Disease In Breast Cancer Patients Research Articles

Incidence of cardiovascular diseases among breast cancer patients: a nationwide registry study 2013-2020

Abstract Background and aims There is evidence to suggest that breast cancer (BC) treatment is associated with an increased risk of developing cardiovascular disease (CVD). Several countries have introduced clinical measures to reduce the impact of breast cancer treatment on cardiovascular function including activated breathing control during radiotherapy, lower radiation doses, and maximum anthracycline doses. The overall aim of this study was therefore to investigate whether breast cancer patients still exhibit higher rates of cardiovascular disease than the general population. Methods We conducted a registry-based cohort study using linked data from four nationwide health registries. Out study population included all Norwegian patients diagnosed with BC between 2013-2020 and matched them by age to 10 controls without BC. Health outcomes were measured from 2008 to 2021. We estimated the cumulative incidence from index date, for ten selected CVDs. For BC patients, the index date was defined as date of BC diagnosis. For controls, the index date was defined as the date of BC diagnosis for the matched BC patient. A wash-out period of 5 years was applied to identify incident cases of CVD. Results The study population included 27,535 patients with BC and 269,9994 matched controls. Median age in both groups was 62 years (IQR: 20). Prior to index date, there were no significant differences in the prevalence of heart valve disease, chronic ischemic heart disease heart failure and peripheral vascular disease in BC patients compared to controls (p>0.05) (Table 1). Hypertensive heart disease, pulmonary embolism, atrial fibrillation, and other cardiac arrythmias were more prevalent in BC patients, while angina pectoris and acute myocardial infarction were more prevalent among controls. After the index date, the incidence proportion for heart valve disease, hypertensive heart disease, pulmonary embolism, atrial fibrillation, other cardiac arrythmias, and heart failure were higher in BC patients compared to controls (p<0.001) (Table 2). No significant differences were found for angina pectoris, acute myocardial infarction, chronic ischemic heart disease, and peripheral vascular disease. Conclusion Breast cancer is still associated with an increased risk of developing several CVDs in current clinical practice, compared to matched controls without breast cancer.Baseline characteristicsIncidence of CVD

Adherence to cardiovascular medications and risk of cardiovascular disease in breast cancer patients: A causal inference approach in the Pathways Heart Study

Purpose Women with breast cancer (BC) are at high risk of developing cardiovascular disease (CVD). We examined adherence to CVD medications and their association with major CVD events over 14 years of follow-up in the Pathways Heart Study, a prospective study of 4,776 stage I-III BC patients diagnosed from 2005–2013. Methods Eligibility included being alive 6 months post-BC diagnosis, with dyslipidemia, hypertension, or diabetes at diagnosis along with ≥1 prior outpatient order or dispensing for a statin, anti-hypertensive, or diabetes medication, respectively, in the 30 months prior. Medication adherence was measured from pharmacy data to calculate cumulative average adherence (CAA). Incident heart failure (HF), ischemic heart disease (IHD), and stroke were determined via validated diagnosis and procedure codes. Working marginal structural models (MSM) fitted with inverse probability weighting evaluated the effect of adherence regimens on the hazards for each CVD event, while controlling for baseline and time-varying confounders. MSM parameterizations included: 1) CAA<100% versus CAA = 100% (ref), 2) CAA<80% versus CAA≥80% (ref) and 3) CAA<80% versus 80%≤CAA<100% versus CAA = 100%. Results Poor statin adherence (CAA<80%) was associated with higher risk of composite CVD (HR = 2.54; 95% CI: 1.09, 5.94) versus CAA≥80%. Poor statin adherence was also associated with a higher risk of stroke (HR = 8.13; 95% CI: 2.03, 32.51) but not risk of IHD and HF. Further, compared with perfect adherence (CAA = 100%), good adherence (80%≤CAA<100%) was associated with lower risk (HR = 0.35; 95% CI: 0.13, 0.92) while poor adherence (CAA<80%) was associated with higher risk of composite CVD (HR = 2.45; 95% CI: 1.05, 5.70). Levels of adherence to anti-hypertensives and diabetes medications had mixed or null associations with risk of CVD. Conclusions Maintaining good adherence (≥80%) to statins after BC treatment is beneficial for cardiovascular health in patients with dyslipidemia. Future studies should determine factors associated with lower adherence to statins and ways to improve adherence.

18 F FDG PET/CT versus 99m Tc MDP Bone scintigraphy in imaging of metastatic osseous disease in breast cancer patients; Solving the discrepancies in light of serum markers.

To assess the performance of 18 F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) versus 99m Tc MDP bone scan in assessment of metastatic osseous disease in breast cancer patients in relation to serum markers. We reviewed PET/CT studies and bone scans for 37 patients (mean age of 55.38 ± 13.08 years) with metastatic breast cancer to bone. To assess metastatic osseous burden, we used semiquantitative scores derived from PET/CT (PMS) and bone scans (BMS). We used McNemar test to compare lesion detection between both modalities and receiver operator characteristic analysis to define the cutoff value of serum CA 15-3 that best predicts additional value for PET/CT over bone scan. In 13 patients (35.1%), more lesions or higher-intensity lesions were detected on PET/CT, while only 4 patients (10.8%) had more prominent lesions on bone scans ( P = 0.049). Additional lesions seen on PET/CT are predominantly osteolytic or medullary (early phase). Most lesions with higher uptake on bone scans appear sclerotic (late phase). CA 15-3 was positively correlated to PMS ( r = 0.386; P = 0.018) but not to BMS ( r = -0.027; P = 0.874). However, serum alkaline phosphatase was positively correlated to both PMS ( r = 0.389; P = 0.017) and BMS ( r = 0.363; P = 0.027). CA 15-3 value of >47 U/ml best predicted additional findings on PET/CT compared to bone scans (area under the curve = 0.708; P = 0.0261). FDG PET/CT detects metastatic osseous lesions during an earlier phase. A higher CA 15-3 predicts a higher metastatic burden on PET/CT but not on bone scan. Bone scans are less specific, likely by missing early lesions and detecting persistent uptake in healing sclerotic lesions.

The surgical management of axillary lymph node disease in breast cancer patients

The precise assessment and management of the axillary lymph nodes in breast cancer is crucial for regional control, disease staging, selection of adjuvant chemotherapy strategies, and prediction of prognosis, with a general downward trend in surgical management. For early breast cancer with negative axillary lymph node metastases, sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as the criterion for axillary status measurement. Patients can be exempted from ALND if they have negative SLNB results. However, it remains to be carefully decided in China whether patients with one or two positive nodes in SLNB can be spared from ALND. However, consensus has been met that patients who meet the criteria of the Z0011 study can be exempted from ALND. For breast cancer patients with positive axillary lymph nodes metastases at the beginning of treatment, the clearance of lymph node disease can be achieved by neoadjuvant therapy, with a reduced rate of complications related to ALND. In particular, there are still many debates associated with SLNB after neoadjuvant therapy, such as whether patients who remain axillary lymph node positive can be spared from ALND. Exploratory and validation studies related to the SLNB avoidance criteria are still controversial. In the future, clinicians should consider the characteristics of patients, the risk of recurrence, and adjuvant treatment regimens to develop individualized axillary lymph node management.

A nomogram for predicting pathologic node negativity after neoadjuvant chemotherapy in breast cancer patients: a nationwide, multicenter retrospective cohort study (CSBrS-012).

This study aimed to investigate the factors associated with pathologic node-negativity (ypN0) in patients who received neoadjuvant chemotherapy (NAC) to develop and validate an accurate prediction nomogram. The CSBrS-012 study (2010-2020) included female patients with primary breast cancer treated with NAC followed by breast and axillary surgery in 20 hospitals across China. In the present study, 7,711 eligible patients were included, comprising 6,428 patients in the primary cohort from 15 hospitals and 1,283 patients in the external validation cohort from five hospitals. The hospitals were randomly assigned. The primary cohort was randomized at a 3:1 ratio and divided into a training set and an internal validation set. Univariate and multivariate logistic regression analyses were performed on the training set, after which a nomogram was constructed and validated both internally and externally. In total, 3,560 patients (46.2%) achieved ypN0, and 1,558 patients (20.3%) achieved pathologic complete response in the breast (bpCR). A nomogram was constructed based on the clinical nodal stage before NAC (cN), ER, PR, HER2, Ki67, NAC treatment cycle, and bpCR, which were independently associated with ypN0. The area under the receiver operating characteristic curve (AUC) for the training set was 0.80. The internal and external validation demonstrated good discrimination, with AUCs of 0.79 and 0.76, respectively. We present a real-world study based on nationwide large-sample data that can be used to effectively screen for ypN0 to provide better advice for the management of residual axillary disease in breast cancer patients undergoing NAC.

Correlation of IDH1 gene expression error in breast tumor biopsy in patients with invasive ductal carcinoma.

One of the most important cancers in terms of worldwide prevalence is breast tumors, which have been less investigated in correlation with the enzyme Isocitrate Dehydrogenase 1 (IDH1) gene. The aim of this study was that expression of this gene could have significant effects on the progression of metastasis and invasive disease in breast cancer patients. We used the molecular method of RT-PCR with SYBR-Green to analyze breast tumor tissue from patients with metastasis and non-metastasis, the latter confirmed by the pathology department of Shohada-e Tajrish Hospital (serving as a control group). Also, patients population and its relationship with the degree of tumor in the IDH1 gene was investigated. The IDH1 gene has shown high expression in patients with metastatic breast cancer rather than in patients with non-metastatic breast cancer. The metastatic samples were compared with non-metastatic samples for IDH1 mRNA expression. In this research work, 72.5% (29 samples) were up-regulated in comparison to 27.5% of samples (11 samples) that did not exhibit high expression (P=0.000). This study examined the IDH1 gene expression, suggesting that changes in this gene's expression could impact the prognosis of breast cancer. However, further research is needed to draw definitive conclusions.

Is dobutamine stress echocardiography a good screening tool for coronary artery disease in breast cancer patients that underwent treatment with radiotherapy?

Abstract INTRODUCTION Accelerated atherosclerosis has been described in breast cancer patients receiving cardiac exposure from adjuvant radiotherapy (RT). As a result of multidisciplinary care, breast cancer cure rates have improved in recent decades. Therefore, evaluating radiation-induced heart disease (RIHD), especially coronary artery disease (CAD), is essential. The 2022 cardio-oncology European Society of Cardiology (ESC) guidelines recommend screening patients 5 to 10 years after RT for CAD according to cardiovascular risk factors. This screening is generally recommended with exercise stress echocardiography since it can assess the physiological functional performance. Until now, it is unknown if dobutamine stress echocardiography (DSE) is an equal screening tool and if it can predict major adverse cardiovascular events (MACE) (myocardial infarction, stroke, cardiac death, revascularization). PURPOSE Evaluate if DSE is an adequate tool to stratify and predict MACE in post-radiotherapy patients. Methods A retrospective, descriptive cohort study was conducted. Patients who had chest RT for breast cancer and underwent DSE from 2000 to 2022 were included. A bivariate analysis, including Kruskal Wallis and Pearson Chi-Squared test, was done to identify variables associated with a positive DSE. A multivariable Cox Model for MACE and a time-to-event curve for MACE were also performed. Results We identified 163 patients that underwent DSE after a median time of 5.8 years from the end of RT. The median age was 74 years, 98.2% were female, 50% had left and 45% right breast cancer, 81% had hypertension, 41% diabetes mellitus, 71% dyslipidemia, 34% were smokers, and 19% had a prior myocardial infarction. The average dose of photon RT to the chest was 55Gy in the cohort, and 40% received chemotherapy before RT. Patients were divided into two groups: positive and negative DSE. A positive DSE was seen in 19.6%. The median (Q1, Q3) regional wall motion abnormalities (RWMA) of patients with a positive DSE was 1 (1, 1.015) at baseline and 1.280 (1.190, 1.520) at peak stress, and for a negative DSE, was 1 (1, 1) at baseline and peak stress. 88.2% of negative DSE and 87.5% of positive DSE achieved the target heart rate of 85%. HTN, dyslipidemia, and prior MI were significantly associated with a positive DSE (p <0.023). The cumulative incidence of MACE was higher in the group of positive DSE (p<0.001), even after adjusting for hypertension, diabetes mellitus, dyslipidemia, smoking, and prior myocardial infarction, with a hazard ratio of 2.500 (1.51 – 4.13) and a p< 0.001. Similar results were observed regardless of RT laterality. Conclusions In breast cancer survivors that received adjuvant radiotherapy as part of multidisciplinary care, a positive DSE was an independent predictor of MACE compared to a negative result. These results support the usefulness of dobutamine stress echocardiography as a screening tool in breast cancer survivors.Kaplan-Meier Curve for MACE

Systemic Treatment for Brain Metastasis and Leptomeningeal Disease in Breast Cancer Patients.

Breast cancer with brain metastasis (BCBM) and leptomeningeal disease (LMD) are important clinical problems. Traditionally, patients with metastases to the brain and meninges were excluded from clinical trials; hence, robust, evidence-based treatment recommendations are lacking. In this review, we outline the systemic treatment options and ongoing clinical trials. Several recent studies have added to the systemic treatment options available. Antibody-drug conjugates have changed the therapeutic landscape. Combination treatment modalities that target multiple mechanisms including disruption of the blood brain barrier are increasingly being studied. Breast cancer with brain metastases and LMD is a heterogenous disease. While the prognosis remains grim, with more systemic treatment options, patients with BCBM are now living longer. Many ongoing clinical trials hold promise to further improve outcomes.

Matte Analysis of Self-management Model of Chronic Disease in Breast Cancer Patients

Matte Analysis of Self-management Model of Chronic Disease in Breast Cancer Patients

Quantitative cardiovascular magnetic resonance findings and clinical risk factors predict cardiovascular outcomes in breast cancer patients.

Cardiac magnetic resonance (CMR) global longitudinal strain and circumferential strain abnormalities have been associated with left ventricular ejection fraction (LVEF) reduction and cardiotoxicity from oncologic therapy. However, few studies have evaluated the associations of strain and cardiovascular outcomes. To assess CMR circumferential and global longitudinal strain (GLS) correlations with cardiovascular outcomes including myocardial infarction, systolic dysfunction, diastolic dysfunction, arrhythmias and valvular disease in breast cancer patients treated with and without anthracyclines and/or trastuzumab therapy. Breast cancer patients with a CMR from 2013-2017 at Yale New Haven Hospital were included. Patient co-morbidities, medications, and cardiovascular outcomes were obtained from chart review. Biostatistical analyses, including Pearson correlations, competing risk regression model, and competing risk survival curves comparing the two groups were analyzed. 116 breast cancer with CMRs were included in our analysis to assess differences between Anthracycline/Trastuzumab (AT) (62) treated versus non anthracycline/trastuzumab (NAT) (54) treated patients in terms of imaging characteristics and outcomes. More AT patients 17 (27.4%) developed systolic heart failure compared to the NAT group 6 (10.9%), p = 0.025. Statin use was associated with a significant reduction in future arrhythmias (HR 0.416; 95% CI 0.229-0.755, p = 0.004). In a sub-group of 13 patients that underwent stress CMR, we did not find evidence of microvascular dysfunction by sub-endocardial/sub-epicardial myocardial perfusion index ratio after adjusting for ischemic heart disease. In our study, CMR detected signs of subclinical cardiotoxicity such as strain abnormalities despite normal LV function and abnormal circumferential strain was associated with adverse cardiovascular outcomes such as valvular disease and systolic heart failure. Thus, CMR is an important tool during and after cancer treatment to identity and prognosticate cancer treatment-related cardiotoxicity.

Comparison of Myocardial Perfusion Scintigraphy and Coronary Angiography Results in Breast Cancer Patients Treated with Radiotherapy.

Breast cancer is the most common type of malignancy in women and radiotherapy (RT) is an important part of treatment. Although it reduces cancer recurrence, it has been shown to cause accerelerated athnerosclerosis. This study aimed to compare the results of myocardial perfusion scintigraphy (MPS) for ischemia investigation with coronary angiography (CAG) findings and to investigate the effect of RT on the development of coronary artery disease in breast cancer patients who underwent RT. The results of 660 patients were analyzed and compared with each other in terms of clinical, demographic, laboratory parameters and MPS results. The mean age was 57.5 years and all of them were female. When the groups were compared, the Gensini score and marking of the left anterior descending artery (LAD) area as ischemic area localization were found more, but angiographically, the rate of severe stenosis in the area indicated by MPS was found to be lower in the RT group (p < 0.001). While the sensitivity of MPS in the RT group was 67.5% and non-RT group was 88.5% (p < 0.001), the result of our study shows that the sensitivity of the MPS test is significantly lower in the patient group receiving RT.

Management of liver-confined synchronous metastatic disease in breast cancer patients

Management of liver-confined synchronous metastatic disease in breast cancer patients

Evaluation of clinical features and risk factors related to late recurrence (&gt;5 years) in patients with breast cancer

Background/Aim: Over the years, disease-free survival (DFS) has been considerably prolonged with effective treatments in resectable breast cancer patients. However, a limited number of studies evaluating the predictive and prognostic factors of the disease in breast cancer patients who develop late recurrence are available. In this respect, we investigated clinicopathological features and risk factors affecting the survival of patients who developed breast cancer recurrence (BCR) after 60 months (late BCR). Methods: In this retrospective cohort study, clinicopathological features and survival outcomes of 45 late BCR patients were evaluated. The demographic and medical data of the patients were obtained from the retrospective registry system of our center. Statistical analyses were performed to determine the risk factors affecting DFS. Results: The median age of the cohort was 49 (24–78) years. Twenty-three postmenopausal patients were included in the study, and the mean age of menopause was 50 (43–55) years. Fourteen (31.1%) patients were stage 3 at diagnosis. In the adjuvant period, 80% of the patients underwent radiotherapy, and 79.5% underwent chemotherapy. The mean duration of adjuvant hormone therapy was 64 (69–129) months. Adjuvant ovarian suppression therapy was applied to 14 patients. The three most common sites of recurrence were bones (57.8%), locoregional (26.7%), and distant lymph nodes (26.7%). The median DFS of the cohort was 116.9 (3.7) months (109.6–124.1 months). Disease-related deaths occurred in only five patients, and the median overall survival (OS) could not be achieved. Based on a log-rank analysis, the median DFS was longer in patients whose adjuvant hormone therapy duration was 5–10 years and in those with bone or lymph node recurrence (P = 0.025 and P = 0.001, respectively). DFS was significantly shorter in patients with liver metastases (P = 0.005). Based on a chi-squared analysis, bone and lymph node metastases were higher in luminal A-like group (P = 0.030), and liver metastasis was lower (P = 0.039). Luminal biology did not affect late BCR (P = 0.075). Conclusions: Prolonged adjuvant hormone therapy (5–10 years) delays breast cancer recurrence. However, luminal features are insufficient to predict recurrence as the recurrence period increases. In addition, different sites of metastases are associated with long-term survival and luminal subgroups.

Input function and modeling for determining bone metabolic flux using [18 F] sodium fluoride PET imaging: A step-by-step guide.

Studies of skeletal metabolism using measurements of bone metabolic flux (Ki ) obtained with [18 F] sodium fluoride ([18 F]NaF) positron emission tomography (PET) scans have been used in clinical research for the last 30 years. The technique has proven useful as an imaging biomarker in trials of novel drug treatments for osteoporosis and investigating other metabolic bone diseases, including chronic kidney disease mineral and bone disorder. It has also been shown to be valuable in metastatic bone disease in breast cancer patients and may have potential in other cancer types, such as prostate cancer, to assess early bone fracture risk. However, these studies have usually required a 60-min dynamic PET scan and measurement of the arterial input function (AIF), making them difficult to translate into the clinic for diagnostic purposes. We have previously proposed a simplified method that estimates the Ki value at an imaging site from a short (4-min) static scan and venous blood samples. A key advantage of this method is that, by acquiring a series of static scans, values of Ki can be quickly measured at multiple sites using a single injection of the tracer. To date, the widespread use of [18 F]NaF PET has been limited by the need to measure the AIF required for the mathematical modeling of tracer kinetics to derive Ki and other kinetic parameters. In this report, we review different methods of measuring the AIF, including direct arterial sampling, the use of a semi-population input function (SP-AIF), and image-derived input function, the latter two requiring only two or three venous blood samples obtained between 30 and 60min after injection. We provide an SP-AIF model and a spreadsheet for calculating Ki values using the static scan method that others can use to study bone metabolism in metabolic and metastatic bone diseases without requiring invasive arterial blood sampling. The method shortens scan times, simplifies procedures, and reduces the cost of multicenter trials without losing accuracy or precision.

Role of contrast-enhanced spectral mammography in the assessment of residual disease following neoadjuvant chemotherapy in patients with breast cancer

BackgroundNeoadjuvant chemotherapy (NAC) is currently one of the most commonly utilized treatment options for patients with breast cancer. Evaluating residual disease following NAC is vital in post-chemotherapy treatment planning. Underestimation or overestimation of the residual disease may result in incomplete surgical resection or unnecessary aggressive surgical treatment which can compromise patient survival or result in unwanted morbidity. Contrast-enhanced spectral mammography (CESM) is a new imaging modality that can provide both morphological and anatomical characterization of neoplastic breast lesions when MRI is unavailable or contraindicated. The aim of this prospective observational study was to evaluate the value of CESM in assessing the extent of residual disease following NAC and predicting complete response (CR) with histopathology as the gold standard.ResultsA total of 142 patients were included in our study with invasive duct carcinoma the most prevalent histopathological type seen in 81.7% of cases. The average tumor reduction in size was 40.8% by CESM and 35.8% by histopathology. Comparison between maximum tumor diameter after NAC by CESM and histopathology revealed a high degree of correlation (R = 0.918, p < 0.01). In 45.1% of cases, CESM underestimated the residual tumor size by an average of 1.1 cm. Comparison between CESM and histopathology in predicting CR yielded CESM sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) of 96.7%, 84.6%, 97.2%, and 100%, respectively.ConclusionsCESM is a new effective imaging modality in assessing residual disease in breast cancer patients receiving NAC. Post-NAC CESM correlated well with residual tumor size by histopathology with a tendency for underestimation. Careful assessment of CESM images should be made to accurately measure the exact tumor size to avoid overestimation or underestimation potentially increasing the extent of the operation. Proper assessment of the true extent of residual disease can help the surgeon to select the optimal surgical technique ensuring radical treatment of the disease improving patient survival and reducing morbidity.

34633 Postoperative dermatologic sequelae of breast cancer: A systematic literature review

Introduction: Annually, 1.7 million women are diagnosed with breast cancer worldwide. Surgery is paramount in treatment and dermatologists play a vital role in recognition of postoperative skin changes that may mimic cancer recurrence or metastasis. We sought to provide a comprehensive review for dermatologists to diagnose and manage postoperative skin disease in breast cancer patients.

Imaging features of radiation-induced lung disease and its relationship with clinical and dosimetric factors in breast cancer patients.

The aim is to extensively evaluate imaging features of radiation induced lung disease in breast cancer patients and to determine the relationship of imaging alterations with dosimetric parameters and patient related characteristics. A total of 76 breast cancer patients undergoing radiotherapy (RT) were studied retrospectively by case notes, treatment plans, dosimetric parameters, and chest computed tomography (CT) scans. Time intervals, that chest CT scans were acquired, were grouped as 1-6 months, 7-12 months, 13-18 months and more than 18 months after RT. Chest CTs (one or more for each patient) were assessed for the presence of ground glass opacity, septal thickening, consolidation/patchy pulmonary opacity/alveolar infiltrates, subpleural air cyst, air bronchogram, parenchymal bands, traction bronchiectasis, pleural/subpleural thickening and pulmonary volume loss. These alterations were scored by applying a system devised by Nishioka et al. Nishioka scores were analyzed for the relationship with clinical and dosimetric factors. IBM SPSS Statistics for Windows, version 22.0 (IBM Corp., Armonk, N.Y., USA) was used to analyze data. Median follow-up time was 49 months. Advanced age and aromatase inhibitor intake were correlated with higher Nishioka scores for 1-6 months' period. However, both were found nonsignificant in multivariate analysis. Nishioka scores of CT scans acquired more than 12 months after RT were positively correlated with mean lung dose, V5, V20, V30, and V40. Receiver operating characteristic analysis revealed that V5 for ipsilateral lung was the most robust dosimetric parameter predicting chronic lung injury. V5 >41% indicates the development of radiological lung changes. Keeping V5 ≤41% for ipsilateral lung could provide avoiding chronic lung sequelae.

Tamoxifen induced hepatic steatosis in high-fat feeding rats through SIRT1-Foxo1 suppression and LXR-SREBP1c activation.

Clinically, long-term use of tamoxifen (TAM) would lead to fatty liver disease in breast cancer patients, especially obese women. However, the exact mechanism of TAM-induced hepatic steatosis is still unclear. Meanwhile, there is no drug to prevent and treat it. In view of silent information regulator 1 (SIRT1) playing a key role in hepatic lipid metabolism regulation, this study was conducted to investigate whether SIRT1 is a potential therapeutic target for TAM-induced hepatic steatosis. In this study, obese female Wistar rats fed with high-fat diet (HFD) for 15weeks were given TAM (4, 8mg/kg, intragastric) for 14days. In vitro, human hepatocarcinoma cell line HepG2 was used to establish a high-fat model with 50μM oleic acid and TAM (10μM) was treated simultaneously for 72h. The results showed that TAM was more likely to upregulate the expression of lipid synthetase that caused the increase of lipid content in HepG2 cells and rat liver. The expression of SIRT1 was downregulated both in vitro and in vivo. SIRT1 agonist SRT1720 (15mg/kg, 30mg/kg, i.p.) could resist TAM-induced hepatic lipid synthetase overexpression to relieve TAM-induced hepatic steatosis. Meanwhile, the upregulation of p-forkhead box O1 and LXRα induced by TAM was reversed by SRT1720. These results indicated that TAM-induced hepatic steatosis was based on SIRT1-p-FoxO/LXRα-sterol regulatory element binding protein 1c pathway under HFD condition. SIRT1 agonist might be a potential therapeutic drug to relieve this side effect. Tamoxifen increased lipid synthesis and regulated lipid transport in HFD rat liver.p-FoxO1/LXRα-SREBP1c signaling was upregulated through the inhibition of SIRT1 in tamoxifen-induced hepatic steatosis under HFD condition.SIRT1 agonist SRT1720 could relieve tamoxifen-induced hepatic steatosis.

Risk of heart disease following treatment for breast cancer - results from a population-based cohort study.

There is a rising concern about treatment-associated cardiotoxicities in breast cancer patients. This study aimed to determine the time- and treatment-specific incidence of arrhythmia, heart failure, and ischemic heart disease in women diagnosed with breast cancer. A register-based matched cohort study was conducted including 8015 breast cancer patients diagnosed from 2001 to 2008 in the Stockholm-Gotland region and followed up until 2017. Time-dependent risks of arrhythmia, heart failure, and ischemic heart disease in breast cancer patients were assessed using flexible parametric models as compared to matched controls from general population. Treatment-specific effects were estimated in breast cancer patients using Cox model. Time-dependent analyses revealed long-term increased risks of arrhythmia and heart failure following breast cancer diagnosis. Hazard ratios (HRs) within the first year of diagnosis were 2.14 (95% CI = 1.63-2.81) for arrhythmia and 2.71 (95% CI = 1.70-4.33) for heart failure. HR more than 10 years following diagnosis was 1.42 (95% CI = 1.21-1.67) for arrhythmia and 1.28 (95% CI = 1.03-1.59) for heart failure. The risk for ischemic heart disease was significantly increased only during the first year after diagnosis (HR = 1.45, 95% CI = 1.03-2.04). Trastuzumab and anthracyclines were associated with increased risk of heart failure. Aromatase inhibitors, but not tamoxifen, were associated with risk of ischemic heart disease. No increased risk of heart disease was identified following locoregional radiotherapy. Administration of systemic adjuvant therapies appears to be associated with increased risks of heart disease. The risk estimates observed in this study may aid adjuvant therapy decision-making and patient counseling in oncology practices. This work was supported by the Swedish Research Council (grant no: 2018-02547); Swedish Cancer Society (grant no: CAN-19-0266); and FORTE (grant no: 2016-00081).

Abstract P4-07-14: Long-term prognosis of minimal residual disease in breast cancer patients with breast or nodal pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC)

Abstract Background: Achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is known important for predicting survival. However, few studies have reported prognosis of minimal residual disease. In this study, we evaluated the long term survival of the patients with breast or nodal pCR and compare patients with minimal residual disease to the breast and node pCR group. As it is difficult to analyze residual cancer burden and tumor-infiltrating lymphocytes in the retrospective study, we assessed the residual tumor or nodal status according to the pathologic report after surgery based on the AJCC 8th edition staging system. Methods: This study retrospectively reviewed 753 patients who achieved pCR of breast or node after NAC from 2010 to 2017 at Severance Hospital. We divided patients into five groups based on the residual disease; breast and node pCR (ypT0/TisN0), minimal residual disease (ypT1mi/T1aN0, ypT0/TisN0i+/N1+), breast-only pCR (ypT0/TisN1+), node-only pCR with residual tumor size no larger than 20mm (ypT1b/T1cN0), and node-only pCR with residual tumor size larger than 20mm (ypT2+N0). The basic characteristics and the 10-year event free survival (EFS) were evaluated. EFS was defined as time from surgery to last follow-up date without any events. Results: We analyzed the data until May 26, 2021, and 50.2% (n=378) of the patients achieved breast and node pCR. Minimal residual disease, defined as residual tumor size no larger than 5mm and residual nodal size 2mm, included 126 patients (16.7%). Overall, there was significant difference in 10-year EFS among five groups (ypT0/TisN0; 94.7%, ypT1mi/T1aN0, ypT0/TisN0i+/N1+; 93.7%, ypT1b/T1cN0; 86.8%, ypT0/TisN1+; 87.9%, ypT2+N0; 71.9%, p&amp;lt;0.001). As the variables such as age, subtypes, clinical T and N stage, regimen of chemotherapy, response to the chemotherapy and operation type were adjusted, the minimal residual disease group showed no significant difference with the breast and node pCR group (HR 1.410, 95% CI 0.615 - 3.235, p=0.417), yet the other groups showed poorer outcomes (ypT1b/T1cN0; HR 3.183, 95% CI 1.687- 6.004, p&amp;lt;0.001, ypT0/TisN1+; HR 3.186, 95% CI 1.047 - 9.694, p=0.041, ypT2+N0; HR 6.089, 95% CI 3.019- 12.281, p&amp;lt;0.001). Conclusion: Patients with minimal residual tumor 5mm or less, or residual metastatic lymph node with a maximal diameter of 2mm have shown equivalent 10-year EFS compared to the patients who achieved breast or node pCR after NAC. Keywords: Neoadjuvant chemotherapy, Pathologic complete response, Minimal residual disease, Long-term survival, Breast cancer Citation Format: Jieon Go, Jee Hyun Ahn, Jung Min Park, Soon Bo Choi, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong-Woo Park, Seho Park. Long-term prognosis of minimal residual disease in breast cancer patients with breast or nodal pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-14.