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新辅助化疗后肿瘤床中反应性基质和残留乳腺癌细胞的下一代测序

Next Generation Sequencing of Reactive Stroma and Residual Breast Cancer Cells in Tumor Bed after Neoadjuvant Chemotherapy.

作者信息

Varga Zsuzsanna, Christiansen Ailsa, Lukamowicz-Rajska Magdalena, Batavia Aashil A, von Teichman Adriana, Schraml Peter, Moch Holger

机构信息

Department of Pathology and Molecular Pathology, University Hospital Zurich, CH-8091 Zurich, Switzerland.

出版信息

Cancers (Basel). 2022 Nov 15;14(22):5609. doi: 10.3390/cancers14225609.

DOI:10.3390/cancers14225609
PMID:36428702
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9688915/
Abstract

Primary systemic or neoadjuvant chemotherapy of breast cancer has become a standard therapy option in locally advanced or predefined intrinsic subtypes such as triple negative or Her2 positive breast cancer. Neoadjuvant chemotherapy can result in complete pathological response without residual tumor cells (tumor bed) or partial response and non-response with different amounts of reactive stroma and residual tumor cells. The interaction between therapy regimens and tumoral driver mutations have been extensively studied, although the reactive stroma of the tumor bed received less attention. In this study, we characterized the mutational status of residual breast cancer cells and reactive tumor stroma devoid of residual tumor cells in partial or non-responders using next generation sequencing. Twenty-one post-therapeutic breast surgical specimens after neoadjuvant chemotherapy underwent pathogenic driver-mutation screening using microdissected residual breast cancer cells and in reactive stroma adjacent to tumor bed areas. In reactive stroma, no mutations could be validated. In residual breast cancer cells, mutations were detected in sixteen of twenty-one cases (76%). In nine of these twenty-one cases (43%), pathogenic driver mutations () were identified. Pathogenic driver-mutations are exclusively restricted to residual carcinoma cells and are absent in reactive stroma independently from intrinsic breast cancer subtypes or tumor stage. These data suggest that the absence of pathogenic mutations in a tumor bed without residual tumor cells may have prognostic implications after neoadjuvant chemotherapy.

摘要

乳腺癌的原发性全身化疗或新辅助化疗已成为局部晚期或预定义的内在亚型(如三阴性或人表皮生长因子受体2阳性乳腺癌)的标准治疗选择。新辅助化疗可导致完全病理缓解(无残留肿瘤细胞,即肿瘤床)或部分缓解及无反应,伴有不同数量的反应性基质和残留肿瘤细胞。尽管肿瘤床的反应性基质较少受到关注,但治疗方案与肿瘤驱动基因突变之间的相互作用已得到广泛研究。在本研究中,我们使用下一代测序对部分或无反应者中残留乳腺癌细胞和无残留肿瘤细胞的反应性肿瘤基质的突变状态进行了表征。对21例新辅助化疗后的乳腺手术标本,使用显微切割的残留乳腺癌细胞以及肿瘤床区域相邻的反应性基质进行致病驱动基因突变筛查。在反应性基质中,未发现可验证的突变。在残留乳腺癌细胞中,21例中有16例(76%)检测到突变。在这21例中的9例(43%)中,鉴定出致病驱动基因突变。致病驱动基因突变仅局限于残留癌细胞,在反应性基质中不存在,与内在乳腺癌亚型或肿瘤分期无关。这些数据表明,在无残留肿瘤细胞的肿瘤床中不存在致病突变可能对新辅助化疗后的预后有影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0355/9688915/d72830d4a27f/cancers-14-05609-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0355/9688915/a1116034853d/cancers-14-05609-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0355/9688915/15c05ae9267f/cancers-14-05609-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0355/9688915/ef99fffd8418/cancers-14-05609-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0355/9688915/7a10caa0d933/cancers-14-05609-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0355/9688915/d72830d4a27f/cancers-14-05609-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0355/9688915/a1116034853d/cancers-14-05609-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0355/9688915/15c05ae9267f/cancers-14-05609-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0355/9688915/ef99fffd8418/cancers-14-05609-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0355/9688915/7a10caa0d933/cancers-14-05609-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0355/9688915/d72830d4a27f/cancers-14-05609-g005.jpg

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