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Importance Online prognostication tools such as PREDICT and Adjuvant! are increasingly used in clinical practice by oncologists to inform patients and guide treatment decisions about adjuvant systemic therapy. However, their validity for young breast cancer patients is debated. Objective To assess first, the prognostic accuracy of PREDICT's and Adjuvant! 10-year all-cause mortality, and second, its breast cancer–specific mortality estimates, in a large cohort of breast cancer patients diagnosed <50 years. Design Hospital-based cohort. Setting General and cancer hospitals. Participants A consecutive series of 2710 patients without a prior history of cancer, diagnosed between 1990 and 2000 with unilateral stage I–III breast cancer aged <50 years. Main outcome measures Calibration and discriminatory accuracy, measured with C-statistics, of estimated 10-year all-cause and breast cancer–specific mortality. Results Overall, PREDICT's calibration for all-cause mortality was good (predicted versus observed) mean difference : −1.1% (95%CI: −3.2%–0.9%; P = 0.28). PREDICT tended to underestimate all-cause mortality in good prognosis subgroups (range mean difference : −2.9% to −4.8%), overestimated all-cause mortality in poor prognosis subgroups (range mean difference : 2.6%–9.4%) and underestimated survival in patients < 35 by −6.6%. Overall, PREDICT overestimated breast cancer–specific mortality by 3.2% (95%CI: 0.8%–5.6%; P = 0.007); and also overestimated it seemingly indiscriminately in numerous subgroups (range mean difference : 3.2%–14.1%). Calibration was poor in the cohort of patients with the lowest and those with the highest mortality probabilities. Discriminatory accuracy was moderate-to-good for all-cause mortality in PREDICT (0.71 [95%CI: 0.68 to 0.73]), and the results were similar for breast cancer–specific mortality. Adjuvant!'s calibration and discriminatory accuracy for both all-cause and breast cancer–specific mortality were in line with PREDICT's findings. Conclusions Although imprecise at the extremes, PREDICT's estimates of 10-year all-cause mortality seem reasonably sound for breast cancer patients <50 years; Adjuvant! findings were similar. Prognostication tools should be used with caution due to the intrinsic variability of their estimates, and because the threshold to discuss adjuvant systemic treatment is low. Thus, seemingly insignificant mortality overestimations or underestimations of a few percentages can significantly impact treatment decision-making. [ABSTRACT FROM AUTHOR]

Abstract: Background: The MINDACT (Microarray In Node-negative and 1–3 node positive Disease may Avoid ChemoTherapy) trial investigates the clinical utility of the 70-gene profile (MammaPrint) for the selection of breast cancer patients for adjuvant chemotherapy (CT) together with standard clinicopathological criteria. We present the results of the pilot phase consisting of first 800 patients included. Methods: MINDACT has enrolled 6600 patients, classified into high or low risk by MammaPrint and clinicopathological risk through Adjuvant! Online. Patients with both clinical (C) and genomic (G) high risks are offered adjuvant CT; those with both C and G low risks do not receive CT; patients with discordant risk are randomised for the decision of adjuvant CT based on C or G risk. CT randomisation of anthracycline-based versus docetaxel/capecitabine and endocrine therapy randomisation between letrozole and tamoxifen→letrozole are offered. Results: During the pilot phase 46% of screened patients were enrolled. Main reasons for non-enrolment were node positivity before trial amendment, sample quality problems and failure to meet logistic settings. Among the 800 patients, 386 (48%) were C-low/G-low, 198 (24.8%) as C-high/G-high, 75 (9.4%) as C-low/G-high and 141 (17.6%) as C-high/G-low. In total 216 (27%) cases were discordant. The difference between patients with C-high (42%) and G-high risk (34%) is 8.25% (95% confidence interval (CI), 4.7–11.8%; P <.0001). Compliance with the treatment decision was high (>92%). Conclusions: The logistically complex MINDACT trial is feasible in a multinational setting. The proportion of discordant patients, the potential reduction in CT by using the genomic signature and compliance to treatment assignment are in accordance with the trial hypotheses. [Copyright &y& Elsevier]