Gene signature evaluation as a prognostic tool: challenges in the design of the MINDACT trial
The development of the 70-gene prognosis signature for breast cancer was evaluated in the MINDACT (Microarray In Node negative Disease may Avoid ChemoTherapy) trial to assess the clinical relevance of the 70-gene prognosis signature, and how this compares with traditional prognostic factors for assi...
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| Veröffentlicht in: | Nature clinical practice. Oncology 2006-10, Vol.3 (10), p.540-551 |
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| creator | Bogaerts, Jan Cardoso, Fatima Buyse, Marc Braga, Sofia Loi, Sherene Harrison, Jillian A Bines, Jacques Mook, Stella Decker, Nuria Ravdin, Peter Therasse, Patrick Rutgers, Emiel van 't Veer, Laura J Piccart, Martine |
| description | The development of the 70-gene prognosis signature for breast cancer was evaluated in the MINDACT (Microarray In Node negative Disease may Avoid ChemoTherapy) trial to assess the clinical relevance of the 70-gene prognosis signature, and how this compares with traditional prognostic factors for assigning adjuvant chemotherapy for patients with node-negative breast cancer. This review outlines the background work and rationale behind the final design of the MINDACT trial and how these considerations can help to optimize future trials and aim to improve individualization of cancer therapy.
This Review describes the work conducted by the TRANSBIG consortium in the development of the MINDACT (Microarray In Node negative Disease may Avoid ChemoTherapy) trial. The goal of the trial is to provide definitive evidence regarding the clinical relevance of the 70-gene prognosis signature, and to assess the performance of this signature compared with that of traditional prognostic indicators for assigning adjuvant chemotherapy to patients with node-negative breast cancer. We outline the background work and the key questions in node-negative early-stage breast cancer, and then focus on the MINDACT trial design and statistical considerations. The challenges inherent in this trial in terms of logistics, implementation and interpretation of the results are also discussed. We hope that this article will trigger further discussion about the difficulties of setting up and analyzing trials aimed at establishing the worth of new methods for better selection of patients for cancer treatment.
Key Points
In the past 20 years, little progress has been made regarding new prognostic markers that can assist oncologists in treatment decision-making for node-negative early-stage breast cancer
By using gene-expression profiling, the Netherlands Cancer Institute developed a 70-gene prognostic signature for node-negative breast cancer that has now been commercialized. This signature was developed as a dichotomous risk classification for the endpoint of distant metastasis within 5 years and has been retrospectively validated in two series of patients
The MINDACT clinical trial will prospectively validate the 70-gene prognostic signature
Validation of the risk of distant relapse will be assessed through clinicopathologic criteria, using Adjuvant! Online and MammaPrint
®
(Agendia). In case of discordant results, patients will be randomized to treatment decision-making based on clinicopatholog |
| doi_str_mv | 10.1038/ncponc0591 |
| format | Article |
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This Review describes the work conducted by the TRANSBIG consortium in the development of the MINDACT (Microarray In Node negative Disease may Avoid ChemoTherapy) trial. The goal of the trial is to provide definitive evidence regarding the clinical relevance of the 70-gene prognosis signature, and to assess the performance of this signature compared with that of traditional prognostic indicators for assigning adjuvant chemotherapy to patients with node-negative breast cancer. We outline the background work and the key questions in node-negative early-stage breast cancer, and then focus on the MINDACT trial design and statistical considerations. The challenges inherent in this trial in terms of logistics, implementation and interpretation of the results are also discussed. We hope that this article will trigger further discussion about the difficulties of setting up and analyzing trials aimed at establishing the worth of new methods for better selection of patients for cancer treatment.
Key Points
In the past 20 years, little progress has been made regarding new prognostic markers that can assist oncologists in treatment decision-making for node-negative early-stage breast cancer
By using gene-expression profiling, the Netherlands Cancer Institute developed a 70-gene prognostic signature for node-negative breast cancer that has now been commercialized. This signature was developed as a dichotomous risk classification for the endpoint of distant metastasis within 5 years and has been retrospectively validated in two series of patients
The MINDACT clinical trial will prospectively validate the 70-gene prognostic signature
Validation of the risk of distant relapse will be assessed through clinicopathologic criteria, using Adjuvant! Online and MammaPrint
®
(Agendia). In case of discordant results, patients will be randomized to treatment decision-making based on clinicopathologic risk or genomic risk
Two further randomizations will be possible in the MINDACT trial: randomization to chemotherapy, based on anthracycline-based regimens, and randomization to endocrine therapy, based on the outcome of 2 years of tamoxifen followed by 5 years of letrozole, compared with 7 years of letrozole</description><identifier>ISSN: 1743-4254</identifier><identifier>ISSN: 1759-4774</identifier><identifier>EISSN: 1743-4262</identifier><identifier>EISSN: 1759-4782</identifier><identifier>DOI: 10.1038/ncponc0591</identifier><identifier>PMID: 17019432</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adjuvant treatment ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - genetics ; Breast Neoplasms - surgery ; Cancer ; Care and treatment ; Chemotherapy, Adjuvant ; Diagnosis ; Endpoint Determination ; Female ; Gene Expression Profiling ; Health aspects ; Humans ; Medicine ; Medicine & Public Health ; Multicenter Studies as Topic ; Oligonucleotide Array Sequence Analysis ; Oncologists ; Oncology ; Practice ; Prognosis ; Psychological aspects ; Randomized Controlled Trials as Topic ; Research Design ; review-article ; Risk factors ; Sample Size</subject><ispartof>Nature clinical practice. Oncology, 2006-10, Vol.3 (10), p.540-551</ispartof><rights>Springer Nature Limited 2006</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Oct 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-237940e80e365add7946764f892964b67a510d1589ebfc7af2aa40cdc8a3f9a3</citedby><cites>FETCH-LOGICAL-c416t-237940e80e365add7946764f892964b67a510d1589ebfc7af2aa40cdc8a3f9a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17019432$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bogaerts, Jan</creatorcontrib><creatorcontrib>Cardoso, Fatima</creatorcontrib><creatorcontrib>Buyse, Marc</creatorcontrib><creatorcontrib>Braga, Sofia</creatorcontrib><creatorcontrib>Loi, Sherene</creatorcontrib><creatorcontrib>Harrison, Jillian A</creatorcontrib><creatorcontrib>Bines, Jacques</creatorcontrib><creatorcontrib>Mook, Stella</creatorcontrib><creatorcontrib>Decker, Nuria</creatorcontrib><creatorcontrib>Ravdin, Peter</creatorcontrib><creatorcontrib>Therasse, Patrick</creatorcontrib><creatorcontrib>Rutgers, Emiel</creatorcontrib><creatorcontrib>van 't Veer, Laura J</creatorcontrib><creatorcontrib>Piccart, Martine</creatorcontrib><creatorcontrib>TRANSBIG consortium</creatorcontrib><title>Gene signature evaluation as a prognostic tool: challenges in the design of the MINDACT trial</title><title>Nature clinical practice. Oncology</title><addtitle>Nat Rev Clin Oncol</addtitle><addtitle>Nat Clin Pract Oncol</addtitle><description>The development of the 70-gene prognosis signature for breast cancer was evaluated in the MINDACT (Microarray In Node negative Disease may Avoid ChemoTherapy) trial to assess the clinical relevance of the 70-gene prognosis signature, and how this compares with traditional prognostic factors for assigning adjuvant chemotherapy for patients with node-negative breast cancer. This review outlines the background work and rationale behind the final design of the MINDACT trial and how these considerations can help to optimize future trials and aim to improve individualization of cancer therapy.
This Review describes the work conducted by the TRANSBIG consortium in the development of the MINDACT (Microarray In Node negative Disease may Avoid ChemoTherapy) trial. The goal of the trial is to provide definitive evidence regarding the clinical relevance of the 70-gene prognosis signature, and to assess the performance of this signature compared with that of traditional prognostic indicators for assigning adjuvant chemotherapy to patients with node-negative breast cancer. We outline the background work and the key questions in node-negative early-stage breast cancer, and then focus on the MINDACT trial design and statistical considerations. The challenges inherent in this trial in terms of logistics, implementation and interpretation of the results are also discussed. We hope that this article will trigger further discussion about the difficulties of setting up and analyzing trials aimed at establishing the worth of new methods for better selection of patients for cancer treatment.
Key Points
In the past 20 years, little progress has been made regarding new prognostic markers that can assist oncologists in treatment decision-making for node-negative early-stage breast cancer
By using gene-expression profiling, the Netherlands Cancer Institute developed a 70-gene prognostic signature for node-negative breast cancer that has now been commercialized. This signature was developed as a dichotomous risk classification for the endpoint of distant metastasis within 5 years and has been retrospectively validated in two series of patients
The MINDACT clinical trial will prospectively validate the 70-gene prognostic signature
Validation of the risk of distant relapse will be assessed through clinicopathologic criteria, using Adjuvant! Online and MammaPrint
®
(Agendia). In case of discordant results, patients will be randomized to treatment decision-making based on clinicopathologic risk or genomic risk
Two further randomizations will be possible in the MINDACT trial: randomization to chemotherapy, based on anthracycline-based regimens, and randomization to endocrine therapy, based on the outcome of 2 years of tamoxifen followed by 5 years of letrozole, compared with 7 years of letrozole</description><subject>Adjuvant treatment</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - surgery</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Chemotherapy, Adjuvant</subject><subject>Diagnosis</subject><subject>Endpoint Determination</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Multicenter Studies as Topic</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Oncologists</subject><subject>Oncology</subject><subject>Practice</subject><subject>Prognosis</subject><subject>Psychological aspects</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Research Design</subject><subject>review-article</subject><subject>Risk factors</subject><subject>Sample Size</subject><issn>1743-4254</issn><issn>1759-4774</issn><issn>1743-4262</issn><issn>1759-4782</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkU1vEzEQhi0EoqVw4QcgS0gcilLstdfe7S1KoVQqcMkVrSbecerKsYPtReLf4zQR4Us-2GM_887rGUJecnbBmejeBbONwbC254_IKddSzGSjmse_zq08Ic9yvmdMaC3ZU3LCNeO9FM0p-XqNAWl26wBlSkjxO_gJiouBQqZAtymuQ8zFGVpi9JfU3IH3GNaYqQu03CEdcZdOo32IPt18vpovlrQkB_45eWLBZ3xx2M_I8sP75eLj7PbL9c1ifjszkqsya4TuJcOOoVAtjGONlFbSdn3TK7lSGlrORt52Pa6s0WAbAMnMaDoQtgdxRt7sZavbbxPmMmxcNug9BIxTHlQV6nTTVfD1X-B9nFKo1obayb52rVo5UmvwOLhgY0lgdpLDnHdCKMkeqIv_UHWNuHEmBrSu3v-RcL5PMCnmnNAO2-Q2kH7U2rvy3XAcZIVfHZxOqw2OR_QwuQq83QO5PtVxpN-_8o_cT6SLpac</recordid><startdate>20061001</startdate><enddate>20061001</enddate><creator>Bogaerts, Jan</creator><creator>Cardoso, Fatima</creator><creator>Buyse, Marc</creator><creator>Braga, Sofia</creator><creator>Loi, Sherene</creator><creator>Harrison, Jillian A</creator><creator>Bines, Jacques</creator><creator>Mook, Stella</creator><creator>Decker, Nuria</creator><creator>Ravdin, Peter</creator><creator>Therasse, Patrick</creator><creator>Rutgers, Emiel</creator><creator>van 't Veer, Laura J</creator><creator>Piccart, Martine</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20061001</creationdate><title>Gene signature evaluation as a prognostic tool: challenges in the design of the MINDACT trial</title><author>Bogaerts, Jan ; Cardoso, Fatima ; Buyse, Marc ; Braga, Sofia ; Loi, Sherene ; Harrison, Jillian A ; Bines, Jacques ; Mook, Stella ; Decker, Nuria ; Ravdin, Peter ; Therasse, Patrick ; Rutgers, Emiel ; van 't Veer, Laura J ; Piccart, Martine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-237940e80e365add7946764f892964b67a510d1589ebfc7af2aa40cdc8a3f9a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adjuvant treatment</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - surgery</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>Chemotherapy, Adjuvant</topic><topic>Diagnosis</topic><topic>Endpoint Determination</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Multicenter Studies as Topic</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Oncologists</topic><topic>Oncology</topic><topic>Practice</topic><topic>Prognosis</topic><topic>Psychological aspects</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Research Design</topic><topic>review-article</topic><topic>Risk factors</topic><topic>Sample Size</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bogaerts, Jan</creatorcontrib><creatorcontrib>Cardoso, Fatima</creatorcontrib><creatorcontrib>Buyse, Marc</creatorcontrib><creatorcontrib>Braga, Sofia</creatorcontrib><creatorcontrib>Loi, Sherene</creatorcontrib><creatorcontrib>Harrison, Jillian A</creatorcontrib><creatorcontrib>Bines, Jacques</creatorcontrib><creatorcontrib>Mook, Stella</creatorcontrib><creatorcontrib>Decker, Nuria</creatorcontrib><creatorcontrib>Ravdin, Peter</creatorcontrib><creatorcontrib>Therasse, Patrick</creatorcontrib><creatorcontrib>Rutgers, Emiel</creatorcontrib><creatorcontrib>van 't Veer, Laura J</creatorcontrib><creatorcontrib>Piccart, Martine</creatorcontrib><creatorcontrib>TRANSBIG consortium</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Nature clinical practice. Oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bogaerts, Jan</au><au>Cardoso, Fatima</au><au>Buyse, Marc</au><au>Braga, Sofia</au><au>Loi, Sherene</au><au>Harrison, Jillian A</au><au>Bines, Jacques</au><au>Mook, Stella</au><au>Decker, Nuria</au><au>Ravdin, Peter</au><au>Therasse, Patrick</au><au>Rutgers, Emiel</au><au>van 't Veer, Laura J</au><au>Piccart, Martine</au><aucorp>TRANSBIG consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gene signature evaluation as a prognostic tool: challenges in the design of the MINDACT trial</atitle><jtitle>Nature clinical practice. Oncology</jtitle><stitle>Nat Rev Clin Oncol</stitle><addtitle>Nat Clin Pract Oncol</addtitle><date>2006-10-01</date><risdate>2006</risdate><volume>3</volume><issue>10</issue><spage>540</spage><epage>551</epage><pages>540-551</pages><issn>1743-4254</issn><issn>1759-4774</issn><eissn>1743-4262</eissn><eissn>1759-4782</eissn><abstract>The development of the 70-gene prognosis signature for breast cancer was evaluated in the MINDACT (Microarray In Node negative Disease may Avoid ChemoTherapy) trial to assess the clinical relevance of the 70-gene prognosis signature, and how this compares with traditional prognostic factors for assigning adjuvant chemotherapy for patients with node-negative breast cancer. This review outlines the background work and rationale behind the final design of the MINDACT trial and how these considerations can help to optimize future trials and aim to improve individualization of cancer therapy.
This Review describes the work conducted by the TRANSBIG consortium in the development of the MINDACT (Microarray In Node negative Disease may Avoid ChemoTherapy) trial. The goal of the trial is to provide definitive evidence regarding the clinical relevance of the 70-gene prognosis signature, and to assess the performance of this signature compared with that of traditional prognostic indicators for assigning adjuvant chemotherapy to patients with node-negative breast cancer. We outline the background work and the key questions in node-negative early-stage breast cancer, and then focus on the MINDACT trial design and statistical considerations. The challenges inherent in this trial in terms of logistics, implementation and interpretation of the results are also discussed. We hope that this article will trigger further discussion about the difficulties of setting up and analyzing trials aimed at establishing the worth of new methods for better selection of patients for cancer treatment.
Key Points
In the past 20 years, little progress has been made regarding new prognostic markers that can assist oncologists in treatment decision-making for node-negative early-stage breast cancer
By using gene-expression profiling, the Netherlands Cancer Institute developed a 70-gene prognostic signature for node-negative breast cancer that has now been commercialized. This signature was developed as a dichotomous risk classification for the endpoint of distant metastasis within 5 years and has been retrospectively validated in two series of patients
The MINDACT clinical trial will prospectively validate the 70-gene prognostic signature
Validation of the risk of distant relapse will be assessed through clinicopathologic criteria, using Adjuvant! Online and MammaPrint
®
(Agendia). In case of discordant results, patients will be randomized to treatment decision-making based on clinicopathologic risk or genomic risk
Two further randomizations will be possible in the MINDACT trial: randomization to chemotherapy, based on anthracycline-based regimens, and randomization to endocrine therapy, based on the outcome of 2 years of tamoxifen followed by 5 years of letrozole, compared with 7 years of letrozole</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>17019432</pmid><doi>10.1038/ncponc0591</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
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| source | MEDLINE; Springer Journals; Springer Nature - Connect here FIRST to enable access |
| subjects | Adjuvant treatment Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - genetics Breast Neoplasms - surgery Cancer Care and treatment Chemotherapy, Adjuvant Diagnosis Endpoint Determination Female Gene Expression Profiling Health aspects Humans Medicine Medicine & Public Health Multicenter Studies as Topic Oligonucleotide Array Sequence Analysis Oncologists Oncology Practice Prognosis Psychological aspects Randomized Controlled Trials as Topic Research Design review-article Risk factors Sample Size |
| title | Gene signature evaluation as a prognostic tool: challenges in the design of the MINDACT trial |
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