Universität zu Köln

Kast, Karin, Schmutzler, Rita K., Rhiem, Kerstin, Kiechle, Marion, Fischer, Christine, Niederacher, Dieter, Arnold, Norbert ORCID: 0000-0003-4523-8808, Grimm, Tiemo, Speiser, Dorothee, Schlegelberger, Brigitte, Varga, Dominic, Horvath, Judit, Beer, Marit, Briest, Susanne, Meindl, Alfons and Engel, Christoph ORCID: 0000-0002-7247-282X (2014). Validation of the Manchester scoring system for predicting BRCA1/2 mutations in 9,390 families suspected of having hereditary breast and ovarian cancer. Int. J. Cancer, 135 (10). S. 2352 - 2362. HOBOKEN: WILEY-BLACKWELL. ISSN 1097-0215

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Abstract

The Manchester scoring system (MSS) allows the calculation of the probability for the presence of mutations in BRCA1 or BRCA2 genes in families suspected of having hereditary breast and ovarian cancer. In 9,390 families, we determined the predictive performance of the MSS without (MSS-2004) and with (MSS-2009) consideration of pathology parameters. Moreover, we validated a recalibrated version of the MSS-2009 (MSS-recal). Families were included in the registry of the German Consortium for Hereditary Breast and Ovarian Cancer, using defined clinical criteria. Receiver operating characteristics (ROC) analysis was used to determine the predictive performance. The recalibrated model was developed using logistic regression analysis and tested using an independent random validation sample. The area under the ROC curves regarding a mutation in any of the two BRCA genes was 0.77 (95%CI 0.75-0.79) for MSS-2004, 0.80 (95%CI 0.78-0.82) for MSS-2009, and 0.82 (95%CI 0.80-0.83) for MSS-recal. Sensitivity at the 10% mutation probability cutoff was similar for all three models (MSS-2004 92.2%, MSS-2009 92.2%, and MSS-recal 90.3%), but specificity of MSS-recal (46.0%) was considerably higher than that of MSS-2004 (25.4%) and MSS-2009 (32.3%). In the MSS-recal model, almost all predictors of the original MSS were significantly predictive. However, the score values of some predictors, for example, high grade triple negative breast cancers, differed considerably from the originally proposed score values. The original MSS performed well in our sample of high risk families. The use of pathological parameters increased the predictive performance significantly. Recalibration improved the specificity considerably without losing much sensitivity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kast, Karin UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmutzler, Rita K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rhiem, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Kiechle, Marion UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Niederacher, Dieter UNSPECIFIED UNSPECIFIED UNSPECIFIED Arnold, Norbert UNSPECIFIED orcid.org/0000-0003-4523-8808 UNSPECIFIED Grimm, Tiemo UNSPECIFIED UNSPECIFIED UNSPECIFIED Speiser, Dorothee UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlegelberger, Brigitte UNSPECIFIED UNSPECIFIED UNSPECIFIED Varga, Dominic UNSPECIFIED UNSPECIFIED UNSPECIFIED Horvath, Judit UNSPECIFIED UNSPECIFIED UNSPECIFIED Beer, Marit UNSPECIFIED UNSPECIFIED UNSPECIFIED Briest, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Meindl, Alfons UNSPECIFIED UNSPECIFIED UNSPECIFIED Engel, Christoph UNSPECIFIED orcid.org/0000-0002-7247-282X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-423301
DOI:	10.1002/ijc.28875
Journal or Publication Title:	Int. J. Cancer
Volume:	135
Number:	10
Page Range:	S. 2352 - 2362
Date:	2014
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1097-0215
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CARRIER PROBABILITIES; ESTROGEN-RECEPTOR; MODELS; RISK; SUSCEPTIBILITY; POPULATION; BOADICEA; BRCAPRO; INDIVIDUALS; CLINICS Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42330