-Mutated Estrogen Receptor-Positive Breast Cancer Shows BRCAness, Suggesting Sensitivity to Drugs Targeting Homologous Recombination Deficiency.

As estrogen receptor-positive (ER) breast cancer in mutation carriers arises at an older age with less aggressive tumor characteristics than ER-negative (ER) -mutated breast cancer, it has been suggested that these tumors are "sporadic" and not driven. With the introduction of targeted treatments specific for tumors with a nonfunctioning or gene, the question whether the genes are impaired in the tumor is highly relevant. Therefore, we performed genomic profiling of -mutated ER tumors. Genomic profiling, promoter methylation assessment, and loss of heterozygosity analysis were done on 16 -mutated ER tumors. Results were compared with 57 -mutated ER tumors, 36 -mutated ER-associated tumors, and 182 sporadic ER tumors. The genomic profile of -mutated ER tumors was different from -mutated ER breast tumors, but highly similar to -mutated ER tumors. In 83% of the -mutated ER tumors, loss of the wild-type allele was observed. In addition, clinicopathologic variables in -mutated ER cancer were also more similar to -mutated ER and sporadic ER breast cancer than to -mutated ER cancers. As -mutated ER tumors show a BRCAness copy number profile and LOH, it is likely that the loss of a functional BRCA1 protein plays a role in tumorigenesis in -mutated ER tumors. Therefore, we hypothesize that these tumors are sensitive to drugs targeting the gene defect, providing new targeted treatment modalities for advanced BRCA-deficient, ER breast cancer. .