怀孕期间（PrBC）和产后（PPBC）发生的乳腺癌通常比其他乳腺癌晚期诊断，加重了预后。PPBC尤其具有侵袭性，增加了转移风险和死亡率。因此，需要有效的筛查方法来早期检测PrBC和PPBC。我们首次报道乳腺癌患者乳汁中存在游离肿瘤DNA（ctDNA）。通过液滴数字PCR分析，BM ctDNA检测到87%的病例中的肿瘤变异，而92%的匹配血浆样本中未检测到变异。回顾性的下一代测序分析表明，BM ctDNA重现了肿瘤变异，总体临床敏感性为71.4%，特异性为100%。在两例中，BM乳汁中的ctDNA在标准诊断前18个月和6个月就可检测到。我们的结果首次展示了将BM用作PPBC检测的新型液体活检来源的潜力。我们首次展示，与基于血浆的液体活检相比，来自乳腺癌患者的BM中携带ctDNA，可用于早期乳腺癌的检测和分子分型，甚至在影像诊断之前。 ©2023 The Authors; Published by the American Association for Cancer Research.

Breast cancer occurring during pregnancy (PrBC) and postpartum (PPBC) is usually diagnosed at more advanced stages compared with other breast cancer, worsening its prognosis. PPBC is particularly aggressive, with increased metastatic risk and mortality. Thus, effective screening methods to detect early PrBC and PPBC are needed. We report for the first time that cell-free tumor DNA (ctDNA) is present in breast milk (BM) collected from patients with breast cancer. Analysis of ctDNA from BM detects tumor variants in 87% of the cases by droplet digital PCR, while variants remain undetected in 92% of matched plasma samples. Retrospective next-generation sequencing analysis in BM ctDNA recapitulates tumor variants, with an overall clinical sensitivity of 71.4% and specificity of 100%. In two cases, ctDNA was detectable in BM collected 18 and 6 months prior to standard diagnosis. Our results open up the potential use of BM as a new source for liquid biopsy for PPBC detection.For the first time, we show that BM obtained from patients with breast cancer carries ctDNA, surpassing plasma-based liquid biopsy for detection and molecular profiling of early-stage breast cancer, even prior to diagnosis by image.©2023 The Authors; Published by the American Association for Cancer Research.