Discussion
TNBC, HER2-enriched tumors, breast cancer
BREAST CANCER, DISEASE, METASTATIC BREAST CANCER, PROLIFERATIVE, METASTASES
To our knowledge, the GELATO trial is the earliest reported clinical trial conducted specifically in patients with ILC based on a hypothesis founded on preclinical and translational data. While carboplatin alone neither led to significant changes in immune cell composition nor in an increase in cGAS–STING signaling or MHC class I expression, the addition of anti-PD-L1 caused an increase in CD8Recent research has suggested that TN-ILCs have different biological characteristics than TN-NST and EROnly one patient with TN-ILC was classified as basal like by PAM50 in the metastatic setting, and four of five patients with TN-ILC had ERInterestingly, most metastases were classified as HER2 enriched. This might be an artifact of PAM50 assessment on metastatic lesions and/or fresh-frozen (FF) material. However, a particularly high proportion of HER2-enriched tumors was also observed in paired lesions of the AURORA program for metastatic breast cancer and another retrospective seriesDuring treatment with carboplatin with or without anti-PD-L1, we also observed PAM50 subtype switching in 6 of 16 patients, of which 5 switched toward a luminal or normal-like phenotype. Because we studied serial biopsies of the same lesions, this suggests that treatment modified the tumor-intrinsic characteristics of these lesions toward a less proliferative phenotype. Most notably, the baseline metastatic lesion of the patient with a durable response was characterized as HER2 enriched but switched to a basal-like phenotype during anti-PD-L1 treatment, suggesting increased susceptibility to ICB.On the immune cell level, we observed higher levels of CD8Our trial is limited by a small sample size and lack of a control arm. Of note, the inclusion of a relatively small number of patients (Although ILCs comprise a separate disease entity within the breast cancer subtypes, so far, reports of clinical trials specific for patients with ILC are lackingIn conclusion, we report on a clinical trial specific for metastatic ILC representing a difficult-to-treat breast cancer subtype, and we demonstrate that the combination of carboplatin and anti-PD-L1 induces clinical and immunological responses in a subset of patients with ILC. Most of the responses were observed in patients with TN-ILC, highlighting that patients with TNBC should be considered for ICB regardless of histological subtype. Our work provides hypotheses and paves the way for highly needed ILC-specific clinical trials.