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

Author

Giardiello, D, Hauptmann, M, Steyerberg, EW, Adank, MA, Akdeniz, D, Blom, JC, Blomqvist, C, Bojesen, SE, Bolla, MK, Brinkhuis, M, Chang-Claude, J, Czene, K, Devilee, P, Dunning, AM, Easton, DF, Eccles, DM, Fasching, PA, Figueroa, J, Flyger, H, Garcia-Closas, M, Haeberle, L, Haiman, CA, Hall, P, Hamann, U, Hopper, JL, Jager, A, Jakubowska, A, Jung, A, Keeman, R, Koppert, LB, Kramer, I, Lambrechts, D, Le Marchand, L, Lindblom, A, Lubinski, J, Manoochehri, M, Mariani, L, Nevanlinna, H, Oldenburg, HSA, Pelders, S, Pharoah, PDP, Shah, M, Siesling, S, Smit, VTHBM, Southey, MC, Tapper, WJ, Tollenaar, RAEM, van den Broek, AJ, van Deurzen, CHM, van Leeuwen, FE, van Ongeval, C, Van't Veer, LJ, Wang, Q, Wendt, C, Westenend, PJ, Hooning, MJ, Schmidt, MK, Giardiello, D, Hauptmann, M, Steyerberg, EW, Adank, MA, Akdeniz, D, Blom, JC, Blomqvist, C, Bojesen, SE, Bolla, MK, Brinkhuis, M, Chang-Claude, J, Czene, K, Devilee, P, Dunning, AM, Easton, DF, Eccles, DM, Fasching, PA, Figueroa, J, Flyger, H, Garcia-Closas, M, Haeberle, L, Haiman, CA, Hall, P, Hamann, U, Hopper, JL, Jager, A, Jakubowska, A, Jung, A, Keeman, R, Koppert, LB, Kramer, I, Lambrechts, D, Le Marchand, L, Lindblom, A, Lubinski, J, Manoochehri, M, Mariani, L, Nevanlinna, H, Oldenburg, HSA, Pelders, S, Pharoah, PDP, Shah, M, Siesling, S, Smit, VTHBM, Southey, MC, Tapper, WJ, Tollenaar, RAEM, van den Broek, AJ, van Deurzen, CHM, van Leeuwen, FE, van Ongeval, C, Van't Veer, LJ, Wang, Q, Wendt, C, Westenend, PJ, Hooning, MJ, and Schmidt, MK

Abstract

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.

Published
2020

3. The impact of the temporary suspension of national cancer screening programmes due to the COVID-19 epidemic on the diagnosis of breast and colorectal cancer in the Netherlands

Author

Dinmohamed, Avinash, Cellamare, M, Visser, O, de Munck, L, Elferink, MA, Westenend, PJ (Pieter), Wesseling, J, Broeders, MJ, Kuipers, Ernst, Merkx, MAW, Nagtegaal, ID, Siesling, S, Dinmohamed, Avinash, Cellamare, M, Visser, O, de Munck, L, Elferink, MA, Westenend, PJ (Pieter), Wesseling, J, Broeders, MJ, Kuipers, Ernst, Merkx, MAW, Nagtegaal, ID, and Siesling, S

Published
2020

4. Prediction and clinical utility of a contralateral breast cancer risk model

Author

Giardiello, D, Steyerberg, EW, Hauptmann, M, Adank, MA, Akdeniz, D, Blomqvist, C, Bojesen, SE, Bolla, MK, Brinkhuis, M, Chang-Claude, J, Czene, K, Devilee, P, Dunning, AM, Easton, DF, Eccles, DM, Fasching, PA, Figueroa, J, Flyger, H, Garcia-Closas, M, Haeberle, L, Haiman, CA, Hall, P, Hamann, U, Hopper, JL, Jager, A, Jakubowska, A, Jung, A, Keeman, R, Kramer, I, Lambrechts, D, Le Marchand, L, Lindblom, A, Lubinski, J, Manoochehri, M, Mariani, L, Nevanlinna, H, Oldenburg, HSA, Pelders, S, Pharoah, PDP, Shah, M, Siesling, S, Smit, VTHBM, Southey, MC, Tapper, WJ, Tollenaar, RAEM, Van den Broek, AJ, Van Deurzen, CHM, Van Leeuwen, FE, Van Ongeval, C, Van't Veer, LJ, Wang, Q, Wendt, C, Westenend, PJ, Hooning, MJ, Schmidt, MK, Giardiello, D, Steyerberg, EW, Hauptmann, M, Adank, MA, Akdeniz, D, Blomqvist, C, Bojesen, SE, Bolla, MK, Brinkhuis, M, Chang-Claude, J, Czene, K, Devilee, P, Dunning, AM, Easton, DF, Eccles, DM, Fasching, PA, Figueroa, J, Flyger, H, Garcia-Closas, M, Haeberle, L, Haiman, CA, Hall, P, Hamann, U, Hopper, JL, Jager, A, Jakubowska, A, Jung, A, Keeman, R, Kramer, I, Lambrechts, D, Le Marchand, L, Lindblom, A, Lubinski, J, Manoochehri, M, Mariani, L, Nevanlinna, H, Oldenburg, HSA, Pelders, S, Pharoah, PDP, Shah, M, Siesling, S, Smit, VTHBM, Southey, MC, Tapper, WJ, Tollenaar, RAEM, Van den Broek, AJ, Van Deurzen, CHM, Van Leeuwen, FE, Van Ongeval, C, Van't Veer, LJ, Wang, Q, Wendt, C, Westenend, PJ, Hooning, MJ, and Schmidt, MK

Abstract

BACKGROUND: Breast cancer survivors are at risk for contralateral breast cancer (CBC), with the consequent burden of further treatment and potentially less favorable prognosis. We aimed to develop and validate a CBC risk prediction model and evaluate its applicability for clinical decision-making. METHODS: We included data of 132,756 invasive non-metastatic breast cancer patients from 20 studies with 4682 CBC events and a median follow-up of 8.8 years. We developed a multivariable Fine and Gray prediction model (PredictCBC-1A) including patient, primary tumor, and treatment characteristics and BRCA1/2 germline mutation status, accounting for the competing risks of death and distant metastasis. We also developed a model without BRCA1/2 mutation status (PredictCBC-1B) since this information was available for only 6% of patients and is routinely unavailable in the general breast cancer population. Prediction performance was evaluated using calibration and discrimination, calculated by a time-dependent area under the curve (AUC) at 5 and 10 years after diagnosis of primary breast cancer, and an internal-external cross-validation procedure. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. RESULTS: In the multivariable model, BRCA1/2 germline mutation status, family history, and systemic adjuvant treatment showed the strongest associations with CBC risk. The AUC of PredictCBC-1A was 0.63 (95% prediction interval (PI) at 5 years, 0.52-0.74; at 10 years, 0.53-0.72). Calibration-in-the-large was -0.13 (95% PI: -1.62-1.37), and the calibration slope was 0.90 (95% PI: 0.73-1.08). The AUC of Predict-1B at 10 years was 0.59 (95% PI: 0.52-0.66); calibration was slightly lower. Decision curve analysis for preventive contralateral mastectomy showed potential clinical utility of PredictCBC-1A between thresholds of 4-10% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers. CONCLUSIONS: We developed a reasonably c

Published
2019

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