C Solinas1, M Ceppi2, M Lambertini3, M Scartozzi4, L Buisseret5, S Garaud6, D Fumagalli7, E de Azambuja8, R Salgado9, C Sotiriou10, K Willard-Gallo11, M Ignatiadis12. 1. Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address: czsolinas@gmail.com. 2. Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genova, Italy. Electronic address: marcello.ceppi@hsanmartino.it. 3. Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address: matteo.lambertini@bordet.be. 4. Medical Oncology, University of Cagliari, Cagliari, Italy. Electronic address: marioscartozzi@gmail.com. 5. Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address: laurence.buisseret@bordet.be. 6. Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address: soizic.garaud@bordet.be. 7. Breast International Group (BIG), Brussels, Belgium. Electronic address: Debora.Fumagalli@bigagainstbc.org. 8. Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address: evandro.azambuja@bordet.be. 9. Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Department of Pathology, GZA Ziekenhuizen, Sint-Augustinus campus, Wilrijk, Belgium. Electronic address: roberto@salgado.be. 10. Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address: christos.sotiriou@bordet.be. 11. Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address: karen.willard-gallo@bordet.be. 12. Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address: michail.Ignatiadis@bordet.be.
Abstract
BACKGROUND: A relationship between baseline tumor-infiltrating lymphocytes (TIL) and outcomes has been described in HER2-positive breast cancer. Nevertheless, the magnitude of this association and whether this effect differs based on the type of anti-HER2 agent remain controversial. This meta-analysis investigated the association between baseline TIL and pathologic complete response (pCR) rates in HER2-positive breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab and lapatinib either alone or in combination. METHODS: A literature search covering PubMed, Embase and the Cochrane library up to October 31, 2016 identified randomized, controlled trials investigating neoadjuvant chemotherapy plus trastuzumab and lapatinib either alone or in combination where published data for pCR based on pre-treatment TIL scores were available. Two subgroups were considered: high baseline TIL vs. non-high TIL, according to each study definition. Summary risk estimates (odds ratio) and 95% confidence intervals (CI) were calculated for pCR using pre-treatment TIL levels for each trial. Pooled analyses were conducted using random and fixed effects models. Interaction P-values were computed using a Monte Carlo permutation test. RESULTS: A total of 5 studies (N=1256 patients) were included. Overall, high TIL subgroup was associated with a significantly increased pCR rate (OR 2.46; 95% CI 1.36-4.43; P=0.003). No interaction was observed between TIL subgroup (high vs. non-high TIL) and response to anti-HER2 agent(s) (trastuzumab vs. lapatinib vs. their combination; P=0.747) and chemotherapy (anthracycline and taxanes vs. taxanes only; P=0.201). A stronger association between high TIL subgroup and pCR rates was observed when examining only the 4 studies using anthracycline- and taxane- based neoadjuvant chemotherapy and the 60% cut-off for high TIL (N=869, NeoALTTO excluded) with an OR of 2.88 (95% CI 2.03-4.08; P<0.001). CONCLUSIONS: In HER2-positive breast cancer, high baseline TIL are associated with increased pCR probability irrespective of neoadjuvant anti-HER2 agent(s) and chemotherapy regimens used.
BACKGROUND: A relationship between baseline tumor-infiltrating lymphocytes (TIL) and outcomes has been described in HER2-positive breast cancer. Nevertheless, the magnitude of this association and whether this effect differs based on the type of anti-HER2 agent remain controversial. This meta-analysis investigated the association between baseline TIL and pathologic complete response (pCR) rates in HER2-positive breast cancerpatients treated with neoadjuvant chemotherapy plus trastuzumab and lapatinib either alone or in combination. METHODS: A literature search covering PubMed, Embase and the Cochrane library up to October 31, 2016 identified randomized, controlled trials investigating neoadjuvant chemotherapy plus trastuzumab and lapatinib either alone or in combination where published data for pCR based on pre-treatment TIL scores were available. Two subgroups were considered: high baseline TIL vs. non-high TIL, according to each study definition. Summary risk estimates (odds ratio) and 95% confidence intervals (CI) were calculated for pCR using pre-treatment TIL levels for each trial. Pooled analyses were conducted using random and fixed effects models. Interaction P-values were computed using a Monte Carlo permutation test. RESULTS: A total of 5 studies (N=1256 patients) were included. Overall, high TIL subgroup was associated with a significantly increased pCR rate (OR 2.46; 95% CI 1.36-4.43; P=0.003). No interaction was observed between TIL subgroup (high vs. non-high TIL) and response to anti-HER2 agent(s) (trastuzumab vs. lapatinib vs. their combination; P=0.747) and chemotherapy (anthracycline and taxanes vs. taxanes only; P=0.201). A stronger association between high TIL subgroup and pCR rates was observed when examining only the 4 studies using anthracycline- and taxane- based neoadjuvant chemotherapy and the 60% cut-off for high TIL (N=869, NeoALTTO excluded) with an OR of 2.88 (95% CI 2.03-4.08; P<0.001). CONCLUSIONS: In HER2-positive breast cancer, high baseline TIL are associated with increased pCR probability irrespective of neoadjuvant anti-HER2 agent(s) and chemotherapy regimens used.
Authors: Khalid El Bairi; Harry R Haynes; Elizabeth Blackley; Susan Fineberg; Jeffrey Shear; Sophia Turner; Juliana Ribeiro de Freitas; Daniel Sur; Luis Claudio Amendola; Masoumeh Gharib; Amine Kallala; Indu Arun; Farid Azmoudeh-Ardalan; Luciana Fujimoto; Luz F Sua; Shi-Wei Liu; Huang-Chun Lien; Pawan Kirtani; Marcelo Balancin; Hicham El Attar; Prerna Guleria; Wenxian Yang; Emad Shash; I-Chun Chen; Veronica Bautista; Jose Fernando Do Prado Moura; Bernardo L Rapoport; Carlos Castaneda; Eunice Spengler; Gabriela Acosta-Haab; Isabel Frahm; Joselyn Sanchez; Miluska Castillo; Najat Bouchmaa; Reena R Md Zin; Ruohong Shui; Timothy Onyuma; Wentao Yang; Zaheed Husain; Karen Willard-Gallo; An Coosemans; Edith A Perez; Elena Provenzano; Paula Gonzalez Ericsson; Eduardo Richardet; Ravi Mehrotra; Sandra Sarancone; Anna Ehinger; David L Rimm; John M S Bartlett; Giuseppe Viale; Carsten Denkert; Akira I Hida; Christos Sotiriou; Sibylle Loibl; Stephen M Hewitt; Sunil Badve; William Fraser Symmans; Rim S Kim; Giancarlo Pruneri; Shom Goel; Prudence A Francis; Gloria Inurrigarro; Rin Yamaguchi; Hernan Garcia-Rivello; Hugo Horlings; Said Afqir; Roberto Salgado; Sylvia Adams; Marleen Kok; Maria Vittoria Dieci; Stefan Michiels; Sandra Demaria; Sherene Loi Journal: NPJ Breast Cancer Date: 2021-12-01
Authors: Santiago Moragon; Cristina Hernando; Maria Teresa Martinez-Martinez; Marta Tapia; Belen Ortega-Morillo; Ana Lluch; Begoña Bermejo; Juan Miguel Cejalvo Journal: Cancers (Basel) Date: 2022-06-28 Impact factor: 6.575
Authors: J Fay; S Toomey; A J Eustace; S F Madden; D M Collins; E W Kay; K M Sheehan; S Furney; B Moran; A Fagan; P G Morris; A Teiserskiene; A D Hill; L Grogan; J M Walshe; O Breathnach; C Power; D Duke; K Egan; W M Gallagher; N O'Donovan; J Crown; B T Hennessy Journal: Breast Cancer Res Treat Date: 2021-05-13 Impact factor: 4.872
Authors: Franziska Würfel; Ramona Erber; Hanna Huebner; Alexander Hein; Michael P Lux; Sebastian Jud; Anita Kremer; Hannah Kranich; Andreas Mackensen; Lothar Häberle; Carolin C Hack; Claudia Rauh; Marius Wunderle; Paul Gaß; Shahrooz Rabizadeh; Anna-Lisa Brandl; Hanna Langemann; Bernhard Volz; Naiba Nabieva; Rüdiger Schulz-Wendtland; Diana Dudziak; Matthias W Beckmann; Arndt Hartmann; Peter A Fasching; Matthias Rübner Journal: Breast Care (Basel) Date: 2018-02-15 Impact factor: 2.860