Biomaterial Database

Patterns and changes in gene expression following neo-adjuvant anti-estrogen treatment in estrogen receptor-positive breast cancer. 2008

Vera Cappelletti, and Manuela Gariboldi, and Loris De Cecco, and Sara Toffanin, and James F Reid, and Lara Lusa, and Emilio Bajetta, and Luigi Celio, and Marco Greco, and Alessandra Fabbri, and Marco A Pierotti, and Maria Grazia Daidone

Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milano, Italy.

This study aimed to define a gene expression profile associated with response to anti-estrogen treatment in estrogen receptor alpha (ERalpha)-positive breast cancer from elderly patients and to identify possible candidate genes associated with resistance by detecting those modulated by treatment. Using cDNA microarrays containing 16 702 unique clones, 21 pre-treatment and 11 paired post-treatment samples collected in a neo-adjuvant toremifene trial on elderly patients with operable and locally advanced ERalpha-positive breast cancer were profiled. Gene expression profiles generated from pre-treatment samples were correlated with treatment-induced tumor shrinkage and compared with those obtained from post-treatment paired samples to define genes differentially modulated following anti-estrogen treatment. Correlation analysis on 21 pre-treatment samples highlighted 53 genes significantly related to treatment response (P<0.001). Genes involved in cell cycle and proliferation were more frequently upregulated in responders compared with non-responders. Class comparison analysis identified 101 genes significantly modulated independently of treatment response; 82 genes were modulated in non-responders, whereas only 8 genes were differently expressed after treatment in responders. Gene expression profiles appear to be more frequently modulated by anti-estrogen treatment in non-responding patients and may harbor interesting genes possibly involved in anti-estrogen resistance, including clusterin, MAPK6, and MMP2. This concept was corroborated by in vitro studies showing that silencing of CLU restored toremifene sensitivity in the ER anti-estrogen-resistant breast cancer cell line T47D. Integration between neo-adjuvant therapy and transcriptional profiling has therefore the potential to identify therapeutic targets to be challenged for overcoming treatment resistance.

UI	MeSH Term	Description	Entries
D001943	Breast Neoplasms	Tumors or cancer of the human BREAST.	Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368	Aged	A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available.	Elderly
D001706	Biopsy	Removal and pathologic examination of specimens from the living body.	Biopsies
D015972	Gene Expression Regulation, Neoplastic	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.	Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
D017024	Chemotherapy, Adjuvant	Drug therapy given to augment or stimulate some other form of treatment such as surgery or radiation therapy. Adjuvant chemotherapy is commonly used in the therapy of cancer and can be administered before or after the primary treatment.	Adjuvant Chemotherapy,Drug Therapy, Adjuvant,Adjuvant Drug Therapy
D017312	Toremifene	A first generation selective estrogen receptor modulator (SERM). Like TAMOXIFEN, it is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on mammary and uterine tissue.	FC-1157a,Fareston,Toremifene Citrate,Toremifene Citrate (1:1),Toremifene, (E)-Isomer,Citrate, Toremifene,FC 1157a,FC1157a
D047628	Estrogen Receptor alpha	One of the ESTROGEN RECEPTORS that has marked affinity for ESTRADIOL. Its expression and function differs from, and in some ways opposes, ESTROGEN RECEPTOR BETA.	ERalpha,Estradiol Receptor alpha,Estrogen Receptor 1,Estrogen Receptors alpha,Receptor alpha, Estrogen,Receptor alpha, Estradiol,alpha, Estradiol Receptor
D051152	Clusterin	A highly conserved heterodimeric glycoprotein that is differentially expressed during many severe physiological disturbance states such as CANCER; APOPTOSIS; and various NEUROLOGICAL DISORDERS. Clusterin is ubiquitously expressed and appears to function as a secreted MOLECULAR CHAPERONE.	ApoJ Protein,Apolipoprotein J,Complement Lysis Inhibitor,Complement-Associated Protein SP-40,40,Ionizing Radiation-Induced Protein-8,MAC393 Antigen,SGP-2 Protein,SP 40,40 Protein,Sulfated Glycoprotein 2,Sulfated Glycoprotein-2,TRPM-2 Protein,Testosterone-Repressed Prostate Message-2 Protein,X-Ray-Inducible Protein 8,XIP8 Protein,Complement Associated Protein SP 40,40,Ionizing Radiation Induced Protein 8,Radiation-Induced Protein-8, Ionizing,SGP 2 Protein,SP-40,40, Complement-Associated Protein,TRPM 2 Protein,Testosterone Repressed Prostate Message 2 Protein,X Ray Inducible Protein 8