Breast Cancer

Since late 2019, the French association "MON PARCOURS DE VIE" has developed books donated by caregivers at cancer centers in France. These documents are available online: https://www.monparcoursdevie.fr/. They are highly acclaimed by women suffering from the breast cancer, as well as by caregivers. Four volumes have been written: 'Metastatic breast cancer', 'Localized breast cancer', 'Preserving my well-being', 'After breast cancer', and finally 'Breast cancer, support and accompaniment'. The aim in writing these information brochures is to provide clear, concise, useful information, with pedagogy, gentleness, benevolence, humility, cheerfulness, imagination, simplicity and an innovative presentation. These documents are a new and innovative method of providing information, delivered by caregivers who work with women suffering from breast cancer. It extends the human support so necessary in this disease. It seemed important to us to evaluate, through a clinical study, the impact of the written documents "Mon Parcours de Vie" - volume 2: Breast cancer and volume 3: Preserving my well-being, concerning the announcement of a localized breast cancer in the initial management for the first time in the breast pathway. The objectives of the clinical study are to evaluate the acceptability and impact of these two written information documents on anxiety generated by the announcement of cancer and treatment.

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.

Patients with cancer receiving systemic anti-cancer treatments have been generally assumed by many to be at a higher risk from the disease than their counterparts are who are not receiving anticancer treatment. However, their risk of morbidity and mortality from COVID-19 as a consequence of severe acute respiratory syndrome coronavirus 2 infection is not uniform across the world. The evidence to support this claim is scarce and limited to retrospective series arising from China, the epicenter of the COVID-19 pandemic, and involving small numbers of patients. However, despite these severe limitations, the promulgation of this hypothesis has led to widespread global changes to patterns of prescribing chemotherapy and anticancer treatment. In a global health emergency, oncologists, must secure evidence from a large datasets, which can then inform their risk-benefit analyses for individual patients in terms of the use of anticancer treatments. On March 18, 2020, the investigators launched the UK Coronavirus Cancer Monitoring Project (UKCCMP), with widespread support across our national cancer network. 8 Within 5 weeks, the UKCCMP had generated the largest prospective database of COVID-19 in patients with cancer that had been generated to date. the investigators aimed to describe the clinical and demographic characteristics and COVID-19 outcomes in this cohort of patients with cancer and symptomatic COVID-19, and attempted to assess how the presence of cancer and the receipt of cytotoxic chemotherapy and other anticancer treatments affects the COVID-19 disease phenotype. New Taipei City Municipal Hospital has established a special infectious pneumonia ward in May 2021 to treat patients infected with symptomatic severe acute respiratory syndrome coronavirus 2 patients. During the period, 97 patients were admitted and treated with 10 infection-related deaths. In light of the current timing of the pandemic, most published serological studies are predominantly cross-sectional, or at most, include a longitudinal follow-up of few months. Severe acute respiratory syndrome coronavirus 2 has spread globally over the past year, infecting an immunologically naive population and causing significant morbidity and mortality. Immunity to severe acute respiratory syndrome coronavirus 2 induced either through natural infection or vaccination has been shown to afford a degree of protection against reinfection and/or reduce the risk of clinically significant outcomes. Seropositive recovered subjects have been estimated to have 89% protection from reinfection, and vaccine efficacies from 50 to 95% have been reported. However, the duration of protective immunity is presently unclear, primary immune responses are inevitably waning, and there is ongoing transmission of increasingly concerning viral variants that may escape control by both vaccine-induced and convalescent immune responses. Age is considered one of the most crucial covariates that affect phenotypes. However, aging rate may vary among different populations due to genetic variation or miscellaneous environmental exposures. Chronological age is not a perfect proxy for the true biological aging status of the body. A new biological aging measure, phenotypic age (PhenoAge), has been shown to capture morbidity and mortality risk in the general US population and diverse subpopulations. However, how the phenotypic age affect host immunity is not well investigated. There are currently no effective therapies for severe acute respiratory syndrome coronavirus 2, which causes severe respiratory illness or death. Serum neutralizing antibodies rapidly appear after severe acute respiratory syndrome coronavirus 2 infection and vaccination. However, little was known about the change of protective antibody titers both to nature infection and post vaccination. And there is ongoing transmission of increasingly concerning viral variants that may escape control by both vaccine-induced and convalescent immune responses. Defining the antibody response to severe acute respiratory syndrome coronavirus 2 in patients with cancer receiving anti-cancer therapy, (including chemotherapy, targeted therapy and immunotherapy) will be essential for understanding infection progression, long-term immunity, vaccine efficacy and how phenotypic age affect associated antibodies.

This open-label research study is studying (Z)-endoxifen as a possible treatment for pre-menopausal women with ER+/HER2- breast cancer. (Z)-endoxifen belongs to a group of drugs called selective estrogen receptor modulators or "SERM", which help block estrogen from attaching to cancer cells. This study has two parts: a pharmacokinetic part and a treatment part. The PK part (how the body processes the drug) will enroll about 18 participants. All participants will take (Z)-endoxifen capsules daily. Twelve participants will be randomly assigned (50/50 chance) to take (Z)-endoxifen alone or (Z)-endoxifen with a monthly injection of goserelin a drug that temporarily stops the ovaries from making estrogen. This part will help determine the best dose of (Z)-endoxifen by measuring the drug levels in the blood and how long the body takes to remove it. The Treatment Cohort has been simplified to a single study arm (Z)-endoxifen + goserelin. Up to 20 participants will be enrolled that have a baseline Ki-67 ≤ 10% and 45 participants will be enrolled that have a baseline Ki-67\>10%. A key goal of the study is to see if (Z)-endoxifen can slow down or stop tumor growth as measured by a reduction in Ki-67 levels. Tumor tissue samples will be taken by breast biopsy after about 4 weeks of treatment to check levels of this biomarker. If the tumor shows signs of response, participants can continue treatment for up to 24 weeks or until they have surgery. Study participation is up to 6 months (24 weeks of treatment) followed by surgery and a one-month follow up visit.

This is a first in human, Phase 0/1, open-label study of 177Lu-RAD204 consisting of an Imaging Period with 177Lu-RAD204im (imaging dose) and a Treatment Period with 177Lu-RAD204tr (treatment dose) to determine the recommended dose(s) for future exploration of 177Lu-RAD204 in participants with PDL1+ advanced solid tumors. Screening Period: Screening Period of up to 4 weeks. Phase 0 (Imaging Period): Low dose (10mCi) of 177Lu-RAD204 administered on Imaging Day 1 with a follow-up period of up to 2 weeks to assess imaging, safety and dosimetry. The dose may be increased, if needed, to improve image quality. Phase 1 (treatment Period): 177Lu-RAD204tr dose escalation * Treatment Period with each cycle lasting 6 weeks. Extension of the planned dose intervals are possible following discussion and agreement between the Sponsor and Investigator. * Participants may be treated with multiple cycles, as long as they appear to derive clinical benefit as determined by the Investigator and provided there is adequate clinical safety and organ dosimetry data. * Dose Limiting Toxicity (DLT) observation period for 177Lu-RAD204tr is 6 weeks following the first injection of 177Lu-RAD204tr. * Should an alternative treatment schedule be explored, the DLT observation period for 177Lu-RAD204tr at that dose level will be the proposed cycle duration.

The purpose of this study is to establish the safety profile, biodistribution, pharmacokinetics (pk), and radiation dosimetry of 177Lu-BetaBart, to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), and to evaluate preliminary anti-tumor activity in select patient populations. The study is divided into 2 phases. Phase 1 is the dose escalation phase to establish the safety profile of 177Lu-BetaBart and to determine the MTD and/or RP2D of 177Lu-BetaBart using a Bayesian Optimal Interval (BOIN) design. Phase 2a is the dose expansion phase at the RP2D to confirm the safety of the MTD and/or RP2D and to evaluate preliminary anti-tumor activity of 177Lu-BetaBart in select patient populations using a probability of success design for the objective response rate (ORR) based on a Bayesian beta-binomial design. Participants ≥ 18 years of age with castration-resistant prostate cancer (CRPC), colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), head and neck squamous cell carcinoma (HNSCC), ovarian cancer, cervical cancer, endometrial cancer, triple negative breast cancer (TNBC), or esophageal squamous cell carcinoma (ESCC) who have documented disease progression during or after their most recent line of anticancer therapy will be eligible to enroll. CRC will be capped at 33% of enrollment per cohort. Each phase consists of a Screening Period, a Treatment and Imaging Period, and a Safety and Long-term Follow-up Period.

Subjects with various types of cancer underwent 18F-FAPI-04 PET/CT and PET/MR imaging either for an initial assessment, recurrence detection or assessment of pathologic response. Tumor uptake was quantified by the maximum standard uptake value (SUVmax) and tumor to background (TBR). Using histopathology and follow-up as gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 18F-FAPI-04 PET/CT and PET/MR were calculated.

Purpose To investigate the ability of 18F-FDG PET/CT imaging to detect metastases not detected by conventional imaging (CT and bone scintigraphy) in patients diagnosed with stage II/III and locoregional recurrent breast cancer (BC) which can affect the choice of treatment. Hypothesis The hypothesis is that 18F-FDG PET/CT can provide information about disease stage beyond the currently used conventional imaging (CT and bone scintigraphy) in patients diagnosed with stage II/III or locoregional recurrent BC. Objectives Primary: To evaluate if a 18F-FDG PET/CT scan in the initial work up of patients diagnosed with stage II/III or locoregional recurrent BC will lead to change in staging and/or treatment. Secondary: * Overall survival (OS) and progression-free survival (PFS) in the patients with upstaging based on findings on 18F-FDG PET/CT scan compared with the patients with unchanged stage of disease following 18F-FDG PET/CT. * Obtain size of the primary BC from CT/MRI scan and evaluate if these metrics are correlated to outcome. * Obtain PET parameters from the primary BC: maximum, mean, and peak standardized uptake value (SUVmax, SUVmean, SUVpeak), metabolic tumour volume (MTV), total lesion glycolysis (TLG), total MTV and total TLG and evaluate if these metrics are correlated with outcome. * Obtain CT and PET texture parameters from the primary BC and evaluate if these metrics are correlated with outcome. * Blood and tumor samples for molecular characterisation:

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.

This study is a single-center, bidirectional cohort study. It aims to include 35 elderly (≥65 years old) Luminal A type breast cancer patients with axillary lymph node metastasis after surgery as the research subjects. After signing the informed consent, the patients who meet the inclusion criteria will have their various clinical and pathological data collected (preoperative imaging examinations, clinical and pathological information of the patients, basic disease conditions and medication strategies, surgical records, postoperative planned treatment plans and actual treatment situations, etc.), and their real adjuvant treatment situations (whether chemotherapy, radiotherapy, endocrine therapy, targeted therapy, etc. were performed after surgery) will be followed up and recorded. At the same time, paraffin tissues of breast cancer and metastatic lymph nodes of the patients will be collected from the pathology department of our hospital for 21-gene assay, and the recurrence risk index of the primary lesion and metastatic lymph nodes will be obtained using the risk index calculation logic of Amoy Diagnostics Company. An assessment will be conducted every 12 months after surgery until disease recurrence. After disease recurrence, survival follow-up will be conducted every three months until the patient's death. The predictive value of 21-gene assay for patient survival and whether chemotherapy is beneficial will be evaluated based on the follow-up data of the patients.