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Prediction of contralateral breast cancer: external validation of risk calculators in 20 international cohorts

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


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  • Daniele Giardiello
  • Michael Hauptmann
  • Ewout W Steyerberg
  • Muriel A Adank
  • Delal Akdeniz
  • Jannet C Blom
  • Carl Blomqvist
  • Stig E Bojesen
  • Manjeet K Bolla
  • Mariël Brinkhuis
  • Jenny Chang-Claude
  • Kamila Czene
  • Peter Devilee
  • Alison M Dunning
  • Douglas F Easton
  • Diana M Eccles
  • Peter A Fasching
  • Jonine Figueroa
  • Henrik Flyger
  • Montserrat García-Closas
  • Lothar Haeberle
  • Christopher A Haiman
  • Per Hall
  • Ute Hamann
  • John L Hopper
  • Agnes Jager
  • Anna Jakubowska
  • Audrey Jung
  • Renske Keeman
  • Linetta B Koppert
  • Iris Kramer
  • Diether Lambrechts
  • Loic Le Marchand
  • Annika Lindblom
  • Jan Lubiński
  • Mehdi Manoochehri
  • Luigi Mariani
  • Heli Nevanlinna
  • Hester S A Oldenburg
  • Saskia Pelders
  • Paul D P Pharoah
  • Mitul Shah
  • Sabine Siesling
  • Vincent T H B M Smit
  • Melissa C Southey
  • William J Tapper
  • Rob A E M Tollenaar
  • Alexandra J van den Broek
  • Carolien H M van Deurzen
  • Flora E van Leeuwen
  • Chantal van Ongeval
  • Laura J Van't Veer
  • Qin Wang
  • Camilla Wendt
  • Pieter J Westenend
  • Maartje J Hooning
  • Marjanka K Schmidt
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BACKGROUND: Three tools are currently available to predict the risk of contralateral breast cancer (CBC). We aimed to compare the performance of the Manchester formula, CBCrisk, and PredictCBC in patients with invasive breast cancer (BC).

METHODS: We analyzed data of 132,756 patients (4682 CBC) from 20 international studies with a median follow-up of 8.8 years. Prediction performance included discrimination, quantified as a time-dependent Area-Under-the-Curve (AUC) at 5 and 10 years after diagnosis of primary BC, and calibration, quantified as the expected-observed (E/O) ratio at 5 and 10 years and the calibration slope.

RESULTS: The AUC at 10 years was: 0.58 (95% confidence intervals [CI] 0.57-0.59) for CBCrisk; 0.60 (95% CI 0.59-0.61) for the Manchester formula; 0.63 (95% CI 0.59-0.66) and 0.59 (95% CI 0.56-0.62) for PredictCBC-1A (for settings where BRCA1/2 mutation status is available) and PredictCBC-1B (for the general population), respectively. The E/O at 10 years: 0.82 (95% CI 0.51-1.32) for CBCrisk; 1.53 (95% CI 0.63-3.73) for the Manchester formula; 1.28 (95% CI 0.63-2.58) for PredictCBC-1A and 1.35 (95% CI 0.65-2.77) for PredictCBC-1B. The calibration slope was 1.26 (95% CI 1.01-1.50) for CBCrisk; 0.90 (95% CI 0.79-1.02) for PredictCBC-1A; 0.81 (95% CI 0.63-0.99) for PredictCBC-1B, and 0.39 (95% CI 0.34-0.43) for the Manchester formula.

CONCLUSIONS: Current CBC risk prediction tools provide only moderate discrimination and the Manchester formula was poorly calibrated. Better predictors and re-calibration are needed to improve CBC prediction and to identify low- and high-CBC risk patients for clinical decision-making.

TidsskriftBreast Cancer Research and Treatment
Udgave nummer2
Sider (fra-til)423-434
Antal sider12
StatusUdgivet - jun. 2020

ID: 61975528