EGAGenomicsWhole Genome Sequencinghttps://ega-archive.org/studies/EGAS00001004756EGAEGA study EGAS00001004756Rucaparib in patients presenting a metastatic breast cancerEGArestrictedRNF53, chromosomal crossover, hereditary breast ovarian cancer, Breast Carcinoma, Human Mammary Neoplasm, primary breast cancer, Carcinoma, malignant tumor of the breast, Breast Carcinomas, "breast neoplasm" EXACT [MTH:120], BRCA1, BRCA2, Homologous Recombinations, Neoplasms, AG 014699, mammary neoplasm, BRCAI, Mammary Cancers, Human Mammary Neoplasms, PSCP, Tumor, "breast tumor" EXACT [NCI2004_11_17:C2910], PPP1R53, Client, Human, Breast Malignant Neoplasm, Mutations, WGS., Breast Malignant Tumor, Recombinations, "neoplasm of breast (disorder)" EXACT [SNOMEDCT_2005_07_31:126926005], Mammary Carcinomas, PF-01367338, Breast Tumor, Rubraca, Neoplasm, Familiar breast and Ovarian cancer syndrome, IRIS, Human Mammary Carcinoma, "mammary tumor" EXACT [CSP2005:2016-0671], NOS, breast tumor, cancer of the breast, BROVCA1, Malignant Neoplasm of Breast, Carcinomas, BC, Mammary Neoplasms, malignant neoplasm of breast, Recombination, Human Mammary, Breast Neoplasm, BRCC1, Mammary Neoplasm, Homologous, Mammary Carcinoma, reciprocal DNA recombination, Human Mammary Carcinomas, PNCA4, AG-014699, Cancers, "mammary neoplasm" RELATED [], FANCS, Cancer of the Breast, metastatic, Patient, breast cancer, cancer of breast, Malignant Tumor of Breast, Clients, Mammary, Mammary Cancer, Breast Tumors, Breast Cancer, Breast Malignant Tumors, AG014699, Cancer of Breast, Breast, mammary cancer, cancer, mammary tumor, Breast Malignant Neoplasms, breast, Tumors, CancerErbb-2, RNF53, Voltage-gated calcium channel subunit alpha Cav1.2, chromosomal crossover, primary breast cancer, deceased, malignant tumor of the breast, DmelCG40411, Neoplasms, LD21673.3prime, mammary neoplasm, Mammary Cancers, Human Mammary Neoplasms, BEST:LD21673, Cardiac Death, Tumor, PPP1R53, End-Of-Life, Cav1.2, AW122239, DOCK180, Human, CD340, Mutations, Adprt1, Breast Malignant Tumor, Recombinations, Cardiac, Kiaa3023, L type, CG40411, RRG6, reduced, "neoplasm of breast (disorder)" EXACT [SNOMEDCT_2005_07_31:126926005], Breast Tumor, dock180, Calcium channel, responsivity, Heterozygosity, Familiar breast and Ovarian cancer syndrome, IRIS, "mammary tumor" EXACT [CSP2005:2016-0671], breast tumor, cancer of the breast, BROVCA1, tiny, C80510, HER-2/neu, ADPRT, CG17696, BC, Mammary Neoplasms, malignant neoplasm of breast, reactivity, Human Mammary, Adprp, BRCC1, ARTD1, Mammary Neoplasm, ADPRT1, Homologous, AI893648, HER-2, Dm MBC, Mammary Carcinoma, Mbc, MBC, Human Mammary Carcinomas, hypoplasia, PNCA4, End Of Life, adprt1, FANCS, Cancer of the Breast, GEP6, cancer of breast, Malignant Tumor of Breast, Mammary, Mammary Cancer, Clients, Allelic Loss, Breast, mammary cancer, parp-1, mammary tumor, Breast Malignant Neoplasms, Mouse brain class C, Tumors, Cancer, Neu, NEU, Dock180, small, hereditary breast ovarian cancer, Breast Carcinoma, Human Mammary Neoplasm, Carcinoma, Breast Carcinomas, "breast neoplasm" EXACT [MTH:120], BRCA1, BRCA2, Homologous Recombinations, HER-2|neu, mKIAA3023, MELC-CC, pADPRT-1, BRCAI, AG 014699, PSCP, MLN19, Loss of, "breast tumor" EXACT [NCI2004_11_17:C2910], CED-5, Client, cardiac muscle, DFNA13, Breast Malignant Neoplasm, Allelic Losses, PARP1, Mammary Carcinomas, PF-01367338, sPARP-1, Hch, Rubraca, STL3, post-mortem, Neoplasm, Human Mammary Carcinoma, NGL, NOS, Near-Death Experience, median, Death, Malignant Neoplasm of Breast, c-neu, Carcinomas, CG10379, AI662014, Cchl1a1, Recombination, CG17696., death, Breast Neoplasm, Heterozygosity Loss, PARP, underdeveloped, Determination of Death, c-erbB2, reciprocal DNA recombination, DmelCG10379, AG-014699, Cancers, MBC/DOCK180, "mammary neoplasm" RELATED [], alpha-1 polypeptide, parp, DFNB53, CG17685, CG17718, MLN 19, metastatic, Su(rac)1, padprt-1, breast cancer, ppol, Patient, FBCG2, ADPRT 1, Breast Tumors, Breast Cancer, PARP-1, D.PARP, Breast Malignant Tumors, TKR1, HKE5, Cancer of Breast, AG014699, dPARP, Dm.pARTa, isoform 1, D930026N18Rik, response, PPOL, 5830444G22Rik, cancer, HER2, breastfalseRucaparib in patients presenting a metastatic breast cancer with Homologous Recombination Deficiency, without germline BRCA1/2 mutation, pronostic value of high LOH genomic score and predictive value of HRDetect (WGS)Breast cancer may present genomic alterations leading to homologous recombination deficiency. PARP inhibitors have proved their efficacy in patients with HER2-negative metastatic breast cancer (mBC) harboring germline (g) BRCA1/2 mutations. We conducted the phase 2 RUBY trial to assess the efficacy of rucaparib in HER2-negative mBC with high genomic loss of heterozygosity (LOH) score or somatic, without gBRCA1/2 mutation. 220 of 711 patients with mBC screened for LOH presented high LOH score which was associated with a higher likelihood of death (HR = 1.39, 95% CI: 1.11-1.75, p = 0.005). The primary objective was not reached with a clinical benefit rate (objective response or SD>16 weeks) of 13.5%. Two LOH-high patients, without somatic BRCA1/2 mutation, presented a complete and durable response (14 and 32 months). HRDetect tended to be associated with response to rucaparib, whithout reaching statistical significance (median HRDetect responders versus non responders: 0.465 versus, 0.040, p = 0.2135). Our data suggests that a small subset of patients with high LOH score could derive benefit from PARP inhibitors.2020-11-13 10:19:35EGAS000010047569606EGAD00001006458EGAC00001001775