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DOI: 10.1055/s-0038-1651710
Impact of tumor-infiltrating lymphocytes on response to neoadjuvant chemotherapy in triple-negative early breast cancer: Translational subproject of the WSG-ADAPT TN trial
Publication History
Publication Date:
22 May 2018 (online)
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