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


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 calibrated model to predict the risk of CBC in women of European-descent; however, prediction accuracy was moderate. Our model shows potential for improved risk counseling, but decision-making regarding contralateral preventive mastectomy, especially in the general breast cancer population where limited information of the mutation status in BRCA1/2 is available, remains challenging.

SUBMITTER: Giardiello D 

PROVIDER: S-EPMC6918633 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Giardiello Daniele D   Steyerberg Ewout W EW   Hauptmann Michael M   Adank Muriel A MA   Akdeniz Delal D   Blomqvist Carl C   Bojesen Stig E SE   Bolla Manjeet K MK   Brinkhuis Mariël M   Chang-Claude Jenny J   Czene Kamila K   Devilee Peter P   Dunning Alison M AM   Easton Douglas F DF   Eccles Diana M DM   Fasching Peter A PA   Figueroa Jonine J   Flyger Henrik H   García-Closas Montserrat M   Haeberle Lothar L   Haiman Christopher A CA   Hall Per P   Hamann Ute U   Hopper John L JL   Jager Agnes A   Jakubowska Anna A   Jung Audrey A   Keeman Renske R   Kramer Iris I   Lambrechts Diether D   Le Marchand Loic L   Lindblom Annika A   Lubiński Jan J   Manoochehri Mehdi M   Mariani Luigi L   Nevanlinna Heli H   Oldenburg Hester S A HSA   Pelders Saskia S   Pharoah Paul D P PDP   Shah Mitul M   Siesling Sabine S   Smit Vincent T H B M VTHBM   Southey Melissa C MC   Tapper William J WJ   Tollenaar Rob A E M RAEM   van den Broek Alexandra J AJ   van Deurzen Carolien H M CHM   van Leeuwen Flora E FE   van Ongeval Chantal C   Van't Veer Laura J LJ   Wang Qin Q   Wendt Camilla C   Westenend Pieter J PJ   Hooning Maartje J MJ   Schmidt Marjanka K MK  

Breast cancer research : BCR 20191217 1


<h4>Background</h4>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.<h4>Methods</h4>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 F  ...[more]

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