Cancer Surgery

Breast cancer is considered as one of the most frequent malignancies in women worldwide and one of the leading cause of death among women globally. Even with remarkable advances in diagnosis and therapy, the prognosis of breast cancer patients remains disappointing\[1\]\[2\]. Breast cancer is a highly heterogeneous disease that is classified into four subtypes based on the expression of certain hormonal receptors as estrogen receptor ER, progesterone receptor PR and human epidermal growth factor receptor HER2\[2\]. The following are the four subtypes of breast cancer: Luminal A tumors are characterized by the presence of ER and/or PR and the absence of HER2, Luminal B tumors are of higher grade and worse prognosis compared to Luminal A, they are ER positive and can be PR negative and have a high expression of Ki67 (greater than 20%), the HER2-positive group constitutes 10-15% of breast cancers and is characterized by high HER2 expression with absence of ER and PR and Triple-negative breast cancer which lack the expression of the previous three receptors\[3\]\[4\]. Epigenetics regulation of gene expression is the alteration in gene expression function without changing the nucleotide sequence. Both activation and inactivation of cancer-associated genes can occur by epigenetic mechanisms. The major players in epigenetic mechanisms of gene regulation are DNA methylation, histone modification, chromatin remodelers , and noncoding RNA expression\[5\]. Histone modifications are one of the important regulators of chromatin structure which is very crucial for gene expression as it defines accessibility of DNA for transcriptional regulators, affects gene expression, and influences vital cellular processes \[6\]. Histone modifications can recruit transcription factors, chromatin remodelers, and chromatin structural proteins so contribute to the formation and maintenance of active or repressive chromatin state\[6\]. The most important histone modifications are: lysine acetylation, lysine and arginine methylation, serine/threonine/tyrosine phosphorylation, and serine/threonine ubiquitylation \[6\]. Many of histone modification enzymes are frequently mutated in different types of cancer by example: EHMT2 (G9A) encodes a methyltransferase that methylates lysine residues of histone H3, Methylation of H3 at lysine 9 by this protein results in recruitment of additional epigenetic regulators and repression of transcription. The histone methyltransferase G9a is well-documented for its implication in neoplastic growth\[7\]. Another example on histone modification enzymes is KMT5B (SUV420H1) a methyl transferase enzyme that catalyzes the deposition of H4k20me mark, a repressive mark and is believed to have a tumor suppressor role in many cancer types\[8\]. The chromatin structure can also be regulated by chromatin remodelers' complexes, they are four conserved families of ATP-dependent chromatin remodelers in mammals (CHD), (ISWI), (INO80), and (SWI/SNF), and are involved in most essential cell processes \[9\]. Chromatin modification machinery is highly dysregulated in cancers including breast cancer by example: mutations or inactivation of genes encoding subunits of the SWI/SNF complex are found in approximately 20% of cancers\[10\]. Another important epigenetic mechanism is the effect of non-coding RNAs on gene expression. Non-coding RNAs (ncRNAs) are a heterogeneous group of transcripts that are not translated into proteins. They have emerged as important regulators of multiple biological functions, and their dysregulation has been implicated in diseases including cancer. They have gained a huge interest among the scientific community due to their use as disease biomarkers. There are many types of ncRNAs including miRNAs and lncRNAs\[11\]. MicroRNAs (miRNAs) are small, highly conserved non-coding RNA molecules (18-25) nucleotides involved in the regulation of gene expression. Accumulating studies have identified that microRNAs (miRNAs) are novel regulators acting as tumor suppressors or oncogenes in tumor progression\[12\]. It was reported that exosomal miR-138-5p exerts an oncogenic function in breast cancer patients via inhibiting KDM6B protein\[13\]. Peng Bian MD et al reported that The expression of miR-4306 was reported to be downregulated in breast cancer tissues if compared to adjacent tissues\[14\]. Long non-coding RNAs (lncRNAs) are another type of non-coding RNAs that are more than 200 nucleotides in length and most of them are not translated into proteins\[15\]. In spite of the fact that most lncRNAs are not translated, they have gained huge interest in research due to their regulatory functions on gene expression of other target genes\[15\]. LncRNAs regulate gene expression at the epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels by interacting with mRNA, DNA, protein, and miRNA\[16\]. Additionally, they have a crucial role in maintaining biological processes as histone modification, chromatin remodeling, transcriptional interference, transcriptional activation, mRNA translation and RNA processing\[16\]. Recently it was stated that lncRNAs are involved in many cancers as lung cancer, liver cancer, prostate cancer, bladder cancer and breast cancer\[2\] so, they can be used as a novel biomarker and pharmaceutical target in cancer therapy \[17\]. For example, the oncogenic lncRNA PVT1 promotes the proliferation of breast cancer cell via miR-181a-2-3p/ESR1 axis \[18\]. Importantly, lncRNAs can have a crosstalk with chromatin modifying and remodeling complexes to tightly regulate many normal cellular pathways as well as carcinogenic pathways. They can regulate the chromatin modification machinery whether by direct interaction or indirectly via sponging certain miRNAs. Example on direct interaction in cancer: LncRNA UCA1 regulates chromatin remodeling via binding with SMARCA4 to impair its binding to its region on p21 promoter which leads to bladder cancer proliferation\[19\]. Example on indirect interaction in cancer: LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH2 by sponging miR-150-5p\[20\]. LncRNAs can be detected in plasma/serum so function as non-invasive biomarker\[21\]. LncRNA UPK1A-AS1 is a newly identified biomarker in cancer. It was reported that, it has an oncogenic role in pancreatic cancer via conferring platinum resistance through double strand break repair\[22\]. Moreover, it was stated that UPK1A-AS1 promoted the proliferation of HCC by interacting with EZH2\[23\]. Despite the fact that lncRNA UPK1A-AS1 was reported to be oncogenic in HCC, pancreatic cancer and lung cancer cell lines, it was believed that it has a tumor suppressor role in esophageal squamous cell carcinoma cells cancer via sponging miR-1248\[24\]\[25\]. LncRNA UNC5B-AS1 has been recognized as an oncogene in thyroid cancer, prostate cancer and HCC\[26\] \[27\]. It also was stated that it has oncogenic role in ovarian cancer via regulating histone modification\[28\]. However, the role of lncRNAs UPK1A-AS1 and UNC5B-AS1 in the pathogenesis of breast cancer patients haven't been revealed yet. 1.2. Problem Definition. In Egypt, breast cancer is the most common malignancy among females with most of the cases being diagnosed at a late stage with poor prognosis\[29\]. Approximately 46,000 incident cases are forecasted in 2050. Although the incidence rate in Egypt is lower than the global figures., the mortality rate is much higher if compared with the developed countries by approximately 2 folds (41% v 23%) \[30\]. So, providing novel markers for breast cancer diagnosis and/or prognosis as well as understanding the molecular mechanisms underlying their link with carcinogenesis remains a challenge in management and treatment of breast cancer. 1.3. Hypothesis. As the problem statement is to provide novel markers that haven't been studied in breast cancer patients before to help in the diagnosis and prognosis of this aggressive disease. Accordingly, in the present study we will investigate the role of long non-coding RNAs UPK1A-AS1 and/or UNC5B-AS1 as possible diagnostic and/or prognostic markers in breast cancer. In addition, the possible crosstalk and correlation between these long non coding RNAs and chromatin modification enzymes and/or remodeling complexes as KMT5B and G9A via sponging certain target miRNAs as mir-138-5p and mir-4306 will be investigated. 2. PREVIOUS STUDIES FINDINGS 2.1. Zhang et al. reported that: UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p\[23\]. 2.2. Wang et al. reported that: UNC5B-AS1 promoted ovarian cancer progression by regulating the H3K27me on NDRG2 via EZH2\[28\]. 2.3. Hauang et al. reported that: UNC5B-AS1 promotes the proliferation, migration and EMT of hepatocellular carcinoma cells via regulating miR-4306/KDM2A axis\[26\]. 3\. AIM OF THE WORK Estimating the expression levels of our candidate lncRNAs UPK1A-AS1 and/or UNC5B-AS1 and correlate it with different clinical parameters in breast cancer patients and, shedding light on their possible crosstalk with chromatin modifying and/or remodeling proteins as KMT5B and G9A in breast cancer patients via sponging certain target miRNAs as mir-138-5p and mir-4306. 4\. RESEARCH OBJECTIVE(S) 4.1. Measure lncRNA UPK1A- AS1 and/or UNC5B-AS1 and their target miRNAs gene expression in serum samples (liquid biopsy) and/or tissue samples from breast cancer patients, using quantitative real time polymerase chain reaction technique (qRT-PCR). 4.2. Measure serum and/or tissue target proteins level, by ELISA. 4.3. Compare these ncRNAs expression level to the classical protein tumor markers, 4.4. Correlate these ncRNAs and target protein level axis, to the clinicopathological characteristics of breast cancer as tumor stage and grade, tumor progression (TNM), and other classical clinicopathological prognostic biomarkers such carcinoembryonic antigen (CEA), cancer antigen 15-3 (CA15-3), (ER), (PR), human epidermal growth factor receptor 2 (HER2/neu), the proliferation marker Ki-67 or PCNA and complete blood count (CBC), BMI, BP, blood glucose level and insulin. 5\. RESEARCH OUTCOME 5.1. Primary. Elucidate the role of our candidate lncRNAs and their downstream targets obtained from breast cancer patients' liquid biopsy and/or tissue samples. 5.2. Publication(s)/Visibility outcome. Review article + one international Scopus Q1 publication addressing results found + presenting finding(s) in an international high reputation conference. 6\. RESEARCH SIGNIFICANCE 6.1. To the best of our knowledge, This is the first research work measuring the expression level of UPK1A-AS1 and/or UNC5B-AS1 in breast cancer clinical samples. 6.2. These data could provide a promising approach in introducing a novel markers that help in the diagnosis and prognosis of breast cancer and provide a potential targets for gene therapy. 7\. RESEARCH METHODOLOGY 7.1. Bioinformatics Analysis 7.1.1. Investigating our candidate lncRNAs expression in breast cancer samples from gene expression profiling interactive analysis (GEPIA) based on data from The Cancer Genome Atlas data (TCGA). 7.1.2. Investigating target miRNAs by bioinformatics tools and/or experimental studies by using the online software miRcode (http://mircode.org/index.php). 7.1.3. Investigating selected miRNAs target genes via miRNA online tools: miRDB https://mirdb.org/index.html, starBase or ENCORI: https://rnasysu.com/encori/ and target scan: https://www.targetscan.org/vert\_80/. 7.1.4. Pathway analysis or Gene Ontology for list of target genes via enrichr database, the list of target genes was analyzed for their relation with chromatin modifying and/or remodeling proteins. 8\. ETHICAL STATEMENT 8.1.1. This research will be performed in accordance with the guidelines set by Declaration of Helsinki referring to the World Medical Association's (WMA) ethics guidelines for medical research with human subjects, originally published in 1964, revised in 2013 and October 2018. (https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/). Samples will be collected after participant's announcement and signing informed consent. 8.1.2. Ethical Approval and Consent to Participate. This study was first approved by the Research Ethical Committee (REC) of Faculty of Pharmacy, Ain Shams University 9. SAMPLE SIZE AND THE POWER OF STUDY 9.1. Estimated sample size was calculated by G power\* sample size online calculator http://www.gpower.hhu.de/en.html, using the following input data: α error probability is (0.05), the power of study (0.8). Based on the previous studies conducted by Bian et al, 2021 ;Huang et al,2021; Tan et al,2020; Madhvan et al,2014 \[31\] \[12\] \[24\] \[25\] that showed moderate to high effect size, a moderate effect size (0.5) was chosen to calculate the sample size. Total sample size will be 102 cases, this number will be subdivided into 2 groups either by ratio 50:50 or by ratio 60:40. 9.2. Study Design. Case-controlled, retrospective, mono-center study. 9.3. Study Participants. A series of Egyptian female breast cancer patients will be recruited from the Breast Cancer Unit, Clinical Oncology Department, Ain Shams University, Cairo, Egypt. Group 1; malignant non-metastatic breast cancer patients; newly diagnosed breast cancer patients. Group 2; control group; healthy volunteers. 9.3.1Clinico-pathological Criteria. Clinical data obtained from medical records and the original pathology reports. These data to be compiled in a detailed Excel file. The following clinical data to be recorded and assessed as in the attached excel file. * Full family history will be recorded for all breast cancer participants. * Individual cancer history and the tumor clinical assessment done using the (TNM) classification of American Joint Committee on Cancer (AJCC). * The Bloom-Richardson Scale will be used for histological grading. * The characteristics of the breast cancer patients with regards to body mass index (BMI), CBC, menopausal status, breast cancer histopathological types; invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). Breast cancer molecular classifications luminal A, B, triple negative breast cancer. * Tumor size, as well as clinico-pathological biomarkers CEA, CA15-3, ER, PR, Her2/neu, Ki-67 or PCNA (if any) data will be collected from patient files for further correlations and statistical analysis. 9.3.2. Inclusion Criteria; Egyptian females breast cancer patients aged 18 years and above, newly diagnosed with breast cancer. 9.3.3 Exclusion Criteria; blood diseases, any cancer other than breast cancer, liver cirrhosis and uterine and urinary bladder diseases or breast cancer patients with any evidence of distant metastases. 9.4. Blood Sampling: 6 mls peripheral blood will be collected into polymer gel vacutainers with clot activator (Greiner Bio-One GmbH, Australia), left for 15 min. at room temperature to clot, followed by a 10 min. centrifugation at 10,000g at 4°C, sera obtained will be aliquoted into 5 clean Eppendorf tubes and stored at -80°C, until biochemical assessment at Biochemistry Department, Faculty of Pharmacy, Ain-Shams University. 9.4.1 Stored sera will be used for ELISA technique measurements of target protein levels, using commercially available ELISA kits according to the manufacturer's instructions. 9.4.2. Genomic RNA will be extracted; ncRNAs extraction from serum samples and purification evaluation. ncRNAs expression level quantification, using qRT-PCR by step one plus. We will proceed with total RNA extraction from serum sample using miRNeasy Mini Kit. The c-DNA synthesis will be done afterwards using VERSO c-DNA synthesis kit (Thermo Scientific, USA). Next, we will carry out quantitative real time PCR (qRT-PCR) analyses using sybr green PCR master mix (Thermo Scientific, USA) and specific primers designed for the target ncRNAs as well as the housekeeping reference gene. 10\. STATISTICAL ANALYSIS 10.1. Data will be collected, excel tabulated, 10.2. SPSS IMB USA (SPSS, Chicago, IL) version 20, will be the used program or Stat4 or Graphpad Prism for figures, 10.3. Data will be tested for normality by Shapiro-Wilk calculator, 10.3.1. Normally distributed variables are to be expressed as mean+(S.E.M) and analyzed using two samples independent students t-test and ANOVA are to be used for comparison of 2 or more groups, if normally distributed, respectively. 10.3.2. Adjustment and normalization for confounders as age and BMI, .. between control and patients as well as multiple regression analysis or ANCOVA to predict a confounder, 10.3.3. Data to be presented as median (Range), if not normally distributed, Mann-Whitney (U) or Kruskal-Wallis (H) will be conducted to compare between any two or more independent groups, respectively, 10.4. P-values were two-tailed and considered significant if P \<0.05.11.

The extent of breast cancer is an important prognostic factor in patients diagnosed with this disease. Therefore, adequate staging at diagnosis is a requisite for optimal treatment. In all patients diagnosed with locally advanced breast cancer (LABC), distant staging using 18F-FDG PET/CT is recommended. However, the degree of metabolic uptake in the primary breast tumor is significantly lower in the ER+ subtype compared to HER2+ and triple negative breast cancer (TNBC). As a consequence, a suboptimal 18F-FDG uptake in ER+ breast cancer patients can potentially lead to missed distant metastases. Fibroblast-activating protein inhibitor (FAPI) is a recently developed radiotracer that binds to FAP, a stromal antigen overexpressed in more than 90% of epithelial-derived tumors and their metastases. Previous studies all show 68Ga-FAPI PET/CT to have a higher detection rate compared to 18F-FDG PET/CT. However, all previous studies were performed without considering breast cancer subtype. If the metabolic uptake by 68Ga-FAPI-46 is higher in ER+ breast cancer patients, more lesions will be detected, resulting in a more appropriate treatment for these patients. Therefore, in this pilot study, the investigators aim to compare the diagnostic performance of 18F-FDG with 68Ga-FAPI-46 as PET-tracer in ER+ breast cancer patients.

PRIMARY OBJECTIVES: I. To evaluate the relationship between 18F-FSPG PET/computed tomography (CT), pathology, and cancer metabolism in patients with suspected hepatocellular carcinoma (HCC) scheduled for liver resection surgery and orthotopic liver transplant (OLT). II. To compare 18F-FSPG PET/CT with standard-of-care (SOC) diagnostic MRI imaging in patients with suspected HCC scheduled for liver resection surgery or OLT. III. To compare the uptake of 18F-FSPG PET/CT with 11C-acetate PET/CT AND 18F-FDG PET/CT in suspected HCC and background liver in patients scheduled for liver resection surgery or OLT. IV. To evaluate uptake of 18F-FSPG PET/CT in benign liver lesions compared to background. V. To evaluate uptake of 18F-FSPG PET/CT in malignant non-HCC liver tumors. OUTLINE: Patients undergo 18F-FSPG PET and either carbon-11 (11C)-acetate PET or 18F-FDG PET scans within 4 weeks of surgery or OLT.

Historically, most pathologists have had little direct contact or communication with patients. In the past two decades, however, there has been a modest movement toward patient-pathologist visits in which pathologists review with patients their pathology slides. Very few studies of such encounters have been conducted. Most surveyed patients reported that the experience was positive and helpful to them. Our basic goal is to determine if such meetings are useful to patients; a secondary goal is to determine if such encounters are useful to, and practical for, pathologists.

This is a prospective, multicenter, controlled clinical study divided into three groups. The experimental group receives breast reconstruction using 3D-printed biodegradable material breast implants, while the control groups undergo traditional breast-conserving surgery or breast reconstruction with silicone implants. After providing full informed consent, subjects voluntarily choose their surgical approach, sign the informed consent form, and enter the trial period after passing screening. The specific treatment protocols are as follows: 1. Preoperative Patient-Reported Outcome Assessment: The Chinese version of the BREAST-Q V2.0 scale is used to evaluate breast aesthetics, satisfaction, and quality of life, with calculation of the Q-score. 2. Imaging Assessment: Enrolled patients undergo preoperative thin-slice breast magnetic resonance imaging (MRI), including conventional plain scan (SE T1WI sequence) and 3D dynamic contrast-enhanced scanning (FLASH sequence) to obtain three-dimensional enhanced images. 3. Surgical Simulation, Design, and 3D Printing of Fillers for the Experimental Group: Three-dimensional model data of the breast tissue to be resected are acquired via MRI scanning. The Mimics software is used to extract models of diseased and healthy tissues for surgical planning. Subsequently, Geomagic and 3-matic software are employed to design the breast filler model, which is optimized for mechanical properties, cell ingrowth conditions, and degradation time requirements. Finally, the breast implant model is layer-by-layer printed using polycaprolactone (PCL) as the material via selective laser sintering (SLS) technology, followed by sterilization for standby use. 4. Surgery: Experimental Group: Tumors are resected through transverse arc, periareolar, or radial incisions to ensure negative margins, followed by axillary lymph node dissection or sentinel lymph node biopsy. The 3D-printed filler is then implanted and sutured in place. Control Groups: Conventional breast-conserving surgery or nipple-areola-preserving subcutaneous gland resection combined with simultaneous breast reconstruction using implants is performed according to clinical routines. Incision types are selected by the surgeon. Tissue behind the nipple is sent for intraoperative pathological examination, and patch application is decided as needed. 5. Postoperative Managemen: Wound dressing changes are performed on schedule, and the occurrence of complications or adverse reactions (e.g., infection) is recorded. 6. Postoperative Systemic Therapy: Systemic chemotherapy or endocrine therapy is administered according to standard protocols. All patients in the experimental group receive local radiotherapy following the regimen for conventional breast-conserving surgery, including boost irradiation to the tumor bed. Radiotherapy for the control groups is decided according to current clinical guidelines and specifications. 7. Postoperative Follow-Up Imaging and Assessments: Ultrasound Examinations: Routine breast ultrasound is conducted weekly within the first postoperative month, then monthly thereafter, to record changes in blood supply in the filler area. Full-volume breast ultrasound is performed every 3 months. MRI Examinations and PRO Assessments: MRI is conducted at 3, 6, 12, and 24 months postoperatively. Concurrently, the Chinese version of the BREAST-Q V2.0 scale is used to evaluate breast aesthetics, satisfaction, and quality of life, with calculation of the Q-score. 8. Database Follow-Up: Telephone follow-ups are conducted once monthly, and in-person follow-ups are conducted once every 3 months.

The project refers to a study on patients with T1-T3 Nx-N3 breast cancer, aged under 40 years or with unfavorable histology (lobular carcinoma, multifocal tumor, or histological subtypes Luminal B Her2 positive, Hormonal Receptors negative Her 2 positive, Triple Negative Breast Cancer-TNBC-) treated with breast-conserving surgery (BCS) and radiotherapy to the whole breast (+/- lymph node areas) to a total dose of 26 Gy in 5 fractions, with simultaneous boost (SIB) to the tumor bed to the total dose of 30 Gy, that will be compared with the current departmental standard of moderately hypofractionated radiotherapy to the whole breast, to 40.05 Gy in 15 fractions, with SIB to the tumor bed to a total dose of 48 Gy.

The goal of this study is to evaluate 5 days vs. 9 days of whole breast radiation.

Previous studies have shown that compared with conventional 18F-FDG PET/CT, 68Ga-FAPI PET/CT has the characteristics of not being affected by blood glucose, good tumor specificity, and high tumor-to-background ratio, and studies have shown that 68Ga- FAPI PET/CT can detect parts of breast cancer primary lesions and lymph node metastases with low 18F-FDG uptake, thereby increasing the lesion detection rate and improving the sensitivity of imaging examinations. Therefore, 68Ga-FAPI PET/CT may be used as a new effective methods for evaluating axillary lymph node efficacy after neoadjuvant treatment for breast cancer. Therefore, we plan to conduct this study to explore the ability of 68Ga-FAPI PET/CT to detect residual disease in axillary lymph nodes in patients with clinically positive axillary node (cN+) breast cancer after neoadjuvant treatment. By this way, we may explore an accurate and non-invasive assessment of axillary lymph node status after neoadjuvant therapy in breast cancer patients.

Conventional 18F-FDG PET/CT has important diagnostic value in cell metabolism level, early metastasis, judging malignant potential and prognosis of tumors. It has been routinely used for staging and restaging of most tumors, but there are still some tumors with low uptake of 18F-FDG PET/CT. Receptor imaging with a single target also has some limitations in clinical application. For example, not all diseased cells express a large amount of single receptor on the surface, which greatly affects the judgment of the nature of the lesion. The dual-target molecular imaging based on GRPr expressed in the lesion site and integrin αvβ3 receptor highly expressed on the surface of the lesion neovascularization will overcome the above limitations and make full use of the advantages of the dual-target molecular imaging, which will greatly assist the diagnosis of malignant tumors such as breast\\brain\\prostate tumor which have high GRPr and αvβ3 receptor expression . In this study, a novel dual-target imaging agent 68Ga-RM26-RGD was used for PET/CT imaging of breast\\brain\\prostate cancer, compared with conventional 18F-FDG, or single target imaging agent 68Ga-RGD or 68Ga-RM26 PET/CT imaging.

Human trophoblast cell-surface glycoprotein antigen 2 (Trop2) is a membrane surface receptor that plays an important role in the occurrence and development of tumors. Studies have shown that Trop2 is highly expressed in a variety of cancers (such as breast cancer, lung cancer, gastric cancer, colorectal cancer, pancreatic cancer, prostate cancer, cervical cancer, head and neck cancer, and ovarian cancer, etc.) and is related to the proliferation, invasion, and metastasis of tumor cells. and other processes related. According to statistics, more than 80% of breast cancer patients highly express Trop2, and high expression of Trop2 is positively correlated with shortened survival and poor prognosis of cancer patients. In this study, a single-domain antibody targeting Trop2 was selected to prepare a new nuclear medicine molecular probe 99mTc-MY6349, so as to monitor the expression level of Trop2 in patients' systemic tumors through SPECT/CT imaging. Breast cancer patients who intend to use gosatuzumab for subsequent treatment can first undergo 99mTc-MY6349 SPECT/CT imaging to detect Trop2 expression levels in systemic tumors. Subsequently, 18F-FDG PET/CT imaging was performed to compare and detect the distribution of primary tumors and systemic metastases in patients with breast cancer. This study analyzes the heterogeneity of Trop2 expression levels within the primary tumor and the heterogeneity of expression levels in systemic metastases, thereby providing a basis for testing whether the patient is suitable for subsequent treatment and conducive to the formulation of subsequent treatment plans.