Frederik Deman1,2, Kevin Punie3,4, Annouschka Laenen5, Patrick Neven3,6, Eva Oldenburger3,7, Ann Smeets3,8, Ines Nevelsteen3,8, Chantal Van Ongeval9,10, Adinda Baten3,7, Timothy Faes9,11, Melissa Christiaens3,7, Hilde Janssen3,7, Caroline Weltens3,7, Christine Desmedt12, Hans Wildiers3,4, Giuseppe Floris9,11. 1. Laboratory of Translational Cell & Tissue Research, Department of Imaging and Pathology, KU Leuven - University of Leuven, Leuven, Belgium. Frederik.deman@student.kuleuven.be. 2. Department of Pathology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium. Frederik.deman@student.kuleuven.be. 3. Department of Oncology, KU Leuven - University of Leuven, Leuven, Belgium. 4. Department of General Medical Oncology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium. 5. Interuniversity Centre for Biostatistics and Statistical Bioinformatics, KU Leuven - University of Leuven, Leuven, Belgium. 6. Department of Gynecology and Obstetrics, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium. 7. Department of Radiotherapy Oncology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium. 8. Department of Surgical Oncology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium. 9. Laboratory of Translational Cell & Tissue Research, Department of Imaging and Pathology, KU Leuven - University of Leuven, Leuven, Belgium. 10. Department of Radiology, University Hospitals Leuven, Leuven, Belgium. 11. Department of Pathology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium. 12. Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven - University of Leuven, Leuven, Belgium.
Abstract
PURPOSE: We studied the long-term outcomes of invasive micropapillary carcinoma (IMPCs) of the breast in relation to stromal tumor infiltrating lymphocytes (sTILs), prognostic biomarkers and clinicopathological features. METHODS: Stage I-III IMPCs treated with upfront surgery at our institution (January 2000 and December 2016) were included. Central pathology review was performed and sTILs (including zonal distribution and hot spot analysis) and tumor-associated plasma cells (TAPC) were evaluated. Expression of P53, BCL2, FOXP3, and WT1, which are variably linked to breast cancer prognosis, was measured by immunohistochemistry using tissue microarrays. Time-to-event endpoints were distant recurrence free interval (DRFI) and breast cancer-specific survival (BCSS). RESULTS: We included 111 patients of whom 59% were pure IMPCs. Standard clinicopathological features were comparable between pure and non-pure IMPCs. Overall, the mean sTILs level was 20% with higher proportion of sTILs present at the invasive front. There were no significant differences between pure- and non-pure IMPCs in sTILs levels, nor in the spatial distribution of the hot spot regions or in the distribution of TAPC. Higher sTILs correlated with worse DRFI (HR = 1.55; p = 0.0172) and BCSS (HR = 2.10; p < 0.001). CONCLUSIONS: Clinicopathological features, geographical distribution of sTILs and TAPC are similar between pure and non-pure IMPCs. Despite a high proportion of grade 3 tumors and lymph node involvement, we observed a low rate of distant recurrences and breast cancer-related death in this cohort of stage I-III IMPCs treated with primary surgery. Caution in interpretation of the observed prognostic correlations is required given the very low number of events, warranting validation in other cohorts.
PURPOSE: We studied the long-term outcomes of invasive micropapillary carcinoma (IMPCs) of the breast in relation to stromal tumor infiltrating lymphocytes (sTILs), prognostic biomarkers and clinicopathological features. METHODS: Stage I-III IMPCs treated with upfront surgery at our institution (January 2000 and December 2016) were included. Central pathology review was performed and sTILs (including zonal distribution and hot spot analysis) and tumor-associated plasma cells (TAPC) were evaluated. Expression of P53, BCL2, FOXP3, and WT1, which are variably linked to breast cancer prognosis, was measured by immunohistochemistry using tissue microarrays. Time-to-event endpoints were distant recurrence free interval (DRFI) and breast cancer-specific survival (BCSS). RESULTS: We included 111 patients of whom 59% were pure IMPCs. Standard clinicopathological features were comparable between pure and non-pure IMPCs. Overall, the mean sTILs level was 20% with higher proportion of sTILs present at the invasive front. There were no significant differences between pure- and non-pure IMPCs in sTILs levels, nor in the spatial distribution of the hot spot regions or in the distribution of TAPC. Higher sTILs correlated with worse DRFI (HR = 1.55; p = 0.0172) and BCSS (HR = 2.10; p < 0.001). CONCLUSIONS: Clinicopathological features, geographical distribution of sTILs and TAPC are similar between pure and non-pure IMPCs. Despite a high proportion of grade 3 tumors and lymph node involvement, we observed a low rate of distant recurrences and breast cancer-related death in this cohort of stage I-III IMPCs treated with primary surgery. Caution in interpretation of the observed prognostic correlations is required given the very low number of events, warranting validation in other cohorts.
Authors: Georgios-Ioannis Verras; Levan Tchabashvili; Francesk Mulita; Ioanna Maria Grypari; Sofia Sourouni; Evangelia Panagodimou; Maria-Ioanna Argentou Journal: Breast Cancer (Dove Med Press) Date: 2022-03-12