Zusammenfassung
Immunologische Parameter werden seit vielen Jahren beim triple-negativen Mammakarzinom als prognostische Marker in translationalen Forschungsprojekten beschrieben. In den letzten Jahren haben sich aus diesen Forschungskonzepten neue Therapiekonzepte entwickelt, die ganz aktuell in klinischen Studien validiert werden konnten. Somit bestehen jetzt auch für das Mammakarzinom die Möglichkeit einer Immuncheckpoint-Inhibitor-Therapie in Kombination mit einer Chemotherapie.
Abstract
Immunological parameters have been evaluated in breast cancer for many years in translational research projects. In the recent years, innovative therapy concepts have been developed from these research approaches, and very recently, first clinical trials have reported positive results. Based on these results there are now new options for combinations of immune checkpoint inhibitors and chemotherapy in breast cancer.
Literatur
Denkert C, Loibl S, Budczies J, Wienert S, Klauschen F (2018) Standardisierte Bestimmung tumorinfiltrierender Lymphozyten beim Mammakarzinom: Ein prognostischer Marker für die histologische Diagnostik [Standardized determination of tumor-infiltrating lymphocytes in breast cancer: A prognostic marker for histological diagnosis. Pathologe 39(6):520–531
Denkert C, Liedtke C, Tutt A, von Minckwitz G (2017) Molecular alterations in triple-negative breast cancer-the road to new treatment strategies. Lancet 389(10087):2430–2442
Luporsi E, André F, Spyratos F, Martin PM, Jacquemier J, Penault-Llorca F, Tubiana-Mathieu N, Sigal-Zafrani B, Arnould L, Gompel A, Egele C, Poulet B, Clough KB, Crouet H, Fourquet A, Lefranc JP, Mathelin C, Rouyer N, Serin D, Spielmann M, Haugh M, Chenard MP, Brain E, de Cremoux P, Bellocq JP (2012) Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review. Breast Cancer Res Treat 132(3):895–915
Denkert C, Loibl S, Müller BM, Eidtmann H, Schmitt WD, Eiermann W, Gerber B, Tesch H, Hilfrich J, Huober J, Fehm T, Barinoff J, Jackisch C, Prinzler J, Rüdiger T, Erbstösser E, Blohmer JU, Budczies J, Mehta KM, von Minckwitz G (2013) Ki67 levels as predictive and prognostic parameters in pretherapeutic breast cancer core biopsies: a translational investigation in the neoadjuvant GeparTrio trial. Ann Oncol 24(11):2786–2793
Denkert C, Loibl S, Noske A, Roller M, Müller BM, Komor M, Budczies J, Darb-Esfahani S, Kronenwett R, Hanusch C, von Törne C, Weichert W, Engels K, Solbach C, Schrader I, Dietel M, von Minckwitz G (2010) Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 28(1):105–113
Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, Ellis M, Henry NL, Hugh JC, Lively T, McShane L, Paik S, Penault-Llorca F, Prudkin L, Regan M, Salter J, Sotiriou C, Smith IE, Viale G, Zujewski JA, Hayes DF (2011) International Ki-67 in Breast Cancer Working Group. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst 103(22):1656–1664
Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, Wienert S, Van den Eynden G, Baehner FL, Penault-Llorca F, Perez EA, Thompson EA, Symmans WF, Richardson AL, Brock J, Criscitiello C, Bailey H, Ignatiadis M, Floris G, Sparano J, Kos Z, Nielsen T, Rimm DL, Allison KH, Reis-Filho JS, Loibl S, Sotiriou C, Viale G, Badve S, Adams S, Willard-Gallo K, Loi S, International TILs Working Group 2014 (2015) The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol 26(2):259–271
Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, Budczies J, Huober J, Klauschen F, Furlanetto J, Schmitt WD, Blohmer JU, Karn T, Pfitzner BM, Kümmel S, Engels K, Schneeweiss A, Hartmann A, Noske A, Fasching PA, Jackisch C, van Mackelenbergh M, Sinn P, Schem C, Hanusch C, Untch M, Loibl S (2018) Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol 19(1):40–50
Fridman WH, Zitvogel L, Sautès-Fridman C, Kroemer G (2017) The immune contexture in cancer prognosis and treatment. Nat Rev Clin Oncol 14(12):717–734
Budczies J, Bockmayr M, Denkert C, Klauschen F, Lennerz JK, Györffy B, Dietel M, Loibl S, Weichert W, Stenzinger A (2015) Classical pathology and mutational load of breast cancer—integration of two worlds. J Pathol Clin Res 1(4):225–238
Galluzzi L, Buqué A, Kepp O, Zitvogel L, Kroemer G (2017) Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol 17(2):97–111
Loibl S, Untch M, Burchardi N, Huober J, Sinn BV, Blohmer JU, Grischke EM, Furlanetto J, Tesch H, Hanusch C, Engels K, Rezai M, Jackisch C, Schmitt WD, von Minckwitz G, Thomalla J, Kümmel S, Rautenberg B, Fasching PA, Weber K, Rhiem K, Denkert C, Schneeweiss A (2019) A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol 30(8):1279–1288
Schmid P, Cortes L, Dent R, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Jia L, Karantza V, Zhao J, Aktan G, O’Shaughnessy J (2019) KEYNOTE-522: phase 3 study of pembrolizumab + chemotherapy versus placebo + chemotherapy as neoadjuvant treatment, followed by pembrolizumab versus placebo as adjuvant treatment for early triple-negative breast cancer (TNBC). Oral presentation. ESMO, Barcelona
Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA, IMpassion130 Trial Investigators. (2018) Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 379(22):2108–2121
Denkert C, von Minckwitz G, Brase JC, Sinn BV, Gade S, Kronenwett R, Pfitzner BM, Salat C, Loi S, Schmitt WD, Schem C, Fisch K, Darb-Esfahani S, Mehta K, Sotiriou C, Wienert S, Klare P, André F, Klauschen F, Blohmer JU, Krappmann K, Schmidt M, Tesch H, Kümmel S, Sinn P, Jackisch C, Dietel M, Reimer T, Untch M, Loibl S (2015) Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2‑positive and triple-negative primary breast cancers. J Clin Oncol 33(9):983–991
McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelekanou V, Rehman J, Velcheti V, Herbst R, LoRusso P, Rimm DL (2016) Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung cancer. JAMA Oncol 2(1):46–54
WHO Classification of Tumours Editorial Board (2019) Breast tumors. International Agency for Research on Cancer, Lyon
https://www.tilsinbreastcancer.org. Zugegriffen: 2.4.2020
Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B, Christie M, van de Vijver K, Estrada MV, Gonzalez-Ericsson PI, Sanders M, Solomon B, Solinas C, Van den Eynden GGGM, Allory Y, Preusser M, Hainfellner J, Pruneri G, Vingiani A, Demaria S, Symmans F, Nuciforo P, Comerma L, Thompson EA, Lakhani S, Kim SR, Schnitt S, Colpaert C, Sotiriou C, Scherer SJ, Ignatiadis M, Badve S, Pierce RH, Viale G, Sirtaine N, Penault-Llorca F, Sugie T, Fineberg S, Paik S, Srinivasan A, Richardson A, Wang Y, Chmielik E, Brock J, Johnson DB, Balko J, Wienert S, Bossuyt V, Michiels S, Ternes N, Burchardi N, Luen SJ, Savas P, Klauschen F, Watson PH, Nelson BH, Criscitiello C, O’Toole S, Larsimont D, de Wind R, Curigliano G, André F, Lacroix-Triki M, van de Vijver M, Rojo F, Floris G, Bedri S, Sparano J, Rimm D, Nielsen T, Kos Z, Hewitt S, Singh B, Farshid G, Loibl S, Allison KH, Tung N, Adams S, Willard-Gallo K, Horlings HM, Gandhi L, Moreira A, Hirsch F, Dieci MV, Urbanowicz M, Brcic I, Korski K, Gaire F, Koeppen H, Lo A, Giltnane J, Rebelatto MC, Steele KE, Zha J, Emancipator K, Juco JW, Denkert C, Reis-Filho J, Loi S, Fox SB (2017) Assessing tumor-infiltrating lymphocytes in solid tumors: a practical review for pathologists and proposal for a standardized method from the international immunooncology biomarkers working group: part 1: assessing the host immune response, TILs in invasive breast carcinoma and ductal carcinoma in situ, metastatic tumor deposits and areas for further research. Adv Anat Pathol 24(5):235–251
Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B, Christie M, van de Vijver K, Estrada MV, Gonzalez-Ericsson PI, Sanders M, Solomon B, Solinas C, Van den Eynden GGGM, Allory Y, Preusser M, Hainfellner J, Pruneri G, Vingiani A, Demaria S, Symmans F, Nuciforo P, Comerma L, Thompson EA, Lakhani S, Kim SR, Schnitt S, Colpaert C, Sotiriou C, Scherer SJ, Ignatiadis M, Badve S, Pierce RH, Viale G, Sirtaine N, Penault-Llorca F, Sugie T, Fineberg S, Paik S, Srinivasan A, Richardson A, Wang Y, Chmielik E, Brock J, Johnson DB, Balko J, Wienert S, Bossuyt V, Michiels S, Ternes N, Burchardi N, Luen SJ, Savas P, Klauschen F, Watson PH, Nelson BH, Criscitiello C, O’Toole S, Larsimont D, de Wind R, Curigliano G, André F, Lacroix-Triki M, van de Vijver M, Rojo F, Floris G, Bedri S, Sparano J, Rimm D, Nielsen T, Kos Z, Hewitt S, Singh B, Farshid G, Loibl S, Allison KH, Tung N, Adams S, Willard-Gallo K, Horlings HM, Gandhi L, Moreira A, Hirsch F, Dieci MV, Urbanowicz M, Brcic I, Korski K, Gaire F, Koeppen H, Lo A, Giltnane J, Rebelatto MC, Steele KE, Zha J, Emancipator K, Juco JW, Denkert C, Reis-Filho J, Loi S, Fox SB (2017) Assessing tumor-infiltrating lymphocytes in solid tumors: a practical review for pathologists and proposal for a standardized method from the international immuno-oncology biomarkers working group: part 2: TILs in melanoma, gastrointestinal tract carcinomas, non-small cell lung carcinoma and Mesothelioma, Endometrial and ovarian carcinomas, squamous cell carcinoma of the head and neck, genitourinary carcinomas, and primary brain tumors. Adv Anat Pathol 24(6):311–335
Fuchs TL, Sioson L, Sheen A, Jafari-Nejad K, Renaud CJ, Andrici J, Ahadi M, Chou A, Gill AJ (2019) Assessment of tumor-infiltrating lymphocytes using international TILs working group (ITWG) system is a strong predictor of overall survival in colorectal carcinoma: a study of 1034 patients. Am J Surg Pathol. https://doi.org/10.1097/PAS.0000000000001409
Klauschen F, Müller KR, Binder A, Bockmayr M, Hägele M, Seegerer P, Wienert S, Pruneri G, de Maria S, Badve S, Michiels S, Nielsen TO, Adams S, Savas P, Symmans F, Willis S, Gruosso T, Park M, Haibe-Kains B, Gallas B, Thompson AM, Cree I, Sotiriou C, Solinas C, Preusser M, Hewitt SM, Rimm D, Viale G, Loi S, Loibl S, Salgado R, Denkert C, International Immuno-Oncology Biomarker Working Group (2018) Scoring of tumor-infiltrating lymphocytes: from visual estimation to machine learning. Semin Cancer Biol 52(Pt 2):151–157
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C. Denkert war Mitgründer der Firma Sividon Diagnostics (jetzt Myriad) und ist in Kooperation mit der Firma vmScope an der Entwicklung von standardisierten Bildanalysesystemen, u. a. für Ki-67 und TILs beteiligt. Er übte für die Firmen Roche, AstraZeneca, Novartis, Daiichi und MSD eine Beratertätigkeit aus.
Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.
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Peter Möller; Ulm
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Denkert, C. Immunonkologie und tumorinfiltrierende Lymphozyten – neue Strategien für Therapie und Diagnostik des Mammakarzinoms. Pathologe 41, 248–253 (2020). https://doi.org/10.1007/s00292-020-00783-y
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DOI: https://doi.org/10.1007/s00292-020-00783-y