nach oben

Erschienen in:

18.08.2020 | Preclinical study

Prognostication of a 13-immune-related-gene signature in patients with early triple-negative breast cancer

verfasst von: Ji-Yeon Kim, Hae Hyun Jung, Insuk Sohn, Sook Young Woo, Hyun Cho, Eun Yoon Cho, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Yeon Hee Park, Jin Seok Ahn, Young-Hyuck Im

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2020

Einloggen, um Zugang zu erhalten

Abstract

Purpose

We investigated the expression profiles of immune genes in patients with triple-negative breast cancer (TNBC) to identify the prognostic value of immune genes and their clinical implications.

Methods

NanoString nCounter Analysis of 770 immune-related genes was used to measure immune gene expression in patients with TNBC who underwent curative surgery followed by adjuvant chemotherapy at Samsung Medical Center between 2000 and 2004. Statistical analyses were conducted to identify the associations between gene expression and distant recurrence-free survival (DRFS).

Results

Of 1189 patients who underwent curative BC surgery, 200 TNBC patients were included and stage was the only clinical factor predictive of DRFS. In terms of immune genes, 155 of 770 genes were associated with DRFS (p < 0.01). Further multivariate analysis revealed that 13 genes, CD1B, CD53, CT45A1, GTF3C1, IL11RA, IL1RN, LRRN3, MAPK1, NEFL, PRKCE, PTPRC, SPACA3 and TNFSF11, were associated with patient prognosis (p < 0.05). The prognostic value of stage and expression levels of 13 immune genes was analyzed and the area under the receiver operating characteristic curve (AUC) was 0.923. Based on the AUC, we divided patients into three genetic risk groups and DRFS rate was significantly different according to genetic risk groups, even in the same stage (p < 0.001).

Conclusions

In this study, a 13-gene expression profile in combination with stage precisely predicted distant recurrence of early TNBC. Therefore, this 13-immune-gene signature could help predict TNBC prognosis and provide guidance for treatment as well as the opportunity to develop new targets for immunotherapy in TNBC patients.

Nur mit Berechtigung zugänglich

Bonotto M, Gerratana L, Poletto E, Driol P, Giangreco M, Russo S, Minisini AM, Andreetta C, Mansutti M, Pisa FE, Fasola G, Puglisi F (2014) Measures of outcome in metastatic breast cancer: insights from a real-world scenario. Oncologist 19:608–615. https://doi.org/10.1634/theoncologist.2014-0002CrossRefPubMed

den Brok WD, Speers CH, Gondara L, Baxter E, Tyldesley SK, Lohrisch CA (2017) Survival with metastatic breast cancer based on initial presentation, de novo versus relapsed. Breast Cancer Res Treat 161:549–556. https://doi.org/10.1007/s10549-016-4080-9CrossRef

(2019) National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology — breast cancer. V1. 2019

Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 121:2750–2767. https://doi.org/10.1172/JCI45014CrossRefPubMed

Burstein MD, Tsimelzon A, Poage GM, Covington KR, Contreras A, Fuqua SA, Savage MI, Osborne CK, Hilsenbeck SG, Chang JC, Mills GB, Lau CC, Brown PH (2015) Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res 21:1688–1698. https://doi.org/10.1158/1078-0432.CCR-14-0432CrossRefPubMed

Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454. https://doi.org/10.1056/NEJMoa1200690CrossRefPubMed

Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465. https://doi.org/10.1056/NEJMoa1200694CrossRefPubMed

Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A, investigators K (2015) Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med 372:2521–2532. https://doi.org/10.1056/NEJMoa1503093CrossRefPubMed

Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L, Investigators K (2015) Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372:2018–2028. https://doi.org/10.1056/NEJMoa1501824CrossRefPubMed

10.

Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Petrylak DP, Choueiri TK, Necchi A, Gerritsen W, Gurney H, Quinn DI, Culine S, Sternberg CN, Mai Y, Poehlein CH, Perini RF, Bajorin DF, Investigators K (2017) Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 376:1015–1026. https://doi.org/10.1056/NEJMoa1613683CrossRefPubMed

11.

Mittendorf EA, Philips AV, Meric-Bernstam F, Qiao N, Wu Y, Harrington S, Su X, Wang Y, Gonzalez-Angulo AM, Akcakanat A, Chawla A, Curran M, Hwu P, Sharma P, Litton JK, Molldrem JJ, Alatrash G (2014) PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res 2:361–370. https://doi.org/10.1158/2326-6066.CIR-13-0127CrossRefPubMed

12.

Schalper KA, Velcheti V, Carvajal D, Wimberly H, Brown J, Pusztai L, Rimm DL (2014) In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas. Clin Cancer Res 20:2773–2782. https://doi.org/10.1158/1078-0432.CCR-13-2702CrossRefPubMed

13.

Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Dieras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA, Investigators IMT (2018) Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med 379:2108–2121. https://doi.org/10.1056/NEJMoa1809615CrossRefPubMed

14.

Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J, Investigators K (2020) Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med 382:810–821. https://doi.org/10.1056/NEJMoa1910549CrossRefPubMed

15.

Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L (2016) Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol 34:2460–2467. https://doi.org/10.1200/JCO.2015.64.8931CrossRefPubMed

16.

Katz H, Alsharedi M (2017) Immunotherapy in triple-negative breast cancer. Med Oncol 35:13. https://doi.org/10.1007/s12032-017-1071-6CrossRefPubMed

17.

Liu L, Wang Y, Miao L, Liu Q, Musetti S, Li J, Huang L (2018) Combination Immunotherapy of MUC1 mRNA Nano-vaccine and CTLA-4 Blockade Effectively Inhibits Growth of Triple Negative Breast Cancer. Mol Ther 26:45–55. https://doi.org/10.1016/j.ymthe.2017.10.020CrossRefPubMed

18.

Bloom HJ, Richardson WW (1957) Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer 11:359–377CrossRefPubMed

19.

McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, Statistics Subcommittee of the NCIEWGoCD (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23:9067–9072. https://doi.org/10.1200/JCO.2004.01.0454CrossRefPubMed

20.

Emens LA, Cruz C, Eder JP, Braiteh F, Chung C, Tolaney SM, Kuter I, Nanda R, Cassier PA, Delord JP, Gordon MS, ElGabry E, Chang CW, Sarkar I, Grossman W, O'Hear C, Fasso M, Molinero L, Schmid P (2019) Long-term Clinical Outcomes and Biomarker Analyses of Atezolizumab Therapy for Patients With Metastatic Triple-Negative Breast Cancer: A Phase 1 Study. JAMA Oncol 5:74–82. https://doi.org/10.1001/jamaoncol.2018.4224CrossRef

21.

Adams S, Diamond JR, Hamilton E, Pohlmann PR, Tolaney SM, Chang CW, Zhang W, Iizuka K, Foster PG, Molinero L, Funke R, Powderly J (2018) Atezolizumab Plus nab-Paclitaxel in the Treatment of Metastatic Triple-Negative Breast Cancer With 2-Year Survival Follow-up: A Phase 1b Clinical Trial. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2018.5152CrossRefPubMed

22.

Mori H, Kubo M, Yamaguchi R, Nishimura R, Osako T, Arima N, Okumura Y, Okido M, Yamada M, Kai M, Kishimoto J, Oda Y, Nakamura M (2017) The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer. Oncotarget 8:15584–15592. https://doi.org/10.18632/oncotarget.14698CrossRefPubMed

23.

Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L (2018) Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med 378:2093–2104. https://doi.org/10.1056/NEJMoa1801946CrossRefPubMed

24.

Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr (2015) PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 372:2509–2520. https://doi.org/10.1056/NEJMoa1500596CrossRefPubMed

25.

Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, Miller ML, Rekhtman N, Moreira AL, Ibrahim F, Bruggeman C, Gasmi B, Zappasodi R, Maeda Y, Sander C, Garon EB, Merghoub T, Wolchok JD, Schumacher TN, Chan TA (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124–128. https://doi.org/10.1126/science.aaa1348CrossRefPubMed

26.

Muenst S, Schaerli AR, Gao F, Daster S, Trella E, Droeser RA, Muraro MG, Zajac P, Zanetti R, Gillanders WE, Weber WP, Soysal SD (2014) Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat 146:15–24. https://doi.org/10.1007/s10549-014-2988-5CrossRefPubMed

27.

Botti G, Collina F, Scognamiglio G, Rao F, Peluso V, De Cecio R, Piezzo M, Landi G, De Laurentiis M, Cantile M, Di Bonito M (2017) Programmed Death Ligand 1 (PD-L1) Tumor Expression Is Associated with a Better Prognosis and Diabetic Disease in Triple Negative Breast Cancer Patients. Int J Mol Sci. https://doi.org/10.3390/ijms18020459CrossRefPubMed

28.

Cheng WY, Ou Yang TH, Anastassiou D (2013) Development of a prognostic model for breast cancer survival in an open challenge environment. Sci Transl Med. https://doi.org/10.1126/scitranslmed.3005974CrossRefPubMed

29.

Cheng WY, Ou Yang TH, Anastassiou D (2013) Biomolecular events in cancer revealed by attractor metagenes. PLoS Comput Biol 9:e1002920. https://doi.org/10.1371/journal.pcbi.1002920CrossRefPubMed

30.

Cheng ML, Fong L (2014) Effects of RANKL-Targeted Therapy in Immunity and Cancer. Front Oncol 3:329. https://doi.org/10.3389/fonc.2013.00329CrossRefPubMed

31.

Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, Lichinitser M, Fujiwara Y, Yardley DA, Viniegra M, Fan M, Jiang Q, Dansey R, Jun S, Braun A (2010) Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol 28:5132–5139. https://doi.org/10.1200/JCO.2010.29.7101CrossRefPubMed

32.

Tan W, Zhang W, Strasner A, Grivennikov S, Cheng JQ, Hoffman RM, Karin M (2011) Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling. Nature 470:548–553. https://doi.org/10.1038/nature09707CrossRefPubMed

33.

Reyes ME, Fujii T, Branstetter D, Krishnamurthy S, Masuda H, Wang X, Reuben JM, Woodward WA, Edwards BJ, Hortobagyi GN, Tripathy D, Dougall WC, Eckhardt BL, Ueno NT (2017) Poor prognosis of patients with triple-negative breast cancer can be stratified by RANK and RANKL dual expression. Breast Cancer Res Treat 164:57–67. https://doi.org/10.1007/s10549-017-4233-5CrossRefPubMed

34.

Shang B, Gao A, Pan Y, Zhang G, Tu J, Zhou Y, Yang P, Cao Z, Wei Q, Ding Y, Zhang J, Zhao Y, Zhou Q (2014) CT45A1 acts as a new proto-oncogene to trigger tumorigenesis and cancer metastasis. Cell Death Dis 5:e1285. https://doi.org/10.1038/cddis.2014.244CrossRefPubMed

35.

Ahmad DA, Negm OH, Alabdullah ML, Mirza S, Hamed MR, Band V, Green AR, Ellis IO, Rakha EA (2016) Clinicopathological and prognostic significance of mitogen-activated protein kinases (MAPK) in breast cancers. Breast Cancer Res Treat 159:457–467. https://doi.org/10.1007/s10549-016-3967-9CrossRefPubMed

36.

Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Goetz MP, Olson JA Jr, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin PM, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge GW Jr (2018) Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med 379:111–121. https://doi.org/10.1056/NEJMoa1804710CrossRefPubMed

37.

F Cardoso van't Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S, Pierga JY, Brain E, Causeret S, DeLorenzi M, Glas AM, Golfinopoulos V, Goulioti T, Knox S, Matos E, Meulemans B, Neijenhuis PA, Nitz U, Passalacqua R, Ravdin P, Rubio IT, Saghatchian M, Smilde TJ, Sotiriou C, Stork L, Straehle C, Thomas G, Thompson AM, van der Hoeven JM, Vuylsteke P, Bernards R, Tryfonidis K, Rutgers E, Piccart M, Investigators M, 2016 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer N Engl J Med 375 717 729 10.1056/NEJMoa1602253

38.

Kim J-Y JH, Lim JE, Cho EY, Lee SK, Yu JH, Lee JE, Kim SW, Nam SJ, Park YH, Ahn JS, Im Y-H (2018) Prognostication of immune related gene expression in patients with triple negative breast cancer [abstract].In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4–8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4–08–30. Doi: 10.1158/1538-7445.SABCS18-P4-08-30

Titel: Prognostication of a 13-immune-related-gene signature in patients with early triple-negative breast cancer
verfasst von: Ji-Yeon Kim
Hae Hyun Jung
Insuk Sohn
Sook Young Woo
Hyun Cho
Eun Yoon Cho
Jeong Eon Lee
Seok Won Kim
Seok Jin Nam
Yeon Hee Park
Jin Seok Ahn
Young-Hyuck Im
Publikationsdatum: 18.08.2020
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2020
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-05874-1

Neu im Fachgebiet Onkologie

Hodgkin Lymphom: BrECADD-Regime übertrifft die Erwartungen

05.06.2024 ASCO 2024 Kongressbericht

Das Kombinationsregime BrECADD mit Brentuximab vedotin ermöglichte in der Studie HD21 beim fortgeschrittenen klassischen Hodgkin-Lymphom eine unerwartet hohe progressionsfreie Überlebensrate von 94,3% nach vier Jahren. Gleichzeitig war das Regime besser tolerabel als der bisherige Standard eBEACOPP.

Antikörper-Drug-Konjugat verdoppelt PFS bei Multiplem Myelom

05.06.2024 ASCO 2024 Nachrichten

Zwei Phase-3-Studien deuten auf erhebliche Vorteile des Antikörper-Wirkstoff-Konjugats Belantamab-Mafodotin bei vorbehandelten Personen mit Multiplem Myelom: Im Vergleich mit einer Standard-Tripeltherapie wurde das progressionsfreie Überleben teilweise mehr als verdoppelt.

Neuer TKI gegen CML: Höhere Wirksamkeit, seltener Nebenwirkungen

05.06.2024 Chronische myeloische Leukämie Nachrichten

Der Tyrosinkinasehemmer (TKI) Asciminib ist älteren Vertretern dieser Gruppe bei CML offenbar überlegen: Personen mit frisch diagnostizierter CML entwickelten damit in einer Phase-3-Studie häufiger eine gut molekulare Response, aber seltener ernste Nebenwirkungen.

Brustkrebs-Prävention wird neu gedacht

04.06.2024 ASCO 2024 Kongressbericht

Zurzeit untersuchen Forschende verschiedene neue Ansätze zur Prävention von Brustkrebs bei Personen mit hohem Risiko. Darunter Denosumab, die prophylaktische Bestrahlung der Brust – und Impfungen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2020

Impact of fibroblast growth factor receptor 1 (FGFR1) amplification on the prognosis of breast cancer patients

Accuracy of breast MRI in patients receiving neoadjuvant endocrine therapy: comprehensive imaging analysis and correlation with clinical and pathological assessments

Management of early breast cancer during the COVID-19 pandemic in Brazil

Breast cancer survival among Japanese individuals and US residents of Japanese and other origins: a comparative registry-based study

Fertility preservation does not delay the initiation of chemotherapy in breast cancer patients treated with adjuvant or neo-adjuvant chemotherapy