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A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

Terry, Kathryn L; Schock, Helena; Fortner, Renée T; Hüsing, Anika; Fichorova, Raina N; Yamamoto, Hidemi S; Vitonis, Allison F; Johnson, Theron; Overvad, Kim and Tjønneland, Anne, et al. (2016) In Clinical Cancer Research
Abstract

PURPOSE: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

EXPERIMENTAL DESIGN: We measured CA125, HE4, CA72.4 and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity... (More)

PURPOSE: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

EXPERIMENTAL DESIGN: We measured CA125, HE4, CA72.4 and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as Area under the Receiver Operator Curve (C-statistic) for each marker individually and in combination. Additionally, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis.

RESULTS: We observed the best discrimination between cases and controls within six months of diagnosis for CA125 (C-statistic=0.92), HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker.

CONCLUSIONS: CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early stage cases.

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Clinical Cancer Research
publisher
American Association for Cancer Research
external identifiers
  • Scopus:84990062718
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-16-0316
language
English
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yes
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e91031e6-db61-4003-a924-49c959297fc3
date added to LUP
2016-05-03 15:12:47
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2016-11-06 04:37:24
@misc{e91031e6-db61-4003-a924-49c959297fc3,
  abstract     = {<p>PURPOSE: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.</p><p>EXPERIMENTAL DESIGN: We measured CA125, HE4, CA72.4 and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as Area under the Receiver Operator Curve (C-statistic) for each marker individually and in combination. Additionally, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis.</p><p>RESULTS: We observed the best discrimination between cases and controls within six months of diagnosis for CA125 (C-statistic=0.92), HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker.</p><p>CONCLUSIONS: CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early stage cases.</p>},
  author       = {Terry, Kathryn L and Schock, Helena and Fortner, Renée T and Hüsing, Anika and Fichorova, Raina N and Yamamoto, Hidemi S and Vitonis, Allison F and Johnson, Theron and Overvad, Kim and Tjønneland, Anne and Boutron-Ruault, Marie-Christine and Mesrine, Sylvie and Severi, Gianluca and Dossus, Laure and Rinaldi, Sabina and Boeing, Heiner and Benetou, Vassiliki and Lagiou, Pagona and Trichopoulou, Antonia and Krogh, Vittorio and Kuhn, Elisabetta and Panico, Salvatore and Bueno-de-Mesquita, H Bas and Onland-Moret, N Charlotte and Peeters, Petra H and Gram, Inger Torhild and Weiderpass, Elisabete and Duell, Eric J and Sanchez, Maria-Jose and Ardanaz, Eva and Etxezarreta, Nerea and Navarro, Carmen and Idahl, Annika and Lundin, Eva and Jirström, Karin and Manjer, Jonas and Wareham, Nicholas J and Khaw, Kay-Tee and Smith Byrne, Karl and Travis, Ruth C and Gunter, Marc J and Merritt, Melissa A and Riboli, Elio and Cramer, Daniel and Kaaks, Rudolf},
  issn         = {1078-0432},
  language     = {eng},
  month        = {04},
  publisher    = {ARRAY(0x911fda8)},
  series       = {Clinical Cancer Research},
  title        = {A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-16-0316},
  year         = {2016},
}