The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer

TCR repertoire; Breast cancer; Clade mutationsRepertori TCR; Càncer de mama; Mutacions cladeRepertorio TCR; Cáncer de mama; Mutaciones cladoThe detailed molecular characterization of lethal cancers is a prerequisite to understanding resistance to therapy and escape from cancer immunoediting. We performed extensive multi-platform profiling of multi-regional metastases in autopsies from 10 patients with therapy-resistant breast cancer. The integrated genomic and immune landscapes show that metastases propagate and evolve as communities of clones, reveal their predicted neo-antigen landscapes, and show that they can accumulate HLA loss of heterozygosity (LOH). The data further identify variable tumor microenvironments and reveal, through analyses of T cell receptor repertoires, that adaptive immune responses appear to co-evolve with the metastatic genomes. These findings reveal in fine detail the landscapes of lethal metastatic breast cancer

The economic burden of metastatic breast cancer in Spain.

The study aimed to estimate the burden of metastatic breast cancer (mBC) in Spain over 5 years. An incidence-based cost-of-illness model was developed in which a cohort of patients with mBC was followed from the diagnosis of metastatic disease over 5 years or death. Resource use data were collected through a physician survey conducted with 10 clinical experts in Spain. The model distinguished patients according to HER2 and hormonal receptor (HR) status, and followed the patient cohort in monthly cycles. The incident cohort was estimated to be 2,923 patients with mBC, consisting of 1,575 HER2-/HR+, 520 HER2+/HR+, 324 HER2+/HR-, and 503 triple negative patients. The estimated mean survival over the 5-year time period was 2.51 years, on average, with longer survival of 3.36 years for HER2+/HR+, 2.41 years for HER2-/HR+, 2.82 years for HER2+/HR- and shortest mean survival of 1.74 years for triple negative patients. The total costs were €469,92,731 for the overall population, €190,079,787 for the HER2-/HR+, €151,045,260 for the HER2+/HR+, €80,827,171 for the HER2+/HR- and €47,540,512 for the triple negative subgroups over 5 years. Per patient total costs were €160,642 on average, €120,664 for HER2-/HR+, €290,346 for HER2+/HR+, €249,152 for HER2+/HR-and €94,572 for triple negative patients over 5 years. The economic burden of mBC in Spain is significant, but differs by HER2 and HR status. HER2-/HR +patients account for the highest burden due to the prevalence of this category, but HER2+/HR +patients have the highest per patient costs