TY - JOUR
T1 - Long-term prognosis of young breastcancer patients (≤40 years) who did not receive adjuvant systemic treatment
T2 - protocol for the PARADIGM initiative cohort study
AU - Dackus, Gwen M. H. E.
AU - ter Hoeve, Natalie D.
AU - Opdam, Mark
AU - Vreuls, Willem
AU - Varga, Zsuzsanna
AU - Koop, Esther
AU - Willems, Stefan M.
AU - Van Deurzen, Carolien H. M.
AU - Groen, Emilie J.
AU - Cordoba, Alicia
AU - Bart, Jos
AU - Mooyaart, Antien L.
AU - van den Tweel, Jan G.
AU - Zolota, Vicky
AU - Wesseling, Jelle
AU - Sapino, Anna
AU - Chmielik, Ewa
AU - Ryska, Ales
AU - Amant, Frederic
AU - Broeks, Annegien
AU - Kerkhoven, Ron
AU - Stathonikos, Nikolas
AU - Veta, Mitko
AU - Voogd, Adri
AU - Jozwiak, Katarzyna
AU - Hauptmann, Michael
AU - Hoogstraat, Marlous
AU - Schmidt, Marjanka K.
AU - Sonke, Gabe
AU - van der Wall, Elsken
AU - Siesling, Sabine
AU - van Diest, Paul J.
AU - Linn, Sabine C.
PY - 2017/11
Y1 - 2017/11
N2 - Introduction Currently used tools for breast cancer prognostication and prediction may not adequately reflect a young patient's prognosis or likely treatment benefit because they were not adequately validated in young patients. Since breast cancers diagnosed at a young age are considered prognostically unfavourable, many treatment guidelines recommend adjuvant systemic treatment for all young patients. Patients cured by locoregional treatment alone are, therefore, overtreated. Lack of prognosticators for young breast cancer patients represents an unmet medical need and has led to the initiation of the PAtients with bReAst cancer DIaGnosed preMenopausally (PARADIGM) initiative. Our aim is to reduce overtreatment of women diagnosed with breast cancer agedMethods and analysis All young, adjuvant systemic treatment naive breast cancer patients, who had no prior malignancy and were diagnosed between 1989 and 2000, were identified using the population based Netherlands Cancer Registry (n=3525). Archival tumour tissues were retrieved through linkage with the Dutch nationwide pathology registry. Tissue slides will be digitalised and placed on an online image database platform for clinicopathological revision by an international team of breast pathologists. Immunohistochemical subtype will be assessed using tissue microarrays. Tumour RNA will be isolated and subjected to next-generation sequencing. Differences in gene expression found between patients with a favourable and those with a less favourable prognosis will be used to establish a prognostic classifier, using the triple negative patients as proof of principle.Ethics and dissemination Observational data from the Netherlands Cancer Registry and left over archival patient material are used. Therefore, the Dutch law on Research Involving Human Subjects Act (WMO) is not applicable. The PARADIGM study received a 'non-WMO' declaration from the Medical Ethics Committee of the Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, waiving individual patient consent. All data and material used are stored in a coded way. Study results will be presented at international (breast cancer) conferences and published in peer-reviewed, open-access journals.
AB - Introduction Currently used tools for breast cancer prognostication and prediction may not adequately reflect a young patient's prognosis or likely treatment benefit because they were not adequately validated in young patients. Since breast cancers diagnosed at a young age are considered prognostically unfavourable, many treatment guidelines recommend adjuvant systemic treatment for all young patients. Patients cured by locoregional treatment alone are, therefore, overtreated. Lack of prognosticators for young breast cancer patients represents an unmet medical need and has led to the initiation of the PAtients with bReAst cancer DIaGnosed preMenopausally (PARADIGM) initiative. Our aim is to reduce overtreatment of women diagnosed with breast cancer agedMethods and analysis All young, adjuvant systemic treatment naive breast cancer patients, who had no prior malignancy and were diagnosed between 1989 and 2000, were identified using the population based Netherlands Cancer Registry (n=3525). Archival tumour tissues were retrieved through linkage with the Dutch nationwide pathology registry. Tissue slides will be digitalised and placed on an online image database platform for clinicopathological revision by an international team of breast pathologists. Immunohistochemical subtype will be assessed using tissue microarrays. Tumour RNA will be isolated and subjected to next-generation sequencing. Differences in gene expression found between patients with a favourable and those with a less favourable prognosis will be used to establish a prognostic classifier, using the triple negative patients as proof of principle.Ethics and dissemination Observational data from the Netherlands Cancer Registry and left over archival patient material are used. Therefore, the Dutch law on Research Involving Human Subjects Act (WMO) is not applicable. The PARADIGM study received a 'non-WMO' declaration from the Medical Ethics Committee of the Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, waiving individual patient consent. All data and material used are stored in a coded way. Study results will be presented at international (breast cancer) conferences and published in peer-reviewed, open-access journals.
KW - GENE-EXPRESSION
KW - WOMEN
KW - AGE
KW - RECURRENCE
KW - DIAGNOSIS
KW - PATTERNS
KW - SUBTYPES
U2 - 10.1136/bmjopen-2017-017842
DO - 10.1136/bmjopen-2017-017842
M3 - Article
C2 - 29138205
VL - 7
JO - BMJ Open
JF - BMJ Open
SN - 2044-6055
IS - 11
M1 - 017842
ER -