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Transcription profiling of human breast cancer patients treated with Letrozole (Femara) early response to treatment

ABSTRACT: 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. Experiment Overall Design: Biopsies were taken from the same subjects both pretreatment and after 10-14 days Letrozol, 2.5 mg/day, oral.

ORGANISM(S): Homo sapiens

SUBMITTER: Creighton Chad

PROVIDER: S-ECPF-GEOD-10281 | biostudies-other |

REPOSITORIES: biostudies-other

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Transcription profiling of human breast cancer patients treated with 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 âsignatureâ 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 âclaudin-lowâ 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 âclaudin-lowâ 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. Experiment Overall Design: Biopsies were taken from the same subjects both pretreatment and after 10-14 days Letrozol, 2.5 mg/day, oral.

2009-08-22 | E-GEOD-10281 | biostudies-arrayexpress

Transcription profiling of human sequential breast cancer biopsies during letrozole treatment

Project description:In the present investigation, we have exploited the opportunity provided by neoadjuvant treatment of a group of postmenopausal women with large operable or locally advanced breast cancer (in which therapy is given with the primary tumour remaining within the breast) to take sequential biopsies of the same cancers before and after 10-14 days treatment with letrozole. RNA extracted from the biopsies has been subjected to Affymetrix microarray analysis and the data from paired biopsies interrogated to discover genes whose expression is most influenced by oestrogen deprivation. Experiment Overall Design: biopsies were taken from the same subjects both pretreatment and after 10-14 days Letrozol, 2.5 mg/day, oral

| S-ECPF-GEOD-5462 | biostudies-other

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

Letrozole (Femara) early response to treatment

2007-12-10 | GSE5462 | GEO

Bone Quality Test (BQT) scores of fingernails in postmenopausal patients treated with adjuvant letrozole or tamoxifen for early breast cancer.

Project description:BackgroundThe relationship between nail and bone may be measurable, thus making the fingernail a potentially valuable tool for assessing bone health for women receiving treatment for breast cancer. In the BIG 1-98 Fingernail Pilot Substudy, Bone Quality Test (BQT) scores of fingernails were measured at two assessment timepoints.MethodsThirteen eligible patients were enrolled into the substudy during their treatment with tamoxifen (four patients) or letrozole (nine patients). Two fingernails were tested and BQT scores averaged for two assessments six months apart.ResultsBQT scores collected six months later (second assessment) significantly decreased compared with those at first collection (p=0.007) regardless of treatment and prior fracture.ConclusionThe reduction of BQT scores observed in the patients of our small exploratory study during exposure to bone-altering breast cancer treatments is an incentive for larger studies using this technique.

| S-EPMC3588857 | biostudies-literature

Early operable breast cancer in elderly women treated with an aromatase inhibitor letrozole as sole therapy.

Project description:BACKGROUND: Primary endocrine therapy (PET) with aromatase inhibitors (AIs) is an option in elderly patients unfit for or unwilling to undergo surgery. We studied the outcome of patients treated with letrozole as PET. METHODS: Patients with early oestrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer treated with letrozole from February 2001 to September 2009 were reviewed. Inoperable and locally advanced tumours were excluded. Reasons for offering PET, response, survival, cause of death, time to initial and best response, fracture incidence, and late failure rates were studied. RESULTS: In all, 104 patients received PET due to frailty (n=48), comorbidity (n=30), old age (n=9), and patient preference (n=17). Median follow-up was 56 months (4-106). Eighty-five cancers responded to letrozole (stable disease (SD, n=19), reduction in size (PR, n=42), and complete response ((CR), n=24)). Median survival was 51 months (4-103), time to initial response (PR/CR) 4.5 months (2-24), and time to best response 8.5 months (3-50). Letrozole was stopped in 25 patients due to progressive disease (n=19), side effects (n=5), and patient choice (n=1). Only 12 of 49 deaths were from breast cancer. CONCLUSION: Letrozole is a reasonable alternative in elderly women with early ER/PR-positive invasive breast cancer who are unfit or unwilling to undergo standard therapy.

| S-EPMC3251885 | biostudies-other

Assessment of Quality of Life and Safety in Postmenopausal Breast Cancer Patients Receiving Letrozole as an Early Adjuvant Treatment.

Project description:PurposeThere are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer.MethodsSelf-reported quality of life (QoL) scores were serially assessed for 3 years during adjuvant letrozole treatment using the Korean version of the Functional Assessment of Cancer Therapy-Breast questionnaires (version 3). Changes in bone mineral density (BMD) and serum cholesterol levels were also examined.ResultsAll 897 patients received the documented informed consent form and completed a baseline questionnaire before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects, and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer, respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The dropout rate was 16.5%. The serial trial outcome index, the sum of the physical and functional well-being subscales, increased gradually and significantly from baseline during letrozole treatment (p<0.001). The mean serum cholesterol level increased significantly from 199 to 205 after 36 months (p=0.042). The mean BMD significantly decreased from -0.39 at baseline to -0.87 after 36 months (p<0.001).ConclusionQoL gradually improved during letrozole treatment. BMD and serum cholesterol level changes were similar to those in Western countries, indicating that adjuvant letrozole treatment is well tolerated in Korean women, with minimal ethnic variation.

| S-EPMC6015975 | biostudies-literature

Transcription profiling of human sequential breast cancer biopsies during letrozole treatment

2008-06-13 | E-GEOD-5462 | biostudies-arrayexpress

Transcription profiling of human HMLER breast cancer cells treated with paclitaxel and salinomycin-treated HMLER breast cancer cells

Project description:Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs Experiment Overall Design: Experimentally transformed HMLER breast cancer cells were treated in culture with either paclitaxel (10nM) or salinomycin (1uM) for one week. There were three biologic replicates for each treatment condition.

| S-ECPF-GEOD-17215 | biostudies-other

Transcription profiling by array of breast cancer samples treated and non-treated with celecoxib

Project description:Biopsies and surgical specimens were obtained from breast tumours treated and non-treated with celecoxib 400mg twice daily for 2 weeks

| S-ECPF-MTAB-566 | biostudies-other

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