Gene expression profiles of multiple breast cancer phenotypes and response to neoadjuvant chemotherapy.
OBJECTIVE
Breast cancer is a heterogeneous disease, and markers for disease subtypes and therapy response remain poorly defined. For that reason, we employed a prospective neoadjuvant study in locally advanced breast cancer to identify molecular signatures of gene expression correlating with known prognostic clinical phenotypes, such as inflammatory breast cancer or the presence of hypoxia. In addition, we defined molecular signatures that correlate with response to neoadjuvant chemotherapy.


METHODS
Tissue was collected under ultrasound guidance from patients with stage IIB/III breast cancer before four cycles of neoadjuvant liposomal doxorubicin paclitaxel chemotherapy combined with local whole breast hyperthermia. Gene expression analysis was done using Affymetrix U133 Plus 2.0 GeneChip arrays.


RESULTS
Gene expression patterns were identified that defined the phenotypes of inflammatory breast cancer as well as tumor hypoxia. In addition, molecular signatures were identified that predicted the persistence of malignancy in the axillary lymph nodes after neoadjuvant chemotherapy. This persistent lymph node signature significantly correlated with disease-free survival in two separate large populations of breast cancer patients.


CONCLUSIONS
Gene expression signatures have the capacity to identify clinically significant features of breast cancer and can predict which individual patients are likely to be resistant to neoadjuvant therapy, thus providing the opportunity to guide treatment decisions.
Dressman
Holly K
HK
Duke Institute for Genome Sciences and Policy, Duke University Medical Center, Duke University, Durham, North Carolina 27710, USA. dress002@mc.duke.edu
Hans
Christopher
C
Bild
Andrea
A
Olson
John A
JA
Rosen
Eric
E
Marcom
P Kelly
PK
Liotcheva
Vlayka B
VB
Jones
Ellen L
EL
Vujaskovic
Zeljko
Z
Marks
Jeffrey
J
Dewhirst
Mark W
MW
West
Mike
M
Nevins
Joseph R
JR
Blackwell
Kimberly
K
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate