Hugo Arias-Pulido1, Ashley Marie Cimino-Mathews2, Nabila Chaher3, Clifford Ray Qualls4, Nancy Joste5, Cecile Colpaert6, Jonathan Douglas Marotti7, Mary Dickinson Chamberlin8, Maxwell Gabriel Foisey9,10, Eric Robert Prossnitz11, Leisha Ann Emens12, Steven Fiering9. 1. Department of Microbiology, and Immunology and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 621 Rubin Building-HB7936, 1 Medical Center Drive, Lebanon, NH, 03756, USA. hugo.ariaspulido@dartmouth.edu. 2. Departments of Pathology and Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3. Department of Pathology, Centre Pierre et Marie Curie, EHS Salim Zemirli et Faculté de Médecine d'Alger, Université Alger 1, Algiers, Algeria. 4. Department of Mathematics and Statistics, University of New Mexico, Albuquerque, NM, USA. 5. Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. 6. Department of Pathology, AZ Turnhout/UZ, Leuven, Belgium. 7. Department of Pathology and Laboratory Medicine, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA. 8. Department of Medical Oncology, and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA. 9. Department of Microbiology, and Immunology and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 621 Rubin Building-HB7936, 1 Medical Center Drive, Lebanon, NH, 03756, USA. 10. Biomedical Sciences Graduate Training Program, University of California, San Francisco, CA, 94143, USA. 11. Division of Molecular Medicine, Department of Internal Medicine, Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. 12. University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA.
Abstract
PURPOSE: This study evaluated epidemiologic and immune factors associated with pathologic complete response (pCR), breast cancer-specific survival (BCSS) and disease-free survival (DFS) outcomes in inflammatory (IBC) and locally advanced breast cancer (LABC) patients. METHODS: Tumor-infiltrating lymphocytes (TILs) and CD20+ B-cell frequencies (CD20+), and PD-L1 expression on tumor (PD-L1+carcinoma cells) and immune (PD-L1+TILs) cells were analyzed by immunohistochemistry along with clinicopathologic factors as modifiers of pCR and outcomes in 221 IBC and 162 LABC patients. Analysis included Kaplan-Meier curves and Cox proportional hazard models. RESULTS: IBC and LABC display similar levels of TILs, CD20+, and combined CD20+ and PD-L1+TILs (CD20+PD-L1+TILs), while LABC contained more PD-L1+TILs and PD-L1+ carcinoma cells. Absence of lymphovascular involvement, high TILs, PD-L1+ carcinoma cells, and combined CD20+ and PD-L1+ carcinoma cells correlated with pCR in IBC and LABC patients. High PD-L1+TILs correlated with pCR only in LABC; less lymph node involvement at diagnosis, CD20+ and CD20+PD-L1+TILs correlated with pCR only in IBC (P < 0.04, all comparisons). Achievement of pCR in IBC and LABC patients correlated with BCSS and DFS (P < 0.02). In multivariate analyses, pCR remained an independent prognostic factor of improved DFS in IBC and LABC patients, but of BCSS in only LABC. CD20+PD-L1+TILs remained an independent prognostic factor of improved DFS and BCSS only in IBC. CONCLUSION: CD20+PD-L1+TILs are an independent prognostic biomarker of improved outcomes in IBC, but not LABC. Selecting IBC patients by CD20 and PD-L1 status could stratify patients and potentially identify those in whom activating CD20 agents and anti-PD-1/PD-L1 therapy could be explored.
PURPOSE: This study evaluated epidemiologic and immune factors associated with pathologic complete response (pCR), breast cancer-specific survival (BCSS) and disease-free survival (DFS) outcomes in inflammatory (IBC) and locally advanced breast cancer (LABC) patients. METHODS: Tumor-infiltrating lymphocytes (TILs) and CD20+ B-cell frequencies (CD20+), and PD-L1 expression on tumor (PD-L1+carcinoma cells) and immune (PD-L1+TILs) cells were analyzed by immunohistochemistry along with clinicopathologic factors as modifiers of pCR and outcomes in 221 IBC and 162 LABC patients. Analysis included Kaplan-Meier curves and Cox proportional hazard models. RESULTS: IBC and LABC display similar levels of TILs, CD20+, and combined CD20+ and PD-L1+TILs (CD20+PD-L1+TILs), while LABC contained more PD-L1+TILs and PD-L1+ carcinoma cells. Absence of lymphovascular involvement, high TILs, PD-L1+ carcinoma cells, and combined CD20+ and PD-L1+ carcinoma cells correlated with pCR in IBC and LABC patients. High PD-L1+TILs correlated with pCR only in LABC; less lymph node involvement at diagnosis, CD20+ and CD20+PD-L1+TILs correlated with pCR only in IBC (P < 0.04, all comparisons). Achievement of pCR in IBC and LABC patients correlated with BCSS and DFS (P < 0.02). In multivariate analyses, pCR remained an independent prognostic factor of improved DFS in IBC and LABC patients, but of BCSS in only LABC. CD20+PD-L1+TILs remained an independent prognostic factor of improved DFS and BCSS only in IBC. CONCLUSION: CD20+PD-L1+TILs are an independent prognostic biomarker of improved outcomes in IBC, but not LABC. Selecting IBC patients by CD20 and PD-L1 status could stratify patients and potentially identify those in whom activating CD20 agents and anti-PD-1/PD-L1 therapy could be explored.
Authors: R Salgado; C Denkert; S Demaria; N Sirtaine; F Klauschen; G Pruneri; S Wienert; G Van den Eynden; F L Baehner; F Penault-Llorca; E A Perez; E A Thompson; W F Symmans; A L Richardson; J Brock; C Criscitiello; H Bailey; M Ignatiadis; G Floris; J Sparano; Z Kos; T Nielsen; D L Rimm; K H Allison; J S Reis-Filho; S Loibl; C Sotiriou; G Viale; S Badve; S Adams; K Willard-Gallo; S Loi Journal: Ann Oncol Date: 2014-09-11 Impact factor: 32.976
Authors: Jieqiong Liu; Kai Chen; Wen Jiang; Kai Mao; Shunrong Li; Min Ji Kim; Qiang Liu; Lisa K Jacobs Journal: J Cancer Res Clin Oncol Date: 2016-10-04 Impact factor: 4.553
Authors: S Dawood; S D Merajver; P Viens; P B Vermeulen; S M Swain; T A Buchholz; L Y Dirix; P H Levine; A Lucci; S Krishnamurthy; F M Robertson; W A Woodward; W T Yang; N T Ueno; M Cristofanilli Journal: Ann Oncol Date: 2010-07-05 Impact factor: 32.976
Authors: Catherine Schairer; Yan Li; Peter Frawley; Barry I Graubard; Robert D Wellman; Diana S M Buist; Karla Kerlikowske; Tracy L Onega; William F Anderson; Diana L Miglioretti Journal: J Natl Cancer Inst Date: 2013-09-18 Impact factor: 13.506
Authors: S Dawood; X Lei; R Dent; S Gupta; B Sirohi; J Cortes; M Cristofanilli; T Buchholz; A M Gonzalez-Angulo Journal: Ann Oncol Date: 2014-03-24 Impact factor: 32.976
Authors: Z A Nahleh; W E Barlow; D F Hayes; A F Schott; J R Gralow; W M Sikov; E A Perez; S Chennuru; H R Mirshahidi; S W Corso; D L Lew; L Pusztai; R B Livingston; G N Hortobagyi Journal: Breast Cancer Res Treat Date: 2016-07-08 Impact factor: 4.872
Authors: Dominique J P van Uden; Marissa C van Maaren; Peter Bult; Luc J A Strobbe; J J M van der Hoeven; Charlotte F J M Blanken-Peeters; Sabine Siesling; Johannes H W de Wilt Journal: Breast Cancer Res Treat Date: 2019-04-10 Impact factor: 4.872