Metastatic Breast Cancer: One Size Does Not Fit All

Clifford Hudis, M.D.Chief, Breast Cancer Medicine Service

MSKCC

Breast cancer is predictable but not absolutely.

Invasive Ductal Carcinoma

Message Pathways Inside Cancer Cells

We define invasive breast cancer on the basis of 2 genes: ER and HER2

ER Negative

HER2 Positive

HER2/neu FISH Test

Outcomes are widely variable.

We have to consider the genome of the tumor AND

the patient.

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-3.0 -2.9 -2.7 -2.6 -2.4 -2.3 -2.1 -2.0 -1.8 -1.7 -1.5 -1.4 -1.2 -1.1 -1.0 -0.8 -0.7 -0.5 -0.4 -0.2 -0.1 0.1 0.2 0.4 0.5 0.7 0.8 1.0 1.1 1.2 1.4 1.5 1.7 1.8 2.0 2.1 2.3 2.4 2.6 2.7 2.9 3.0

204614_at, serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 2208588_at, apoptosis inhibitor213581_at, programmed cell death 2209311_at, BCL2-like 2217955_at, BCL2-like 13 (apoptosis facilitator)215913_s_at, CED-6 protein202076_at, baculoviral IAP repeat-containing 2201746_at, tumor protein p53 (Li-Fraumeni syndrome)211300_s_at, tumor protein p53 (Li-Fraumeni syndrome)211786_at, tumor necrosis factor receptor superfamily, member 9203627_at, insulin-like growth factor 1 receptor209308_s_at, BCL2/adenovirus E1B 19kDa interacting protein 2203728_at, BCL2-antagonist/killer 1202535_at, Fas (TNFRSF6)-associated via death domain209863_s_at, tumor protein p73-like201502_s_at, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha202284_s_at, cyclin-dependent kinase inhibitor 1A (p21, Cip1)219624_at, BCL2-associated athanogene 4209462_at, amyloid beta (A4) precursor-like protein 1205481_at, adenosine A1 receptor202387_at, BCL2-associated athanogene211475_s_at, BCL2-associated athanogene211152_s_at, protease, serine, 25214992_s_at, deoxyribonuclease II, lysosomal214329_x_at, tumor necrosis factor (ligand) superfamily, member 10202687_s_at, tumor necrosis factor (ligand) superfamily, member 10202688_at, tumor necrosis factor (ligand) superfamily, member 10206536_s_at, baculoviral IAP repeat-containing 4209941_at, receptor (TNFRSF)-interacting serine-threonine kinase 1206680_at, CD5 antigen-like (scavenger receptor cysteine rich family)203089_s_at, protease, serine, 2537226_at, BCL2/adenovirus E1B 19kDa interacting protein 1207829_s_at, BCL2/adenovirus E1B 19kDa interacting protein 1206665_s_at, BCL2-like 1211255_x_at, death effector domain containing207181_s_at, caspase 7, apoptosis-related cysteine protease207782_s_at, presenilin 1 (Alzheimer disease 3)213220_at, programmed cell death 4 (neoplastic transformation inhibitor)221833_at, seven in absentia homolog 1 (Drosophila)221834_at, seven in absentia homolog 1 (Drosophila)204860_s_at, baculoviral IAP repeat-containing 1204861_s_at, baculoviral IAP repeat-containing 1205851_at, non-metastatic cells 6, protein expressed in (nucleoside-diphosphate kinase)203685_at, B-cell CLL/lymphoma 2203930_s_at, microtubule-associated protein tau203929_s_at, microtubule-associated protein tau203928_x_at, microtubule-associated protein tau206401_s_at, microtubule-associated protein tau208945_s_at, beclin 1 (coiled-coil, myosin-like BCL2 interacting protein)208946_s_at, beclin 1 (coiled-coil, myosin-like BCL2 interacting protein)203187_at, dedicator of cyto-kinesis 1218398_at, mitochondrial ribosomal protein S30219786_at, metallothionein-like 5, testis-specific (tesmin)221666_s_at, apoptosis-associated speck-like protein containing a CARD212593_s_at, programmed cell death 4 (neoplastic transformation inhibitor)202730_s_at, programmed cell death 4 (neoplastic transformation inhibitor)202731_at, programmed cell death 4 (neoplastic transformation inhibitor)214960_at, apoptosis inhibitor 5201085_s_at, SON DNA binding protein213538_at, SON DNA binding protein201086_x_at, SON DNA binding protein214988_s_at, SON DNA binding protein218325_s_at, death associated transcription factor 1201631_s_at, immediate early response 3210026_s_at, caspase recruitment domain family, member 10204859_s_at, apoptotic protease activating factor202116_at, requiem, apoptosis response zinc finger gene204352_at, TNF receptor-associated factor 5203533_s_at, cullin 5203891_s_at, death-associated protein kinase 3218996_at, TCF3 (E2A) fusion partner (in childhood Leukemia)211833_s_at, BCL2-associated X protein204274_at, estrogen receptor binding site associated, antigen, 9204278_s_at, estrogen receptor binding site associated, antigen, 9204933_s_at, tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)211373_s_at, presenilin 2 (Alzheimer disease 4)218145_at, chromosome 20 open reading frame 97208822_s_at, death associated protein 3219275_at, programmed cell death 5201244_s_at, v-raf-1 murine leukemia viral oncogene homolog 1222201_s_at, CASP8 associated protein 2212312_at, BCL2-like 1219350_s_at, second mitochondria-derived activator of caspase200803_s_at, testis enhanced gene transcript (BAX inhibitor 1)200804_at, testis enhanced gene transcript (BAX inhibitor 1)205084_at, B-cell receptor-associated protein BAP29220864_s_at, cell death-regulatory protein GRIM19200837_at, accessory protein BAP31205512_s_at, programmed cell death 8 (apoptosis-inducing factor)204862_s_at, non-metastatic cells 3, protein expressed in1861_at, BCL2-antagonist of cell death209364_at, BCL2-antagonist of cell death217840_at, DEAD-box protein abstrakt202676_x_at, FAST kinase210975_x_at, FAST kinase214114_x_at, FAST kinase208905_at, cytochrome c, somatic212038_s_at, voltage-dependent anion channel 1201095_at, death-associated protein213786_at, Tax1 (human T-cell leukemia virus type I) binding protein 1200976_s_at, Tax1 (human T-cell leukemia virus type I) binding protein 1200977_s_at, Tax1 (human T-cell leukemia virus type I) binding protein 1201715_s_at, apoptotic chromatin condensation inducer in the nucleus206508_at, tumor necrosis factor (ligand) superfamily, member 7201588_at, thioredoxin-like, 32kDa209790_s_at, caspase 6, apoptosis-related cysteine protease211464_x_at, caspase 6, apoptosis-related cysteine protease204068_at, serine/threonine kinase 3 (STE20 homolog, yeast)203005_at, lymphotoxin beta receptor (TNFR superfamily, member 3)201848_s_at, BCL2/adenovirus E1B 19kDa interacting protein 3201849_at, BCL2/adenovirus E1B 19kDa interacting protein 3200608_s_at, RAD21 homolog (S. pombe)201111_at, CSE1 chromosome segregation 1-like (yeast)201112_s_at, CSE1 chromosome segregation 1-like (yeast)210766_s_at, CSE1 chromosome segregation 1-like (yeast)205780_at, BCL2-interacting killer (apoptosis-inducing)201370_s_at, cullin 3203078_at, cullin 2207922_s_at, macrophage erythroblast attacher213026_at, APG12 autophagy 12-like (S. cerevisiae)207163_s_at, v-akt murine thymoma viral oncogene homolog 1201371_s_at, cullin 3203460_s_at, presenilin 1 (Alzheimer disease 3)205928_at, Kruppel-type zinc finger (C2H2)201423_s_at, cullin 4A201424_s_at, cullin 4A204025_s_at, programmed cell death 2201687_s_at, apoptosis inhibitor 5207738_s_at, NCK-associated protein 1200071_at, splicing factor 30, survival of motor neuron-related212367_at, fem-1 homolog b (C. elegans)212373_at, fem-1 homolog b (C. elegans)217911_s_at, BCL2-associated athanogene 3204004_at, PRKC, apoptosis, WT1, regulator204005_s_at, PRKC, apoptosis, WT1, regulator201446_s_at, TIA1 cytotoxic granule-associated RNA binding protein201450_s_at, TIA1 cytotoxic granule-associated RNA binding protein202980_s_at, seven in absentia homolog 1 (Drosophila)202981_x_at, seven in absentia homolog 1 (Drosophila)203489_at, CD27-binding (Siva) protein210792_x_at, CD27-binding (Siva) protein202984_s_at, BCL2-associated athanogene 5202985_s_at, BCL2-associated athanogene 5205263_at, B-cell CLL/lymphoma 10218286_s_at, ring finger protein 7202763_at, caspase 3, apoptosis-related cysteine protease200046_at, defender against cell death 1202406_s_at, TIA1 cytotoxic granule-associated RNA binding protein-like 1202123_s_at, v-abl Abelson murine leukemia viral oncogene homolog 1203415_at, programmed cell death 6202820_at, aryl hydrocarbon receptor209165_at, apoptosis antagonizing transcription factor212048_s_at, tyrosyl-tRNA synthetase208893_s_at, dual specificity phosphatase 6208891_at, dual specificity phosphatase 6208892_s_at, dual specificity phosphatase 6202039_at, TGFB1-induced anti-apoptotic factor 1203804_s_at, acid-inducible phosphoprotein209230_s_at, p8 protein (candidate of metastasis 1)209803_s_at, tumor suppressing subtransferable candidate 3218368_s_at, tumor necrosis factor receptor superfamily, member 12A207643_s_at, tumor necrosis factor receptor superfamily, member 1A1729_at, TNFRSF1A-associated via death domain205641_s_at, TNFRSF1A-associated via death domain221566_s_at, nucleolar protein 3 (apoptosis repressor with CARD domain)59625_at, hypothetical protein LOC283849221567_at, nucleolar protein 3 (apoptosis repressor with CARD domain)207428_x_at, cell division cycle 2-like 1 (PITSLRE proteins)202693_s_at, serine/threonine kinase 17a (apoptosis-inducing)209406_at, BCL2-associated athanogene 2201739_at, serum/glucocorticoid regulated kinase204121_at, growth arrest and DNA-damage-inducible, gamma209305_s_at, growth arrest and DNA-damage-inducible, beta207574_s_at, growth arrest and DNA-damage-inducible, beta209304_x_at, growth arrest and DNA-damage-inducible, beta219366_at, apoptosis, caspase activation inhibitor207180_s_at, HIV-1 Tat interactive protein 2, 30kDa209448_at, HIV-1 Tat interactive protein 2, 30kDa222043_at, clusterin (complement lysis inhibitor, SP-40,40, sulfated glycoprotein 2, testosterone-repressed prostate message 2, apolipoprotein J)210405_x_at, tumor necrosis factor receptor superfamily, member 10b209833_at, CASP2 and RIPK1 domain containing adaptor with death domain208791_at, clusterin (complement lysis inhibitor, SP-40,40, sulfated glycoprotein 2, testosterone-repressed prostate message 2, apolipoprotein J)208792_s_at, clusterin (complement lysis inhibitor, SP-40,40, sulfated glycoprotein 2, testosterone-repressed prostate message 2, apolipoprotein J)221479_s_at, BCL2/adenovirus E1B 19kDa interacting protein 3-like209295_at, tumor necrosis factor receptor superfamily, member 10b221478_at, BCL2/adenovirus E1B 19kDa interacting protein 3-like204261_s_at, presenilin 2 (Alzheimer disease 4)211078_s_at, serine/threonine kinase 3 (STE20 homolog, yeast)202512_s_at, APG5 autophagy 5-like (S. cerevisiae)202511_s_at, APG5 autophagy 5-like (S. cerevisiae)210639_s_at, APG5 autophagy 5-like (S. cerevisiae)211553_x_at, apoptotic protease activating factor204132_s_at, forkhead box O3A204131_s_at, forkhead box O3A210655_s_at, forkhead box O3A217399_s_at, forkhead box O3A203725_at, growth arrest and DNA-damage-inducible, alpha204932_at, tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)209929_s_at, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma40273_at, D site of albumin promoter (albumin D-box) binding protein202389_s_at, huntingtin (Huntington disease)202468_s_at, catenin (cadherin-associated protein), alpha-like 1208368_s_at, breast cancer 2, early onset2028_s_at, E2F transcription factor 1204947_at, E2F transcription factor 1210165_at, deoxyribonuclease I202094_at, baculoviral IAP repeat-containing 5 (survivin)202095_s_at, baculoviral IAP repeat-containing 5 (survivin)210334_x_at, baculoviral IAP repeat-containing 5 (survivin)209539_at, Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6218573_at, APR-1 protein207816_at, lactalbumin, alpha-201105_at, lectin, galactoside-binding, soluble, 1 (galectin 1)219398_at, cell death activator CIDE-3202178_at, protein kinase C, zeta211316_x_at, CASP8 and FADD-like apoptosis regulator207953_at, neuronal thread protein209831_x_at, deoxyribonuclease II, lysosomal217465_at, NCK-associated protein 1202037_s_at, secreted frizzled-related protein 1202035_s_at, secreted frizzled-related protein 1202036_s_at, secreted frizzled-related protein 1205013_s_at, adenosine A2a receptor211282_x_at, tumor necrosis factor receptor superfamily, member 25211841_s_at, tumor necrosis factor receptor superfamily, member 25210847_x_at, tumor necrosis factor receptor superfamily, member 25219423_x_at, tumor necrosis factor receptor superfamily, member 25203989_x_at, coagulation factor II (thrombin) receptor215184_at, death-associated protein kinase 2220451_s_at, baculoviral IAP repeat-containing 7 (livin)207004_at, B-cell CLL/lymphoma 2214491_at, somatostatin receptor 3205858_at, nerve growth factor receptor (TNFR superfamily, member 16)210654_at, tumor necrosis factor receptor superfamily, member 10d, decoy with truncated death domain202694_at, serine/threonine kinase 17a (apoptosis-inducing)206248_at, protein kinase C, epsilon220804_s_at, tumor protein p73206975_at, lymphotoxin alpha (TNF superfamily, member 1)211195_s_at, tumor protein p73-like205754_at, coagulation factor II (thrombin)210865_at, tumor necrosis factor (ligand) superfamily, member 6213585_s_at, programmed cell death 2206444_at, phosphodiesterase 1B, calmodulin-dependent211490_at, adrenergic, alpha-1A-, receptor204833_at, APG12 autophagy 12-like (S. cerevisiae)211489_at, adrenergic, alpha-1A-, receptor203277_at, DNA fragmentation factor, 45kDa, alpha polypeptide206879_s_at, neuregulin 2204930_s_at, BCL2/adenovirus E1B 19kDa interacting protein 1208000_at, GPI anchored molecule like protein205554_s_at, deoxyribonuclease I-like 3207433_at, interleukin 10208478_s_at, BCL2-associated X protein215037_s_at, BCL2-like 1202480_s_at, death effector domain containing200607_s_at, RAD21 homolog (S. pombe)201686_x_at, apoptosis inhibitor 5214959_s_at, apoptosis inhibitor 5210765_at, CSE1 chromosome segregation 1-like (yeast)207500_at, caspase 5, apoptosis-related cysteine protease221454_at, BCL2-related ovarian killer205387_s_at, chorionic gonadotropin, beta polypeptide203084_at, transforming growth factor, beta 1 (Camurati-Engelmann disease)210025_s_at, caspase recruitment domain family, member 10213596_at, caspase 4, apoptosis-related cysteine protease222292_at, tumor necrosis factor receptor superfamily, member 5216876_s_at, interleukin 17 (cytotoxic T-lymphocyte-associated serine esterase 8)220599_s_at, caspase recruitment domain family, member 14211526_s_at, tumor necrosis factor receptor superfamily, member 6b, decoy206907_at, tumor necrosis factor (ligand) superfamily, member 9208315_x_at, TNF receptor-associated factor 3211491_at, adrenergic, alpha-1A-, receptor212849_at, axin 1208536_s_at, BCL2-like 11 (apoptosis facilitator)209310_s_at, caspase 4, apoptosis-related cysteine protease203532_x_at, cullin 5201710_at, v-myb myeloblastosis viral oncogene homolog (avian)-like 2220066_at, caspase recruitment domain family, member 15207075_at, cold autoinflammatory syndrome 1206687_s_at, protein tyrosine phosphatase, non-receptor type 6211163_s_at, tumor necrosis factor receptor superfamily, member 10c, decoy without an intracellular domain214617_at, perforin 1 (pore forming protein)201763_s_at, death-associated protein 6209857_s_at, sphingosine kinase 2210118_s_at, interleukin 1, alpha206923_at, protein kinase C, alpha209812_x_at, caspase 2, apoptosis-related cysteine protease (neural precursor cell expressed, developmentally down-regulated 2)211140_s_at, caspase 2, apoptosis-related cysteine protease (neural precursor cell expressed, developmentally down-regulated 2)203948_s_at, myeloperoxidase207005_s_at, B-cell CLL/lymphoma 2221073_s_at, caspase recruitment domain family, member 4216325_x_at, tumor necrosis factor receptor superfamily, member 6b, decoy204466_s_at, synuclein, alpha (non A4 component of amyloid precursor)207827_x_at, synuclein, alpha (non A4 component of amyloid precursor)211546_x_at, synuclein, alpha (non A4 component of amyloid precursor)204467_s_at, synuclein, alpha (non A4 component of amyloid precursor)206044_s_at, v-raf murine sarcoma viral oncogene homolog B1206531_at, D4, zinc and double PHD fingers family 1206545_at, CD28 antigen (Tp44)207907_at, tumor necrosis factor (ligand) superfamily, member 14220598_at, caspase recruitment domain family, member 14208014_x_at, neuronal thread protein211269_s_at, interleukin 2 receptor, alpha218426_s_at, TRIAD3 protein214727_at, breast cancer 2, early onset39402_at, interleukin 1, beta205067_at, interleukin 1, beta205598_at, TRAF interacting protein207294_at, angiotensin II receptor, type 2202893_at, unc-13-like (C. elegans)211554_s_at, apoptotic protease activating factor216016_at, cold autoinflammatory syndrome 1206864_s_at, harakiri, BCL2 interacting protein (contains only BH3 domain)211338_at, interferon, alpha 234449_at, caspase 2, apoptosis-related cysteine protease (neural precursor cell expressed, developmentally down-regulated 2)216252_x_at, tumor necrosis factor receptor superfamily, member 6216015_s_at, cold autoinflammatory syndrome 1202390_s_at, huntingtin (Huntington disease)208173_at, interferon, beta 1, fibroblast214618_at, CASP8 and FADD-like apoptosis regulator211492_s_at, adrenergic, alpha-1A-, receptor206362_x_at, mitogen-activated protein kinase kinase kinase 10206939_at, deleted in colorectal carcinoma207468_s_at, secreted frizzled-related protein 5209802_at, tumor suppressing subtransferable candidate 3206977_at, parathyroid hormone36004_at, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma216038_x_at, myosin, light polypeptide, regulatory, non-sarcomeric (20kD)213921_at, somatostatin218056_at, bifunctional apoptosis regulator207216_at, tumor necrosis factor (ligand) superfamily, member 8215346_at, tumor necrosis factor receptor superfamily, member 5221295_at, cell death-inducing DFFA-like effector a209544_at, receptor-interacting serine-threonine kinase 2210538_s_at, baculoviral IAP repeat-containing 3211214_s_at, death-associated protein kinase 1209294_x_at, tumor necrosis factor receptor superfamily, member 10b203111_s_at, PTK2B protein tyrosine kinase 2 beta35150_at, tumor necrosis factor receptor superfamily, member 5208060_at, paired box gene 7206863_x_at, harakiri, BCL2 interacting protein (contains only BH3 domain)203684_s_at, B-cell CLL/lymphoma 2211834_s_at, tumor protein p73-like206569_at, interleukin 24207293_s_at, angiotensin II receptor, type 2206865_at, harakiri, BCL2 interacting protein (contains only BH3 domain)211193_at, tumor protein p73-like221571_at, TNF receptor-associated factor 3202014_at, protein phosphatase 1, regulatory (inhibitor) subunit 15A202405_at, TIA1 cytotoxic granule-associated RNA binding protein-like 1203890_s_at, death-associated protein kinase 3204262_s_at, presenilin 2 (Alzheimer disease 4)206752_s_at, DNA fragmentation factor, 40kDa, beta polypeptide (caspase-activated DNase)218080_x_at, Fas (TNFRSF6) associated factor 1208309_s_at, mucosa associated lymphoid tissue lymphoma translocation gene 1210018_x_at, mucosa associated lymphoid tissue lymphoma translocation gene 1203079_s_at, cullin 2207614_s_at, cullin 1208050_s_at, caspase 2, apoptosis-related cysteine protease (neural precursor cell expressed, developmentally down-regulated 2)209811_at, caspase 2, apoptosis-related cysteine protease (neural precursor cell expressed, developmentally down-regulated 2)213213_at, death associated transcription factor 1201372_s_at, cullin 3207113_s_at, tumor necrosis factor (TNF superfamily, member 2)205153_s_at, tumor necrosis factor receptor superfamily, member 5202723_s_at, forkhead box O1A (rhabdomyosarcoma)205611_at, tumor necrosis factor (ligand) superfamily, member 12203508_at, tumor necrosis factor receptor superfamily, member 1B205859_at, lymphocyte antigen 86206706_at, neurotrophin 3219422_at, tumor necrosis factor receptor superfamily, member 25203984_s_at, caspase 9, apoptosis-related cysteine protease207680_x_at, paired box gene 3 (Waardenburg syndrome 1)209239_at, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)222030_at, CD27-binding (Siva) protein211333_s_at, tumor necrosis factor (ligand) superfamily, member 6215915_at, CED-6 protein221371_at, tumor necrosis factor (ligand) superfamily, member 18216059_at, paired box gene 3 (Waardenburg syndrome 1)211277_x_at, amyloid beta (A4) precursor protein (protease nexin-II, Alzheimer disease)216220_s_at, adenosine A1 receptor205848_at, growth arrest-specific 2206467_x_at, tumor necrosis factor receptor superfamily, member 6b, decoy206092_x_at, tumor necrosis factor receptor superfamily, member 6b, decoy213829_x_at, tumor necrosis factor receptor superfamily, member 6b, decoy204164_at, signal-induced proliferation-associated gene 1213443_at, TNFRSF1A-associated via death domain221601_s_at, regulator of Fas-induced apoptosis207634_at, programmed cell death 1221320_at, BCL2-like 10 (apoptosis facilitator)207384_at, peptidoglycan recognition protein214237_x_at, PRKC, apoptosis, WT1, regulator221405_at, neutral sphingomyelinase206341_at, interleukin 2 receptor, alpha214207_s_at, caspase recruitment domain family, member 10203110_at, PTK2B protein tyrosine kinase 2 beta204950_at, tumor up-regulated CARD-containing antagonist of caspase nine202724_s_at, forkhead box O1A (rhabdomyosarcoma)213560_at, growth arrest and DNA-damage-inducible, beta208200_at, interleukin 1, alpha211856_x_at, CD28 antigen (Tp44)211861_x_at, CD28 antigen (Tp44)207679_at, paired box gene 3 (Waardenburg syndrome 1)210401_at, purinergic receptor P2X, ligand-gated ion channel, 1220048_at, ectodysplasin 1, anhidrotic receptor206537_at, baculoviral IAP repeat-containing 4216042_at, tumor necrosis factor receptor superfamily, member 25203949_at, myeloperoxidase214090_at, PRKC, apoptosis, WT1, regulator207536_s_at, tumor necrosis factor receptor superfamily, member 9206295_at, interleukin 18 (interferon-gamma-inducing factor)206324_s_at, death-associated protein kinase 2206222_at, tumor necrosis factor receptor superfamily, member 10c, decoy without an intracellular domain221602_s_at, regulator of Fas-induced apoptosis207062_at, islet amyloid polypeptide221142_s_at, peroxisomal trans 2-enoyl CoA reductase202695_s_at, serine/threonine kinase 17a (apoptosis-inducing)210017_at, mucosa associated lymphoid tissue lymphoma translocation gene 1210775_x_at, caspase 9, apoptosis-related cysteine protease208062_s_at, neuregulin 2212374_at, fem-1 homolog b (C. elegans)205504_at, Bruton agammaglobulinemia tyrosine kinase206150_at, tumor necrosis factor receptor superfamily, member 7216995_x_at, v-raf-1 murine leukemia viral oncogene homolog 1208485_x_at, CASP8 and FADD-like apoptosis regulator211862_x_at, CASP8 and FADD-like apoptosis regulator221359_at, glial cell derived neurotrophic factor208402_at, interleukin 17 (cytotoxic T-lymphocyte-associated serine esterase 8)221129_at, apoptosis related protein217500_at, TIA1 cytotoxic granule-associated RNA binding protein-like 1218425_at, TRIAD3 protein210253_at, HIV-1 Tat interactive protein 2, 30kDa203139_at, death-associated protein kinase 1210164_at, granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1)215158_s_at, death effector domain containing205214_at, serine/threonine kinase 17b (apoptosis-inducing)208351_s_at, mitogen-activated protein kinase 1211194_s_at, tumor protein p73-like221188_s_at, cell death-inducing DFFA-like effector b215329_s_at, cell division cycle 2-like 1 (PITSLRE proteins)204780_s_at, tumor necrosis factor receptor superfamily, member 6209939_x_at, CASP8 and FADD-like apoptosis regulator210563_x_at, CASP8 and FADD-like apoptosis regulator207382_at, tumor protein p73-like207943_x_at, pleiomorphic adenoma gene-like 1212271_at, mitogen-activated protein kinase 1204493_at, BH3 interacting domain death agonist211725_s_at, BH3 interacting domain death agonist218845_at, mitogen-activated protein kinase phosphatase x200602_at, amyloid beta (A4) precursor protein (protease nexin-II, Alzheimer disease)214953_s_at, amyloid beta (A4) precursor protein (protease nexin-II, Alzheimer disease)204235_s_at, CED-6 protein204237_at, CED-6 protein203836_s_at, mitogen-activated protein kinase kinase kinase 5203837_at, mitogen-activated protein kinase kinase kinase 5220162_s_at, caspase recruitment domain family, member 9207002_s_at, pleiomorphic adenoma gene-like 1209318_x_at, pleiomorphic adenoma gene-like 1207686_s_at, caspase 8, apoptosis-related cysteine protease213373_s_at, caspase 8, apoptosis-related cysteine protease209545_s_at, receptor-interacting serine-threonine kinase 2214057_at, myeloid cell leukemia sequence 1 (BCL2-related)200796_s_at, myeloid cell leukemia sequence 1 (BCL2-related)200797_s_at, myeloid cell leukemia sequence 1 (BCL2-related)200798_x_at, myeloid cell leukemia sequence 1 (BCL2-related)214056_at, myeloid cell leukemia sequence 1 (BCL2-related)204211_x_at, protein kinase, interferon-inducible double stranded RNA dependent202086_at, myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse)200887_s_at, signal transducer and activator of transcription 1, 91kDa209969_s_at, signal transducer and activator of transcription 1, 91kDa205681_at, BCL2-related protein A1217028_at, chemokine (C-X-C motif) receptor 4209201_x_at, chemokine (C-X-C motif) receptor 4211919_s_at, chemokine (C-X-C motif) receptor 4210564_x_at, CASP8 and FADD-like apoptosis regulator211317_s_at, CASP8 and FADD-like apoptosis regulator209508_x_at, CASP8 and FADD-like apoptosis regulator214486_x_at, CASP8 and FADD-like apoptosis regulator37028_at, protein phosphatase 1, regulatory (inhibitor) subunit 15A211367_s_at, caspase 1, apoptosis-related cysteine protease (interleukin 1, beta, convertase)206011_at, caspase 1, apoptosis-related cysteine protease (interleukin 1, beta, convertase)211368_s_at, caspase 1, apoptosis-related cysteine protease (interleukin 1, beta, convertase)209970_x_at, caspase 1, apoptosis-related cysteine protease (interleukin 1, beta, convertase)211366_x_at, caspase 1, apoptosis-related cysteine protease (interleukin 1, beta, convertase)205692_s_at, CD38 antigen (p45)202643_s_at, tumor necrosis factor, alpha-induced protein 3202644_s_at, tumor necrosis factor, alpha-induced protein 3204781_s_at, tumor necrosis factor receptor superfamily, member 6215719_x_at, tumor necrosis factor receptor superfamily, member 6203528_at, sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D205488_at, granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)205831_at, CD2 antigen (p50), sheep red blood cell receptor208296_x_at, TNF-induced protein210260_s_at, TNF-induced protein203085_s_at, transforming growth factor, beta 1 (Camurati-Engelmann disease)201743_at, CD14 antigen214467_at, G protein-coupled receptor 65

Cytoskeleton genes (n=641)Apoptosis genes (n=641)

HER-2+/ER-

Luminal ALuminal BNormal

Sorlie T et al, PNAS 2001

Basal-like

Five Kinds Of Breast Cancer?

Challenges

• Molecular profiles are:– Variable by population studied– Poorly adapted for clinical use– Biology as yet not well characterized– Relationship to conventional chemotherapy

response not well characterized– Ability to correctly identify molecular targets

not yet proven

Unsupervised Cluster Analysis of 99 primary breast carcinomas from MSKCC tumor bank

Class A Class B

ALCAMp=0.023

SPDEFp<0.0001

ARp=0.04

IHC for differentially expressed genes in ER(-) Class A

p<0.0001

ALCAM

p<0.0001

AR

SPDEF

p<0.0001

A B

B

B

A

A

Class AClass B

Real World - Now

• Your doctor makes an educated guess about the pace of the disease and treats accordingly.

• You and your doctor regularly assess the benefits of specific treatments and adjust accordingly

Real World - Future

• Your doctor tests your cancer AND your normal cells.

• You and your doctor rationally select therapy predicted to control or cure the disease.

Breast Cancer Medicine Service, MSKCC: 2005