Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer.
OBJECTIVE
We sought to identify gene expression markers that predict the likelihood of chemotherapy response. We also tested whether chemotherapy response is correlated with the 21-gene Recurrence Score assay that quantifies recurrence risk.


METHODS
Patients with locally advanced breast cancer received neoadjuvant paclitaxel and doxorubicin. RNA was extracted from the pretreatment formalin-fixed paraffin-embedded core biopsies. The expression of 384 genes was quantified using reverse transcriptase polymerase chain reaction and correlated with pathologic complete response (pCR). The performance of genes predicting for pCR was tested in patients from an independent neoadjuvant study where gene expression was obtained using DNA microarrays.


RESULTS
Of 89 assessable patients (mean age, 49.9 years; mean tumor size, 6.4 cm), 11 (12%) had a pCR. Eighty-six genes correlated with pCR (unadjusted P < .05); pCR was more likely with higher expression of proliferation-related genes and immune-related genes, and with lower expression of estrogen receptor (ER) -related genes. In 82 independent patients treated with neoadjuvant paclitaxel and doxorubicin, DNA microarray data were available for 79 of the 86 genes. In univariate analysis, 24 genes correlated with pCR with P < .05 (false discovery, four genes) and 32 genes showed correlation with P < .1 (false discovery, eight genes). The Recurrence Score was positively associated with the likelihood of pCR (P = .005), suggesting that the patients who are at greatest recurrence risk are more likely to have chemotherapy benefit.


CONCLUSIONS
Quantitative expression of ER-related genes, proliferation genes, and immune-related genes are strong predictors of pCR in women with locally advanced breast cancer receiving neoadjuvant anthracyclines and paclitaxel.
Gianni
Luca
L
Medical Oncology, Istituto Nazionale Tumori, Via Venezian, 1, 20133 Milano, Italy. gianni@istitutotumori.mi.it
Zambetti
Milvia
M
Clark
Kim
K
Baker
Joffre
J
Cronin
Maureen
M
Wu
Jenny
J
Mariani
Gabriella
G
Rodriguez
Jaime
J
Carcangiu
Marialuisa
M
Watson
Drew
D
Valagussa
Pinuccia
P
Rouzier
Roman
R
Symmans
W Fraser
WF
Ross
Jeffrey S
JS
Hortobagyi
Gabriel N
GN
Pusztai
Lajos
L
Shak
Steven
S
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001707:Biopsy, Needle; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000627:therapeutic use; D011237:Predictive Value of Tests; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D004317:Doxorubicin; D017239:Paclitaxel