The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer.
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ABSTRACT:
SUBMITTER: De Mattos-Arruda L
PROVIDER: S-EPMC6546974 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
Publications
The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer.
De Mattos-Arruda Leticia L Sammut Stephen-John SJ Ross Edith M EM Bashford-Rogers Rachael R Greenstein Erez E Markus Havell H Morganella Sandro S Teng Yvonne Y Maruvka Yosef Y Pereira Bernard B Rueda Oscar M OM Chin Suet-Feung SF Contente-Cuomo Tania T Mayor Regina R Arias Alexandra A Ali H Raza HR Cope Wei W Tiezzi Daniel D Dariush Aliakbar A Dias Amarante Tauanne T Reshef Dan D Ciriaco Nikaoly N Martinez-Saez Elena E Peg Vicente V Ramon Y Cajal Santiago S Cortes Javier J Vassiliou George G Getz Gad G Nik-Zainal Serena S Murtaza Muhammed M Friedman Nir N Markowetz Florian F Seoane Joan J Caldas Carlos C
Cell reports 20190501 9
The detailed molecular characterization of lethal cancers is a prerequisite to understanding resistance to therapy and escape from cancer immunoediting. We performed extensive multi-platform profiling of multi-regional metastases in autopsies from 10 patients with therapy-resistant breast cancer. The integrated genomic and immune landscapes show that metastases propagate and evolve as communities of clones, reveal their predicted neo-antigen landscapes, and show that they can accumulate HLA loss ...[more]
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Project description:PURPOSE:Circulating tumour cells (CTCs) are a marker of poor prognosis and are associated with increased risk of venous thromboembolism in metastatic breast cancer (MBC). We aimed to determine if the presence of CTCs and plasma markers of hypercoagulability [thrombin-antithrombin III (TAT), fibrinogen and D-dimer] are biomarkers of survival in MBC. METHODS/PATIENTS:In a prospective study of MBC patients, CTC (CellSearch®) enumeration and plasma TAT, fibrinogen and D-dimer measured prior to commencement of treatment for disease progression were correlated to overall survival. RESULTS:At study completion, of 50 MBC patients recruited (median age 59 years, range 36-82), 40 patients had died (median survival 417 days, range 58-2141). CTCs (??1/7.5 ml) were identified in 16 patients (median number of cells per 7.5 ml, 3 (range 1-31) and were associated with systemic hypercoagulability (medians TAT: 8.1 vs. 5.2 ng/ml, p?=?0.03; fibrinogen: 4.3 vs. 3.1 g/l, p?=?0.03; D-dimer: 1327 vs. 683 ng/ml, p?=?0.0001). At 1 year, of 16 patients with ??1 CTC, 7 had died (44%), compared to 5 of 26 (19%) patients in the no-CTC group. The presence of ??1 CTC was associated with a trend for reduced overall survival (median 455 days vs. 614 days, p?=?0.15). Plasma TAT inversely correlated with survival and was significantly higher in patients dying within 1 year (median 9.8 vs. 5.2 ng/ml, p?=?0.004) whilst D-dimer showed a trend for reduced 1-year survival (median 1211 vs. 817 ng/ml, p?=?0.06). MBC patients with combined high D-dimer (??895 ng/ml) and CTC positivity (??1/7.5 ml whole peripheral blood) had significantly reduced survival (p?=?0.04). CONCLUSIONS:The correlation between CTCs, hypercoagulability and reduced survival in MBC suggests the coagulation system supports tumour cell metastasis and is, therefore, a potential therapeutic target.
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