| Autor: |
Seager RJ; Labcorp Oncology, Buffalo, NY 14263, USA., Ko H; Labcorp Oncology, Durham, NC 27710, USA., Pabla S; Labcorp Oncology, Buffalo, NY 14263, USA., Senosain MF; Labcorp Oncology, Buffalo, NY 14263, USA., Kalinski P; Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA., Van Roey E; Labcorp Oncology, Buffalo, NY 14263, USA., Gao S; Labcorp Oncology, Buffalo, NY 14263, USA., Strickland KC; Labcorp Oncology, Durham, NC 27710, USA.; Department of Pathology, Duke University Medical Center, Duke Cancer Institute, Durham, NC 27710, USA., Previs RA; Labcorp Oncology, Durham, NC 27710, USA.; Department of Obstetrics & Gynecology, Duke University Medical Center, Duke Cancer Institute, Division of Gynecologic Oncology, Durham, NC 27710, USA., Nesline MK; Labcorp Oncology, Durham, NC 27710, USA., Hastings S; Labcorp Oncology, Durham, NC 27710, USA., Zhang S; Labcorp Oncology, Buffalo, NY 14263, USA., Conroy JM; Labcorp Oncology, Buffalo, NY 14263, USA., Jensen TJ; Labcorp Oncology, Durham, NC 27710, USA., Eisenberg M; Labcorp, Burlington, NC 27710, USA., Caveney B; Labcorp, Burlington, NC 27710, USA., Severson EA; Labcorp Oncology, Durham, NC 27710, USA., Ramkissoon S; Labcorp Oncology, Durham, NC 27710, USA.; Wake Forest Comprehensive Cancer Center and Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC 27710, USA., Gandhi S; Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. |
| Abstrakt: |
Background: KEYNOTE-522 resulted in FDA approval of the immune checkpoint inhibitor pembrolizumab in combination with neoadjuvant chemotherapy for patients with early-stage, high-risk, triple-negative breast cancer (TNBC). Unfortunately, pembrolizumab is associated with several immune-related adverse events (irAEs). We aimed to identify potential tumor microenvironment (TME) biomarkers which could predict patients who may attain pathological complete response (pCR) with chemotherapy alone and be spared the use of anti-PD-1 immunotherapy. Methods: Comprehensive immune profiling, including RNA-seq gene expression assessment of 395 immune genes, was performed on matched FFPE tumor samples from 22 stage I-III TNBC patients (14 patients treated with neoadjuvant chemotherapy alone (NAC) and 8 treated with neoadjuvant chemotherapy combined with pembrolizumab (NAC+I)). Results: Differential gene expression analysis revealed that in the NAC group, IL12B and IL13 were both significantly associated with pCR. In the NAC+I group, LCK and TP63 were significantly associated with pCR. Patients in both treatment groups exhibiting pCR tended to have greater tumor inflammation than non-pCR patients. In the NAC+I group, patients with pCR tended to have greater cell proliferation and higher PD-L1 expression, while in the NAC group, patients with pCR tended to have lower cancer testis antigen expression. Additionally, the NAC+I group trended toward a lower relative dose intensity averaged across all chemotherapy drugs, suggesting that more dose reductions or treatment delays occurred in the NAC+I group than the NAC group. Conclusions : A comprehensive understanding of immunologic factors could potentially predict pCR to chemotherapy alone, enabling the avoidance of the unnecessary treatment of these patients with checkpoint inhibitors. |
