The absence of effective therapeutic targets and aggressive nature of triple-negative breast cancer (TNBC) renders this disease subset difficult to treat. Although estrogen receptor beta (ERβ) is expressed in TNBC, studies on its functional role have yielded inconsistent results. However, recently, our preclinical studies, along with other observations, have shown the potential therapeutic utility of ERβ in the context of mutant p53 expression.
View Article and Find Full Text PDFPurpose: Actionable mutations can guide genotype-directed matched therapy. We evaluated the utility of tissue-based and plasma-based genotyping for the identification of actionable mutations and selection of matched therapy in patients with metastatic breast cancer (MBC).
Experimental Design: Patients with MBC who underwent tissue genotyping (institutional platform, 91-gene assay) or plasma-based cell-free DNA (cfDNA, Guardant360, 73-gene assay) between January 2016 and December 2017 were included.
Purpose: Accurate monitoring of therapeutic response remains an important unmet need for patients with metastatic breast cancer (MBC). Analysis of tumor genomics obtained via circulating tumor DNA (ctDNA) can provide a comprehensive overview of tumor evolution. Here, we evaluated ctDNA change as an early prognostic biomarker of subsequent radiologic progression and survival in MBC.
View Article and Find Full Text PDFPurpose: Plasma genotyping may identify mutations in potentially "actionable" cancer genes, such as , but their clinical significance is not well-defined. We evaluated the characteristics of somatically acquired mutations in patients with metastatic breast cancer (MBC).
Experimental Design: Patients with MBC undergoing routine cell-free DNA (cfDNA) next-generation sequencing (73-gene panel) before starting a new therapy were included.
Purpose: While amplification has been described in breast cancer, the optimal treatment approach for -amplified (FGFR1) metastatic breast cancer (MBC) remains undefined. We evaluated clinical response to endocrine and targeted therapies in a cohort of patients with hormone receptor-positive (HR)/HER2 MBC and validated the functional role of -amplification in mediating response/resistance to hormone therapy .
Results: In the clinical cohort ( = 110), we identified that patients with FGFR1 tumors were more likely to have progesterone receptor (PR)-negative disease (47% vs.
Plasma genotyping identifies potentially actionable mutations at variable mutant allele frequencies, often admixed with multiple subclonal variants, highlighting the need for their clinical and functional validation. We prospectively monitored plasma genotypes in 143 women with endocrine-resistant metastatic breast cancer (MBC), identifying multiple novel mutations including mutations (8.4%), albeit at different frequencies highlighting clinical heterogeneity.
View Article and Find Full Text PDFBackground: Research biopsies (RBs) are essential to understanding tumor biology and mechanisms of resistance and to advancing precision medicine. However, RBs have associated risks and may not benefit the patient.
Objectives: The purpose of this integrative review is to summarize and synthesize the current literature on the experience, attitudes, and understanding of patients with cancer related to RBs.