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Clinical

ER+, early clinical stage (T1/2, N0, M0), age <45 and >70

Purpose

Signaling pathways that converge on two different transcription factor complexes, NF? and AP-1, have been identified in estrogen receptor (ER)-positive breast cancers resistant to the antiestrogen, tamoxifen. The aim of this study was to explore the potential of linking genes upregulated by both NF?B and AP-1 with tamoxifen resistance.

Hypothesis

The hypothesis of this study was that genes upregulated by NF?B and AP-1 in ER+, node-negative breast cancer have a prognostic association with patient outcome after adjuvant tamoxifen therapy.

Experimental Design

This dataset contains cryobanked breast cancer specimens from the University of California San Francisco (UCSF) Comprehensive Cancer Center Breast Oncology Program Tissue Core, collected under UCSF approved protocols following patient consent. From an archive of over 1,000 liquid nitrogen frozen breast cancer specimens, 54 primary breast cancer samples (UCSF cases) had been selected, using the following criteria: early clinical stage (T1/2, N0, M0) invasive breast cancer, ER-positive status (>10% nuclear immunohistochemical staining), known primary systemic therapy (treatment era: 1989–2004, with 33/54 receiving adjuvant tamoxifen and 18/54 receiving adjuvant chemotherapy), known clinical outcome (relapse-free survival, RFS), and stratification into young (? 45 years, n = 29) or old (? 70 years, n = 25) age-at-diagnosis. The age stratification groups were balanced for standard prognostic markers (tumor size, grade, proliferation index, ERBB2 status) and adjuvant therapy, but showed differences in clinical outcome with the younger cases experiencing more frequent (7/29) and earlier metastatic relapses (median RFS = 4.84 years, range 0.13–14.14 years) than the older age-at-diagnosis cases (2/25; median RFS = 5.52 years, range 0.74–12.72 years). Sample requirements also included a minimum frozen-wet weight of 100 mg and histologic confirmation of >50% cancer cells per sample section.

Experimental Variables

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Controls

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Methods

Total RNA from each tissue sample was formamide extracted, purified and reconstituted in aqueous solution using RNeasy (Qiagen, CA) according to manufacturer's instructions; and the resulting RNA samples were quality verified by micro-analysis (Agilent Bioanalyzer, CA).

Total RNA (3–5 ?g per sample) was labeled and analyzed using Affymetrix (Santa Clara, CA) high-density oligonucleotide microarrays, HG-U133A (v2), in 96-well chips each with 22.2 K annotated probes representing ~13 K unique Unigenes. Gene expression analysis was performed using standard Affymetrix procedures within the Lawrence Berkeley National Lab and Life Science Division's Molecular Profiling Laboratory (MPL). Probe set measurements were generated from quantified Affymetrix image files (.CEL files) using the RMA algorithm from BioConductor R. The resulting data matrix consisted of normalized log abundance values for each probe set and sample; these data files and associated clinical parameters for each sample have been entered into the NCBI Gene Expression Omnibus (GEO) repository (GSE7378).

Additional Information

Zhou, Yamei, Christina Yau, Joe W. Gray, Karen Chew, Shanaz H. Dairkee, Dan H. Moore, Urs Eppenberger, Serenella Eppenberger-Castori, and Christopher C. Benz. “Enhanced NF Kappa B and AP-1 Transcriptional Activity Associated with Antiestrogen Resistant Breast Cancer.” BMC Cancer 7 (2007): 59. doi:10.1186/1471-2407-7-59.

Microarray
Affymetrix HG-U133A
54 Samples Loaded: 54
Human (Homo sapiens)
Nagalla 2013 , National Cancer Institute, Bari, Italy , Breast Cancer Tissue , U C San Francisco Comprehensive Cancer Center
ER+ Breast Cancer
Sample Set Spreadsheet
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Samples Preview
Sample ID series IMS IBS IDS ICR
GSM177493 NA LumB IBE PID ICR2
GSM177494 NA Basal IBE WID ICR3
GSM177495 NA Normal IBE NA ICR4
GSM177496 NA LumA IBD WID ICR1
GSM177497 NA LumA IBD PID ICR1
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File
GSE7378_appended.meta.data_v1.csv
Sample Set Spreadsheet
Log2 Transformed
Raw Signal
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Samples Viewer / Editor

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Sample ID Series IMS IBS IDS ICR Array Sample ID Sample Title DMFS 10Y EVENT DMFS 10Y TIME Disease Free Survival Event Distant Met Free Survival Event Distant Met Free Survival Age At Initial Pathologic Diagnosis Lymph Node Status ER Status PR Status Histology Differentiation Grade Tumor Size Cm Pathology T Stage Disease Free Survival Years
GSM177493
NA
LumB
IBE
PID
ICR2
400003188
breast tumor-b0166
DistantMetastasis
5
Recurred/Progressed
NA
NA
71
LN-
ER+
NA
NA
NA
NA
5
GSM177494
NA
Basal
IBE
WID
ICR3
400003189
breast tumor-b0175
DistantMetastasis
2.71
Recurred/Progressed
NA
NA
74
LN-
ER+
NA
NA
NA
NA
2.71
GSM177495
NA
Normal
IBE
NA
ICR4
400003190
breast tumor-b0243
DistantMetastasisFree
10
DiseaseFree
NA
NA
40
LN-
ER+
NA
NA
NA
NA
14.14
GSM177496
NA
LumA
IBD
WID
ICR1
400003191
breast tumor-b0255
DistantMetastasisFree
10
Recurred/Progressed
NA
NA
42
LN-
ER+
NA
NA
NA
NA
12.6
GSM177497
NA
LumA
IBD
PID
ICR1
400003192
breast tumor-b0296
DistantMetastasisFree
6.02
DiseaseFree
NA
NA
82
LN-
ER+
NA
NA
NA
NA
7.2
GSM177498
NA
LumA
IBD
PID
ICR1
400003193
breast tumor-b0316
DistantMetastasisFree
5.38
DiseaseFree
NA
NA
82
LN-
ER+
NA
NA
NA
NA
5.38
GSM177499
NA
LumA
IBD
PID
ICR1
400003194
breast tumor-b0317
DistantMetastasisFree
8.67
DiseaseFree
NA
NA
73
LN-
ER+
NA
NA
NA
NA
11.45
GSM177500
NA
LumA
IBD
PID
ICR2
400003195
breast tumor-b0337
DistantMetastasisFree
10
DiseaseFree
NA
NA
70
LN-
ER+
NA
NA
NA
NA
12.72
GSM177501
NA
LumA
IBD
PID
ICR2
400003196
breast tumor-b0341
DistantMetastasisFree
3.32
Recurred/Progressed
NA
NA
37
LN-
ER+
NA
NA
NA
NA
3.27
GSM177502
NA
LumA
IBD
PID
ICR1
400003197
breast tumor-b0370
DistantMetastasisFree
10
DiseaseFree
NA
NA
43
LN-
ER+
NA
NA
NA
NA
10.98
GSM177503
NA
LumA
IBD
WID
ICR2
400003198
breast tumor-b0395
DistantMetastasisFree
6.2
DiseaseFree
NA
NA
78
LN-
ER+
NA
NA
NA
NA
6.2
GSM177504
NA
LumA
IBD
PID
ICR1
400003199
breast tumor-b0404
DistantMetastasisFree
10
DiseaseFree
NA
NA
76
LN-
ER+
NA
NA
NA
NA
11.7
GSM177505
NA
LumA
IBD
PID
ICR1
400003200
breast tumor-b0414
DistantMetastasisFree
9.98
DiseaseFree
NA
NA
43
LN-
ER+
NA
NA
NA
NA
11.69
GSM177506
NA
Normal
IBE
NA
ICR2
400003201
breast tumor-b0420
DistantMetastasis
4.33
Recurred/Progressed
NA
NA
37
LN-
ER+
NA
NA
NA
NA
4.29
GSM177507
NA
Normal
IBE
NA
ICR2
400003202
breast tumor-b0442
DistantMetastasisFree
3.27
DiseaseFree
NA
NA
86
LN-
ER+
NA
NA
NA
NA
3.27
GSM177508
NA
LumB
IBD
FID
ICR4
400003203
breast tumor-b0468
DistantMetastasisFree
5.13
DiseaseFree
NA
NA
70
LN-
ER+
NA
NA
NA
NA
5.13
GSM177509
NA
Normal
IBE
NA
ICR3
400003204
breast tumor-b0491
DistantMetastasisFree
8.12
DiseaseFree
NA
NA
43
LN-
ER+
NA
NA
NA
NA
8.12
GSM177510
NA
Normal
IBE
NA
ICR3
400003205
breast tumor-b0493
DistantMetastasisFree
3.78
DiseaseFree
NA
NA
70
LN-
ER+
NA
NA
NA
NA
3.78
GSM177511
NA
NA
NA
NA
NA
400003206
breast tumor-b0513
NA
NA
Recurred/Progressed
NA
NA
41
LN-
ER+
NA
NA
NA
NA
4.84
GSM177512
NA
Normal
IBE
NA
ICR2
400003207
breast tumor-b0524
DistantMetastasisFree
9.54
DiseaseFree
NA
NA
70
LN-
ER+
NA
NA
NA
NA
9.54
GSM177513
NA
Her2
IBD
WID
ICR4
400003208
breast tumor-b0592
DistantMetastasisFree
0.86
DiseaseFree
NA
NA
39
LN-
ER+
NA
NA
NA
NA
0.86
GSM177514
NA
Her2
IBD
WID
ICR3
400003209
breast tumor-b0639
DistantMetastasisFree
1.01
DiseaseFree
NA
NA
36
LN-
ER+
NA
NA
NA
NA
1.01
GSM177515
NA
LumA
IBD
PID
ICR1
400003210
breast tumor-b0668
DistantMetastasisFree
0.43
DiseaseFree
NA
NA
42
LN-
ER+
NA
NA
NA
NA
6.99
GSM177516
NA
Normal
IBE
NA
ICR2
400003211
breast tumor-b0729
DistantMetastasisFree
0.13
DiseaseFree
NA
NA
37
LN-
ER+
NA
NA
NA
NA
0.13
GSM177517
NA
LumA
IBD
PID
ICR1
400003212
breast tumor-b0862
DistantMetastasisFree
3.84
DiseaseFree
NA
NA
31
LN-
ER+
NA
NA
NA
NA
3.84
GSM177518
NA
Basal
IBE
FID
ICR3
400003213
breast tumor-b1067
DistantMetastasisFree
0.74
DiseaseFree
NA
NA
76
LN-
ER+
NA
NA
NA
NA
0.74
GSM177519
NA
LumA
IBD
WID
ICR3
400003214
breast tumor-b1144
DistantMetastasisFree
2
DiseaseFree
NA
NA
36
LN-
ER+
NA
NA
NA
NA
2
GSM177520
NA
LumB
IBD
PID
ICR1
400003215
breast tumor-b1148
DistantMetastasisFree
1.88
DiseaseFree
NA
NA
40
LN-
ER+
NA
NA
NA
NA
1.88
GSM177521
NA
LumA
IBD
PID
ICR1
400003216
breast tumor-b1279
DistantMetastasisFree
0.81
DiseaseFree
NA
NA
86
LN-
ER+
NA
NA
NA
NA
0.81
GSM177522
NA
Normal
IBE
NA
ICR2
400003217
breast tumor-b1285
DistantMetastasisFree
0.85
DiseaseFree
NA
NA
42
LN-
ER+
NA
NA
NA
NA
0.85
GSM177523
NA
Normal
IBE
NA
ICR4
400003218
breast tumor-b1306
DistantMetastasisFree
0.54
DiseaseFree
NA
NA
41
LN-
ER+
NA
NA
NA
NA
0.54
GSM177524
NA
LumB
IBE
PID
ICR1
400003219
breast tumor-s0006
DistantMetastasis
2.27
Recurred/Progressed
NA
NA
34
LN-
ER+
NA
NA
NA
NA
2.12
GSM177525
NA
Her2
IBE
WID
ICR3
400003220
breast tumor-s0021
DistantMetastasisFree
8.07
DiseaseFree
NA
NA
70
LN-
ER+
NA
NA
NA
NA
8.07
GSM177526
NA
LumA
IBD
PID
ICR1
400003221
breast tumor-s0033
DistantMetastasisFree
10
DiseaseFree
NA
NA
71
LN-
ER+
NA
NA
NA
NA
11.25
GSM177527
NA
LumA
IBD
PID
ICR1
400003222
breast tumor-s0035
DistantMetastasisFree
10
DiseaseFree
NA
NA
70
LN-
ER+
NA
NA
NA
NA
11.97
GSM177528
NA
LumA
IBD
PID
ICR1
400003223
breast tumor-s0047
DistantMetastasisFree
9.6
DiseaseFree
NA
NA
82
LN-
ER+
NA
NA
NA
NA
11.69
GSM177529
NA
LumA
IBD
PID
ICR2
400003224
breast tumor-s0069
DistantMetastasisFree
5.14
DiseaseFree
NA
NA
79
LN-
ER+
NA
NA
NA
NA
5.14
GSM177530
NA
Normal
IBE
NA
ICR2
400003225
breast tumor-s0099
DistantMetastasisFree
10
DiseaseFree
NA
NA
73
LN-
ER+
NA
NA
NA
NA
11.08
GSM177531
NA
LumA
IBD
PID
ICR1
400003226
breast tumor-s0100
DistantMetastasisFree
8.91
DiseaseFree
NA
NA
42
LN-
ER+
NA
NA
NA
NA
8.85
GSM177532
NA
Her2
IBE
PID
ICR2
400003227
breast tumor-s0116
DistantMetastasisFree
8.51
DiseaseFree
NA
NA
80
LN-
ER+
NA
NA
NA
NA
8.41
GSM177533
NA
LumB
IBD
PID
ICR2
400003228
breast tumor-s0117
DistantMetastasisFree
4.84
DiseaseFree
NA
NA
84
LN-
ER+
NA
NA
NA
NA
4.84
GSM177534
NA
LumB
IBE
PID
ICR1
400003229
breast tumor-s0141
DistantMetastasis
2.47
Recurred/Progressed
NA
NA
40
LN-
ER+
NA
NA
NA
NA
2.47
GSM177535
NA
Her2
IBE
FID
ICR4
400003230
breast tumor-s0148
DistantMetastasisFree
2.31
DiseaseFree
NA
NA
29
LN-
ER+
NA
NA
NA
NA
2.31
GSM177536
NA
LumB
IBE
PID
ICR1
400003231
breast tumor-s0202
DistantMetastasis
6.91
Recurred/Progressed
NA
NA
40
LN-
ER+
NA
NA
NA
NA
6.91
GSM177537
NA
Her2
IBE
FID
ICR3
400003232
breast tumor-s0248
DistantMetastasisFree
9
DiseaseFree
NA
NA
44
LN-
ER+
NA
NA
NA
NA
9
GSM177538
NA
Normal
IBE
NA
ICR2
400003233
breast tumor-s0260
DistantMetastasisFree
0.46
DiseaseFree
NA
NA
41
LN-
ER+
NA
NA
NA
NA
0.46
GSM177539
NA
NA
IBE
NA
ICR2
400003234
breast tumor-s0268
DistantMetastasisFree
5.5
DiseaseFree
NA
NA
76
LN-
ER+
NA
NA
NA
NA
5.5
GSM177540
NA
Her2
IBE
PID
ICR3
400003235
breast tumor-s0278
DistantMetastasisFree
8.56
DiseaseFree
NA
NA
41
LN-
ER+
NA
NA
NA
NA
8.56
GSM177541
NA
Basal
IBD
WID
ICR3
400003236
breast tumor-s0320
DistantMetastasisFree
7.8
DiseaseFree
NA
NA
44
LN-
ER+
NA
NA
NA
NA
7.8
GSM177542
NA
ClaudinLow
IBD
WID
ICR3
400003237
breast tumor-s0367
DistantMetastasisFree
2.19
DiseaseFree
NA
NA
74
LN-
ER+
NA
NA
NA
NA
2.19
GSM177543
NA
Basal
IBE
FID
ICR4
400003238
breast tumor-s1518
DistantMetastasisFree
6.82
DiseaseFree
NA
NA
36
LN-
ER+
NA
NA
NA
NA
6.82
GSM177544
NA
Basal
IBE
PID
ICR3
400003239
breast tumor-s1521
DistantMetastasisFree
5.15
DiseaseFree
NA
NA
40
LN-
ER+
NA
NA
NA
NA
5.15
GSM177545
NA
Normal
IBE
NA
ICR3
400003240
breast tumor-s1545
DistantMetastasisFree
6.62
DiseaseFree
NA
NA
40
LN-
ER+
NA
NA
NA
NA
6.62
GSM177546
NA
Normal
IBE
NA
ICR2
400003241
breast tumor-s1615
DistantMetastasisFree
2.84
DiseaseFree
NA
NA
70
LN-
ER+
NA
NA
NA
NA
2.84

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