Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy—A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study
Tumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the effica...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/22/5635 |
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| author | Nikolaos Spathas Anna C. Goussia Georgia-Angeliki Koliou Helen Gogas Flora Zagouri Anna Batistatou Antonia V. Charchanti Alexandra Papoudou-Bai Mattheos Bobos Sofia Chrisafi Kyriakos Chatzopoulos Ioannis Kostopoulos Triantafyllia Koletsa Petroula Arapantoni Dimitrios Pectasides Eleni Galani Angelos Koutras George Zarkavelis Emmanouil Saloustros Dimitrios Bafaloukos Charisios Karanikiotis Iliada Bompolaki Gerasimos Aravantinos Amanda Psyrri Evangelia Razis Anna Koumarianou Eleni Res Helena Linardou George Fountzilas |
| author_facet | Nikolaos Spathas Anna C. Goussia Georgia-Angeliki Koliou Helen Gogas Flora Zagouri Anna Batistatou Antonia V. Charchanti Alexandra Papoudou-Bai Mattheos Bobos Sofia Chrisafi Kyriakos Chatzopoulos Ioannis Kostopoulos Triantafyllia Koletsa Petroula Arapantoni Dimitrios Pectasides Eleni Galani Angelos Koutras George Zarkavelis Emmanouil Saloustros Dimitrios Bafaloukos Charisios Karanikiotis Iliada Bompolaki Gerasimos Aravantinos Amanda Psyrri Evangelia Razis Anna Koumarianou Eleni Res Helena Linardou George Fountzilas |
| author_sort | Nikolaos Spathas |
| collection | DOAJ |
| description | Tumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the efficacy and safety, we report the results of the translational part of our study. We examined the patients’ tumors for total (t), stromal (s), and intratumoral (i) CD8 lymphocyte density (counts/mm<sup>2</sup>) on tissue-microarray cores. The impact of CD8+ TILs counts on DFS and OS, and its correlation with breast cancer subtypes and standard clinicopathological parameters, were investigated, along with efficacy and safety data. Among the 928 eligible patients, 627 had available CD8+ data. Of which, 24.9% had a high expression of sCD8, iCD8, and total CD8, which were correlated with higher Ki67, TILs density, ER/PgR negativity, and higher histological grade. The 5year DFS and OS rates were 86.1% and 91.4%, respectively. Patients with high iCD8 and tCD8 had longer DFS and OS compared to those with low counts/mm<sup>2</sup> (DFS: HR = 0.58, <i>p</i> = 0.011 and HR = 0.65, <i>p</i> = 0.034 and OS: HR = 0.63, <i>p</i> = 0.043 and HR = 0.58, <i>p</i> = 0.020, respectively). Upon adjustment for clinicopathological parameters, iCD8 and tCD8 retained their favorable prognostic significance for DFS and OS, whereas high sCD8 was only prognostic for DFS. Menopausal status, tumor size, and nodal status retained their prognostic significance in all examined multivariate models. CD8+ TILs, and especially their intratumoral subset, represent a potential favorable prognostic factor in early BC. |
| first_indexed | 2024-03-09T18:26:17Z |
| format | Article |
| id | doaj.art-5294f11514274634ad89d3fd4db943d8 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T18:26:17Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5294f11514274634ad89d3fd4db943d82023-11-24T07:54:18ZengMDPI AGCancers2072-66942022-11-011422563510.3390/cancers14225635Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy—A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational StudyNikolaos Spathas0Anna C. Goussia1Georgia-Angeliki Koliou2Helen Gogas3Flora Zagouri4Anna Batistatou5Antonia V. Charchanti6Alexandra Papoudou-Bai7Mattheos Bobos8Sofia Chrisafi9Kyriakos Chatzopoulos10Ioannis Kostopoulos11Triantafyllia Koletsa12Petroula Arapantoni13Dimitrios Pectasides14Eleni Galani15Angelos Koutras16George Zarkavelis17Emmanouil Saloustros18Dimitrios Bafaloukos19Charisios Karanikiotis20Iliada Bompolaki21Gerasimos Aravantinos22Amanda Psyrri23Evangelia Razis24Anna Koumarianou25Eleni Res26Helena Linardou27George Fountzilas28Fourth Oncology Department, Metropolitan Hospital, 18547 Athens, GreeceDepartment of Pathology, Ioannina University Hospital, 45500 Ioannina, GreeceSection of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, 11526 Athens, GreeceFirst Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, 11527 Athens, GreeceDepartment of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, 11528 Athens, GreeceDepartment of Pathology, Ioannina University Hospital, 45500 Ioannina, GreeceDepartment of Pathology, Ioannina University Hospital, 45500 Ioannina, GreeceDepartment of Pathology, Ioannina University Hospital, 45500 Ioannina, GreeceLaboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, 54006 Thessaloniki, GreeceLaboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, 54006 Thessaloniki, GreeceLaboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, 54006 Thessaloniki, GreeceDepartment of Pathology, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Pathology, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Pathology, Henry Dunant Hospital, 11526 Athens, GreeceOncology Section, Second Department of Internal Medicine, Hippokration Hospital, 11527 Athens, GreeceSecond Department of Medical Oncology, Metropolitan Hospital, 18547 Piraeus, GreeceDivision of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, 26504 Patras, GreeceDepartment of Medical Oncology, Medical School, University of Ioannina, 45500 Ioannina, GreeceDepartment of Oncology, University Hospital of Larissa, 41334 Larissa, GreeceFirst Department of Medical Oncology, Metropolitan Hospital, 18547 Piraeus, GreeceDepartment of Medical Oncology, 424 Army General Hospital, 56429 Thessaloniki, GreeceOncology Department, General Hospital of Chania, 73300 Crete, GreeceSecond Department of Medical Oncology, Agii Anargiri Cancer Hospital, 14564 Athens, GreeceSection of Medical Oncology, Department of Internal Medicine, Attikon University Hospital, Faculty of Medicine, National and Kapodistrian University of Athens School of Medicine, 12462 Athens, GreeceThird Department of Medical Oncology, Hygeia Hospital, 15123 Athens, GreeceHematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens School of Medicine, 12462 Athens, GreeceThird Department of Medical Oncology, Agii Anargiri Cancer Hospital, 14564 Athens, GreeceFourth Oncology Department, Metropolitan Hospital, 18547 Athens, GreeceLaboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, 54006 Thessaloniki, GreeceTumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the efficacy and safety, we report the results of the translational part of our study. We examined the patients’ tumors for total (t), stromal (s), and intratumoral (i) CD8 lymphocyte density (counts/mm<sup>2</sup>) on tissue-microarray cores. The impact of CD8+ TILs counts on DFS and OS, and its correlation with breast cancer subtypes and standard clinicopathological parameters, were investigated, along with efficacy and safety data. Among the 928 eligible patients, 627 had available CD8+ data. Of which, 24.9% had a high expression of sCD8, iCD8, and total CD8, which were correlated with higher Ki67, TILs density, ER/PgR negativity, and higher histological grade. The 5year DFS and OS rates were 86.1% and 91.4%, respectively. Patients with high iCD8 and tCD8 had longer DFS and OS compared to those with low counts/mm<sup>2</sup> (DFS: HR = 0.58, <i>p</i> = 0.011 and HR = 0.65, <i>p</i> = 0.034 and OS: HR = 0.63, <i>p</i> = 0.043 and HR = 0.58, <i>p</i> = 0.020, respectively). Upon adjustment for clinicopathological parameters, iCD8 and tCD8 retained their favorable prognostic significance for DFS and OS, whereas high sCD8 was only prognostic for DFS. Menopausal status, tumor size, and nodal status retained their prognostic significance in all examined multivariate models. CD8+ TILs, and especially their intratumoral subset, represent a potential favorable prognostic factor in early BC.https://www.mdpi.com/2072-6694/14/22/5635biomarkerstumor-infiltrating lymphocytesbreast canceradjuvant chemotherapy |
| spellingShingle | Nikolaos Spathas Anna C. Goussia Georgia-Angeliki Koliou Helen Gogas Flora Zagouri Anna Batistatou Antonia V. Charchanti Alexandra Papoudou-Bai Mattheos Bobos Sofia Chrisafi Kyriakos Chatzopoulos Ioannis Kostopoulos Triantafyllia Koletsa Petroula Arapantoni Dimitrios Pectasides Eleni Galani Angelos Koutras George Zarkavelis Emmanouil Saloustros Dimitrios Bafaloukos Charisios Karanikiotis Iliada Bompolaki Gerasimos Aravantinos Amanda Psyrri Evangelia Razis Anna Koumarianou Eleni Res Helena Linardou George Fountzilas Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy—A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study Cancers biomarkers tumor-infiltrating lymphocytes breast cancer adjuvant chemotherapy |
| title | Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy—A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study |
| title_full | Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy—A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study |
| title_fullStr | Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy—A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study |
| title_full_unstemmed | Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy—A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study |
| title_short | Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy—A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study |
| title_sort | association between cd8 tumor infiltrating lymphocytes and the clinical outcome of patients with operable breast cancer treated with adjuvant dose dense chemotherapy a 10 year follow up report of a hellenic cooperative oncology group observational study |
| topic | biomarkers tumor-infiltrating lymphocytes breast cancer adjuvant chemotherapy |
| url | https://www.mdpi.com/2072-6694/14/22/5635 |
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