Meme Kanseri ve İmmünoterapi
Özet
Meme kanseri, kadınlarda en sık karşılaşılan malignite olup, biyolojik çeşitliliği nedeniyle alt gruplara ayrılarak tedavi edilmektedir. HER2 (human epidermal growth factor receptor 2) reseptörü, tedavi ve prognozda önemli bir biyobelirteçtir. Geleneksel olarak HER2 pozitif ve negatif olarak sınıflandırılan meme kanserlerinde, son yıllarda IHC +1 veya IHC +2 olup in situ hibridizasyon (ISH) negatif olan hastaları içeren “HER2 düşük ekspresyonlu” bir alt grup tanımlanmıştır. HER2 düşük tümörlerin, HER2 pozitif tümörlerden farklı biyolojik özellikler gösterdiği ve klasik kemoterapiye ek olarak anti-HER2 ajanlara sınırlı yanıt verdiği görülmüştür. Trastuzumab deruxtecan (T-DXd) gibi yeni nesil antikor-ilaç konjugatları bu alt grupta belirgin progresyonsuz sağkalım (progression free survival; PFS) ve genel sağkalım avantajı sağlamıştır. Ayrıca sacituzumab govitecan (SG) gibi diğer hedefe yönelik tedaviler de HER2 düşük ve HER2-0 hasta gruplarında umut vadetmektedir. Bununla birlikte, HER2 düşük ekspresyonun prognostik önemi, ideal tedavi sıralaması ve hasta seçim kriterleri gibi konular hâlâ araştırma alanıdır. Bu derlemede, HER2 düşük ekspresyonlu meme kanserinin tanı yöntemleri, biyolojik özellikleri ve güncel tedavi yaklaşımları detaylı şekilde ele alınmıştır.
Referanslar
GLOBOCAN 2020: New global cancer data. https://www.uicc.org/news/globocan-2020-new-global-cancer-data (Accessed on November 24, 2021).
Onkar SS, Carleton NM, Lucas PC, Bruno TC, Lee AV, Vignali DAA, Oesterreich S. The Great Immune Escape: Understanding the Divergent Immune Response in Breast Cancer Subtypes. Cancer Discov. 2023 Jan 9;13(1):23-40. doi: 10.1158/2159-8290.CD-22-0475. PMID: 36620880; PMCID: PMC9833841.
Zhao J, Huang J. Breast cancer immunology and immunotherapy: targeting the programmed cell death protein-1/programmed cell death protein ligand-1. Chin Med J (Engl). 2020 Apr 5;133(7):853-862. doi: 10.1097/CM9.0000000000000710. Erratum in: Chin Med J (Engl). 2021 Mar 08;134(6):756. doi: 10.1097/CM9.0000000000001392. PMID: 32106121; PMCID: PMC7147660.
Dvir K, Giordano S, Leone JP. Immunotherapy in Breast Cancer. Int J Mol Sci. 2024 Jul 9;25(14):7517. doi: 10.3390/ijms25147517. PMID: 39062758; PMCID: PMC11276856.
Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, Postow MA, Wolchok JD. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015 Dec;26(12):2375-91. doi: 10.1093/annonc/mdv383. Epub 2015 Sep 14. Erratum in: Ann Oncol. 2016 Jul;27(7):1362. doi: 10.1093/annonc/mdw141. PMID: 26371282; PMCID: PMC6267867.
Chhabra N, Kennedy J. A Review of Cancer Immunotherapy Toxicity: Immune Checkpoint Inhibitors. J Med Toxicol. 2021 Oct;17(4):411-424. doi: 10.1007/s13181-021-00833-8. Epub 2021 Apr 7. PMID: 33826117; PMCID: PMC8455777.
Thomssen C. Nebenwirkungsmanagement immunonkologischer Therapien – was gibt es zu beachten? [Management of immune-related adverse events (irAEs) - what needs to be respected?]. Gynakologe. 2022;55(5):344-350. German. doi: 10.1007/s00129-022-04941-6. Epub 2022 Apr 26. PMID: 35494537; PMCID: PMC9041287.
Qin Y, Huo M, Liu X, Li SC. Biomarkers and computational models for predicting efficacy to tumor ICI immunotherapy. Front Immunol. 2024 Mar 8;15:1368749. doi: 10.3389/fimmu.2024.1368749. Erratum in: Front Immunol. 2024 Jun 04;15:1438587. doi: 10.3389/fimmu.2024.1438587. PMID: 38524135; PMCID: PMC10957591.
Hanna A, Balko JM. Breast cancer resistance mechanisms: challenges to immunotherapy. Breast Cancer Res Treat. 2021 Nov;190(1):5-17. doi: 10.1007/s10549-021-06337-x. Epub 2021 Jul 28. PMID: 34322780; PMCID: PMC8560575.
Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, Chien AJ, Forero-Torres A, Ellis E, Han H, Clark A, Albain K, Boughey JC, Jaskowiak NT, Elias A, Isaacs C, Kemmer K, Helsten T, Majure M, Stringer-Reasor E, Parker C, Lee MC, Haddad T, Cohen RN, Asare S, Wilson A, Hirst GL, Singhrao R, Steeg K, Asare A, Matthews JB, Berry S, Sanil A, Schwab R, Symmans WF, van 't Veer L, Yee D, DeMichele A, Hylton NM, Melisko M, Perlmutter J, Rugo HS, Berry DA, Esserman LJ. Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer: An Analysis of the Ongoing Phase 2 Adaptively Randomized I-SPY2 Trial. JAMA Oncol. 2020 May 1;6(5):676-684. doi: 10.1001/jamaoncol.2019.6650. PMID: 32053137; PMCID: PMC7058271.
Dent R, Cortés J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Untch M, Fasching PA, Cardoso F, Haiderali A, Jia L, Nguyen AM, Pan W, O'Shaughnessy J, Schmid P. Neoadjuvant pembrolizumab plus chemotherapy/adjuvant pembrolizumab for early-stage triple-negative breast cancer: quality-of-life results from the randomized KEYNOTE-522 study. J Natl Cancer Inst. 2024 Oct 1;116(10):1654-1663. doi: 10.1093/jnci/djae129. PMID: 38913881; PMCID: PMC11461162.
Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020 Oct 10;396(10257):1090-1100. doi: 10.1016/S0140-6736(20)31953-X. Epub 2020 Sep 20. PMID: 32966830.
Hattori M, Masuda N, Takano T, Tsugawa K, Inoue K, Matsumoto K, Ishikawa T, Itoh M, Yasojima H, Tanabe Y, Yamamoto K, Suzuki M, Pan W, Cortes J, Iwata H. Pembrolizumab plus chemotherapy in Japanese patients with triple-negative breast cancer: Results from KEYNOTE-355. Cancer Med. 2023 May;12(9):10280-10293. doi: 10.1002/cam4.5757. Epub 2023 Mar 14. PMID: 36916728; PMCID: PMC10225213.
Emens LA, Adams S, Barrios CH, Diéras V, Iwata H, Loi S, Rugo HS, Schneeweiss A, Winer EP, Patel S, Henschel V, Swat A, Kaul M, Molinero L, Patel S, Chui SY, Schmid P. First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis. Ann Oncol. 2021 Aug;32(8):983-993. doi: 10.1016/j.annonc.2021.05.355. Epub 2021 Jul 1. Erratum in: Ann Oncol. 2021 Oct;32(10):1308. doi: 10.1016/j.annonc.2021.07.013. Erratum in: Ann Oncol. 2021 Dec;32(12):1650. doi: 10.1016/j.annonc.2021.10.002. PMID: 34272041.
Miles D, Gligorov J, André F, Cameron D, Schneeweiss A, Barrios C, Xu B, Wardley A, Kaen D, Andrade L, Semiglazov V, Reinisch M, Patel S, Patre M, Morales L, Patel SL, Kaul M, Barata T, O'Shaughnessy J; IMpassion131 investigators. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021 Aug;32(8):994-1004. doi: 10.1016/j.annonc.2021.05.801. Epub 2021 Jul 1. PMID: 34219000.
Cardoso F, O'Shaughnessy J, Liu Z, McArthur H, Schmid P, Cortes J, Harbeck N, Telli ML, Cescon DW, Fasching PA, Shao Z, Loirat D, Park YH, Fernandez MG, Rubovszky G, Spring L, Im SA, Hui R, Takano T, André F, Yasojima H, Ding Y, Jia L, Karantza V, Tryfonidis K, Bardia A. Pembrolizumab and chemotherapy in high-risk, early-stage, ER+/HER2- breast cancer: a randomized phase 3 trial. Nat Med. 2025 Feb;31(2):442-448. doi: 10.1038/s41591-024-03415-7. Epub 2025 Jan 21. PMID: 39838117; PMCID: PMC11835712.
