间期乳腺癌 (IBC) 是在两次筛查之间诊断出的癌症。了解 IBC 和筛查检测乳腺癌 (SDBC) 之间的生物学差异有可能改善乳房 X 光检查和患者管理。我们通过对作为英国 100,000 基因组计划的一部分收集的配对肿瘤-正常患者样本的全基因组测序，分析和比较了 288 个 IBC 和 473 个 SDBC 的基因组图谱。与 SDBC 相比，IBC 更有可能是小叶状、更高级别和三阴性。具有基因组不稳定特征的 IBC 反映了更具侵袭性的临床表型，包括更高的突变率和染色体结构异常数量、同源重组缺陷和 TP53 突变。然而，我们没有找到证据表明 IBC 与显着不同的免疫反应相关。虽然 IBC 并不代表浸润性乳腺癌的独特分子类别，但它们表现出更具侵袭性的表型，这可能是肿瘤发生时间的结果。此信息与治疗相关，并告知乳房 X 光检查的筛查间隔。© 2024。作者。

Interval breast cancers (IBCs) are cancers diagnosed between screening episodes. Understanding the biological differences between IBCs and screen-detected breast-cancers (SDBCs) has the potential to improve mammographic screening and patient management. We analysed and compared the genomic landscape of 288 IBCs and 473 SDBCs by whole genome sequencing of paired tumour-normal patient samples collected as part of the UK 100,000 Genomes Project. Compared to SDBCs, IBCs were more likely to be lobular, higher grade, and triple negative. A more aggressive clinical phenotype was reflected in IBCs displaying features of genomic instability including a higher mutation rate and number of chromosomal structural abnormalities, defective homologous recombination and TP53 mutations. We did not however, find evidence to indicate that IBCs are associated with a significantly different immune response. While IBCs do not represent a unique molecular class of invasive breast cancer they exhibit a more aggressive phenotype, which is likely to be a consequence of the timing of tumour initiation. This information is relevant both with respect to treatment as well as informing the screening interval for mammography.© 2024. The Author(s).