Author:
Giardiello Daniele,Hooning Maartje J.,Hauptmann Michael,Keeman Renske,Heemskerk-Gerritsen B. A. M.,Becher Heiko,Blomqvist Carl,Bojesen Stig E.,Bolla Manjeet K.,Camp Nicola J.,Czene Kamila,Devilee Peter,Eccles Diana M.,Fasching Peter A.,Figueroa Jonine D.,Flyger Henrik,García-Closas Montserrat,Haiman Christopher A.,Hamann Ute,Hopper John L.,Jakubowska Anna,Leeuwen Floor E.,Lindblom Annika,Lubiński Jan,Margolin Sara,Martinez Maria Elena,Nevanlinna Heli,Nevelsteen Ines,Pelders Saskia,Pharoah Paul D. P.,Siesling Sabine,Southey Melissa C.,van der Hout Annemieke H.,van Hest Liselotte P.,Chang-Claude Jenny,Hall Per,Easton Douglas F.,Steyerberg Ewout W.,Schmidt Marjanka K.
Abstract
Abstract
Background
Prediction of contralateral breast cancer (CBC) risk is challenging due to moderate performances of the known risk factors. We aimed to improve our previous risk prediction model (PredictCBC) by updated follow-up and including additional risk factors.
Methods
We included data from 207,510 invasive breast cancer patients participating in 23 studies. In total, 8225 CBC events occurred over a median follow-up of 10.2 years. In addition to the previously included risk factors, PredictCBC-2.0 included CHEK2 c.1100delC, a 313 variant polygenic risk score (PRS-313), body mass index (BMI), and parity. Fine and Gray regression was used to fit the model. Calibration and a time-dependent area under the curve (AUC) at 5 and 10 years were assessed to determine the performance of the models. Decision curve analysis was performed to evaluate the net benefit of PredictCBC-2.0 and previous PredictCBC models.
Results
The discrimination of PredictCBC-2.0 at 10 years was higher than PredictCBC with an AUC of 0.65 (95% prediction intervals (PI) 0.56–0.74) versus 0.63 (95%PI 0.54–0.71). PredictCBC-2.0 was well calibrated with an observed/expected ratio at 10 years of 0.92 (95%PI 0.34–2.54). Decision curve analysis for contralateral preventive mastectomy (CPM) showed the potential clinical utility of PredictCBC-2.0 between thresholds of 4 and 12% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers.
Conclusions
Additional genetic information beyond BRCA1/2 germline mutations improved CBC risk prediction and might help tailor clinical decision-making toward CPM or alternative preventive strategies. Identifying patients who benefit from CPM, especially in the general breast cancer population, remains challenging.
Publisher
Springer Science and Business Media LLC
Reference74 articles.
1. Chen Y, Thompson W, Semenciw R, Mao Y. Epidemiology of contralateral breast cancer. Cancer Epidemiol Biomarkers Prev. 1999;8(10):855–61.
2. Gao X, Fisher SG, Emami B. Risk of second primary cancer in the contralateral breast in women treated for early-stage breast cancer: a population-based study. Int J Radiat Oncol Biol Phys. 2003;56(4):1038–45.
3. Curtis RE, Ron E, Hankey BF, Hoover RN. New malignancies following breast cancer. In: New malignancies among cancer survivors: SEER Cancer Registries, 1973–2000; 181–205.
4. Yu GP, Schantz SP, Neugut AI, Zhang ZF. Incidences and trends of second cancers in female breast cancer patients: a fixed inception cohort-based analysis (United States). Cancer Causes Control. 2006;17(4):411–20.
5. Soerjomataram I, Louwman WJ, Lemmens VE, de Vries E, Klokman WJ, Coebergh JW. Risks of second primary breast and urogenital cancer following female breast cancer in the south of The Netherlands, 1972–2001. Eur J Cancer. 2005;41(15):2331–7.