Gene expression profiling spares early breast cancer patients from adjuvant therapy: derived and validated in two population-based cohorts

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Fältnamn	Indikatorer	Metadata
000		05234naa a2200793 4500
001		oai:DiVA.org:uu-76645
003		SwePub
008		060626s2005 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:prod.swepub.kib.ki.se:1937140
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-766452 URI
024	7	a https://doi.org/10.1186/bcr13252 DOI
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:19371402 URI
040		a (SwePub)uud (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Pawitan, Yudiu Karolinska Institutet4 aut
245	1 0	a Gene expression profiling spares early breast cancer patients from adjuvant therapy :b derived and validated in two population-based cohorts
264		c 2005-10-03
264	1	b Springer Science and Business Media LLC,c 2005
338		a print2 rdacarrier
520		a INTRODUCTION: Adjuvant breast cancer therapy significantly improves survival, but overtreatment and undertreatment are major problems. Breast cancer expression profiling has so far mainly been used to identify women with a poor prognosis as candidates for adjuvant therapy but without demonstrated value for therapy prediction. METHODS: We obtained the gene expression profiles of 159 population-derived breast cancer patients, and used hierarchical clustering to identify the signature associated with prognosis and impact of adjuvant therapies, defined as distant metastasis or death within 5 years. Independent datasets of 76 treated population-derived Swedish patients, 135 untreated population-derived Swedish patients and 78 Dutch patients were used for validation. The inclusion and exclusion criteria for the studies of population-derived Swedish patients were defined. RESULTS: Among the 159 patients, a subset of 64 genes was found to give an optimal separation of patients with good and poor outcomes. Hierarchical clustering revealed three subgroups: patients who did well with therapy, patients who did well without therapy, and patients that failed to benefit from given therapy. The expression profile gave significantly better prognostication (odds ratio, 4.19; P = 0.007) (breast cancer end-points odds ratio, 10.64) compared with the Elston-Ellis histological grading (odds ratio of grade 2 vs 1 and grade 3 vs 1, 2.81 and 3.32 respectively; P = 0.24 and 0.16), tumor stage (odds ratio of stage 2 vs 1 and stage 3 vs 1, 1.11 and 1.28; P = 0.83 and 0.68) and age (odds ratio, 0.11; P = 0.55). The risk groups were consistent and validated in the independent Swedish and Dutch data sets used with 211 and 78 patients, respectively. CONCLUSION: We have identified discriminatory gene expression signatures working both on untreated and systematically treated primary breast cancer patients with the potential to spare them from adjuvant therapy.
653		a Adult
653		a Aged
653		a Breast Neoplasms/drug therapy/genetics/surgery
653		a Chemotherapy; Adjuvant
653		a Cohort Studies
653		a Female
653		a Gene Expression Profiling
653		a Genes; Neoplasm
653		a Humans
653		a Middle Aged
653		a Neoplasm Metastasis
653		a Netherlands
653		a Odds Ratio
653		a Prognosis
653		a Research Support; Non-U.S. Gov't
653		a Survival Analysis
653		a Sweden
653		a Treatment Outcome
653		a MEDICINE
653		a MEDICIN
700	1	a Bjöhle, Judithu Karolinska Institutet4 aut
700	1	a Amler, Lukas4 aut
700	1	a Borg, Anna-Lena4 aut
700	1	a Egyhazi, Suzanneu Karolinska Institutet4 aut
700	1	a Hall, Peru Karolinska Institutet4 aut
700	1	a Han, Xia4 aut
700	1	a Holmberg, Larsu Uppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi,Gastrointestinal Surgery4 aut0 (Swepub:uu)larsholmb
700	1	a Huang, Fei4 aut
700	1	a Klaar, Sigrid4 aut
700	1	a Liu, Edison T.4 aut
700	1	a Miller, Lance4 aut
700	1	a Nordgren, Hansu Uppsala universitet,Institutionen för genetik och patologi4 aut0 (Swepub:uu)hansnordg
700	1	a Ploner, Alexanderu Karolinska Institutet4 aut
700	1	a Sandelin, Kerstinu Karolinska Institutet4 aut
700	1	a Shaw, Peter M.4 aut
700	1	a Smeds, Johannau Karolinska Institutet4 aut
700	1	a Skoog, Lambertu Karolinska Institutet4 aut
700	1	a Wedrén, Sarau Karolinska Institutet4 aut
700	1	a Bergh, Jonasu Karolinska Institutet4 aut
710	2	a Karolinska Institutetb Institutionen för kirurgiska vetenskaper4 org
773	0	t Breast cancer research : BCRd : Springer Science and Business Media LLCg 7:6, s. R953-64q 7:6<R953-64x 1465-5411x 1465-542X
856	4	u http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=16280042&dopt=Citation
856	4	u https://breast-cancer-research.biomedcentral.com/track/pdf/10.1186/bcr1325
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-76645
856	4 8	u https://doi.org/10.1186/bcr1325
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:1937140

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