Impact of tumor-infiltrating lymphocytes on response to neoadjuvant chemotherapy in triple-negative early breast cancer: Translational subproject of the WSG-ADAPT TN trial

M Garke; F Feuerhake; O Gluz; M Christgen; R Kates; EM Grischke; H Forstbauer; M Braun; M Warm; C Hackmann; C Uleer; B Aktas; C Schumacher; S Kuemmel; R Würstlein; U Nitz; H Kreipe; N Harbeck; C Liedtke

doi:10.1055/s-0038-1651710

Senologie - Zeitschrift für Mammadiagnostik und -therapie, Table of Contents

Senologie - Zeitschrift für Mammadiagnostik und -therapie 2018; 15(02): e15
DOI: 10.1055/s-0038-1651710

Abstracts

Georg Thieme Verlag KG Stuttgart · New York

Impact of tumor-infiltrating lymphocytes on response to neoadjuvant chemotherapy in triple-negative early breast cancer: Translational subproject of the WSG-ADAPT TN trial

Authors

M Garke

¹Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Deutschland
F Feuerhake

²MHH, Hannover, Deutschland
O Gluz

³Westdeutsche Studiengruppe, Mönchengladbach, Deutschland
M Christgen

²MHH, Hannover, Deutschland
R Kates

³Westdeutsche Studiengruppe, Mönchengladbach, Deutschland
EM Grischke

⁴Universitätsklinikum Tübingen, Tübingen, Deutschland
H Forstbauer

⁵Praxisnetzwerk Hamatologie/Intern. Onkologie, Troisdorf, Deutschland
M Braun

⁶Rotkreuzklinikum München, München, Deutschland
M Warm

⁷Krankenhaus Köln-Holweide, Köln, Deutschland
C Hackmann

⁸EvK Witten, Witten, Deutschland
C Uleer

⁹Gyn.-onkologische Gemeinschaftspraxis, Hildesheim, Deutschland
B Aktas

¹⁰Universitätsklinikum Leipzig, Leipzig, Deutschland
C Schumacher

¹¹St. Elisabeth Hospital Köln-Hohenlind, Köln, Deutschland
S Kuemmel

³Westdeutsche Studiengruppe, Mönchengladbach, Deutschland

¹²Kliniken Essen Mitte, Essen, Deutschland
R Würstlein

³Westdeutsche Studiengruppe, Mönchengladbach, Deutschland

¹³LMU, München, Deutschland
U Nitz

³Westdeutsche Studiengruppe, Mönchengladbach, Deutschland
H Kreipe

²MHH, Hannover, Deutschland
N Harbeck

³Westdeutsche Studiengruppe, Mönchengladbach, Deutschland

¹³LMU, München, Deutschland
C Liedtke

³Westdeutsche Studiengruppe, Mönchengladbach, Deutschland

¹⁴Charite – Universitätsmedizin Berlin/Campus Mitte, Klinik für Gynäkologie mit Brustzentrum, Berlin, Deutschland

Abstract

Full Text

Background:

In TNBC, pCR (ypT0/is/ypN0) is associated with improved prognosis. The WSG-ADAPT-TN trial showed higher pCR with Nab-paclitaxel/carboplatin (NP/C) compared to Nab-paclitaxel/gemcitabine (NP/G) as 12-week neoadjuvant therapy. TILs are associated with pCR after neoadjuvant chemotherapy, but the role of TIL dynamics during chemotherapy regimens remains unknown.

Methods:

This analysis focuses on semi-quantitative TIL measurements in ADAPT-TN at baseline (TIL-0) and after 3 weeks of chemotherapy (TIL-3). Associations of continuous TIL-0/TIL-3 levels with pCR and other clinical/pathological measurements were analyzed using logistic regression, rank correlations, t and chi-square statistics.

Results:

336 patients were enrolled. TIL-0/TIL-3 were available among 311(92.6%)/223(66.4%) patients. “Low cellularity” in the 3-week biopsy (tumor necrosis, lack of invasive tumor cells) was recorded in 82 patients.

TIL-0 and TIL-3 were strongly correlated (0.64, p < 0.001); average relative increase was about 30%. TIL-0 was significantly associated with baseline tumor grade, clinical tumor size, and nodal status. TIL-3 was significantly associated with nodal status and grade in both biopsies.

Overall, higher levels of both TIL-0 (p < 0.001) and TIL-3 (p =.002) were associated with pCR. Higher TIL-0 was also significantly associated with pCR in both arms separately. “Low cellularity” was associated with pCR in all patients (OR = 3.9, 95%-CI: 2.3 – 6.8) and in both arms separately (NP/G: OR = 3.6, 95%-CI: 1.7 to 7.9; NP/C: OR = 4.2, 95%-CI: 1.9 – 9.3).

Interpretation:

In TNBC patients, higher levels of TILs were associated with pCR at baseline and after 3 weeks of neoadjuvant chemotherapy. “Low-cellularity” at week 3 indicates extensive response to chemotherapy and is strongly associated with pCR