Microwave ablation (MWA) is increasingly used in clinical treatment and research of breast cancer, which has good therapeutic effect on primary and metastatic lesions. However, microwave ablation may lead to residual tumor cells due to incomplete ablation. The biological characteristics of residual tumor cells are unknown, and it is necessary to explore new adjuvant treatment methods to achieve better therapeutic effect. In this study, we demonstrated that the migration ability of residual breast cancer cells was enhanced after microwave ablation, but the proliferation ability was not significantly changed. Lawsone, an active ingredient in Chinese herbal medicine, significantly inhibited the proliferation and metastasis of residual breast cancer cells after microwave ablation in vivo and in vitro, and had synergistic effects with microwave ablation therapy. Mechanistic studies have shown that Lawsone exerts its anti-proliferation and anti-migration ability mainly by targeting NCAPG in residual breast cancer after microwave ablation. In addition, Lawsone-induced cellular inhibitory autophagy also plays a key role in its anticancer effect. In addition, NCAPG interacts with AURKB protein and jointly participates in the regulation of AKT/mTOR pathway to affect autophagy process. In short, these consequences demonstrate that Lawsone exerts its anti-proliferation and anti-metastasis effects on residual breast cancer cells after microwave ablation mainly by inhibiting NCAPG/AURKB/AKT/mTOR axis and inducing inhibitory autophagy, which provides more options for adjuvant therapy after microwave ablation.

Background: Multifocal (MF) and multicentric (MC) breast cancer cases have been increasingly diagnosed owing to the extensive use of improved preoperative breast imaging. The current tumor-node-metastasis staging system uses the dimension of the largest tumor and recommends reporting the pathological features of the largest tumor in MF/MC breast cancers.Aim: This study aimed to explore whether the largest or aggregate dimensions of MF and MC breast cancers can better predict tumor behavior. We also attempted to study the histological and biological heterogeneities of separate foci in MF and MC breast cancers to determine whether it was necessary to examine each lesion. Methods:We retrospectively analyzed 121 patients with MF/MC (103 with MF and 18 with MC) breast cancers and 484 patients with unifocal breast cancer who were treated at the First Affiliated Hospital of Nanjing Medical University.Two methods were used to record the T stage (using the dimensions of the largest lesion and aggregate dimensions of all lesions). The histological grade, immunohistochemical parameters, and molecular subtypes of the largest lesion and other lesions in MF/MC breast cancers were studied to assess intertumoral heterogeneity. Results:The use of aggregate dimensions upstaged 63 patients with MF/MC breast cancers to a more advanced stage and removed the independent effect of cancer multiplicity on lymph node positivity compared with the use of the largest dimension. Mismatches were found in the pathological type (9.9%), histological grade (4.1%), and molecular subtype (8.3%) among different foci. Conclusion:The tendency of MF/MC breast tumors to metastasize may be related to tumor load, which can be better predicted by the aggregate dimensions of all foci. The use of the current staging systems may require further evaluation and modification. Intertumoral heterogeneity indicates the necessity for pathological and immunohistochemical assessments of each lesion in patients with MF/MC breast cancers.

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