EGAGenomicsOtherhttps://ega-archive.org/studies/EGAS00001005736EGAEGA study EGAS00001005736Mult-omics Palbociclib Resistance Study in HR+/HER2– Metastatic Breast CancerEGArestrictedErbb-2, Breast Carcinoma, Human Mammary Neoplasm, primary breast cancer, Carcinoma, malignant tumor of the breast, Breast Carcinomas, "breast neoplasm" EXACT [MTH:120], Neoplasms, HER-2|neu, mKIAA3023, mammary neoplasm, Mammary Cancers, Human Mammary Neoplasms, MLN19, PD-0332991, Tumor, "breast tumor" EXACT [NCI2004_11_17:C2910], Human, CD340, Breast Malignant Neoplasm, Breast Malignant Tumor, Kiaa3023, RRG6, "neoplasm of breast (disorder)" EXACT [SNOMEDCT_2005_07_31:126926005], Mammary Carcinomas, Breast Tumor, resistance, Neoplasm, 3-d)pyrimidin-7-one, NGL, Human Mammary Carcinoma, "mammary tumor" EXACT [CSP2005:2016-0671], NOS, breast tumor, cancer of the breast, HER-2/neu, Malignant Neoplasm of Breast, c-neu, Carcinomas, BC, study, Mammary Neoplasms, malignant neoplasm of breast, Human Mammary, Breast Neoplasm, c-erbB2, Mammary Neoplasm, HER-2, Mammary Carcinoma, Human Mammary Carcinomas, Cancers, Breast Malignant Neoplasms., "mammary neoplasm" RELATED [], PD 0332991, Cancer of the Breast, MLN 19, 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-ylpyridin-2-ylamino)-8H-pyrido(2, metastatic, GEP6, breast cancer, cancer of breast, Malignant Tumor of Breast, Mammary, Mammary Cancer, Breast Tumors, Breast Cancer, PD0332991, Breast Malignant Tumors, TKR1, Cancer of Breast, Breast, mammary cancer, cancer, mammary tumor, HER2, breast, Ibrance, Neu, NEU, Tumors, CancerErbb-2, RB1, l(2)k06503, Voltage-gated calcium channel subunit alpha Cav1.2, Biological Markers, Viral Marker, Surrogate Endpoints, PhrB photolyase activity, determination, Laboratory, Compounds, Feature, estrogenes, mental retardation, DPTEN, Biochemical, cdk4/6, Endpoint, RBF, Estra, ER[a], Serum, pigmented epithelium, xlERalpha1, Tp53, xlERalpha2, HALR, DOCK180, CD340, Mutations, RBR, Laboratory Markers, Kiaa3023, cdk, DmelCG4636, congenital, Biological, Calcium channel, responsivity, bbl, RB, rb, symptoms, 3, RETINOBLASTOMA PROTEIN, NUP96, TEP1, rbf, epithelium, xesr-1, Progression, treatment, S4, hypoparathyroidism with short stature, AU041214, Prognoses, BCC7, pp110, Rb, pigmented retina, associated with Dysmorphism, DNA cyclobutane dipyrimidine photolyase activity, PD 0332991, paired, endocrine, SUPPRESSOR OF AUXIN RESISTANCE 3, 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-ylpyridin-2-ylamino)-8H-pyrido(2, Immune, l(2)k03107, Markers, WAVE-1, Viral Markers, ERbeta, dCdk4, disease management, oestrogene, Therapies, Exacerbation, oestrogens, CG7413, l(2)k13811, Estrogene, Estrogenic, HRD, somatic mutation, Ibrance, Nr3a1, Therapy, PRE, screening, retinoblastoma-related 1, Scar, SCAR/WAVE, Viral, Surrogate Endpoint, rbf1, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, Oestrogene, Disease Exacerbation, MELC-CC, retinoblastoma, Estrogen Receptor Agonists, Biochemical Markers, MLN19, Receptor Agonists, CED-5, DmSCAR, Biologic Marker, CG4636, not genetically inherited, RETINOBLASTOMA 1, Cicatrization, hereditary retinoblastoma, SCAR, PTEN3, retinal pigment, PTEN1, BEST:SD02991, Marker, Hch, and developmental delay, ER, dipyrimidine photolyase (photosensitive), 3-d)pyrimidin-7-one, ATRBR1, scar, bfy, Estrogenic Effects, DWave, retinal pigment layer, c-neu, AI662014, D-SCAR, oestrogen, Cchl1a1, pRb, resistance., Factors, DmelCG7413, End Points, AI195380, estrogenes Hormon, Prognostic, wave, MMAC1, WAVE, signs, common, DmelCG10379, Cdk4/6, Immunologic, RPS4, Laboratory Marker, Features, PTENa, Treatments, MLN 19, p105-Rb, CDK4/6, phr A photolyase activity, DNA-photoreactivating enzyme, Agents, antagonists and inhibitors, Patient, familial retinoblastoma, rps4, Biochemical Marker, Estrogen Effect, associated with dysmorphism, P53, l(2)0671, TKR1, p44, bhy, Estrogenic Compounds, dWAVE, isoform 1, EG:34F3.3, BZS, Rbf1, RBF1, Prognostic Factor, 2310035O07Rik, Estrogenic Agents, esr1, XER, Estrogen Receptor, Effects, FBF, GLM2, Clinical Markers, Clinical Marker, p53, SCR10, esr1b, esr1a, AA420328, Pk?7, Prognostic Factors, photoreactivating enzyme activity, LFS1, SAD3, Cav1.2, autosomal dominant, dRBF, AW122239, KIAA1506, Surrogate End Points, MHAM, Surrogate Markers, ccg2, eye cancer, L type, RRG6, dock180, AI463227, Wave, Clinical Progression, OSRC, Dscar, Scars, stratum pigmentosa retinae, CCG2, Era, HER-2/neu, Agonists, Estrogen Effects, intellectual disability, scr10, reactivity, Biomarker, hormones, MOS3, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, Clinical, PRECOCIOUS, CG5072, HER-2, Dm MBC, Growth retardation, NR3A1, Mbc, MBC, Biological Marker, inhibiteur, F23A5.3, ERalpha, ERa, estrogenos, DmelCG5671, Scarring, and seizures, nr3a1, MLL3, cdk4, GEP6, Trp53, ESR, Esr, Immunologic Markers, inhibidor, Clinical Course, Clients, ESR1, xesr1, B430203M17Rik, CDK4, Characteristics, TRP53, RNESTROR, Immunologic Marker, l(2)05428, Mouse brain class C, F23A5_3, ESRA, Biologic, Neu, NEU, Dock180, inhibitors, Disease, findings, PTEN, HER-2|neu, AI838537, mKIAA3023, Serum Markers, End Point, inhibitor, estrogene, dPten, Factor, PD-0332991, pten, Client, cardiac muscle, Xp53, Immune Marker, l(2)s4639, dpten, MODIFIER OF SNC1, Characteristic, estrogens, hypoparathyroidism, Surrogate End Point, estrogeno, CWS1, chemical analysis, deoxyribonucleic photolyase activity, PPP1R130, RAD31, NGL, Oestrogen, KCS1, dPTEN, DmCdk4, Biologic Markers, antagonists, CG10379, Estrogenic Effect, Serum Marker, RPE, Mmac, Estrogen, distinct, 10q23del, CG5671, photolyase activity, c-erbB2, Surrogate, dxs306, Endpoints, DXS306, Rb-1, pac2, severe cutaneous adverse reaction, ESTRR, MBC/DOCK180, DmelCG5072, A130070J02Rik, alpha-1 polypeptide, Surrogate Marker, p. pigmentosa retinae, Rb1, 8-6, growth retardation and developmental delay, DEC, Su(rac)1, Therapeutic, Estr, esr-1, RETINOBLASTOMA-RELATED PROTEIN 1, RETINOBLASTOMA-RELATED, PD0332991, Pk53C, Treatment, deoxyribonucleate pyrimidine dimer lyase (photosensitive), assay, D930026N18Rik, response, RbF, trilateral, KCS, l(2)sh0671, HER2, ER-alpha, oestrogenes, Immune MarkersfalseMult-omics Palbociclib Resistance Study in HR+/HER2– Metastatic Breast CancerResistance to CDK4/6 inhibitors and endocrine therapy (ET) are common and poorly understood since they have been real game changer in patients with HR-positive and HER2-negative MBC. A comprehensive genomic and transcriptomic analysis of pre-treatment and post-treatment tumors from patients treated with palbociclib plus ET identified novel markers associated with poor prognosis such as genomic scar features caused by homologous repair deficiency (HRD), estrogen response signatures, and four unique prognostic clusters with distinct molecular features. Tumors with TP53 mutations co-occurring with a unique HRD-high cluster responded poorly. By comparing genomic and transciptomic profiles of paired samples, tumors were found to be further enriched in HRD genomic scars and many had switched to aggressive molecular subtypes. Furthermore, we identified high frequencies of acquired genomic alterations upon disease progression in RB1, ESR1, PTEN, and KMT2C. Our findings provide new insight into potential predictive biomarkers that could be targeted to overcome resistance. (NCT03401359)2023-05-10 09:18:05EGAS000010057369606EGAD00001008314EGAC00001002381