Chonglin Tian1,2, Sujing Liu3, Yongsheng Wang2, Xianrang Song2. 1. Graduate School, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. 2. Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. 3. Department of Radiation Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
Abstract
OBJECTIVE: The prognosis of breast cancer liver metastasis (BCLM) is poor, and its molecular mechanism is unclear. We aimed to determine the factors that affect the prognosis of patients with BCLM and investigate the genomic landscape of liver metastasis (LM). METHODS: We described the prognosis of patients with BCLM and focused on prognosis prediction for these patients based on clinicopathological factors. Nomogram models were constructed for progression-free survival (PFS) and overall survival (OS) by using a cohort of 231 patients with BCLM who underwent treatment at Shandong Cancer Hospital and Institute (SCHI). We explored the molecular mechanism of LM and constructed driver genes, mutation signatures by using a targeted sequencing dataset of 217 samples of LM and 479 unpaired samples of primary breast cancer (pBC) from Memorial Sloan Kettering Cancer Center (MSKCC). RESULTS: The median follow-up time for 231 patients with BCLM in the SCHI cohort was 46 months. The cumulative incidence of LM at 1, 2, and 5 years was 17.5%, 45.0%, and 86.8%, respectively. The median PFS and OS were 7 months (95% CI, 6-8) and 22 months (95% CI, 19-25), respectively. The independent factors that increased the progression risk of patients with LM were Karnofsky performance status (KPS) ≤ 80, TNBC subtype, grade III, increasing trend of CA153, and disease-free interval (DFS) ≤ 1 year. Simultaneously, the independent factors that increased the mortality risk of patients with LM were Ki-67 ≥ 30%, grade III, increasing trend of CA153, pain with initial LM, diabetes, and DFI ≤ 1 year. In the MSKCC dataset, the LM driver genes were ESR1, AKT1, ERBB2, and FGFR4, and LM matched three prominent mutation signatures: APOBEC cytidine deaminase, ultraviolet exposure, and defective DNA mismatch repair. CONCLUSION: This study systematically describes the survival prognosis and characteristics of LM from the clinicopathological factors to the genetic level. These results not only enable clinicians to assess the risk of disease progression in patients with BCLM to optimize treatment options, but also help us better understand the underlying mechanisms of tumor metastasis and evolution and provide new therapeutic targets with potential benefits for drug-resistant patients.
OBJECTIVE: The prognosis of breast cancer liver metastasis (BCLM) is poor, and its molecular mechanism is unclear. We aimed to determine the factors that affect the prognosis of patients with BCLM and investigate the genomic landscape of liver metastasis (LM). METHODS: We described the prognosis of patients with BCLM and focused on prognosis prediction for these patients based on clinicopathological factors. Nomogram models were constructed for progression-free survival (PFS) and overall survival (OS) by using a cohort of 231 patients with BCLM who underwent treatment at Shandong Cancer Hospital and Institute (SCHI). We explored the molecular mechanism of LM and constructed driver genes, mutation signatures by using a targeted sequencing dataset of 217 samples of LM and 479 unpaired samples of primary breast cancer (pBC) from Memorial Sloan Kettering Cancer Center (MSKCC). RESULTS: The median follow-up time for 231 patients with BCLM in the SCHI cohort was 46 months. The cumulative incidence of LM at 1, 2, and 5 years was 17.5%, 45.0%, and 86.8%, respectively. The median PFS and OS were 7 months (95% CI, 6-8) and 22 months (95% CI, 19-25), respectively. The independent factors that increased the progression risk of patients with LM were Karnofsky performance status (KPS) ≤ 80, TNBC subtype, grade III, increasing trend of CA153, and disease-free interval (DFS) ≤ 1 year. Simultaneously, the independent factors that increased the mortality risk of patients with LM were Ki-67 ≥ 30%, grade III, increasing trend of CA153, pain with initial LM, diabetes, and DFI ≤ 1 year. In the MSKCC dataset, the LM driver genes were ESR1, AKT1, ERBB2, and FGFR4, and LM matched three prominent mutation signatures: APOBEC cytidine deaminase, ultraviolet exposure, and defective DNA mismatch repair. CONCLUSION: This study systematically describes the survival prognosis and characteristics of LM from the clinicopathological factors to the genetic level. These results not only enable clinicians to assess the risk of disease progression in patients with BCLM to optimize treatment options, but also help us better understand the underlying mechanisms of tumor metastasis and evolution and provide new therapeutic targets with potential benefits for drug-resistant patients.
Authors: F Andre; N Cabioglu; H Assi; J C Sabourin; S Delaloge; A Sahin; K Broglio; J P Spano; C Combadiere; C Bucana; J C Soria; M Cristofanilli Journal: Ann Oncol Date: 2006-04-20 Impact factor: 32.976
Authors: François Bertucci; Charlotte K Y Ng; Anne Patsouris; Thomas Filleron; Christophe Le Tourneau; Fabrice André; Nathalie Droin; Salvatore Piscuoglio; Nadine Carbuccia; Jean Charles Soria; Alicia Tran Dien; Yahia Adnani; Maud Kamal; Séverine Garnier; Guillaume Meurice; Marta Jimenez; Semih Dogan; Benjamin Verret; Max Chaffanet; Thomas Bachelot; Mario Campone; Claudia Lefeuvre; Herve Bonnefoi; Florence Dalenc; Alexandra Jacquet; Maria R De Filippo; Naveen Babbar; Daniel Birnbaum Journal: Nature Date: 2019-05-22 Impact factor: 49.962
Authors: Charlotte K Y Ng; Francois-Clement Bidard; Salvatore Piscuoglio; Felipe C Geyer; Raymond S Lim; Ino de Bruijn; Ronglai Shen; Fresia Pareja; Samuel H Berman; Lu Wang; Jean-Yves Pierga; Anne Vincent-Salomon; Agnes Viale; Larry Norton; Brigitte Sigal; Britta Weigelt; Paul Cottu; Jorge S Reis-Filho Journal: Clin Cancer Res Date: 2017-03-28 Impact factor: 12.531
Authors: Marco Gerlinger; Andrew J Rowan; Stuart Horswell; James Larkin; David Endesfelder; Eva Gronroos; Pierre Martinez; Nicholas Matthews; Aengus Stewart; Charles Swanton; M Math; Patrick Tarpey; Ignacio Varela; Benjamin Phillimore; Sharmin Begum; Neil Q McDonald; Adam Butler; David Jones; Keiran Raine; Calli Latimer; Claudio R Santos; Mahrokh Nohadani; Aron C Eklund; Bradley Spencer-Dene; Graham Clark; Lisa Pickering; Gordon Stamp; Martin Gore; Zoltan Szallasi; Julian Downward; P Andrew Futreal Journal: N Engl J Med Date: 2012-03-08 Impact factor: 91.245
Authors: Emily K Law; Anieta M Sieuwerts; Kelly LaPara; Brandon Leonard; Gabriel J Starrett; Amy M Molan; Nuri A Temiz; Rachel Isaksson Vogel; Marion E Meijer-van Gelder; Fred C G J Sweep; Paul N Span; John A Foekens; John W M Martens; Douglas Yee; Reuben S Harris Journal: Sci Adv Date: 2016-10-07 Impact factor: 14.136
Authors: Ahmet Zehir; Ryma Benayed; Ronak H Shah; Aijazuddin Syed; Sumit Middha; Hyunjae R Kim; Preethi Srinivasan; Jianjiong Gao; Debyani Chakravarty; Sean M Devlin; Matthew D Hellmann; David A Barron; Alison M Schram; Meera Hameed; Snjezana Dogan; Dara S Ross; Jaclyn F Hechtman; Deborah F DeLair; JinJuan Yao; Diana L Mandelker; Donavan T Cheng; Raghu Chandramohan; Abhinita S Mohanty; Ryan N Ptashkin; Gowtham Jayakumaran; Meera Prasad; Mustafa H Syed; Anoop Balakrishnan Rema; Zhen Y Liu; Khedoudja Nafa; Laetitia Borsu; Justyna Sadowska; Jacklyn Casanova; Ruben Bacares; Iwona J Kiecka; Anna Razumova; Julie B Son; Lisa Stewart; Tessara Baldi; Kerry A Mullaney; Hikmat Al-Ahmadie; Efsevia Vakiani; Adam A Abeshouse; Alexander V Penson; Philip Jonsson; Niedzica Camacho; Matthew T Chang; Helen H Won; Benjamin E Gross; Ritika Kundra; Zachary J Heins; Hsiao-Wei Chen; Sarah Phillips; Hongxin Zhang; Jiaojiao Wang; Angelica Ochoa; Jonathan Wills; Michael Eubank; Stacy B Thomas; Stuart M Gardos; Dalicia N Reales; Jesse Galle; Robert Durany; Roy Cambria; Wassim Abida; Andrea Cercek; Darren R Feldman; Mrinal M Gounder; A Ari Hakimi; James J Harding; Gopa Iyer; Yelena Y Janjigian; Emmet J Jordan; Ciara M Kelly; Maeve A Lowery; Luc G T Morris; Antonio M Omuro; Nitya Raj; Pedram Razavi; Alexander N Shoushtari; Neerav Shukla; Tara E Soumerai; Anna M Varghese; Rona Yaeger; Jonathan Coleman; Bernard Bochner; Gregory J Riely; Leonard B Saltz; Howard I Scher; Paul J Sabbatini; Mark E Robson; David S Klimstra; Barry S Taylor; Jose Baselga; Nikolaus Schultz; David M Hyman; Maria E Arcila; David B Solit; Marc Ladanyi; Michael F Berger Journal: Nat Med Date: 2017-05-08 Impact factor: 53.440
Authors: Serena Nik-Zainal; Ludmil B Alexandrov; David C Wedge; Peter Van Loo; Christopher D Greenman; Keiran Raine; David Jones; Jonathan Hinton; John Marshall; Lucy A Stebbings; Andrew Menzies; Sancha Martin; Kenric Leung; Lina Chen; Catherine Leroy; Manasa Ramakrishna; Richard Rance; King Wai Lau; Laura J Mudie; Ignacio Varela; David J McBride; Graham R Bignell; Susanna L Cooke; Adam Shlien; John Gamble; Ian Whitmore; Mark Maddison; Patrick S Tarpey; Helen R Davies; Elli Papaemmanuil; Philip J Stephens; Stuart McLaren; Adam P Butler; Jon W Teague; Göran Jönsson; Judy E Garber; Daniel Silver; Penelope Miron; Aquila Fatima; Sandrine Boyault; Anita Langerød; Andrew Tutt; John W M Martens; Samuel A J R Aparicio; Åke Borg; Anne Vincent Salomon; Gilles Thomas; Anne-Lise Børresen-Dale; Andrea L Richardson; Michael S Neuberger; P Andrew Futreal; Peter J Campbell; Michael R Stratton Journal: Cell Date: 2012-05-17 Impact factor: 41.582