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  • Supplementary Figure 1A. R 2 = 0.9694 p < 0.0001 qRT-PCR Illumina BeadChip Supplementary Figure 1B 3 2 1 0 -2 -3 -2 -1 0 1 2 3 4
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Control Trastuzumab Pertuzumab Combination 0 4 8 12 16 KLK11 Control Trastuzumab Pertuzumab Combination 0 1 2 3 CDH1 Control Trastuzumab Pertuzumab Combination 0 1 2 3 SERPINB5 Control Trastuzumab Pertuzumab Combination 0.0 0.5 1.0 1.5 IL8 Control Trastuzumab Pertuzumab Combination 0.0 0.5 1.0 1.5 TGFBI Control Trastuzumab Pertuzumab Combination 0 1 2 3 CDKN1A Control Trastuzumab Pertuzumab Combination 0 1 2 3 PTPRR Control Trastuzumab Pertuzumab Combination 0.0 0.5 1.0 1.5 2.0 STC1 Control Trastuzumab Pertuzumab Combination 0 0.5 1.0 1.5 MMP7 Control Trastuzumab Pertuzumab Combination 0 1 2 3 ENPP2 Supplementary Figure 1A

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Page 1: Supplementary Figure 1A. R 2 = 0.9694 p < 0.0001 qRT-PCR Illumina BeadChip Supplementary Figure 1B 3 2 1 0 -2 -3 -2 -1 0 1 2 3 4

Control Trastuzumab Pertuzumab Combination0

4

8

12

16

KL

K1

1

Control Trastuzumab Pertuzumab Combination0

1

2

3

CD

H1

Control Trastuzumab Pertuzumab Combination0

1

2

3

SE

RP

INB

5

Control Trastuzumab Pertuzumab Combination0.0

0.5

1.0

1.5

IL8

Control Trastuzumab Pertuzumab Combination0.0

0.5

1.0

1.5

TG

FB

I

Control Trastuzumab Pertuzumab Combination0

1

2

3

CD

KN

1A

Control Trastuzumab Pertuzumab Combination0

1

2

3

PT

PR

R

Control Trastuzumab Pertuzumab Combination0.0

0.5

1.0

1.5

2.0S

TC

1

Control Trastuzumab Pertuzumab Combination0

0.5

1.0

1.5

MM

P7

Control Trastuzumab Pertuzumab Combination0

1

2

3

EN

PP

2

Supplementary Figure 1A

Page 2: Supplementary Figure 1A. R 2 = 0.9694 p < 0.0001 qRT-PCR Illumina BeadChip Supplementary Figure 1B 3 2 1 0 -2 -3 -2 -1 0 1 2 3 4

R2 = 0.9694 p < 0.0001

qRT-PCR

Illu

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a B

ead

Ch

ip

Supplementary Figure 1B

3

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-1

-2

-3 -2 -1 0 1 2 3 4

Page 3: Supplementary Figure 1A. R 2 = 0.9694 p < 0.0001 qRT-PCR Illumina BeadChip Supplementary Figure 1B 3 2 1 0 -2 -3 -2 -1 0 1 2 3 4

Trastuzumab Pertuzumab Combination PCNA(ILMN_1706958) 1.03 1.03 -1.03 DNA ReplicationUBE2C(ILMN_1742958) -1.04 -1.07 1.04 Cell cycle, mitosisCKS2(ILMN_1756326) -1.13 1.07 -1.08 Cell cycleCKS2(ILMN_2072296) -1.07 1.02 1.05 Cell cycleTYMS(ILMN_1806040) -1.22* 1.00 -1.04 DNA replicationFEN1(ILMN_2160929) -1.21* -1.05 -1.09 DNA repair and synthesisFEN1(ILMN_1755834) -1.16* 1.01 -1.13* DNA repair and synthesisZWINT(ILMN_1653209) -1.13* -1.08 -1.06 Cell cycle, spindleRFC4(ILMN_2370365) -1.17* -1.03 -1.08 DNA replication and repairUBE2C(ILMN_2265654) -1.17* -1.06 1.01 Cell cycle, mitosisTOP2A(ILMN_1686097) -1.12 -1.04 1.06 DNA replicationAURKA(ILMN_2357438 STK6) -1.20* -1.13 1.00 Cell cycle, spindleAURKA(ILMN_1680955 STK5) -1.18 -1.06 -1.02 Cell cycle, spindleZWINT(ILMN_2362549) -1.09 -1.07 1.05 Cell cycle, spindleHMGB2(ILMN_1654268) -1.14 -1.14* 1.05 ChromatinHMGB2(ILMN_2219712) -1.21 -1.13 1.09 ChromatinSPAG5(ILMN_2141259 DEEPEST) -1.21* -1.08 -1.03 Cell cyclePCNA(ILMN_1694177) -1.13 -1.05 -1.11 DNA ReplicationBUB1B(ILMN_1797307 MAD3L) -1.19* -1.13* -1.14* Cell cycle, mitosisRFC4(ILMN_1724489) -1.17* -1.10* -1.10* DNA replication and repairNDC80(ILMN_1664511 HEC) -1.17 -1.10 -1.05 Cell cycle spindleUBE2C(ILMN_1714730) -1.16 1.03 1.05 Cell cycle, mitosisUBE2C(ILMN_2301083) -1.12 1.02 1.09 Cell cycle, mitosisZWINT(ILMN_2362545) -1.10 -1.07 1.08 Cell cycle, spindleGINS1(ILMN_1697751 KIAA0186) -1.07 1.01 -1.12 UnknownZWINT(ILMN_1673117) -1.00 -1.01 -1.02 Cell cycle, spindlePCNA(ILMN_1685682) 1.05 -1.01 -1.05 DNA ReplicationPHLDA2(ILMN_1671557) 1.08 1.13 1.40* Fas expressionHIST1H4C(ILMN_2075334 H4FG) 1.01 1.08 -1.00 Chromatin

CCNG2(ILMN_1747244) 1.15* -1.08 1.05CCNG2(ILMN_2228732) 1.05 -1.22* -1.01

Trastuzumab Pertuzumab Combined

Supplementary Figure 2A

Page 4: Supplementary Figure 1A. R 2 = 0.9694 p < 0.0001 qRT-PCR Illumina BeadChip Supplementary Figure 1B 3 2 1 0 -2 -3 -2 -1 0 1 2 3 4

Trastuzumab Pertuzumab Combination HER2+ breast

cancer patients KIAA1549(ILMN_1728060) -1.02 1.01 -1.01 Higher in pCRPSMD11(ILMN_1800952) -1.21 1.03 -1.03 Higher in non-pCRSYNCRIP(ILMN_1727740) -1.11* -1.00 -1.11 Higher in pCRLAMA3(ILMN_2293594) -1.07* -1.03 -1.04 Higher in non-pCRGRHL2(ILMN_2060145) -1.03 -1.01 1.02 Higher in pCRP2RX1(ILMN_1758529) -1.04 -1.03 -1.03 Higher in non-pCRSENP7(ILMN_1778294) -1.03 -1.06 -1.00 Higher in pCRPRKACA(ILMN_1786195) -1.07 -1.05 -1.02 Higher in non-pCRDERL1(ILMN_2209748) -1.01 -1.01 -1.02 Higher in non-pCRPPP2CA(ILMN_2196097) 1.02 -1.01 1.01 Higher in non-pCRSENP7(ILMN_2382354) 1.05 -1.25* 1.03 Higher in pCRCDC14A(ILMN_1774930) -1.06 -1.05 1.01 Higher in non-pCRSENP8(ILMN_1767690) -1.01 -1.01 -1.08 Higher in non-pCRWEE1(ILMN_1778561) -1.06* -1.04 1.00 Higher in pCRCDC14A(ILMN_2244653) -1.09* -1.08 -1.06 Higher in non-pCRPEX19(ILMN_1658759) -1.05 -1.05 -1.10 Higher in non-pCRZNF146(ILMN_2054442) -1.02 -1.19* -1.19* Higher in pCRCCDC123(ILMN_1679971) -1.11* -1.10* -1.14* Higher in pCRC5orf3(ILMN_1675701) -1.10* -1.08 -1.11 Higher in non-pCRPPP2CA(ILMN_1722858) -1.05 -1.03 -1.03 Higher in non-pCRSLC30A6(ILMN_1699365) -1.08 -1.05 -1.10 Higher in non-pCRCDC14A(ILMN_1655983) -1.02 -1.03 -1.02 Higher in non-pCRLAMA3(ILMN_1704247) 1.00 1.17* -1.18* Higher in non-pCRLAMA3(ILMN_2406035) 1.31 1.47* -1.54* Higher in non-pCRLAMA3(ILMN_1688892) 1.16 1.34* -1.44* Higher in non-pCRSTX1A(ILMN_1760160) 1.04 -1.00 -1.04 Higher in pCRCDC14A(ILMN_2324537) -1.01 1.02 -1.01 Higher in non-pCRFLJ20160(ILMN_1710209) 1.01 1.03 1.24* Higher in non-pCRCDC14A(ILMN_1774557) 1.02 1.09* 1.01 Higher in non-pCRPITPNA(ILMN_1715804) 1.02 1.03 1.05 Higher in non-pCRCTNS(ILMN_1807719) -1.02 1.09 1.12 Higher in non-pCRSLC35A4(ILMN_2105966) 1.02 1.13 1.14 Higher in non-pCRNFE2L1(ILMN_1739450) 1.05 1.03 1.19 Higher in non-pCRZNF146(ILMN_1699423) 1.04 1.01 1.02 Higher in pCRGPR22(ILMN_1684865) 1.12 1.16* 1.11* Higher in pCRCDC14A(ILMN_1739164) 1.11* 1.04 1.03 Higher in non-pCRCTNS(ILMN_1738010) -1.02 1.04 1.05 Higher in non-pCRPRKACA(ILMN_2395314) 1.03 -1.03 1.02 Higher in non-pCRCTNS(ILMN_1776132) 1.02 -1.03 1.03 Higher in non-pCRSLC30A6(ILMN_2151168) 1.02 1.00 1.06 Higher in pCR

Trastuzumab Pertuzumab Combined

Supplementary Figure 2B

Page 5: Supplementary Figure 1A. R 2 = 0.9694 p < 0.0001 qRT-PCR Illumina BeadChip Supplementary Figure 1B 3 2 1 0 -2 -3 -2 -1 0 1 2 3 4

Either HER2-inhibitor alone

Trastuzumab alone AND combination

Combination only

Trastuzumab alone

Pertuzumab alone

Control Trastuzumab Pertuzumab Combined

JUN, JUP

DST, CDKN1A, CLIC6

JUN, SERPIN-A1/B5, MMP13, KRT-6A/16/7, ANXA8, PAK6

KRT5, ERBB3, CDH1, FOXO1LCN2, KLK11

CD9, KRT14

CD36, CD36, CASP1

NRG4

PAK1

LAMA3FOS, DUSP1, SNAI2

IL4R, CCL26, GADD45

CAV2, JAG1

IL8, IL8

TGFBI, SPARCCDH6, CAV1, CXCL1LAMC2, LAMC2

IL6, IL15

GSTA1, GSTA2ESR1

CDH17

TFF2, TFF3

Supplementary Figure 2C

Pertuzumab alone AND combination

Data from Ghosh et al. (2010) Cancer Research 71:1871-1882

Both HER2 inhibitors AND combination

Co

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ol.

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Co

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Control Trastuzumab Pertuzumab Combined

HE

R2-

HE

R2

HE

R3-

HE

R2

HE

R1-

HE

R2

Homo- or Heterodimers

Page 6: Supplementary Figure 1A. R 2 = 0.9694 p < 0.0001 qRT-PCR Illumina BeadChip Supplementary Figure 1B 3 2 1 0 -2 -3 -2 -1 0 1 2 3 4

Control Trastuzumab Pertuzumab Combined

Supplementary Figure 2D

Heatmap from Ghosh et al. (2010) Cancer Research 71:1871-1882

Co

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HE

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R2

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HE

R2

HE

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HE

R2

Homo- or Heterodimers

Page 7: Supplementary Figure 1A. R 2 = 0.9694 p < 0.0001 qRT-PCR Illumina BeadChip Supplementary Figure 1B 3 2 1 0 -2 -3 -2 -1 0 1 2 3 4

SKOV3 (2.15) HOX486 (0.89) HOX516 (1.2)

HOX424 (7.75) OV1002 (0.94) HOX493 (0.575)

Supplementary Figure 3


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