In Reply Our cost-effectiveness analysis of multigene testing in 11 836 patients with breast cancer¹ showed that unselected triple-gene testing for BRCA1, BRCA2, and PALB2 at breast cancer diagnosis would be cost-effective for the UK and US health systems, with incremental cost-effectiveness ratios of £10 464 or $65 661 per quality-adjusted life-year, respectively. Additionally, 1 year’s unselected genetic testing for BRCA1, BRCA2, and PALB2 could prevent 2101 cases of breast and ovarian cancer and 633 deaths in the UK and 9733 cases of breast and ovarian cancer and 2406 deaths in the US.¹ Approximately 50% of pathogenic variant (formerly mutation) carriers are below the threshold for genetic testing used in most countries and are missed by current clinical criteria. Unselected testing will identify many more women at risk and provide a huge impetus for precision prevention and personalized treatment.

答复我们对 11 836 名乳腺癌患者¹进行的多基因检测的成本效益分析表明，在乳腺癌诊断中对BRCA1、BRCA2和PALB2进行未经选择的三基因检测对于英国和美国的卫生系统来说是具有成本效益的，与每个质量调整生命年的增量成本效益比分别为 10 464 英镑或 65 661 美元。此外，对BRCA1、BRCA2和PALB2进行 1 年未选择的基因检测可以预防英国 2101 例乳腺癌和卵巢癌和 633 例死亡以及美国 9733 例乳腺癌和卵巢癌和 2406 例死亡。¹大约 50% 的致病性变异（以前的突变）携带者低于大多数国家使用的基因检测的阈值，并且被当前的临床标准遗漏。未经选择的检测将识别更多处于危险中的女性，并为精准预防和个性化治疗提供巨大动力。