Tumors with high-density tumor infiltrating lymphocytes constitute a favorable entity in breast cancer: a pooled analysis of four prospective adjuvant trials.
BACKGROUND
Tumor infiltrating lymphocytes (TILs) are considered in the prognosis of breast cancer (BC) patients. Here, we investigated the prognostic/predictive effect of TILs in patients treated in the frame of four prospective trials with adjuvant anthracycline-based chemotherapy in the pre- and post-trastuzumab era.


METHODS
TILs density was histologically assessed as percentage of stromal area on whole routine sections of 2613 BC (1563 Luminal A/B; 477 Luminal HER2; 246 HER2-enriched; 327 triple negative [TNBC]) and were evaluated as high/low at three cut-offs (c/o; 50% [lymphocytic predominance, LP], 35% and 25%), in separate training and validation sets.


RESULTS
High TILs were present in 3.5%, 6.5% and 11.5% of all tumors, using the 50%, 35% and 25% c/o, respectively. TILs status did not interact with BC subtypes or trastuzumab treatment. LPBC patient outcome was not affected by nodal status, while high TILs were favorable in TNBC with unfavorable nodal status. When adjusted for standard clinicopathological parameters and treatment, high TILs independently predicted for favorable outcome, e.g., disease-free survival with the 35% c/o in the entire cohort (HR = 0.44, 95% CI 0.28-0.69, p < 0.001) and in specific subtypes.


CONCLUSIONS
High TILs tumors, especially LPBC seem worthy validating as a separate entity of favorable prognosis in breast cancer.
Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.|Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Thessaloniki, Greece.
Vassiliki
V
Kotoula
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Thessaloniki, Greece.
Kyriakos
K
Chatzopoulos
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Thessaloniki, Greece.
Sotiris
S
Lakis
Health Data Specialists Ltd., Department of Biostatistics, Athens, Greece.
Zoi
Z
Alexopoulou
Department of Medical Oncology, "Papageorgiou" Hospital , Thessaloniki, Greece.
Eleni
E
Timotheadou
Department of Clinical Therapeutics, "Alexandra" Hospital, Athens, Greece.
Flora
F
Zagouri
Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece.
George
G
Pentheroudakis
First Department of Medicine, "Laiko" General Hospital, Athens, Greece.
Helen
H
Gogas
Second Department of Medical Oncology, "Metropolitan" Hospital, Piraeus, Greece.
Eleni
E
Galani
Department of Pathology, "Papageorgiou" Hospital, Thessaloniki, Greece.
Ioannis
I
Efstratiou
Department of Pathology, "Papageorgiou" Hospital, Thessaloniki, Greece.
Thomas
T
Zaramboukas
Division of Oncology, Department of Medicine, University Hospital, Patras, Greece.
Angelos
A
Koutras
Second Department of Medical Oncology, "Agii Anargiri" Cancer Hospital, Athens, Greece.
Gerasimos
G
Aravantinos
Third Department of Medical Oncology, "Agii Anargiri" Cancer Hospital, Athens, Greece.
Epaminontas
E
Samantas
Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece.
Amanda
A
Psyrri
Department of Pathology, University Hospital of Patras, Rion, Greece.
Helen
H
Kourea
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Thessaloniki, Greece.
Mattheos
M
Bobos
Oncology Unit, "Hippokration" Hospital, Athens, Greece.
Pavlos
P
Papakostas
Second Department of Medical Oncology, Hygeia Hospital, Athens, Greece.
Paris
P
Kosmidis
Oncology Section, Second Department of Internal Medicine, "Hippokration" Hospital, Athens, Greece.
Dimitrios
D
Pectasides
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Thessaloniki, Greece.
George
G
Fountzilas
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D015201:Meta-Analysis as Topic; D015337:Multicenter Studies as Topic; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
D014408:Biomarkers, Tumor
breast cancer; clinical breast cancer subtypes; prognostic; trastuzumab; tumor infiltrating lymphocytes