Ablation Of Breast Cancer Research Articles

Prevalence of Occult Ovarian Cancer and Metastatic Breast Cancer in Ovarian Ablation Specimens of Patients With Hormone Receptor-Positive Breast Cancer: Implications for Tissue Sampling Strategies, Early Ovarian Cancer Detection and Resource Utilization.

Bilateral oophorectomy is one method of hormone suppression for premenopausal patients with hormone receptor-positive breast cancer. Such specimens could, in theory, harbor occult early ovarian cancer and/or metastatic breast cancer but guidelines for tissue sampling for pathologic examination remain to be addressed. Therefore, we evaluated oophorectomy specimens from 166 patients who underwent ovarian ablation for hormone receptor-positive breast cancer. Results of germline genetic testing were documented by the surgeon in only 31.3% of the pathology specimen requisition forms, whereas that information was available for 81.3% of patients elsewhere in the electronic medical records. All but 5.2% tested negative for a hereditary ovarian cancer gene pathogenic variant before oophorectomy. Complete tissue sampling was performed in 77.1% of the cases and representative sampling in the remainder. No cases of ovarian cancer were observed. Ovarian metastasis of breast cancer was identified in 9.6% of patients, all of whom were already known to have advanced-stage disease. The number of tissue cassettes per ovary required for complete tissue submission was on average three times higher than that for representative tissue sampling (P < 0.01) and ranged up to 20 cassettes per ovary when multiple follicle cysts were present. We propose that guidelines for tissue sampling in this context be defined by a combination of hereditary risk and macroscopic examination; representative sampling is reasonable for macroscopically normal ovaries in hormone receptor-positive breast cancer patients whose germline genetic testing is negative. Positive genetic test results merit complete tissue submission even if macroscopically normal. This strategy balances the goals of early ovarian cancer detection and optimal resource utilization. However, it depends on clear documentation of genetic test results. Our study demonstrates that many opportunities remain to close gaps in the communication of genetic test results by clinicians submitting oophorectomy specimens for pathologic evaluation.

Thermo-immune synergy: Camrelizumab plus microwave ablation in preoperative early-stage breast cancer

Immunotherapy has enhanced breast cancer outcomes, but optimizing combination therapies is crucial. Integrating additional treatment modalities, like physical therapies, holds promise for optimizing efficacy. Pan etal. recently reported that combining preoperative immunotherapy with microwave ablation is safe and feasible in early-stage breast cancer, effectively sensitizing peripheral CD8+ Tcells.1.

Abstract No. 330 ▪ Featured Abstract Advanced Biphasic Pulsed Electric Field (PEF) Stimulates a More Favorable Immune Response Profile versus Irreversible Electroporation (IRE) Upon Ablation of Murine Breast Cancer

Abstract No. 330 ▪ Featured Abstract Advanced Biphasic Pulsed Electric Field (PEF) Stimulates a More Favorable Immune Response Profile versus Irreversible Electroporation (IRE) Upon Ablation of Murine Breast Cancer

Locoregional Therapies for Primary and Metastatic Breast Cancer: AJR Expert Panel Narrative Review.

Minimally invasive locoregional therapies have a growing role in the multidisciplinary treatment of primary and metastatic breast cancer. Factors contributing to the expanding role of ablation for primary breast cancer include earlier diagnosis, when tumors are small, and increased longevity of patients whose condition precludes surgery. Cryoablation has emerged as the leading ablative modality for primary breast cancer owing to its wide availability, the lack of need for sedation, and the ability to monitor the ablation zone. Emerging evidence suggests that in patients with oligometastatic breast cancer, use of locoregional therapies to eradicate all disease sites may confer a survival advantage. Evidence also suggests that transarterial therapies-including chemoembolization, chemoperfusion, and radioembolization-may be helpful to some patients with advanced liver metastases from breast cancer, such as those with hepatic oligoprogression or those who cannot tolerate systemic therapy. However, the optimal modalities for treatment of oligometastatic and advanced metastatic disease remain unknown. Finally, locoregional therapies may produce tumor antigens that in combination with immunotherapy drive anti-tumor immunity. Although key trials are ongoing, additional prospective studies are needed to establish the inclusion of interventional oncology in societal breast cancer guidelines to support further clinical adoption and improved patient outcomes.

Magnetic resonance imaging-guided radiofrequency ablation of breast cancer: a current state of the art review.

With a gradual increase in breast cancer incidence and mortality rates and an urgent need to improve patient prognosis and cosmetology, magnetic resonance imaging (MRI)-guided radiofrequency ablation (RFA) therapy has attracted wide attention as a new treatment method for breast cancer. MRI-RFA results in a higher complete ablation rate and extremely low recurrence and complication rates. Thus, it may be used as an independent treatment for breast cancer or adjuvant to breast-conserving surgery to reduce the extent of breast resection. Furthermore, with MRI guidance, accurate control of RFA can be achieved, and breast cancer treatment can enter a new stage of minimally invasive, safe, and comprehensive therapy. With progress in MR thermometry technology, the applications of MRI are expected to broaden.

Mild photothermal/radiation therapy potentiates ferroptosis effect for ablation of breast cancer via MRI/PA imaging guided all-in-one strategy

BackgroundNanotheranostics advances anticancer management by providing therapeutic and diagnostic functions, that combine programmed cell death (PCD) initiation and imaging-guided treatment, thus increasing the efficacy of tumor ablation and efficiently fighting against cancer. However, mild photothermal/radiation therapy with imaging-guided precise mediating PCD in solid tumors, involving processes related to apoptosis and ferroptosis, enhanced the effect of breast cancer inhibition is not fully understood.ResultsHerein, targeted peptide conjugated gold nano cages, iRGD-PEG/AuNCs@FePt NPs ternary metallic nanoparticles (Au@FePt NPs) were designed to achieve photoacoustic imaging (PAI)/Magnetic resonance imaging (MRI) guided synergistic therapy. Tumor-targeting Au@FePt forms reactive oxygen species (ROS), initiated by X-ray-induced dynamic therapy (XDT) in collaboration with photothermal therapy (PTT), inducing ferroptosis-augmented apoptosis to realize effective antitumor therapeutics. The relatively high photothermal conversion ability of Au@FePt increases the temperature in the tumor region and hastens Fenton-like processes to achieve enhanced synergistic therapy. Especially, RNA sequencing found Au@FePt inducting the apoptosis pathway in the transcriptome profile.ConclusionAu@FePt combined XDT/PTT therapy activate apoptosis and ferroptosis related proteins in tumors to achieve breast cancer ablation in vitro and in vivo. PAI/MRI images demonstrated Au@FePt has real-time guidance for monitoring synergistic anti-cancer therapy effect. Therefore, we have provided a multifunctional nanotheranostics modality for tumor inhibition and cancer management with high efficacy and limited side effects.Graphical

Cryo-assisted resection of primary breast cancer en bloc and tumor cryoablation connected with local drug delivery and targeting of tumor fluids. Experimental and clinical studies

Objective — to use cryosurgery in combination with simultaneous peritumoral and intratumoral tracer injections of blue dye for further lymphatic mapping in the treatment of primary breast tumors. The effectiveness of intraoperative cryoprobe‑assisted injection of blue dye and cytotoxic‑tracer mixture for locoregional drug targeting in the VX2 tumor model as well as its translational significance for cryo‑assisted breast tumor surgery with blue dye alone were evaluated. Sentinel lymph node mapping, pathological determination of the tumor, and resection margins were achievable.&#x0D; Materials and methods. Thirty‑nine patients with primary breast cancer in stages I to IV, aged 52,4 (±19) years (mean, standard deviation (SD) years), were randomly selected, treated at the Rudolfinerhaus Private Clinic in Vienna, Austria, and included in this preliminary clinical study. Under computed tomography guidance, we injected 2 ml of cytotoxic‑tracer mixture in five aliquots into the margins of 16 frozen or normothermic VX2 tumors. We evaluated the intraoperative and post‑operative drug targeting and therapeutic efficacy at the tumor‑host interface by means of computer tomography, gross examination, and histopathology. In thirty‑four T1 to T4 primary breast cancers, we performed an ultrasound‑guided cryoprobe‑assisted tumor freezing‑thawing cycle, blue dye‑guided lymphatic mapping, and surgery. We examined an intraoperative and freshly resected specimen and the blue dye distribution pattern in the tumor‑host interface, lymph node(s), breast parenchyma, and resection cavity. &#x0D; Results. 29 of the 38 patients had localized primary breast cancer, which was estimated to be resectable without neoadjuvant chemotherapy. 87% of patients had one to twelve stained axillary lymph nodes, while 72% of patients had another quadrant and resection cavity stained. Fluid‑impervious frozen VX2 or breast tumors transported drug(s) in an arc‑like pattern at the tumor‑host interface regardless of freeze dose, number of freeze‑thaw cycles, drug dose fractionation, tumor characteristics, or tumor dimensions. During melting, the cytotoxic‑tracer mixture spread within 50% of the VX2 tumor and mirrored that of the tumor‑host interface; it was massive in normothermia. In VX2, the CT gap corresponded to 20% of the focal margin necrosis in pathology. In both studies, blue dye dose‑staining spread linearly in the tumor‑host interface and tumor.&#x0D; Conclusions. The study paves the way for intraoperative cryo‑assisted cure options for primary breast cancer. We have shown that our cryosurgical technique of repeatedly freezing deep tumors for en bloc resection or for in situ ablation of primary breast cancer, facilitated by IOUS monitoring, can be coupled with the simultaneous injection of dye tracers during conventional surgery, which then allows for lymphatic mapping. Intraoperative freezing‑assisted drug delivery and targeting techniques during cryoablation of the VX2 tumor translate successfully to locoregional blue dye targeting and lymphatic mapping during cryo‑assisted surgery of breast cancer. We explored the ability of our strategy to prevent tumor cell migration, but not that of injected tracers, to the lymphovascular drainage during conventional resection of frozen breast malignancies.&#x0D;

Occam’s Razor-Inspired Nb2C delivery platform potentiates breast cancer therapy and inhibits lung metastasis

Breast cancer exhibits a high rate of lung metastasis and is one of the leading causes of cancer-related mortality in women. Hence, it is critical to develop innovative therapeutic strategies to combat breast cancer and lung metastasis. The physical and optical properties of niobium carbide (Nb2C) nanosheets endow them with excellent photothermal conversion properties and the capacity for drug delivery, making them ideal for photothermal therapy (PTT) in breast cancer and its lung metastasis. To explore a new synergistic strategy for subcutaneous tumor ablation and lung metastasis inhibition in breast cancer, an Occam’s Razor-inspired nanocomposite (Nb2C-BBR) was fabricated based on functionalized Nb2C nanosheets and berberine (BBR), a natural inhibitor that regulates metastasis-related proteins in the tumor microenvironment. The Nb2C nanosheets were ultrathin (thickness of ∼ 124 nm), could be endocytosed into subcellular organelles, showed desirable photothermal-conversion efficiency (38 % and 59 % at 808 nm and 1064 nm, respectively), and achieved multi-modal imaging in the near-infrared (NIR-II) biowindow. With a size of 130.4 nm, the Nb2C-BBR nanocomposites exhibited favorable biocompatibility and reduced the dose of Nb2C nanosheets required under NIR-II irradiation while maintaining photothermal performance and anticancer efficacy. Combined chemotherapy and PTT with the Nb2C-BBR nanocomposites not only eradicated cancer cells notably but also significantly suppressed cell proliferation by activating the mitochondrial apoptotic pathway. By regulating the expression of proteins associated with the epithelial-mesenchymal transition and extracellular matrix both in vitro and in vivo, Nb2C-BBR nanocomposites significantly inhibited the migration and invasion of breast cancer cells following NIR-II irradiation. The functionalized nanoplatform for synergistic therapy efficiently destroyed cancer cells, inhibited metastasis, and induced only minor local tissue damage, demonstrating its potential as a treatment approach for metastatic tumors.

Abstract PL2: Plenary Lecture 2: Premenopausal ER+ Breast Cancer: Past, Present, and Future

Abstract Adjuvant endocrine therapy for premenopausal ER+breast cancer had a relatively challenging initial pathway. The earliest trials testing adjuvant ovarian ablation in premenopausal breast cancer were hampered by the lack of ability to test for the relevant target, namely the estrogen receptor (ER). Therefore, trials testing adjuvant ovarian ablation and subsequently ovarian suppression with gonadotropin releasing hormone agonists (GnRHa) were diluted by the inclusion of women with estrogen receptor negative tumors. The subsequent demonstration of the effectiveness of adjuvant chemotherapy, initially with the CMF regimen, diverted some attention away from adjuvant endocrine therapy in premenopausal women, notwithstanding the fact that CMF, initially given for 12 months, resulted in permanent ovarian function suppression in many premenopausal women. Use of adjuvant CMF made it even more challenging to discern the added value of ovarian ablation or suppression. Oral adjuvant endocrine therapy with the selective estrogen receptor modulator tamoxifen became recommended for postmenopausal women, subsequently refined to only those with ER+ breast cancer, but the value of tamoxifen in premenopausal women was initially considered uncertain. Eventually, 5 years of adjuvant tamoxifen became a standard recommendation for premenopausal ER+ early breast cancer, although it took some time for evidence to emerge on the value of adding tamoxifen in women who received chemotherapy. The value of extending adjuvant endocrine therapy beyond 5 years was subsequently studied. More recent randomized premenopausal adjuvant endocrine therapy trials have focused of delineating the value of ovarian function suppression (OFS) added to tamoxifen or to an aromatase inhibitor. There are now a range of options for adjuvant endocrine therapy for premenopausal ER+ breast cancer, and identifying the clinical-pathologic features most appropriate for intensification of adjuvant endocrine therapy can assist with optimizing recommendations for an individual patient. Citation Format: Carlos Arteaga, Prudence Francis. Plenary Lecture 2: Premenopausal ER+ Breast Cancer: Past, Present, and Future [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PL2.

Optimization of breast cancer ablation volume by ultrasonic pressure field characterization

In order to favor the potential in improving both oncologic and cosmetic results in breast cancer therapy, an Ultrasound (US) probe that increases cancer ablation volume and preserves neighboring healthy tissues in a modeled realistic breast from being ablated is designed using a finite element analysis (FEA) tool in this work. The acoustic pressure field and focal point of the Focused Ultrasound (FUS) are characterized by optimizing the transducer's frequency at 1.3 MHz and the initial water temperature at 20 °C. These optimal conditions yield qualitative properties of the FUS at the focal point, which are extended to wider areas to achieve quantitative results by displacing the probe at reduced time intervals of less than 60s. An elliptical focal volume of 10.2 mm (along the beam axis) × 4 mm (in the transverse direction) at 50s of dosing for a tumor diameter of 10 mm has been generated. Furthermore, a fractional healthy tissue damage of 2.1%, a rise in temperature of 99 °C above the ablation threshold temperature (42 °C) at 100 s of sonication, and an increase in pressure oscillation (favoring cavitation) at the focus are achieved. The optimal conditions of the setup are subjected to sensitivity tests and are found to be mostly sensitive to variations of the transducer frequency on which depend the attenuation coefficient and thermal conductivity of the tissue as well as the surface intensity of the transducer.

PH-Responsive doxorubicin-loaded magnetosomes for magnetic resonance-guided focused ultrasound real-time monitoring and ablation of breast cancer.

MR-guided focused ultrasound surgery (MRgFUS) is driving a new direction in non-invasive thermal ablation therapy with spatial specificity and real-time temperature monitoring. Although widely used in clinical practice, it remains challenging to completely ablate the tumor margin due to fear of damaging the surrounding tissues, thus leading to low efficacy and a series of complications. Herein, we have developed novel pH-responsive drug-loading magnetosomes (STPSD nanoplatform) for increasing the T2-contrast and improved the ablation efficiency with a clinical MRgFUS system. Specifically, this STPSD nanoplatform is functionalized by pH-responsive peptides (STP-TPE), encapsulating superparamagnetic iron oxide (SPIO) and doxorubicin (DOX), which can cause drug release and SPIO deposition at the tumor site triggered by acidity and MRgFUS. Under MRgFUS treatment, the increased vascular permeability caused by hyperthermia can improve the uptake of SPIO and DOX by tumor cells, so as to enhance ultrasound energy absorption and further enhance the efficacy of chemotherapy to completely ablate tumor margins. Moreover, we demonstrated that a series of MR sequences including T2-weighted imaging (T2WI), contrast-enhanced T1WI imaging (T1WI C+), maximum intensity projection (MIP), volume rendering (VR) and ADC mapping can be further utilized to monitor the MRgFUS ablation effect in rat models. Overall, this smart nanoplatform has the capacity to be a powerful tool to promote the therapeutic MRgFUS effect and minimize the side effects to surrounding tissues.

Cancer Cell-Specific and Laser-Activatable NanoSeeds for Targeted Photothermal Ablation of Triple-Negative Breast Cancer.

This investigation reports the quality-by-design (QbD) assisted novel templated approach for developing cancer cell-specific and laser-activatable nanoseeds (AuraTherm) for targeted photothermal ablation of triple-negative breastcancer (TNBC). AuraTherm was nanometric in size as characterized by SEM, TEM and particle analysis (80.28 ± 2.56 nm; -21.80 ± 0.17 mV) with hemocompatibility and neutrality towards blood components. AuraTherm showed reversible photothermal effect (ΔT: 37 ± 1.2°C → 49.4 ± 1.5°C; 15 min; 2.4 W cm-2 ) employing near-infrared 808 nm laser (NIR-808). The targeted cytosolic localization led to a significant anticancer activity as evaluated using apoptosis assay, cell cycle analysis, Intracellular ROS generation assay, cellular uptake and receptor binding assay. The NIR-808 laser-responsive photothermal ablation of cancer cell was found to be more effective compared to without NIR-808 laser-treated counterparts, suggesting the fundamental role of photothermal ablation in the treatment of TNBC.

Biomimetic nanotherapeutics based on oxygen supply and ultrasmall Cu-Se-Au alloy nanoparticles for boosting radio-photothermal ablation of breast cancer

Radiotherapy (RT) is one of the important tools for clinical treatment of breast cancer. Currently, some nanoradiosensitizers have been developed for augmenting the therapeutic efficiency of RT. However, some limitations still exist for their further applications, such as oxygen dependence in hypoxic tumors, nonideal selectivity for tumors, and inevasible damages to normal tissues. To resolve these problems, a biomimetic nanoplatform was developed for efficient co-loading and precise co-delivery of oxygen and nanoradiosensitizer by taking advantage of large pore volumes and easy surface modification of dendritic large pore mesoporous silica nanoparticles (DLMSNs). The outer surfaces of DLMSNs were modified with citric acid for attaching firmly and chelating stably with ultrasmall Cu-Se-Au alloy nanoparticles possessing distinct radiosensitizing and photothermal conversion performances. The inner surfaces of DLMSNs were modified with perfluorosilane for loading perfluorohexane that has extraordinary oxygen-carrying capability to alleviate tumor hypoxia. White blood cells membranes were wrapped onto the surfaces of the resultant DLMSNs for promoting co-delivery of therapeutic agents targeting to tumor and reducing injuries to normal tissues. Biomimetic nanotherapeutic system thus prepared showed powerful suppression effects against breast cancer both in vitro and in vivo by intelligently integrating tumor-targeted delivery, oxygen supply, radiosensitizing and photothermal ablation.

Targeting Tumor Acidosis and Regulatory T Cells Unmasks Anti-Metastatic Potential of Local Tumor Ablation in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an immunologically heterogenous disease that lacks clinically actionable targets and is more likely to progress to metastatic disease than other types of breast cancer. Tumor ablation has been used to increase response rates to checkpoint inhibitors, which remain low for TNBC patients. We hypothesized that tumor ablation could produce an anti-tumor response without using checkpoint inhibitors if immunosuppression (i.e., Tregs, tumor acidosis) was subdued. Tumors were primed with sodium bicarbonate (200 mM p.o.) to reduce tumor acidosis and low-dose cyclophosphamide (100–200 mg/kg i.p.) to deplete regulatory T cells, as has been shown independently in previous studies. A novel injectable ablative was then used to necrose the tumor, release tumor antigens, and initiate an immune event that could create an abscopal effect. This combination of bicarbonate, cyclophosphamide, and ablation, called “BiCyclA”, was tested in three syngeneic models of TNBC: E0771 (C57BL/6), 67NR (BALB/c), and 4T1-Luc (BALB/c). In E0771 and 67NR, BiCyclA therapy significantly reduced tumor growth and cured 5/7 and 6/10 mice 50 days after treatment respectively. In the metastatic 4T1-Luc tumors, for which surgery and checkpoint inhibitors fail, BiCyclA cured 5/10 mice of primary tumors and lung metastases. Notably, CD4+ and CD8+ T cells were found to be crucial for the anti-metastatic response, and cured mice were able to resist tumor rechallenge, suggesting production of immune memory. Reduction of tumor acidity and regulatory T cells with ablation is a simple yet effective therapy for local and systemic tumor control with broad applicability as it is not limited by expensive supplies.

CEUS Versus MRI in Evaluation of the Effect of Microwave Ablation of Breast Cancer.

Percutaneous microwave ablation (MWA) is a new minimally invasive technique for breast cancer treatment. The aim of this research was to compare the differences in performance between contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) with respect to the curative effect of MWA in the treatment of breast cancer. Between 2015 and 2019, 26 patients with breast cancer underwent ultrasound-guided MWA. All patients underwent both CEUS and MRI within 3 d after ablation. If either of the two imaging modalities revealed suspicious enhancement of the ablation zone and the ultrasound-guided biopsy confirmed residual tumor in the suspicious area, supplementary MWA was applied. The diagnostic efficacy of CEUS and MRI within 3 d after ablation was evaluated based on a >6-mo follow-up of 26 patients. Two cases were diagnosed with residual tumors by ultrasound that were missed by MRI. Three cases were diagnosed with residual tumors by MRI that were missed by CEUS. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of CEUS in the diagnosis of complete ablation were 100%, 40%, 87.5%, 100% and 88.5%, respectively. The sensitivity, specificity, PPV, NPV and accuracy of MRI in the diagnosis of complete ablation were 100%, 60%, 91.3%, 100% and 92.3%, respectively. Within 3 d, both CEUS and MRI can efficiently assess the efficacy of MWA of breast cancer.

Biomimetic Nanotherapeutics Based on Oxygen Supply and Ultrasmall Cu-Se-Au Alloy Nanoparticles for Boosting Radio-Photothermal Ablation of Breast Cancer

Biomimetic Nanotherapeutics Based on Oxygen Supply and Ultrasmall Cu-Se-Au Alloy Nanoparticles for Boosting Radio-Photothermal Ablation of Breast Cancer

Major depressive symptoms in breast cancer patients with ovarian function suppression: a cross-sectional study comparing ovarian ablation and gonadotropin-releasing hormone agonists

BackgroundOvarian function suppression (OFS) is indicated in premenopausal women with early or metastasis breast cancer, which may be achieved with similar effect by gonadotropin-releasing hormone agonists (GnRHa) or ovarian ablation (OA). We examined whether there were differences in major depressive symptoms outcomes and its associated factors between gonadotropin-releasing hormone agonists (GnRHa) and ovarian ablation (OA) in premenopausal breast cancer patients.MethodsPremenopausal breast cancer patients from seven hospitals who received OFS participated in the study between June 2019 and June 2020. The correlated variable was the type of ovarian suppression, categorized as either OA (n = 174) or GnRHa (n = 389). Major depressive symptoms was evaluated using the Patient Health Questionnaire (PHQ-9), and the Female Sexual Function Index questionnaire was used to assess sexual function.ResultsA total of 563 patients completed the surveys. The mean PHQ-9 sum score was slightly lower in the GnRHa cohort than in the OA cohort (11.4 ± 5.7 vs. 12.8 ± 5.8, P = 0.079). There were significantly fewer patients with major depressive symptoms (PHQ-9 ≥ 15) in the GnRHa cohort (31.1% vs. 40.2%, Exp (B)=1.805, P=0.004). Further, breast-conserving surgery and sexual dysfunction were negatively correlated with major depressive symptoms [mastectomy vs. breast-conserving: Exp (B) = 0.461, P <0.001;[sexual dysfunction vs. normal: Exp (B) = 0.512, P = 0.001].ConclusionsThis is the first study to demonstrate that GnRHa results in more favorable depressive symptoms outcomes than OA. Moreover, most patients preferred alternatives to their OFS treatment. These findings can contribute to improving and alleviating the adverse effects of OFS.

Assessment of Tumor Cell Death After Percutaneous Ultrasound– Guided Radiofrequency Ablation of Breast Carcinoma: A Prospective Study

Background: Current trends in breast cancer treatment include the use of less aggressive surgeries to reduce morbidity, shorten hospital stays and improve cosmetic results. The aim of the study is to assess tumor cell viability after percutaneous ultrasound (US)-guided radiofrequency ablation (RFA) for small breast cancer by a combination of staining techniques. Methods: A prospective study was conducted at a single institution from 2013 to 2017. Twenty women with invasive ductal carcinoma of the breast measuring ≤ 20 mm were treated with US-guided RFA followed immediately by surgical resection. Tumor viability pre- and post-RFA was assessed with Hematoxylin and Eosin (H&amp;E), Nicotinamide adenine dinucleotide (NADH), Succinate dehydrogenase (SDH), Cytochrome c oxidase (COX), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Cytokeratin 18 and 19 (CK18/CK19) staining techniques. Outcomes and correlation with the different techniques were evaluated with principal component analysis Cronbach’s alpha. Results: Oxidative enzymes in frozen sections showed loss of SDH and NADH in 13 of the 16 tumors (81%) and COX in 11 of the 13 tumors (84%). In paraffin-embedded tissues, CK18 was negative or markedly reduced in 98% and CK19 in 100% of the cases. Lack of evidence of cell death was seen in 3 cases where the maximum temperature achieved at the center of the tumor was ≤ 70ºC. The reliability and internal consistency between the different staining techniques was high (Cronbach’s alpha, 0.8), with concordance between the staining results of the oxidative enzymes and of CK18/CK19. Conclusion: Loss of tumor viability in small breast tumors after US-guided percutaneous RFA could be assessed in our series with different staining methods. CK18 and CK19 could be used in paraffin-embedded tissues as surrogate markers of tumor cell viability after immediate RFA.

Evaluation of Microwave Ablation in 4T1 Breast Tumor by a Novel VEFGR2 Targeted Ultrasound Contrast Agents

ObjectivesA novel ultrasound contrast agent (UCA) VEGFR2-targeting iron-doped silica (SiO2) hollow nanoparticles (VEGFR2-PEG-HSNs-Fe NPs) was prepared and applied in microwave ablation for breast cancer to investigate its value in the evaluation of effectiveness after tumor ablation.MethodsVEGFR2-PEG-HSNs-Fe NPs were prepared by using nano-SiO2, which was regarded as a substrate and etched by ferrous acetate, and then modified with anti-VEGFR2 antibody. Laser confocal microscope and flow cytometry were used to observe its main physicochemical properties, and biological safety was also investigated. After the xenograft tumor was treated with microwave ablation, the extent of perfusion defect was evaluated by ultrasound by injecting VEGFR2-PEG-HSNs-Fe NPs.ResultsThe average particle size of VEGFR2-PEG-HSNs-Fe was 276.64 ± 30.31 nm, and the surface potential was −13.46 ± 2.83 mV. In vitro, the intensity of ultrasound signal increased with UCA concentration. Good biosafety was performed in in vivo and in vitro experiments. The enhanced ultrasound signal was detected in tumors after injection of VEGFR2-PEG-HSNs-Fe NPs, covering the whole tumor. The lesions, which were incompletely ablated, presented as contrast agent perfusion at the periphery of the tumor, and contrast enhanced ultrasound (CEUS) was performed again after complementary ablation. It was confirmed that all the lesions were completely ablated.ConclusionNano-targeted UCAs VEGFR2-PEG-HSNs-Fe NPs had good biosafety and ability of specific imaging, which might be used as a contrast agent in CEUS to evaluate the efficacy of tumor ablation.

Visualizing the effects of lactate dehydrogenase (LDH) inhibition and LDH-A genetic ablation in breast and lung cancer with hyperpolarized pyruvate NMR.

In many tumors, cancer cells take up large quantities of glucose and metabolize it into lactate, even in the presence of sufficient oxygen to support oxidative metabolism. It has been hypothesized that this malignant metabolic phenotype supports cancer growth and metastasis, and that reversal of this so-called "Warburg effect" may selectively harm cancer cells. Conversion of glucose to lactate can be reduced by ablation or inhibition of lactate dehydrogenase (LDH), the enzyme responsible for conversion of pyruvate to lactate at the endpoint of glycolysis. Recently developed inhibitors of LDH provide new opportunities to investigate the role of this metabolic pathway in cancer. Here we show that magnetic resonance spectroscopic imaging of hyperpolarized pyruvate and its metabolites in models of breast and lung cancer reveal that inhibition of LDH was readily visualized through reduction in label exchange between pyruvate and lactate, while genetic ablation of the LDH-A isoform alone had smaller effects. During the acute phase of LDH inhibition in breast cancer, no discernible bicarbonate signal was observed and small signals from alanine were unchanged.