Neoadjuvant Immunotherapy in Early, Triple-Negative Breast Cancers: Catching Up with the Rest

Kim, Leah; Coman, M.; Pusztai, Lajos; Park, Tristen S

doi:10.1245/s10434-023-13714-x

Cited by 4 publications

(1 citation statement)

References 69 publications

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“…Currently, due to the lack of biomarker selection for trial eligibility, all patients with high-risk stage II and III TNBC receive pembrolizumab in the neoadjuvant setting, resulting in the potential overtreatment of a large majority of patients. Hence, there is an unmet need to identify biomarkers which could identify patients who may attain pCR with chemotherapy alone and be spared the side effects of the combination with pembrolizumab [2][3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Immunologic Factors Associated with Differential Response to Neoadjuvant Chemoimmunotherapy in Triple-Negative Breast Cancer

Seager,

Ko,

Pabla

et al. 2024

JPM

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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.

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