Skip to main content
Erschienen in: Virchows Archiv 4/2020

01.04.2020 | Original Article

CD73 expression and pathologic response to neoadjuvant chemotherapy in triple negative breast cancer

verfasst von: Bruna Cerbelli, Andrea Botticelli, Annalinda Pisano, Angelina Pernazza, Domenico Campagna, Alessandro De Luca, Paolo Antonio Ascierto, Maria Gemma Pignataro, Maria Pelullo, Carlo Della Rocca, Paolo Marchetti, Lucio Fortunato, Leopoldo Costarelli, Giulia d’Amati

Erschienen in: Virchows Archiv | Ausgabe 4/2020

Einloggen, um Zugang zu erhalten

Abstract

The immune system plays a key role in tumor surveillance and escape. Recently, CD73 has been proposed as a prognostic biomarker associated with disease-free survival and overall survival in triple negative breast cancer (TNBC). In this study, we investigated the role of both CD73 expression and stromal tumor–infiltrating lymphocytes (TILs) in predicting the pathologic response of TNBC to neoadjuvant chemotherapy (NACT). We retrospectively analyzed CD73 immunohistochemical expression and stromal TILs on 61 consecutive biopsies from patients who received standard NACT. Twenty-three patients (38%) achieved pathologic complete response (pCR). TILs were present in the majority of biopsies (93%) with percentages ranging from 2 to 80%. High TILs (≥ 50%) were found in 30% of cases, and in this group, pCR was achieved in 76.5% of cases. Levels of TILs were associated with a better pathologic response only at univariate analysis (p = 0.037). The median value of CD73 expression on tumor cells was 40%. In 32 (52.5%) basal biopsies, CD73 expression was below or equal to median value (“low CD73”). A pCR was obtained in 53% of cases with “low CD73” and in 21% with high CD73, and this was statistically different both at univariate (p = 0.011) and multivariate (p = 0.014) analysis.
Our results suggest that CD73 expression better predicts the response to NACT than TILs in TNBC. Characterization of both TILs and microenvironment could be a promising approach to personalize treatment.
Literatur
1.
Zurück zum Zitat Lin NU, Vanderplas A, Hughes ME, Theriault RL, Edge SB, Wong YN, Blayney DW, Niland JC, Winer EP, Weeks JC (2012) Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer 118(22):5463–5472. https://doi.org/10.1002/cncr.27581 CrossRefPubMed Lin NU, Vanderplas A, Hughes ME, Theriault RL, Edge SB, Wong YN, Blayney DW, Niland JC, Winer EP, Weeks JC (2012) Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer 118(22):5463–5472. https://​doi.​org/​10.​1002/​cncr.​27581 CrossRefPubMed
7.
Zurück zum Zitat Sabatier R, Finetti P, Mamessier E et al (2015) Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget 7:5449–5469 Sabatier R, Finetti P, Mamessier E et al (2015) Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget 7:5449–5469
9.
Zurück zum Zitat Adams S, Loi S, Toppmeyer D et al (2017) Phase 2 study of pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer (mTNBC): preliminary data from KEYNOTE-086 cohort B. J Clin Oncol 35 [suppl; abstr 1088]. Adams S, Loi S, Toppmeyer D et al (2017) Phase 2 study of pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer (mTNBC): preliminary data from KEYNOTE-086 cohort B. J Clin Oncol 35 [suppl; abstr 1088].
22.
Zurück zum Zitat Deaglio S, Dwyer KM, Gao W et al (2007) Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 204:1257–1265CrossRefPubMedPubMedCentral Deaglio S, Dwyer KM, Gao W et al (2007) Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 204:1257–1265CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Supernat A, Markiewicz A, Welnicka-Jaskiewicz M et al (2012) CD73 expression as a potential marker of good prognosis in breast carcinoma. Appl Immunohistochem Mol Morphol 20:103–107CrossRefPubMed Supernat A, Markiewicz A, Welnicka-Jaskiewicz M et al (2012) CD73 expression as a potential marker of good prognosis in breast carcinoma. Appl Immunohistochem Mol Morphol 20:103–107CrossRefPubMed
26.
Zurück zum Zitat Pinder SE, Rakha EA, Purdie CA et al (2015) Translational Subgroup of the NCRI Breast Clinical Studies Group. Macroscopic handling and reporting of breast cancer specimens pre- and post-neoadjuvant chemotherapy treatment: review of pathological issues and suggested approaches. Histopathology 67(3):279–293. https://doi.org/10.1111/his.12649 CrossRefPubMed Pinder SE, Rakha EA, Purdie CA et al (2015) Translational Subgroup of the NCRI Breast Clinical Studies Group. Macroscopic handling and reporting of breast cancer specimens pre- and post-neoadjuvant chemotherapy treatment: review of pathological issues and suggested approaches. Histopathology 67(3):279–293. https://​doi.​org/​10.​1111/​his.​12649 CrossRefPubMed
27.
Zurück zum Zitat Provenzano E, Bossuyt V, Viale G et al (2015) Residual Disease Characterization Working Group of the Breast International Group-North American Breast Cancer Group Collaboration. Standardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group. Mod Pathol 28(9):1185–1201. https://doi.org/10.1038/modpathol.2015.74 CrossRefPubMed Provenzano E, Bossuyt V, Viale G et al (2015) Residual Disease Characterization Working Group of the Breast International Group-North American Breast Cancer Group Collaboration. Standardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group. Mod Pathol 28(9):1185–1201. https://​doi.​org/​10.​1038/​modpathol.​2015.​74 CrossRefPubMed
29.
Zurück zum Zitat Elston CW, Ellis IO (1991 Nov) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 19(5):403–410CrossRefPubMed Elston CW, Ellis IO (1991 Nov) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 19(5):403–410CrossRefPubMed
34.
Zurück zum Zitat Antonioli L, Yegutkin GG, Pacher P, Blandizzi C, Haskó G (2016) Anti-CD73 in cancer immunotherapy: awakening new opportunities. Trends Cancer 2(2):95–109CrossRefPubMedPubMedCentral Antonioli L, Yegutkin GG, Pacher P, Blandizzi C, Haskó G (2016) Anti-CD73 in cancer immunotherapy: awakening new opportunities. Trends Cancer 2(2):95–109CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Schmid P, Park YE, Muñoz-Couselo E et al Pembrolizumab (pembro) + chemotherapy (chemo) as neoadjuvant treatment for triple negative breast cancer (TNBC): Preliminary results from KEYNOTE-173. JCO.2017.35.15_suppl.556. Schmid P, Park YE, Muñoz-Couselo E et al Pembrolizumab (pembro) + chemotherapy (chemo) as neoadjuvant treatment for triple negative breast cancer (TNBC): Preliminary results from KEYNOTE-173. JCO.2017.35.15_suppl.556.
39.
Zurück zum Zitat Loibl S, Untch M, Burchardi N et al (2018) Randomized phase II neoadjuvant study (GeparNuevo) to investigate the addition of durvalumab to a taxane-anthracycline containing chemotherapy in triple negative breast cancer (TNBC). J Clin Oncol 36(15_suppl):104–104CrossRef Loibl S, Untch M, Burchardi N et al (2018) Randomized phase II neoadjuvant study (GeparNuevo) to investigate the addition of durvalumab to a taxane-anthracycline containing chemotherapy in triple negative breast cancer (TNBC). J Clin Oncol 36(15_suppl):104–104CrossRef
Metadaten
Titel
CD73 expression and pathologic response to neoadjuvant chemotherapy in triple negative breast cancer
verfasst von
Bruna Cerbelli
Andrea Botticelli
Annalinda Pisano
Angelina Pernazza
Domenico Campagna
Alessandro De Luca
Paolo Antonio Ascierto
Maria Gemma Pignataro
Maria Pelullo
Carlo Della Rocca
Paolo Marchetti
Lucio Fortunato
Leopoldo Costarelli
Giulia d’Amati
Publikationsdatum
01.04.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Virchows Archiv / Ausgabe 4/2020
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-019-02722-6

Weitere Artikel der Ausgabe 4/2020

Virchows Archiv 4/2020 Zur Ausgabe

Neu im Fachgebiet Pathologie