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


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.


CONCLUSIONS
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.
Hannemann
Juliane
J
Division of Experimental Therapy, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Oosterkamp
Hendrika M
HM
Bosch
Cathy A J
CA
Velds
Arno
A
Wessels
Lodewyk F A
LF
Loo
Claudette
C
Rutgers
Emiel J
EJ
Rodenhuis
Sjoerd
S
van de Vijver
Marc J
MJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003520:Cyclophosphamide / Q000627:therapeutic use; D000077143:Docetaxel; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D005810:Multigene Family; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
D005819:Genetic Markers; D012334:RNA, Neoplasm; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide