (p = 0.06 and 0.06, respectively). CONCLUSION: The clinical utility of early changes in biological marker expression during chemotherapy remains unclear. Until further prospectively validated evidence confirming the reliability of predictive markers is available, clinical decision-making should not be based upon individual biological tumour marker profiles. BioMed Central 2006 2006-06-21 /pmc/articles/PMC1557736/ /pubmed/16790076 http://dx.doi.org/10.1186/bcr1508 Text en Copyright © 2006 Burcombe et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Burcombe, Russell
Wilson, George D
Dowsett, Mitch
Khan, Ifty
Richman, Paul I
Daley, Frances
Detre, Simone
Makris, Andreas
Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer
title Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer
title_full Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer
title_fullStr Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer
title_full_unstemmed Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer
title_short Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer
title_sort evaluation of ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1557736/
https://www.ncbi.nlm.nih.gov/pubmed/16790076
http://dx.doi.org/10.1186/bcr1508
work_keys_str_mv AT burcomberussell evaluationofki67proliferationandapoptoticindexbeforeduringandafterneoadjuvantchemotherapyforprimarybreastcancer
AT wilsongeorged evaluationofki67proliferationandapoptoticindexbeforeduringandafterneoadjuvantchemotherapyforprimarybreastcancer
AT dowsettmitch evaluationofki67proliferationandapoptoticindexbeforeduringandafterneoadjuvantchemotherapyforprimarybreastcancer
AT khanifty evaluationofki67proliferationandapoptoticindexbeforeduringandafterneoadjuvantchemotherapyforprimarybreastcancer
AT richmanpauli evaluationofki67proliferationandapoptoticindexbeforeduringandafterneoadjuvantchemotherapyforprimarybreastcancer
AT daleyfrances evaluationofki67proliferationandapoptoticindexbeforeduringandafterneoadjuvantchemotherapyforprimarybreastcancer
AT detresimone evaluationofki67proliferationandapoptoticindexbeforeduringandafterneoadjuvantchemotherapyforprimarybreastcancer
AT makrisandreas evaluationofki67proliferationandapoptoticindexbeforeduringandafterneoadjuvantchemotherapyforprimarybreastcancer