Mutation and immune profiling of metaplastic breast cancer: Correlation with survival
Autoři:
Michelle Afkhami aff001; Daniel Schmolze aff001; Susan E. Yost aff002; Paul H. Frankel aff003; Andrew Dagis aff003; Idoroenyi U. Amanam aff002; Milhan Telatar aff001; Kim Nguyen aff001; Kim Wai Yu aff004; Thehang Luu aff002; Raju Pillai aff001; Patricia A. Aoun aff001; Joanne Mortimer aff002; Yuan Yuan aff002
Působiště autorů:
Department of Pathology, City of Hope Comprehensive Cancer Center, Duarte, CA, United States of America
aff001; Department of Medical Oncology & Therapeutic Research, City of Hope Comprehensive Cancer Center, Duarte, CA, United States of America
aff002; Department of Biostatistics, City of Hope Comprehensive Cancer Center, Duarte, CA, United States of America
aff003; Department of Clinical Pharmacy, City of Hope Comprehensive Cancer Center, Duarte, CA, United States of America
aff004
Vyšlo v časopise:
PLoS ONE 14(11)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0224726
Souhrn
The goal of this study is to characterize the genomic and immune profiles of metaplastic breast cancer (MpBC) and identify the association with survival through an analysis of archived tumor tissue. A next-generation sequencing-based mutational assay (Onco-48) was performed for 21 MpBC patients. Clinicopathologic characteristics were captured, including relapse free survival (RFS) and overall survival (OS). Immunohistochemistry (IHC) for CD3, CD4, CD8, and programmed death-ligand 1 (PD-L1) was also performed. Recurrence free survival (RFS) at 5 years was 57% (95% CI 0.34–0.75) and overall survival (OS) at 5 years was 66% (95% CI 0.41–0.82). The most commonly altered genes were TP53 (68.4%, 13/19), PIK3CA (42.1%, 8/19), and PTEN (15.8%, 3/19. For patients with PIK3CA mutations, RFS and OS were significantly worse than for those without (HR 5.6, 95% CI 1.33–23.1 and HR 8.0, 95% CI 1.53–41.7, respectively). Cox regression estimated that PD-L1 expression was associated with worse RFS and OS (HR 1.08, 95% CI 1.01–1.16 and HR 1.05, 95% CI 1.00–1.11, respectively, for an absolute increase in PD-L1 expression of 1%). In conclusion, PIK3CA mutation and PD-L1 expression confer poor prognosis in this cohort of patients with MpBC.
Klíčová slova:
Breast cancer – Cancer detection and diagnosis – Cancer chemotherapy – Cancer treatment – Cell staining – Immunohistochemistry techniques – Next-generation sequencing – Radiation therapy
Zdroje
1. Pezzi CM, Patel-Parekh L, Cole K, Franko J, Klimberg VS, Bland K. Characteristics and treatment of metaplastic breast cancer: analysis of 892 cases from the National Cancer Data Base. Annals of surgical oncology. 2007;14(1):166–73. doi: 10.1245/s10434-006-9124-7 17066230
2. Tavassoli FA. Classification of metaplastic carcinomas of the breast. Pathology annual. 1992;27 Pt 2:89–119.
3. Kurman RJ, Carcangiu ML, Herrington S, Young RH. WHO classification of tumours of female reproductive organs: IARC; 2014.
4. Weigelt B, Kreike B, Reis-Filho JS. Metaplastic breast carcinomas are basal-like breast cancers: a genomic profiling analysis. Breast cancer research and treatment. 2009;117(2):273–80. doi: 10.1007/s10549-008-0197-9 18815879
5. Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast cancer research. 2010;12(5):1.
6. Shah DR, Tseng WH, Martinez SR. Treatment Options for Metaplastic Breast Cancer. ISRN Oncology. 2012;2012.
7. Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. Journal of Clinical Oncology. 2016;34(21):2460–7. doi: 10.1200/JCO.2015.64.8931 27138582
8. Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. New England Journal of Medicine. 2018;379(22):2108–21. doi: 10.1056/NEJMoa1809615 30345906
9. Adams S, Loi S, Toppmeyer D, Cescon D, De Laurentiis M, Nanda R, et al. KEYNOTE-086 cohort B: pembrolizumab monotherapy for PD-L1–positive, previously untreated, metastatic triple-negative breast cancer (mTNBC). Cancer Research. 2018.
10. Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, et al. Phase 2 study of pembrolizumab (pembro) monotherapy for previously treated metastatic triple-negative breast cancer (mTNBC): KEYNOTE-086 cohort A. American Society of Clinical Oncology; 2017.
11. Nanda R, Liu MC, Yau C, Asare S, Hylton N, Veer LVt, et al. Pembrolizumab plus standard neoadjuvant therapy for high-risk breast cancer (BC): Results from I-SPY 2. American Society of Clinical Oncology; 2017.
12. Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Annals of oncology. 2015;26(2):259–71. doi: 10.1093/annonc/mdu450 25214542
13. Ventana Medical Systems. Ventana PD-L1 (SP263) Assay [package insert]. Tucson, AZ: A.V.M.S., Inc; 2017.
14. Massard C, Gordon MS, Sharma S, Rafii S, Wainberg ZA, Luke JJ, et al. Safety and efficacy of durvalumab (MEDI4736), a PD-L1 antibody, in urothelial bladder cancer. Journal of Clinical Oncology. 2016;34(15_suppl):4502–.
15. Team RC. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2016. 2017.
16. Alboukadel Kassambara MK, Przemyslaw Biecek, Scheipl Fabian survminer: Drawing Survival Curves using “ggplot2.” https://CRANR-projectorg/package=survminer2018.
17. Therneau TM. A Package for Survival Analysis in S. https://CRANR-projectorg/package=survival2015.
18. Nelson RA, Guye ML, Luu T, Lai LL. Survival outcomes of metaplastic breast cancer patients: results from a US population-based analysis. Annals of surgical oncology. 2015;22(1):24–31. doi: 10.1245/s10434-014-3890-4 25012264
19. Moulder S, Helgason T, Janku F, Wheler J, Moroney J, Booser D, et al. Inhibition of the phosphoinositide 3-kinase pathway for the treatment of patients with metastatic metaplastic breast cancer. Annals of Oncology. 2015:mdv163.
20. Ross JS, Badve S, Wang K, Sheehan CE, Boguniewicz AB, Otto GA, et al. Genomic profiling of advanced-stage, metaplastic breast carcinoma by next-generation sequencing reveals frequent, targetable genomic abnormalities and potential new treatment options. Archives of Pathology and Laboratory Medicine. 2015;139(5):642–9. doi: 10.5858/arpa.2014-0200-OA 25927147
21. Edenfield J, Schammel C, Collins J, Schammel D, Edenfield WJ. Metaplastic Breast Cancer: Molecular Typing and Identification of Potential Targeted Therapies at a Single Institution. Clinical Breast Cancer. 2016.
22. Joneja U, Vranic S, Swensen J, Feldman R, Chen W, Kimbrough J, et al. Comprehensive profiling of metaplastic breast carcinomas reveals frequent overexpression of programmed death-ligand 1. Journal of clinical pathology. 2016.
23. Ng CK, Piscuoglio S, Geyer FC, Burke KA, Pareja F, Eberle CA, et al. The landscape of somatic genetic alterations in metaplastic breast carcinomas. 2017;23(14):3859–70. doi: 10.1158/1078-0432.CCR-16-2857 28153863
24. Khoo KH, Verma CS, Lane DP. Drugging the p53 pathway: understanding the route to clinical efficacy. Nature reviews Drug discovery. 2014;13(3):217–36. doi: 10.1038/nrd4236 24577402
25. Moulder S, Moroney J, Helgason T, Wheler J, Booser D, Albarracin C, et al. Responses to liposomal Doxorubicin, bevacizumab, and temsirolimus in metaplastic carcinoma of the breast: biologic rationale and implications for stem-cell research in breast cancer. Journal of Clinical Oncology. 2011;29(19):e572–e5. doi: 10.1200/JCO.2010.34.0604 21482991
26. Moroney J, Fu S, Moulder S, Falchook G, Helgason T, Levenback C, et al. Phase I study of the antiangiogenic antibody bevacizumab and the mTOR/hypoxia-inducible factor inhibitor temsirolimus combined with liposomal doxorubicin: tolerance and biological activity. Clinical Cancer Research. 2012;18(20):5796–805. doi: 10.1158/1078-0432.CCR-12-1158 22927482
27. Schmid P, Park YH, Muñoz-Couselo E, Kim S-B, Sohn J, Im S-A, et al. Pembrolizumab (pembro) + chemotherapy (chemo) as neoadjuvant treatment for triple negative breast cancer (TNBC): Preliminary results from KEYNOTE-173. Journal of Clinical Oncology. 2017;35(15_suppl):556–.
28. Adams S. Dramatic response of metaplastic breast cancer to chemo-immunotherapy. NPJ breast cancer. 2017;3:8. doi: 10.1038/s41523-017-0011-0 28649648
29. Adams S, Diamond J, Hamilton E, Pohlmann P, Tolaney S, Molinero L, et al., editors. Safety and clinical activity of atezolizumab (anti-PDL1) in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer. Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium; 2015.
30. Beckers RK, Selinger CI, Vilain R, Madore J, Wilmott JS, Harvey K, et al. Programmed death ligand 1 expression in triple‐negative breast cancer is associated with tumour‐infiltrating lymphocytes and improved outcome. Histopathology. 2016;69(1):25–34. doi: 10.1111/his.12904 26588661
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