NDLI: Impact of stromal tumor-infiltrating lymphocytes (sTILs) on response to neoadjuvant chemotherapy in triple-negative early breast cancer in the WSG-ADAPT TN trial

Content Provider	Springer Nature : BioMed Central
Author	Kolberg-Liedtke, Cornelia Feuerhake, Friedrich Garke, Madlen Christgen, Matthias Kates, Ronald Grischke, Eva Maria Forstbauer, Helmut Braun, Michael Warm, Mathias Hackmann, John Uleer, Christoph Aktas, Bahriye Schumacher, Claudia Kuemmel, Sherko Wuerstlein, Rachel Graeser, Monika Nitz, Ulrike Kreipe, Hans Gluz, Oleg Harbeck, Nadia
Abstract	Background Higher density of stromal tumor-infiltrating lymphocytes (sTILs) at baseline has been associated with increased rates of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC). While evidence supports favorable association of pCR with survival in TNBC, an independent impact of sTILs (after adjustment for pCR) on survival is not yet established. Moreover, the impact of sTIL dynamics during NACT on pCR and survival in TNBC is unknown. Methods The randomized WSG-ADAPT TN phase II trial compared efficacy of 12-week nab-paclitaxel with gemcitabine versus carboplatin. This preplanned translational analysis assessed impacts of sTIL measurements at baseline (sTIL-0) and after 3 weeks of chemotherapy (sTIL-3) on pCR and invasive disease-free survival (iDFS). Predictive performance of sTIL-0 and sTIL-3 for pCR was quantified by ROC analysis and logistic regression; Kaplan–Meier estimation and Cox regression (with mediation analysis) were used to determine their impact on iDFS. Results For prediction of pCR, the AUC statistics for sTIL-0 and sTIL-3 were 0.60 and 0.63, respectively, in all patients; AUC for sTIL-3 was higher in NP/G. The positive predictive value (PPV) of “lymphocyte-predominant” status (sTIL-0 ≥ 60%) at baseline was 59.3%, though only 13.0% of patients had this status. To predict non-pCR, the cut point sTIL-0 ≤ 10% yielded PPV = 69.5% while addressing 33.8% of patients. Higher sTIL levels (particularly at 3 weeks) were independently and favorably associated with better iDFS, even after adjusting for pCR. For example, the adjusted hazard ratio for 3-week sTILs ≥ 60% (vs. < 60%) was 0.48 [0.23–0.99]. Low cellularity in 3-week biopsies was the strongest individual predictor for pCR (in both therapy arms), but not for iDFS. Conclusion The independent impact of sTILs on iDFS suggests that favorable immune response can influence key tumor biological processes for long-term survival. The results suggest that the reliability of pCR following neoadjuvant therapy as a surrogate for survival could vary among subgroups in TNBC defined by immune response or other factors. Dynamic measurements of sTILs under NACT could support immune response-guided patient selection for individualized therapy approaches for both very low levels (more effective therapies) and very high levels (de-escalation concepts). Trial registration: Clinical trials No: NCT01815242, retrospectively registered January 25, 2013.
Related Links	https://breast-cancer-research.biomedcentral.com/counter/pdf/10.1186/s13058-022-01552-w.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s13058-022-01552-w
Journal	Breast Cancer Research
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2022-09-02
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Triple-negative breast cancer sTils Neoadjuvant chemotherapy Pathologic complete response 3-Week biopsy
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology
Journal Impact Factor	6.1/2023
5-Year Journal Impact Factor	7.1/2023

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