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

Giardiello, Daniele; Hauptmann, Michael; Adank, Muriel A.; Akdeniz, Delal; Blom, Jannet; Blomqvist, Carl; Bojesen, Stig E.; Bolla, Manjeet K.; Brinkhuis, Mariël; Chang‐Claude, Jenny; Czene, Kamila; Devilee, Peter; Dunning, Alison M.; Easton, Douglas F.; Eccles, Diana; Fasching, Peter A.; Figueroa, Jonine D.; Flyger, Henrik; García‐Closas, Montserrat; Haeberle, Lothar; Haiman, Christopher A.; Hall, Per; Hamann, Ute; Hopper, John L.; Jager, Agnes; Jakubowska, Anna; Jung, Audrey; Keeman, Renske; Koppert, Linetta B.; Kramer, Iris; Lambrechts, Diether; Marchand, Loı̈c Le; Lindblom, Annika; Lubiński, Jan; Manoochehri, Mehdi; Mariani, Luigi; Nevanlinna, Heli; Oldenburg, Hester S. A.; Pelders, Saskia; Pharoah, Paul D.P.; Shah, Mitul; Siesling, Sabine; Smit, Vincent T.H.B.M.; Southey, Melissa C.; Tapper, William; Tollenaar, Rob A.E.M.; Broek, Alexandra J. van den; Deurzen, Carolien H.M. van; Leeuwen, Flora E. van; Ongeval, Chantal Van; Veer, Laura J. van’t; Wang, Qin; Wendt, Camilla; Westenend, Pieter J.; Hooning, Maartje J.; Schmidt, Marjanka K.

doi:10.1007/s10549-020-05611-8

Cited by 17 publications

(15 citation statements)

References 34 publications

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“…Currently available CBC models, such as CBCrisk and the Manchester formula, show only moderate discrimination [51]. In addition, the Manchester formula has been shown to systematically overestimate CBC risk [51].…”

Section: Discussionmentioning

confidence: 99%

PredictCBC-2.0: a contralateral breast cancer risk prediction model developed and validated in ~ 200,000 patients

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 99%

PredictCBC-2.0: a contralateral breast cancer risk prediction model developed and validated in ~ 200,000 patients

et al. 2022

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“…These models calculate an individual's risk of contralateral breast cancer in different ways using patient and tumor characteristics such as age at first primary breast cancer diagnosis, family history, ER status, breast density, first breast cancer type, and adjuvant treatments. However, these models are not widely used yet [37]. Giardiello et al [37], who used individual patient data from a number of studies with a long follow-up, evaluated the accuracy of the three models.…”

Section: Risk Of Contralateral Breast Cancermentioning

confidence: 99%

“…However, these models are not widely used yet [37]. Giardiello et al [37], who used individual patient data from a number of studies with a long follow-up, evaluated the accuracy of the three models. They found only moderate discrimination of all three models and considerable heterogeneity between studies, and concluded that careful re-calibration is required before these models could be used in clinical decision-making [37].…”

Section: Risk Of Contralateral Breast Cancermentioning

confidence: 99%

Contralateral prophylactic mastectomy: A narrative review of the evidence and acceptability

et al. 2021

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The uptake of contralateral prophylactic mastectomy (CPM) has increased steadily over the last twenty years in women of all age groups and breast cancer stages. Since contralateral breast cancer is relatively rare and the breast cancer guidelines only recommend CPM in a small subset of patients with breast cancer, the drivers of this trend are unknown. This review aims to evaluate the evidence for and acceptability of CPM, data on patient rationales for choosing CPM, and some of the factors that might impact patient preferences. Based on the evidence, future recommendations will be provided. First, data on contralateral breast cancer risk and CPM rates and trends are addressed. After that, the evidence is structured around four main patient rationales for CPM formulated as questions that patients might ask their surgeon: Will CPM reduce mortality risk? Will CPM reduce the risk of contralateral breast cancer? Can I avoid future screening with CPM? Will I have better breast symmetry after CPM? Also, three different guidelines regarding CPM will be reviewed. Studies indicate a large gap between patient preferences for radical risk reduction with CPM and the current approaches recommended by important guidelines. We suggest a strategy including shared decision-making to enhance surgeons’ communication with patients about contralateral breast cancer and treatment options, to empower patients in order to optimize the use of CPM incorporating accurate risk assessment and individual patient preferences.

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“…The results of our study can be used to further personalise CBC risk management. In combination with other factors that influence CBC risk [ 4 ], we aim to identify patients at high and low risk of CBC [ 27 , 28 ]. Based on the results of this study, the frequency of screening and choices regarding risk-reducing surgeries cannot be tailored to the different risk-profiles yet, though this would be the subsequent goal.…”

Section: Discussionmentioning

confidence: 99%

Effects of chemotherapy on contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers: A nationwide cohort study

et al. 2022

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Aim BRCA1/2 mutation carriers with primary breast cancer (PBC) are at high risk of contralateral breast cancer (CBC). In a nationwide cohort, we investigated the effects of chemotherapeutic agents given for PBC on CBC risk separately in BRCA1 and BRCA2 mutation carriers. Patients and methods BRCA1 or BRCA2 mutation carriers with an invasive PBC diagnosis from 1990 to 2017 were selected from a Dutch cohort. We estimated cumulative CBC incidence using competing risks analysis. Hazard ratios (HR) for the effect of neo-adjuvant or adjuvant chemotherapy and different chemotherapeutic agents on CBC risk were estimated using Cox regression. Results We included 1090 BRCA1 and 568 BRCA2 mutation carriers; median follow-up was 8.9 and 8.4 years, respectively. Ten-year cumulative CBC incidence for treatment with and without chemotherapy was 6.7% [95%CI: 5.1–8.6] and 16.7% [95%CI: 10.8–23.7] in BRCA1 and 4.8% [95%CI: 2.7–7.8] and 16.0% [95%CI: 9.3–24.4] in BRCA2 mutation carriers, respectively. Chemotherapy was associated with reduced CBC risk in BRCA1 (multivariable HR: 0.46, 95%CI: 0.29–0.74); a similar trend was observed in BRCA2 mutation carriers (HR: 0.63, 95%CI: 0.29–1.39). In BRCA1 , risk reduction was most pronounced in the first 5 years (HR: 0.32, 95%CI: 0.17–0.61). Anthracyclines and the combination of anthracyclines with taxanes were associated with substantial CBC risk reduction in BRCA1 carriers (HR: 0.34, 95%CI: 0.17–0.68 and HR: 0.22, 95%CI: 0.08–0.62, respectively). Conclusion Risk-reducing effects of chemotherapy are substantial for at least 5 years and may be used in personalised CBC risk prediction in any case for BRCA1 mutation carriers.

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

Cited by 17 publications

References 34 publications

PredictCBC-2.0: a contralateral breast cancer risk prediction model developed and validated in ~ 200,000 patients

PredictCBC-2.0: a contralateral breast cancer risk prediction model developed and validated in ~ 200,000 patients

Contralateral prophylactic mastectomy: A narrative review of the evidence and acceptability

Effects of chemotherapy on contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers: A nationwide cohort study

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