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Assessment of stromal tumor infiltrating lymphocytes and immunohistochemical features in invasive micropapillary breast carcinoma with long-term outcomes

  • Epidemiology
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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.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author information

Author notes

  1. Frederik Deman and Kevin Punie have contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Translational Cell & Tissue Research, Department of Imaging and Pathology, KU Leuven - University of Leuven, Leuven, Belgium

    Frederik Deman, Chantal Van Ongeval, Timothy Faes & Giuseppe Floris

  2. Department of Pathology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium

    Frederik Deman, Timothy Faes & Giuseppe Floris

  3. Department of Oncology, KU Leuven - University of Leuven, Leuven, Belgium

    Kevin Punie, Patrick Neven, Eva Oldenburger, Ann Smeets, Ines Nevelsteen, Adinda Baten, Melissa Christiaens, Hilde Janssen, Caroline Weltens & Hans Wildiers

  4. Department of General Medical Oncology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium

    Kevin Punie & Hans Wildiers

  5. Interuniversity Centre for Biostatistics and Statistical Bioinformatics, KU Leuven - University of Leuven, Leuven, Belgium

    Annouschka Laenen

  6. Department of Gynecology and Obstetrics, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium

    Patrick Neven

  7. Department of Surgical Oncology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium

    Ann Smeets & Ines Nevelsteen

  8. Department of Radiology, University Hospitals Leuven, Leuven, Belgium

    Chantal Van Ongeval

  9. Department of Radiotherapy Oncology, KU Leuven – University of Leuven, University Hospitals Leuven, Leuven, Belgium

    Eva Oldenburger, Adinda Baten, Melissa Christiaens, Hilde Janssen & Caroline Weltens

  10. Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven - University of Leuven, Leuven, Belgium

    Christine Desmedt

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  1. Frederik Deman
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  2. Kevin Punie
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  3. Annouschka Laenen
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Contributions

Conception and design: GF, KP; Development of methodology: FD, KP, GF; Acquisition of data: FD, KP; Analysis and interpretation of data: FD, KP, GF, AL; Writing, review and/or revision of the manuscript: all authors; Administrative, technical, or material support: GF; Study supervision: GF.

Corresponding author

Correspondence to Frederik Deman.

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Approval was obtained from the ethics committee of KU Leuven ethics committee (ref. n° MP002896).

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Deman, F., Punie, K., Laenen, A. et al. Assessment of stromal tumor infiltrating lymphocytes and immunohistochemical features in invasive micropapillary breast carcinoma with long-term outcomes. Breast Cancer Res Treat 184, 985–998 (2020). https://doi.org/10.1007/s10549-020-05913-x

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