浸润性导管癌（IDC）是恶性乳腺癌（BC）最常见的组织学亚型，占所有浸润性BC的70-80％。 IDC表现出很大的临床和组织病理学特征、预后、治疗策略、基因表达和蛋白质组学特征的异质性。从乳腺内导管前癌恶性病变（DCIS）到IDC进展的重要蛋白质组学确定因子仍然没有得到很好的识别、验证和临床应用。在“6P”医学时代，确定哪些患者应该过度治疗以及哪些需要积极监测而不进行激进治疗仍然是一个巨大的挑战。确定DCIS到IDC进展的主要困难可能通过理解整合基因组学、转录组学和蛋白质组学侵袭基础而得到解决。在本综述中，我们展示了多种基于蛋白质组学的技术，如LC-MS/MS、MALDI-ToF MS、SELDI-ToF-MS、MALDI-ToF/ToF MS、MALDI-MSI或MasSpec Pen，应用于组织内、离体、BC细胞系和液体活检，改善了IDC的诊断以及其预后和治疗监测。允许鉴定失调的蛋白质表达、生物学过程以及基于异常蛋白质-蛋白质相互作用（PPI）网络的相互关系通路分析的经典蛋白质组学策略已经改进，以执行非侵入性/微创生物标志物检测早期IDC。因此，在现代外科肿瘤学中，高敏感、快速、准确的MS检测已与“蛋白质组点采样”方法相结合，该方法允许通过体内“蛋白质组点表征”或通过最小组织切除进行蛋白质组学分析，以准确确定和划定IDC。为了检测体液中的低分子量蛋白质和蛋白质片段，可以将LC-MS/MS和MALDI-MS技术与富集和捕获方法相结合，以识别先前对于基于MS技术是不可见的早期IDC蛋白质生物标志物。此外，检测和表征蛋白质的亚型，包括蛋白质的翻译后修饰（PTM），也非常重要，以强调特定分子机制，并确保早期检测乳腺IDC。

Invasive ductal carcinoma (IDC) is the most common histological subtype of malignant breast cancer (BC), and accounts for 70-80% of all invasive BCs. IDC demonstrates great heterogeneity in clinical and histopathological characteristics, prognoses, treatment strategies, gene expressions, and proteomic profiles. Significant proteomic determinants of the progression from intraductal pre-invasive malignant lesions of the breast, which characterize a ductal carcinoma in situ (DCIS), to IDC, are still poorly identified, validated, and clinically applied. In the era of "6P" medicine, it remains a great challenge to determine which patients should be over-treated versus which need to be actively monitored without aggressive treatment. The major difficulties for designating DCIS to IDC progression may be solved by understanding the integrated genomic, transcriptomic, and proteomic bases of invasion. In this review, we showed that multiple proteomics-based techniques, such as LC-MS/MS, MALDI-ToF MS, SELDI-ToF-MS, MALDI-ToF/ToF MS, MALDI-MSI or MasSpec Pen, applied to in-tissue, off-tissue, BC cell lines and liquid biopsies, improve the diagnosis of IDC, as well as its prognosis and treatment monitoring. Classic proteomics strategies that allow the identification of dysregulated protein expressions, biological processes, and interrelated pathway analyses based on aberrant protein-protein interaction (PPI) networks have been improved to perform non-invasive/minimally invasive biomarker detection of early-stage IDC. Thus, in modern surgical oncology, highly sensitive, rapid, and accurate MS-based detection has been coupled with "proteome point sampling" methods that allow for proteomic profiling by in vivo "proteome point characterization", or by minimal tissue removal, for ex vivo accurate differentiation and delimitation of IDC. For the detection of low-molecular-weight proteins and protein fragments in bodily fluids, LC-MS/MS and MALDI-MS techniques may be coupled to enrich and capture methods which allow for the identification of early-stage IDC protein biomarkers that were previously invisible for MS-based techniques. Moreover, the detection and characterization of protein isoforms, including posttranslational modifications of proteins (PTMs), is also essential to emphasize specific molecular mechanisms, and to assure the early-stage detection of IDC of the breast.