Abstract YO6
Case summary
BRAFV600E mutations are identified in up to 60% of melanomas and 60% of thyroid cancers. The development of selective BRAF inhibitors was a landmark in the treatment of BRAF-mutant melanoma. Clinical resistance develops in majority of patients with BRAFV600E mutant melanoma treated with monotherapy. BRAF and MEK inhibitor combination therapy is associated with superior response, progression-free survival and overall survival. We illustrate the utility of molecular profiling in identifying BRAF mutation in metastatic breast cancer (mBC). There have only been 4 case reports of BRAF mutation in mBC in the literature. We describe the use of BRAF-directed therapy in mBC, with identification of subsequent resistance mechanisms.
We present a case of a 46 year old lady with stage 4 left breast carcinoma, HR positive and HER2 negative, with extensive metastases to the lungs, liver, bone and lymph node. She was treated with first line Ribociclib and Letrozole but progressed after 8 months. She received second line Abemaciclib and Fulvestrant but progressed rapidly after 3 months. Genomic profiling reported BRAF V600E mutation with a variant allele frequency (VAF) of 6.18%. It was negative for ESR1 and PIK3CA mutations.
She started Dabrafenib and Trametinib with near-complete response. She responded for 9 months before developing progression of disease in her left axillary lymph node. Left axillary lymph node biopsy reported HR positive and HER2-low carcinoma. Genomic profiling showed BRAF V600E with increased VAF of 21.2% and multiple TYW1-BRAF and RABEP1-BRAF fusion genes. Clinical resistance to Dabrafenib and Trametinib was most likely associated with acquisition of the TYW1-BRAF and RABEP1-BRAF fusion genes. The axillary lymph node was resected, as the only oligo-progressing lesion. Serial monitoring the BRAF and RABEP1-BRAF fusion VAF with liquid biopsy aided in informing continuation or changing of subsequent systemic treatment.
We report a rare case of breast cancer with BRAF mutation in which genomic profiling was used to direct therapy and the excellent response to treatment. Serial molecular profiling identified a novel BRAF fusion as the likely acquired resistance to BRAF inhibitors.