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Discordant cellular response to pre-surgical letrozole in bilateral synchronous ER+ breast cancers with a KRAS mutation or FGFR1 gene amplification

ABSTRACT: This clinical case resulted from an ongoing trial at Vanderbilt University and abroad where ER+ breast cancer patients are administered 2-3 weeks of aromatase inhibitor therapy leading up to definitive surgical resection of the tumor. In this case, we describe a study patient presenting with bilateral primary ER+ breast tumors. Short term hormonal therapy substantially reduced proliferation in one tumor, while the second was essentially unchanged. Extensive molecular and genetic workup of the two tumors yielded divergent lesions in the two tumors; an activating KRAS mutation in the responsive tumor, and an amplification of the FGFR1 locus in the treatment-refractory tumor.

ORGANISM(S): Homo sapiens

PROVIDER: GSE39387 | GEO | 2012/07/17

SECONDARY ACCESSION(S): PRJNA170759

REPOSITORIES: GEO

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Discordant cellular response to pre-surgical letrozole in bilateral synchronous ER+ breast cancers with a KRAS mutation or FGFR1 gene amplification

Project description:This clinical case resulted from an ongoing trial at Vanderbilt University and abroad where ER+ breast cancer patients are administered 2-3 weeks of aromatase inhibitor therapy leading up to definitive surgical resection of the tumor. In this case, we describe a study patient presenting with bilateral primary ER+ breast tumors. Short term hormonal therapy substantially reduced proliferation in one tumor, while the second was essentially unchanged. Extensive molecular and genetic workup of the two tumors yielded divergent lesions in the two tumors; an activating KRAS mutation in the responsive tumor, and an amplification of the FGFR1 locus in the treatment-refractory tumor. Surgical tumor specimens from ER+ breast cancer patient 7603 who was administered letrozole for 16 days leading up to definitive surgery were utilized for RNA extraction and hybridization to Affymetrix Gene expression microarrays.

2012-07-16 | E-GEOD-39387 | biostudies-arrayexpress

Discordant cellular response to presurgical letrozole in bilateral synchronous ER+ breast cancers with a KRAS mutation or FGFR1 gene amplification.

Project description: Not available

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Discordant cellular response to pre-surgical letrozole in bilateral synchronous ER+ breast cancers with a KRAS mutation or FGFR1 gene amplification

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Project description:Transcriptome of ER+ breast tumors treated with letrozole were profiled by RNA-seq

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FGFR1 Signature

Project description:The gene encoding fibroblast growth factor receptor 1 (FGFR1) amplification is associated with poor prognosis in estrogen receptor positive (ER+) breast cancer, and thus represents a potential therapeutic target. Fluorescent in situ hybridization (FISH) has been used as the gold standard methodology for detection of FGFR1 amplification, but it is a relatively long labor-intensive procedure and not efficient to process a large number of patient samples, especially formalin fixed paraffin embedded (FFPE) samples. This study sought to identify genes discriminative at the mRNA level for FGFR1 amplification and to construct a multi-gene test to facilitate efficient screening for FGFR1 amplified ER+ breast tumors.

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Project description:Tumorigenic breast cancer cells characterized by high CD44 and low or undetectable CD24 levels (CD44+/CD24-/low) may be resistant to conventional therapies and responsible for cancer relapse. We defined a “signature” expression pattern of hundreds of genes associated with CD44+/CD24-/low, mammosphere-forming cells. In a panel of patient breast tumors, this tumorigenic gene signature was found exclusively manifested in tumors of the recently identified “claudin-low” molecular profile subtype characterized by overexpression of many mesenchymal-associated genes, suggesting that these tumors have pre-existing higher levels of tumorigenic cells. Furthermore, when comparing the expression profiles of paired breast cancer core biopsies before versus after hormone therapy or chemotherapy, both the tumorigenic and “claudin-low” signatures were more active in about half of tumors after treatment, indicative of a greater enrichment of tumorigenic cells as a result of treatments targeting the bulk tumor cells. Keywords: two group comparison

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2017-06-12 | GSE85754 | GEO

Synchronous bilateral warthin tumors: a case report.

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Breast cancer mortality in synchronous bilateral breast cancer patients.

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