With the booming development of nanomedicine, mild photothermal therapy (mPTT, 42– 45°C) has exhibited promising potential in tumor therapy. Compared with traditional PTT (> 50°C), mPTT has less side effects and better biological effects conducive to tumor treatment, such as loosening the dense structure in tumor tissues, enhancing blood perfusion, and improving the immunosuppressive microenvironment. However, such a relatively low temperature cannot allow mPTT to completely eradicate tumors, and therefore, substantial efforts have been conducted to optimize the application of mPTT in tumor therapy. This review extensively summarizes the latest advances of mPTT, including two sections: (1) taking mPTT as a leading role to maximize its effect by blocking the cell defense mechanisms, and (2) regarding mPTT as a supporting role to assist other therapies to achieve synergistic antitumor curative effect. Meanwhile, the special characteristics and imaging capabilities of nanoplatforms applied in various therapies are discussed. At last, this paper puts forward the bottlenecks and challenges in the current research path of mPTT, and possible solutions and research directions in future are proposed correspondingly.

Objectives: Preoperative evaluation of axillary lymph node (ALN) status is an essential part of deciding the appropriate treatment. According to ACOSOG Z0011 trials, the new goal of the ALN status evaluation is tumor burden (low burden, < 3 positive ALNs; high burden, ≥ 3 positive ALNs), instead of metastasis or non-metastasis. We aimed to develop a radiomics nomogram integrating clinicopathologic features, ABUS imaging features and radiomics features from ABUS for predicting ALN tumor burden in early breast cancer. Methods: A total of 310 patients with breast cancer were enrolled. Radiomics score was generated from the ABUS images. Multivariate logistic regression analysis was used to develop the predicting model, we incorporated the radiomics score, ABUS imaging features and clinicopathologic features, and this was presented with a radiomics nomogram. Besides, we separately constructed an ABUS model to analyze the performance of ABUS imaging features in predicting ALN tumor burden. The performance of the models was assessed through discrimination, calibration curve, and decision curve. Results: The radiomics score, which consisted of 13 selected features, showed moderate discriminative ability (AUC 0.794 and 0.789 in the training and test sets). The ABUS model, comprising diameter, hyperechoic halo, and retraction phenomenon, showed moderate predictive ability (AUC 0.772 and 0.736 in the training and test sets). The ABUS radiomics nomogram, integrating radiomics score with retraction phenomenon and US-reported ALN status, showed an accurate agreement between ALN tumor burden and pathological verification (AUC 0.876 and 0.851 in the training and test sets). The decision curves showed that ABUS radiomics nomogram was clinically useful and more excellent than US-reported ALN status by experienced radiologists. Conclusions: The ABUS radiomics nomogram, with non-invasive, individualized and precise assessment, may assist clinicians to determine the optimal treatment strategy and avoid overtreatment.

This prospective study was aimed at evaluating the role of automated breast ultrasound (ABUS) and contrast-enhanced ultrasound (CEUS) in the early prediction of treatment response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. Forty-three patients with pathologically confirmed invasive breast cancer treated with NAC were included. The standard for evaluation of response to NAC was based on surgery within 21 d of completing treatment. The patients were classified as having a pathological complete response (pCR) and a non-pCR. All patients underwent CEUS and ABUS 1 wk before receiving NAC and after two treatment cycles. The rising time (RT), time to peak (TTP), peak intensity (PI), wash-in slope (WIS) and wash-in area under the curve (Wi-AUC) were measured on the CEUS images before and after NAC. The maximum tumor diameters in the coronal and sagittal planes were measured on ABUS, and the tumor volume (V) was calculated. The difference (∆) in each parameter between the two treatment time points was compared. Binary logistic regression analysis was used to identify the predictive value of each parameter. ∆V, ∆TTP and ∆PI were independent predictors of pCR. The CEUS-ABUS model achieved the highest AUC (0.950), followed by those based on CEUS (0.918) and ABUS (0.891) alone. The CEUS-ABUS model could be used clinically to optimize the treatment of patients with breast cancer.

Background: Triple negative breast cancer (TNBC) is one of the worst prognosis types of breast cancer that urgently needs effective therapy methods. However, cancer is a complicated disease that usually requires multiple treatment modalities. Methods: A tumor microenvironment (TME)-responsive PFC/TRIM37@Fe-TA@HA (abbreviated as PTFTH) nanoplatform was constructed by coating Fe³⁺ and tannic acid (TA) on the surface of TRIM37-siRNA loaded phase-transition perfluorocarbon (PFC) nanodroplets and further modifying them with hyaluronic acid (HA) to achieve tumor-specific mild photothermal/gene/ferroptosis synergistic therapy (MPTT/GT/ Ferroptosis) in vitro. Once internalized into tumor cells through CD44 receptor-mediated active targeting, the HA shell of PTFTH would be preliminarily disassembled by hyaluronidase (HAase) to expose the Fe-TA metal-phenolic networks (MPNs), which would further degrade in response to an acidic lysosomal environment, leading to HAase/pH dual-responsive release of Fe³⁺ and PFC/TRIM37. Results: PTFTH showed good biocompatibility in vitro. On the one hand, the released Fe³⁺ could deplete the overexpressed glutathione (GSH) through redox reactions and produce Fe²⁺, which in turn converts endogenous H₂O₂ into highly cytotoxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT). On the other hand, the local hyperthermia generated by PTFTH under 808 nm laser irradiation could not only improve CDT efficacy through accelerating the Fe²⁺-mediated Fenton reaction, but also enhance TRIM37-siRNA delivery for gene therapy (GT). The consumption of GSH and accumulation of •OH synergistically augmented intracellular oxidative stress, resulting in substantial tumor cell ferroptosis. Moreover, PTFTH possessed outstanding contrast enhanced ultrasound (CEUS), photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) ability. Conclusion: This PTFTH based multiple-mode therapeutic strategy has successfully achieved a synergistic anticancer effect in vitro and has the potential to be translated into clinical application for tumor therapy in future.

Objective. Invasive breast cancer can be metastasized through axillary lymph nodes (LNs). This study was to evaluate the effectiveness of quantitative shear wave elastography (SWE) to predict axillary LN metastasis, which also provides prognostic implication of SWE as a histopathologic element of invasive breast cancer. Methods. 72 prospectively enrolled patients received B-mode ultrasound (BUS) and SWE, and the elasticity index (EI) of SWE at the stiffest part of lymph nodes (LNs) was measured. EI of SWE was closely associated with pathologic results and the histopathologic elements. The receiver operating characteristics (ROC) curve was drawn to evaluate the optimal cut-off value for the assessment of disease severity. Results. A significantly longer short-axis diameter and a larger maximal cortex were observed in malignant LNs than that in healthy LNs. The absence of the hilum was associated with metastatic LNs. The EI of SWE varied markedly between the benign and malignant LNs. The combination of E_{max and} BUS showed higher area under the curve (AUC) than BUS alone to predict metastatic LNs (0.7762 vs. 0.7230). EI of SWE in malignant lymph nodes those with extranodal extension are higher than those without extranodal extension. Conclusions. Quantitative SWE provides a viable alternative for the assessment of axillary LN and shows great potential to predict pathological prognostic elements of metastatic axillary LNs in invasive breast cancer. Joint use of SWE and BUS allows examination of the predictive outcome of BUS for axillary lymph node metastasis in invasive breast cancer.

The combination of mild-temperature photothermal and chemotherapy represents a promising therapeutic strategy capable of maximizing anti-cancer efficacy while minimizing adverse reactions, particularly when integrated with multi-modal treatments. Nevertheless, the increase in heat shock protein (HSP) expression induced by mild hyperthermia may significantly influence the therapeutic efficacy. In this study, Isoliensinine (Iso) and the heat shock protein 90 (HSP90) inhibitor ganetespib were loaded into MPDA nanoparticles (NPs) to form GI-MPDA@BSA NPs, establishing a multi-modal therapeutic nanoplatform. The synthesized GI-MPDA@BSA NPs exhibit excellent photothermal conversion performance and favorable biocompatibility. Under 808 nm laser irradiation, the mild photothermal therapy (PTT) generated by MPDA facilitates the rapid release of drugs from BSA, resulting in an effective synergistic cytotoxic effect on cancer cells. Concurrently, the released ganetespib suppressed HSP90 expression, thereby potentiating the effects of mild photothermal/chemotherapy. In vitro and in vivo experimental results indicate that GI-MPDA@BSA exhibits low cytotoxicity while conspicuously inhibiting tumor growth under laser irradiation and eliciting an immune response. Furthermore, the application of two-dimensional ultrasound (2D US) and contrast-enhanced ultrasound (CEUS) to monitor post- tumor treatment changes elucidates the evolutionary process following combined mild-temperature photothermal/chemotherapy, presenting a novel strategy for the treatment and monitoring of triple negative breast cancer (TNBC) in clinical practice.