Changes in gene expression associated with response to neoadjuvant chemotherapy in breast cancer

TY - JOUR

T1 - Changes in gene expression associated with response to neoadjuvant chemotherapy in breast cancer

AU - Hannemann, Juliane

AU - Oosterkamp, Hendrika M

AU - Bosch, Cathy A J

AU - Velds, Arno

AU - Wessels, Lodewyk F A

AU - Loo, Claudette

AU - Rutgers, Emiel J

AU - Rodenhuis, Sjoerd

AU - van de Vijver, Marc J

PY - 2005/5/20

Y1 - 2005/5/20

N2 - PURPOSE: At present, clinically useful markers predicting response of primary breast carcinomas to either doxorubicin-cyclophosphamide (AC) or doxorubicin-docetaxel (AD) are lacking. We investigated whether gene expression profiles of the primary tumor could be used to predict treatment response to either of those chemotherapy regimens.PATIENTS AND METHODS: Within a single-institution, randomized, phase II trial, patients with locally advanced breast cancer received six courses of either AC (n = 24) or AD (n = 24) neoadjuvant chemotherapy. Gene expression profiles were generated from core-needle biopsies obtained before treatment and correlated with the response of the primary tumor to the chemotherapy administered. Additionally, pretreatment gene expression profiles were compared with those in tumors remaining after chemotherapy.RESULTS: Ten (20%) of 48 patients showed a (near) pathologic complete remission of the primary tumor after treatment. No gene expression pattern correlating with response could be identified for all patients or for the AC or AD groups separately. The comparison of the pretreatment biopsy and the tumor excised after chemotherapy revealed differences in gene expression in tumors that showed a partial remission but not in tumors that did not respond to chemotherapy.CONCLUSION: No gene expression profile predicting the response of primary breast carcinomas to AC- or AD-based neoadjuvant chemotherapy could be detected in this interim analysis. More subtle differences in gene expression are likely to be present but can only be reliably identified by studying a larger group of patients. Response of a breast tumor to neoadjuvant chemotherapy results in alterations in gene expression.

AB - PURPOSE: At present, clinically useful markers predicting response of primary breast carcinomas to either doxorubicin-cyclophosphamide (AC) or doxorubicin-docetaxel (AD) are lacking. We investigated whether gene expression profiles of the primary tumor could be used to predict treatment response to either of those chemotherapy regimens.PATIENTS AND METHODS: Within a single-institution, randomized, phase II trial, patients with locally advanced breast cancer received six courses of either AC (n = 24) or AD (n = 24) neoadjuvant chemotherapy. Gene expression profiles were generated from core-needle biopsies obtained before treatment and correlated with the response of the primary tumor to the chemotherapy administered. Additionally, pretreatment gene expression profiles were compared with those in tumors remaining after chemotherapy.RESULTS: Ten (20%) of 48 patients showed a (near) pathologic complete remission of the primary tumor after treatment. No gene expression pattern correlating with response could be identified for all patients or for the AC or AD groups separately. The comparison of the pretreatment biopsy and the tumor excised after chemotherapy revealed differences in gene expression in tumors that showed a partial remission but not in tumors that did not respond to chemotherapy.CONCLUSION: No gene expression profile predicting the response of primary breast carcinomas to AC- or AD-based neoadjuvant chemotherapy could be detected in this interim analysis. More subtle differences in gene expression are likely to be present but can only be reliably identified by studying a larger group of patients. Response of a breast tumor to neoadjuvant chemotherapy results in alterations in gene expression.

KW - Adult

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Breast Neoplasms/drug therapy

KW - Cyclophosphamide/therapeutic use

KW - Docetaxel

KW - Doxorubicin/therapeutic use

KW - Female

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Genetic Markers/genetics

KW - Humans

KW - Middle Aged

KW - Multigene Family

KW - Neoadjuvant Therapy

KW - Neoplasm Invasiveness/pathology

KW - Neoplasm Staging

KW - Prognosis

KW - RNA, Neoplasm/genetics

KW - Risk Assessment

KW - Sensitivity and Specificity

KW - Survival Analysis

KW - Taxoids/therapeutic use

KW - Treatment Outcome

U2 - 10.1200/JCO.2005.09.077

DO - 10.1200/JCO.2005.09.077

M3 - SCORING: Journal article

C2 - 15908647

VL - 23

SP - 3331

EP - 3342

JO - J CLIN ONCOL

JF - J CLIN ONCOL

SN - 0732-183X

IS - 15

ER -