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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:We describe herein a patient presenting with bilateral estrogen-receptor-positive (ER+) breast tumors who was enrolled in a clinical trial exploring molecular aberrations associated with hormone-refractory tumor cell proliferation. Short-term (two week) hormonal therapy with the aromatase inhibitor letrozole substantially reduced proliferation as measured by Ki67 immunohistochemistry in one tumor, whereas the second was essentially unchanged. Extensive molecular and genetic work-up of the two tumors yielded divergent lesions in the two tumors: an activating KRAS mutation in the responsive tumor and an amplification of the fibroblast growth factor receptor-1 (FGFR1) locus in the treatment-refractory tumor. These findings provide an insight to possible mechanisms of resistance to antiestrogen therapy in ER+ breast cancers. First, they illustrate the necessity of clinically approved assays to identify FGFR1 gene amplification, which occur in approximately 5% of breast tumors and have been linked to antiestrogen resistance. It is quite possible that the addition of FGFR inhibitors to ER-targeted therapy will yield a superior antitumor effect and improved patient outcome. Second, they suggest that the role of activating mutations in RAS, although rare in breast cancer, may need to be explored in the context of ER+ breast tumors.

| S-EPMC3682668 | biostudies-literature

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

| S-ECPF-GEOD-39387 | biostudies-other

RNA sequencing of ER+ breast tumor treated with letrozole

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

2020-07-01 | GSE145325 | GEO

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.

2016-12-31 | GSE77626 | GEO

A Case of Bilateral Synchronous Paratesticular Leiomyoma.

Project description:Bilateral synchronous paratesticular leiomyoma (BSPL) is a rare tumor that originates from smooth muscle cells in the paratesticular region. Four BSPL cases have been reported sporadically, starting with the 1991 report by Aus and Boiesen. Herein, we report the case of a 60-year-old male with a bilateral scrotal mass with a maximum size of 7.5 cm. Histological examination revealed oval to spindle-shaped tumor cells with a fascicular growth pattern. Immunohistochemically, the tumor cells were positive for α-smooth muscle actin. The pathological diagnosis was a leiomyoma. Based on the simultaneous bilateral nature of the disease, BSPL was diagnosed. In conclusion, we encountered a rare case of BSPL, and our report may contribute to the understanding of this disease.

| S-EPMC9938400 | biostudies-literature

Letrozole (Femara) early response to treatment

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

2009-08-15 | GSE10281 | GEO

Gene expression profiling of FGFR1 KO mice

Project description:A novel RCAS-Cre-IRES-PyMT (RCI-PyMT) virus was designed to specifically knockout genes of interest in tumors generated in appropriate mutant mouse hosts. We used this tumor knockout, or TuKO, strategy to concisely ablate fgfr1 in PyMT induced mammary tumors in K19-tva/fgfr1loxP/loxP mice. The similarly injected control K19-tva mice developed mammary tumors exhibiting high metastasis penetration to lung, making this an ideal model for breast cancer metastasis. The fgfr1 TuKO tumors showed significantly decreased primary tumor growth, and most importantly, greatly reduced metastasis to lung. Our study suggests that FGFR1 signaling is a key pathway driving breast cancer lung metastasis and that targeting FGFR1 in breast cancer is an exciting approach to inhibit metastasis.

2017-06-12 | GSE85754 | GEO

Small RNA-seq of breast tumor biopsies prior to treatment with letrozole or letrozole with bevacizumab

Project description:Biopsies were collected from post-menopausal women with ER+ HER2- breast cancer who were subsequently treated with either letrozole or letrozole plus bevacizumab.

2019-12-19 | GSE142308 | GEO

Simultaneous bilateral thoracoscopic lobectomy for synchronous bilateral multiple primary lung cancer-single center experience.

Project description:BackgroundThe aim of this study was to investigate the feasibility and safety of simultaneous bilateral thoracoscopic lobectomy and compare perioperative and late outcomes between simultaneous and staged bilateral thoracoscopic lobectomy.MethodsBetween January 2013 and December 2017, the medical records of patients who underwent bilateral thoracoscopic lobectomy for synchronous bilateral multiple primary lung cancer (SPLC) were reviewed retrospectively. Univariate analysis was used to examine the factors associated with morbidity. Survival was estimated with the Kaplan-Meier method.ResultsIn the simultaneous resection group (n=41) and the staged groups (n=66), 11 and 16 patients underwent postoperative complication, respectively, whereas no significant differences existed between two groups (P=0.850). Univariate analysis showed that preoperative comorbidities (P=0.009), FEV1 <2 L (P=0.001), FEV1% <80% (P=0.036), and the number of pulmonary segments resected ≥9 (P=0.014) were the risk factors to increased simultaneous resection postoperative complication. In addition, simultaneous resection could significantly reduce total cost compared to staged resection (10,854.6±1,998.8 vs. 16,241.4±2,972.8 USD, P<0.001). In long-time outcomes, the patients with simultaneous resection showed better disease-free survival (DFS) than patients with staged resection at 5 years (67.7% vs. 45.9%, P=0.039). In subgroup analysis, simultaneous resection also had a significantly better survival than staged resection in patients with bilateral pure solid lesions or the biggest tumor size >3 cm.ConclusionsBilateral thoracoscopic lobectomy could be a feasible option for SPLC based on appropriate patient selection and careful perioperative management. Meanwhile, simultaneous resection has significantly advantaged in reducing the cost, preventing tumor progression compare to staged resection.

| S-EPMC8024796 | biostudies-literature

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