Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast-conservation surgery, with or without postoperative radiotherapy.
BACKGROUND
Some patients with breast cancer develop local recurrence after breast-conservation surgery despite postoperative radiotherapy, whereas others remain free of local recurrence even in the absence of radiotherapy. As clinical parameters are insufficient for identifying these two groups of patients, we investigated whether gene expression profiling would add further information.


METHODS
We performed gene expression analysis (oligonucleotide arrays, 26,824 reporters) on 143 patients with lymph node-negative disease and tumor-free margins. A support vector machine was employed to build classifiers using leave-one-out cross-validation.


RESULTS
Within the estrogen receptor-positive (ER+) subgroup, the gene expression profile clearly distinguished patients with local recurrence after radiotherapy (n = 20) from those without local recurrence (n = 80 with or without radiotherapy). The receiver operating characteristic (ROC) area was 0.91, and 5,237 of 26,824 reporters had a P value of less than 0.001 (false discovery rate = 0.005). This gene expression profile provides substantially added value to conventional clinical markers (for example, age, histological grade, and tumor size) in predicting local recurrence despite radiotherapy. Within the ER- subgroup, a weaker, but still significant, signal was found (ROC area = 0.74). The ROC area for distinguishing patients who develop local recurrence from those who remain local recurrence-free in the absence of radiotherapy was 0.66 (combined ER+/ER-).


CONCLUSIONS
A highly distinct gene expression profile for patients developing local recurrence after breast-conservation surgery despite radiotherapy has been identified. If verified in further studies, this profile might be a most important tool in the decision making for surgery and adjuvant therapy.
Niméus-Malmström
Emma
E
Institute of Clinical Sciences, Department of Oncology, University Hospital, SE 221 85 Lund, Sweden.
Krogh
Morten
M
Malmström
Per
P
Strand
Carina
C
Fredriksson
Irma
I
Karlsson
Per
P
Nordenskjöld
Bo
B
Stål
Olle
O
Ostberg
Görel
G
Peterson
Carsten
C
Fernö
Mårten
M
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism* / Q000517:prevention & control*; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012372:ROC Curve; D018714:Radiotherapy, Adjuvant; D011960:Receptors, Estrogen / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors
D011960:Receptors, Estrogen