TY - JOUR
T1 - Durable complete response with immune checkpoint inhibitor in breast cancer with high tumor mutational burden and APOBEC signature
AU - Chumsri, Saranya
AU - Sokol, Ethan S.
AU - Soyano-Muller, Aixa E.
AU - Parrondo, Ricardo D.
AU - Reynolds, Gina A.
AU - Nassar, Aziza
AU - Thompson, E. Aubrey
N1 - Publisher Copyright:
© 2020 Harborside Press. All rights reserved.
PY - 2020/5
Y1 - 2020/5
N2 - Increasing data support the importance of preexisting host immune response and neoantigen burden for determining response to immune checkpoint inhibitors (ICIs). In lung cancer and melanoma, tumor mutational burden (TMB) has emerged as an independent biomarker for ICI response. However, the significance of TMB in breast cancer, particularly in the context of PD-L1 negativity, remains unclear. This report describes a patient with HER2-negative breast cancer with high TMB and an apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) trinucleotide signature; her disease was refractory to multiple lines of treatments but achieved durable complete response using ICIs and capecitabine. Additional analysis of the tumor revealed a low amount of stromal tumor-infiltrating lymphocytes (sTILs) and PD-L1 negativity, reflecting a poor preexisting host immune response. In collaboration with Foundation Medicine, comprehensive genomic profiling from 14,867 patients with breast cancer with the FoundationOne test was evaluated. Using the cutoff of $10 mutations/megabase (mut/Mb) for high TMB, PD-L1 positivity and TMB-high populations were not significantly overlapping (odds ratio, 1.02; P5.87). Up to 79% of TMB-high tumors with .20 mut/Mb were PD-L1–negative. Our study highlights that despite having low TILs and PD-L1 negativity, some patients may still experience response to ICIs.
AB - Increasing data support the importance of preexisting host immune response and neoantigen burden for determining response to immune checkpoint inhibitors (ICIs). In lung cancer and melanoma, tumor mutational burden (TMB) has emerged as an independent biomarker for ICI response. However, the significance of TMB in breast cancer, particularly in the context of PD-L1 negativity, remains unclear. This report describes a patient with HER2-negative breast cancer with high TMB and an apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) trinucleotide signature; her disease was refractory to multiple lines of treatments but achieved durable complete response using ICIs and capecitabine. Additional analysis of the tumor revealed a low amount of stromal tumor-infiltrating lymphocytes (sTILs) and PD-L1 negativity, reflecting a poor preexisting host immune response. In collaboration with Foundation Medicine, comprehensive genomic profiling from 14,867 patients with breast cancer with the FoundationOne test was evaluated. Using the cutoff of $10 mutations/megabase (mut/Mb) for high TMB, PD-L1 positivity and TMB-high populations were not significantly overlapping (odds ratio, 1.02; P5.87). Up to 79% of TMB-high tumors with .20 mut/Mb were PD-L1–negative. Our study highlights that despite having low TILs and PD-L1 negativity, some patients may still experience response to ICIs.
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U2 - 10.6004/jnccn.2020.7543
DO - 10.6004/jnccn.2020.7543
M3 - Article
C2 - 32380464
AN - SCOPUS:85084402183
SN - 1540-1405
VL - 18
SP - 517
EP - 521
JO - JNCCN Journal of the National Comprehensive Cancer Network
JF - JNCCN Journal of the National Comprehensive Cancer Network
IS - 5
ER -