Dynamic changes in brain glymphatic function during preoperative chemotherapy in breast cancer patients.

Previous studies have indicated a connection between resilience and cognitive function, but critical gaps persist regarding limited data exploring the relationship between resilience profiles and cognition using person-centered methodologies, especially in the context of breast cancer patients. While the general correlation between resilience and cognitive function is known, how various resilience profiles impact cognitive function in breast cancer patients remains unclear. The study aimed to identify resilience profiles and explore the relationship with cognitive function in breast cancer (BC) patients. This study was a cross-sectional study in descriptive research. BC patients (n = 425) from a tertiary oncology hospital completed the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) scale and Connor-Davidson Resilience Scale (CD-RISC- 25). Latent profile analysis was adopted to identify subgroups of patients with distinct resilience profiles according to model fit indices. An ANOVA analysis and Chi-square test were also employed. Three profiles were identified, including Class 3, "High resilience-positive coping group" (n = 187, 44.7%), Class 2, "Medium resilience-effort regulation group" (n = 157, 37.6%), and Class 1, "Low resilience-negative coping" (n = 74, 17.7%). The results demonstrate that perceived cognitive impairment (CogPCI), other people's appraisal (CogOth), perceived cognitive ability (CogPCA), impact on quality of life (CogQOL), and FACT-Cog were significant differences in all three potential latent resilience profiles (P < 0.001). The CogPCI and FACT-Cog scores in Class 3 were the best, while Class 1 was the lowest. The psychological resilience profile contains three classes, and the findings provide evidence that high resilience potentially serves as a crucial protective factor for cognitive function in BC patients. Healthcare providers should improve their ability to recognize and evaluate factors influencing resilience, including social support and physical activity, which will enable the development of precise nursing interventions to mitigate the long-term adverse effects of trauma and reduce the impact of cognitive impairment on BC patients.

The object of this study was to determine, taking into account uncertainty on cost and outcome parameters, the cost-effectiveness of high-dose chemotherapy (HDC) compared with conventional chemotherapy for advanced breast cancer patients. An analysis was conducted for 300 patients included in a randomized clinical trial designed to evaluate the benefits, in terms of disease-free survival and overall survival, of adding a single course of HDC to a four-cycle conventional-dose chemotherapy for breast cancer patients with axillary lymph node invasion. Costs were estimated from a detailed observation of physical quantities consumed, and the Kaplan-Meier method was used to evaluate mean survival times. Incremental cost-effectiveness ratios were evaluated successively considering disease-free survival and overall survival outcomes. Handling of uncertainty consisted in construction of confidence intervals for these ratios, using the truncated Fieller method. The cost per disease-free life year gained was evaluated at 13,074 Euros, a value that seems to be acceptable to society. However, handling uncertainty shows that the upper bound of the confidence interval is around 38,000 Euros, which is nearly three times higher. Moreover, as no difference was demonstrated in overall survival between treatments, cost-effectiveness analysis, that is a cost minimization, indicated that the intensive treatment is a dominated strategy involving an extra cost of 7,400 Euros, for no added benefit. Adding a single course of HDC led to a clinical benefit in terms of disease-free survival for an additional cost that seems to be acceptable, considering the point estimate of the ratio. However, handling uncertainty indicates a maximum ratio for which conclusions have to be discussed.

The purpose of this work was to investigate whether noninvasive early detection (after the first cycle) of response to neoadjuvant chemotherapy (NAC) in breast cancer patients was possible. 31P‐MRSI at 7 T was used to determine different phosphor metabolites ratios and correlate this to pathological response. 31P‐MRSI was performed in 12 breast cancer patients treated with NAC. 31P spectra were fitted and aligned to the frequency of phosphoethanolamine (PE). Metabolic signal ratios for phosphomonoesters/phosphodiesters (PME/PDE), phosphocholine/glycerophosphatidylcholine (PC/GPtC), phosphoethanolamine/glycerophosphoethanolamine (PE/GPE) and phosphomonoesters/in‐organic phosphate (PME/Pi) were determined from spectral fitting of the individual spectra and the summed spectra before and after the first cycle of NAC. Metabolic ratios were subsequently related to pathological response. Additionally, the correlation between the measured metabolic ratios and Ki‐67 levels was determined using linear regression.Four patients had a pathological complete response after treatment, five patients a partial pathological response, and three patients did not respond to NAC. In the summed spectrum after the first cycle of NAC, PME/Pi and PME/PDE decreased by 18 and 13%, respectively. A subtle difference among the different response groups was observed in PME/PDE, where the nonresponders showed an increase and the partial and complete responders a decrease (P = 0.32). No significant changes in metabolic ratios were found. However, a significant association between PE/Pi and the Ki‐67 index was found (P = 0.03).We demonstrated that it is possible to detect subtle changes in 31P metabolites with a 7 T MR system after the first cycle of NAC treatment in breast cancer patients. Nonresponders showed different changes in metabolic ratios compared with partial and complete responders, in particular for PME/PDE; however, more patients need to be included to investigate its clinical value.

An attempt for the identification of potential biomarkers predictive of response to chemotherapy (CHT) in breast cancer patients has been performed by the use of two-dimensional electrophoresis and mass spectrometry analysis. Since growth and progression of tumor cells depend also on stromal factors in the microenvironment, we choose to investigate the proteins secreted in Tumor Interstitial Fluid (TIF) and in Normal Interstitial Fluids (NIF). One-hundred and twenty-two proteins have been analyzed and a comparison was also made between the proteomic profile of responders versus nonresponders to CHT. At baseline, proteins isolated in TIF and NIF of all the 28 patients show significant differences in expression. Two clusters of proteins, differentially expressed in TIF with respect to NIF were found. Most significant is the decreased expression in TIF of CRYAB. In the protein metabolism group, also FIBB was found decreased. Some proteins involved in energy pathways were overexpressed (PGAM-1, ALDO A, PGK1, G3Pcn), while some other were down-regulated (CAH2, G3Pdx, PRDX6, TPIS). The same trend was observed for signal transduction proteins, with 14-3-3-Z overexpressed, and ANXA2 and PEBP 1 down-regulated. Moreover, an analysis has been conducted comparing protein expression in interstitial fluids of responders and nonresponders, irrespective of TIF or NIF source. This analysis lead us to identify two clusters of proteins with a modified expression, which might be predictive of response to CHT. In responders, an increase in expression of LDHA, G3Pdx, PGK1sx (energy pathways), VIME (cell growth and maintenance) and 14-3-3-Z (signal transduction), coupled with a decreased expression of TPIS, CAH 2, G3Psx, PGK 1dx (energy pathways), TBB5 (cell growth and maintenance), LDHB and FIBB (protein metabolism), was found. We observed that CHT modifies the expression of these cluster proteins since, after treatment, their expression in TIF of responder is generally decreased. Patients not responding to CHT show an unchanged expression pattern in TIF, with the exception of protein 14-3-3-Z, which is overexpressed, and a decreased expression in NIF of several cluster proteins. In conclusion, the identification of protein clusters associated with response to CHT might be important for predicting the efficacy of a specific antineoplastic drug and for the development of less empiric strategies in choosing the therapy to be prescribed to the single patient.

Purpose: Weekly paclitaxel plus carboplatin (PCb) regimen is an effective neoadjuvant chemotherapy for breast cancer. However, some patients respond to this regimen poorly and suffer from side effects. In this study, we aimed to define the microRNA (miRNA) biomarker for predicting sensitivity to PCb chemotherapy in breast cancer patients, and to explore the potential molecular mechanisms. Experimental Design: 81 patients with stages II and III breast cancer, who received four cycles of weekly PCb regimen preoperative chemotherapy, were included. Gene expression profiles from 31 patients was used as training set to determine differentially expressed genes (DEGs) and to predict miRNAs that may be associated with chemotherapeutic sensitivity. The other 50 patients were analyzed as validation set to test the accuracy of DEG identification and miRNAs prediction by quantitative real-time PCR. In parallel, in vitro and in vivo analyses were carried out to determine the potential mechanisms of miRNA-dependent drug sensitivity. Results: Gene profiling analyses in the training set revealed significant correlation between high expression level of miR-345 and miR-621 and pathologic complete response (pCR) in breast cancer patients. We further validated that the expression level of miR-621 was significantly higher in tumor tissues of pCR patients than that in non-pCR patients (P = 0.01). In breast cancer cell lines, ectopic overexpression of miR-621 promoted apoptosis and increased chemosensitivity to paclitaxel and carboplatin both in vitro and in vivo. The potential miR-621-target genes were determined by TargetScan and miRNA CLIP-seq database, which were further confirmed as DEGs reversely-correlated to miR-621 in breast cancer patient samples. Among those, FBXO11 was verified as one of the direct targets of miR-621 in breast cancer cells, whose expression level negatively associated with chemosensitivity in breast cancer patients. The molecular mechanisms by which miR-621/FBXO11 axis regulates chemosensitivity may involve regulation of p53 transcriptional activity and epithelial-mesenchymal transition (EMT) in breast cancer cells. Conclusions: Our study revealed a strong correlation between miR-621 expression and chemosensitivity in breast cancers. High level of miR-621 predicts sensitivity to PCb regimen neoadjuvant chemotherapy in breast cancer patients who tend to achieve pCR. The increased chemosensitivity may be mediated by down-regulation of FBXO11 gene, which leads to enhanced p53 transactivity and reduced EMT in breast cancer cells. Therefore, miR-621 may be used as predictive biomarker and the potential therapeutic target in breast cancer treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-07-13.

e14577 Background: The purpose of this study was to perform a meta-analysis of literature data and see if [F-18]FDG and PET imaging can be used to predict the early response to chemotherapy based upon the measure of standard uptake value (SUV) or drug uptake ratio (DUR; a measure of glycolytic index) in breast cancer patients. This intervention may identify the responders for continued therapy or identify the non- responders for change of therapy. Methods: A literature search determined the number of studies that used PET-FDG imaging to monitor the response of various chemotherapies in breast cancer patients. A total of nine studies have been reviewed that used SUV/DUR as a measure of glycolytic activity of the primary tumors. The percent decrease of SUV over baseline was determined for chemotherapy cycle 1 and for subsequent cycles. A paired t-test was performed to see the statistical significance of the SUV decrease. Results: Five (n=158) studies presented the data in % mean reduction in SUV and four (n=59) studies presented SUV values for the individual patient. The average decrease in SUV in responders were 29% and 51% after first and second cycle, respectively. The non responders did not show significant change in SUV as compared to responders. Conclusion: The preliminary data mining and analysis strongly implies that PET imaging using [F-18]FDG may be used to monitor the progress of chemotherapy in breast cancer patients. This study was supported by a grant from OWH, FDA. The results do not represent official FDA position. No significant financial relationships to disclose.

Parkinson's disease is associated with DJ-1/Parkinson protein 7 dysfunction. In contrast, hyperactivity of DJ-1 increases the resistance of cancer cells to apoptosis. Recent genetic studies showed that, in addition to apoptosis pathways, DJ-1 is also involved in cellular defense against reactive oxygen species. The activity of apoptotic and cellular defense pathways is key in determining drug sensitivity. DJ-1 overexpression is associated with various cancers. However, we previously found that there were approximately 50 % patients with breast cancers that expressed low levels of DJ-1 protein, despite mRNA upregulation. Furthermore, low DJ-1 expression was a significant predictor of poor clinical outcome in these patients. This study aimed to determine the association between low DJ-1 protein expression and pathological complete remission (pCR) after neoadjuvant chemotherapy in breast cancer patients. Expression of DJ-1 in pre-therapeutic needle biopsies and surgical specimens obtained from 205 breast cancer cases that received neoadjuvant chemotherapy was determined using immunohistochemistry and in situ hybridization. Chemotherapy comprised epirubicin/cyclophosphamide taxane-based regimens with or without the inclusion of trastuzumab. Univariate and multivariate analyses were used to evaluate the predictive value of DJ-1 on pCR. Low DJ-1 protein expression was detected in 45.3 % (93/205) of all breast cancer cases and in 79.6 % (39/49) of pCR cases, irrespective of maintained mRNA levels. DJ-1 expression [hazard ratio (HR): 1.36; 95 % confidence interval (CI): 1.01-1.84] and HER2 status (HR: 0.84; 95 % CI: 0.62-1.14), in contrast to histological grade, hormone receptors status, Ki-67 labeling index, and intrinsic subtype, were significant predictors of pCR. Low DJ-1 expression predicted pCR in luminal A (P = 0.0004), luminal B (P = 0.0194), and triple negative (P = 0.0143) subtypes breast cancer patients and in patients receiving additional trastuzumab treatment (P = 0.008). In conclusion, low DJ-1 protein expression is a significant predictor of pCR after neoadjuvant chemotherapy in breast cancer patients.

Background: Postmastectomy radiotherapy (PMRT) has been shown to be beneficial in node-positive breast cancer patients. However, the role of PMRT for patients receiving modern neoadjuvant chemotherapy (NAC) are controversial. We aimed to evaluate the efficacy of radiotherapy for breast cancer patients treated with NAC and mastectomy in the Japanese Breast Cancer Registry. Methods: Patients who received NAC and mastectomy for cT1-4 cN0-2 M0 breast cancer were included in this analysis. We assessed locoregional recurrence (LRR), distant disease-free survival (DDFS), and overall survival (OS) using the Kaplan-Meier method and compared them between the groups with and without PMRT by nodal status after NAC; ypN0, ypN1, and ypN2-3. We also performed multivariable cox regression analysis to evaluate the association of radiotherapy and these outcomes adjusting for baseline patient and cancer characteristics. Results: Of the 145,530 patients registered from 2004 to 2009, we identified 3,226 patients who met our inclusion criteria with the 5-year follow-up information including 1,299 ypN0, 1,036 ypN1, and 879 ypN2-3 cases. PMRT was performed in 185 patients (14.2%) with ypN0, 265 patients (25.6%) with ypN1, and 543 patients (61.8%) with ypN2-3. There was no difference in LRR, DDFS, and OS between the groups with and without radiotherapy for ypN1 patients who received NAC (P=0.72, P=0.29, and P=0.36, respectively). For patients with ypN2-3 breast cancer, radiotherapy significantly improved LRR (P&amp;lt;0.001), DDFS (P=0.01), and OS (P&amp;lt;0.001) on univariate analysis. No difference in LRR, DDFS, and OS was observed for ypN0 patients (P=0.81, P=0.15, and P=0.05, respectively). In multivariable analysis, the use of radiotherapy was independently associated with improved LRR [hazard ratio (HR): 0.608, 95% confidence interval (CI): 0.452–0.818, P=0.001] and OS [HR: 0.685, 95% CI: 0.531–0.885, P=0.004] for ypN2-3 patients. Effect of PMRT on locoregional recurrence by the ypN subgroupsypN subgroupHazard ratio95%CI Low95%CI HighP valueypN00.8550.4581.5960.623ypN10.8320.5491.2620.387ypN2-30.6080.4520.8180.001 Effect of PMRT on overall survival by the ypN subgroupsypN subgroupHazard ratio95%CI Low95%CI HighP valueypN01.3250.8412.0870.224ypN10.8800.5991.2930.514ypN2-30.6850.5310.8850.004 Radiotherapy was not associated with OS among patients with ypN0 [HR: 1.325, 95% CI: 0.841–2.087, P=0.224] and ypN1 [HR: 0.880, 95% CI: 0.599–1.293, P=0.514]. There was no significant difference in DDFS with the addition of radiotherapy for all ypN subgroups. Conclusions: The results from this nationwide database study of breast cancer patients following modern NAC showed that PMRT did not improve survival for patients with ypN1 and ypN0. Radiotherapy might be only beneficial for ypN2-3 breast cancer patients who received NAC and mastectomy in the modern era. Randomized clinical trials are needed to optimize the use of PMRT for breast cancer patients treated with neoadjuvant chemotherapy. Citation Format: Miyashita M, Niikura N, Kumamaru H, Miyata H, Ishida T, Kinoshita T, Tsuda H, Nakamura S, Tokuda Y. Role of postmastectomy radiotherapy after neoadjuvant chemotherapy in breast cancer patients: A study from the Japanese breast cancer registry [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-11.

Background: Hepatitis C virus (HCV) infection is a major health problem in the United States and breast cancer is the second most common cancer in US women. Despite these prevalent diseases, there is limited information available on the effects of a concurrent HCV infection among breast cancer patients receiving chemotherapy and the problems they face during their treatment. There are limited guidelines for chemotherapy treatment in HCV positive breast cancer patients. Methods: We performed a retrospective 2:1 matched case control analysis on breast cancer patients with a confirmed active HCV infection who received chemotherapy at Boston Medical Center between January 2000 and April 2015. Cases with HCV infection (n=6) were matched with controls (n=12) who were HCV negative. The controls were matched on age (decade) of diagnosis, stage of breast cancer, and intended chemotherapy regimen. We investigated dose delays, dose changes, hospitalization, hematologic reasons for dose delays, and variation in blood counts during the treatment period in these patients from their medical records. Statistical analysis was done using R version 3.4.0 to compare these outcomes of interest between the two groups. Fisher’s exact and Wilcoxon rank sum tests were used to compare the categorical and continuous variables respectively. Results: The HCV positive group was at a significantly higher risk of dose delays (100% vs. 33%, p = 0.01), dose changes (67% vs. 8%, p = 0.02), and hospitalization during chemotherapy (83% vs. 25%, p = 0.04) than their HCV matched controls. The risk of getting a dose delay due to hematotoxicity was significantly higher in the HCV positive group than the HCV negative group (83% vs. 8%, p = 0.003). The HCV positive patients took longer time to complete their treatment cycles than the HCV negative group. Conclusions: Chronic HCV infection in breast cancer patients receiving chemotherapy may be complicated by their active HCV infection. Treatment challenges due to dose changes, dose delays and hospitalizations were significantly more common when compared to controls. Chemotherapy delays and dose changes during breast cancer treatment has a negative consequence. In the era of curative treatment for HCV, future studies focused on the effect and treatment of concurrent HCV and breast cancer treatment is warranted. Citation Format: Saptaparni Ghosh, Minghua L Chen, Janice Weinberg, Naomi Y Ko. Effects of hepatitis C virus infection on the safety of chemotherapy for breast cancer patients: A retrospective chart analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-14-12.

The feasibility and accuracy of sentinel lymph node (SLN) biopsy in patients with breast cancer after preoperative chemotherapy has been demonstrated in a number of large, single-institution studies. However, a relative contraindication to SLN biopsy after preoperative chemotherapy is the presence of axillary metastases at initial diagnosis. The objective of this study was to determine the feasibility and accuracy of SLN biopsy after preoperative chemotherapy in patients with documented axillary metastases at presentation. Between 1994 and 2002, 69 patients who had axillary metastases identified by ultrasound-guided, fine-needle aspiration underwent SLN biopsy after treatment on prospective, preoperative chemotherapy protocols. All but 8 patients underwent axillary lymph node dissection (ALND). Those 8 patients either declined additional surgery or were offered enrollment in other institutional protocols. The median patient age was 49 years, and the median primary tumor size was 4 cm. The SLN identification rate was 92.8%. Thirty-one of 64 patients (48.4%) had successfully mapped, positive SLNs. Sixty-one patients underwent ALND, including 5 patients who did not have an SLN identified. In the 56 patients in whom a SLN was identified and an ALND was performed, 10 patients had a false-negative SLN (25%). SLN biopsy was feasible after preoperative chemotherapy, even in patients who initially presented with cytologically proven, lymph node-positive disease. However, the false-negative rate of SLN biopsy in this group of patients was much higher than that observed in clinically lymph node-negative patients. Based on the current results, the status of the SLN cannot be used as a reliable indicator of the presence or absence of residual disease in the axilla in this patient population.

Preoperative bevacizumab and chemotherapy may benefit a subset of breast cancer (BC) patients. To explore potential mechanisms of this benefit, we conducted a phase II study of neoadjuvant bevacizumab (single dose) followed by combined bevacizumab and adriamycin/cyclophosphamide/paclitaxel chemotherapy in HER2-negative BC. The regimen was well-tolerated and showed a higher rate of pathologic complete response (pCR) in triple-negative (TN)BC (11/21 patients or 52%, [95% confidence interval (CI): 30,74]) than in hormone receptor-positive (HR)BC [5/78 patients or 6% (95%CI: 2,14)]. Within the HRBCs, basal-like subtype was significantly associated with pCR (P = 0.007; Fisher exact test). We assessed interstitial fluid pressure (IFP) and tissue biopsies before and after bevacizumab monotherapy and circulating plasma biomarkers at baseline and before and after combination therapy. Bevacizumab alone lowered IFP, but to a smaller extent than previously observed in other tumor types. Pathologic response to therapy correlated with sVEGFR1 postbevacizumab alone in TNBC (Spearman correlation 0.610, P = 0.0033) and pretreatment microvascular density (MVD) in all patients (Spearman correlation 0.465, P = 0.0005). Moreover, increased pericyte-covered MVD, a marker of extent of vascular normalization, after bevacizumab monotherapy was associated with improved pathologic response to treatment, especially in patients with a high pretreatment MVD. These data suggest that bevacizumab prunes vessels while normalizing those remaining, and thus is beneficial only when sufficient numbers of vessels are initially present. This study implicates pretreatment MVD as a potential predictive biomarker of response to bevacizumab in BC and suggests that new therapies are needed to normalize vessels without pruning.

Late effects of adjuvant chemotherapy on cognitive function:a follow-up study in breast cancer patients

Objective To observe the effect of TOMATIS auditory training on improving cognitive and post-traumatic stress disorder in patients after breast cancer chemotherapy. Methods Eighty invasive ductal carcinoma of breast cancer patients with cognition and psychological disorders were selected in the breast department of Tangshan People's Hospital from October 2016 to September 2017.All patients were randomly divided into control group (n=40) and experimental group (n=40). The experimental group was given the TOMATIS high and low audio frequency auditory training, and the control group was given ordinary music training.Before and after the intervention, the Chinese version of the Montreal cognitive assessment scale (MoCA) and the post-traumatic stress disorder scale (PTSD-SS) were evaluated for both groups of patients. Results After the intervention, the experimental group had significantly higher scores in visual structure skills((3.83±0.71)vs(2.68±0.57)), executive function ((2.23±0.53)vs(1.55±0.50)), attention and concentration((1.55±0.78)vs(1.23±0.53)), language((1.50±0.75)vs(1.08±0.47)), calculation((2.00±0.60)vs(1.45±0.75)), abstract thinking((1.63±0.54)vs(1.00±0.51)), memory((4.68±0.47)vs(2.70±0.72)), directive force((5.25±0.54)vs(3.90±0.81)) and total score((22.65±2.89)vs(15.58±2.10))than the control group(all P<0.05). After intervention, the scores of subjective assessment of traumatic events((2.60±0.63)vs(3.98±0.62)), repeated recurring experiences((24.05±2.72)vs(26.70±2.28)), avoidance symptoms((24.35±1.64)vs(26.40±1.19)), increased alertness((24.23±1.80)vs(25.45±1.20)), impaired social function((7.28±1.01)vs(8.68±0.66)), and total scores((85.85±5.13)vs(94.63±2.92)) in the experimental group were significantly lower than those in the control group, and the differences were statistically significant (all P<0.01). Conclusion TOMATIS auditory training can effectively improve the cognitive function and psychological state in breast cancer chemotherapy patients, which is worthy of popularization and application. Key words: TOMATIS auditory training; Breast cancer; Chemotherapy; Cognitive dysfunction; Post-traumatic stress disorder

Introduction Circulating tumor DNA (ctDNA), which is detected in the blood as cell free DNA fragment from tumor cells, could indicates genomic landscape, tumor burden and treatment response during chemotherapy as a non-invasive method. Especially, personized ctDNA assay by next-generation sequencing(NGS) is able to detect a trace amount of ctDNA and precisely figure out the change of the amount of ctDNA during NAC and follow up period after curative surgery. Here, we performed serial ctDNA evaluations in EBC patients who diagnosed as TNBC or HER2-positive BC and received NAC followed by curative surgery. We aimed to predict NAC response and detect minimal residual disease (MRD) using personalized ctDNA assay. Methods CtDNA was detected by AlphaLiquid®Detect, a tumor-informed personalized MRD detection assay exploring most of the mutations in tumor. Whole exome sequencing (WES) of tumor tissue and peripheral blood mononuclear cells (PBMCs) was performed. Patient-specific somatic mutations were selected using a proprietary algorithm. In brief, clonal variants were prioritized using integrated information including variant allele frequency, population allele frequency databases, somatic variant databases, variant pathogenicity, and genomic context. Up to 100 variants were selected for patient monitoring. A hybridization capture panel consisting of a pool of 4 patients’ selected variants was synthesized. These bespoke panels (BSPs) were used for ctDNA detection. Patients with more than 2 tumor-derived mutations detected in plasma were considered as ctDNA positive. Inclusion criteria included patient who diagnosed as stage IIA-IIIC BC planned to NAC followed by curative surgery. Among BC subtypes, TNBC and HER2-positive BC were allowed. Collection of specimens and associated clinical data used in this study was approved by the Institutional Review Board of Samsung Medical Center (IRB File No.2021-02-033), and we received informed consents for this study. Results From May 2021 to Sep 2022, 158 patients has been enrolled. Archival tissues were not available in 47 patients and tissue WES had failed in six patients. Therefore, 105 patients were enrolled and analyzed their ctDNA at diagnosis based on tissue WES data. Of 105 patients, Median age of BC patients was 49.3 years of age (range: 26.1, 67.8). Thirty-six patients (34.3%) were post-menopausal status and others (65.7%) were pre-menopausal status. In BC pathology at diagnosis, 56 (53.3%) were TNBC and other 49 (46.7%) were HER2-positive BC. Among HER2-positive BC, hormone receptor (HR)-positive were in 21 (20.0%). In clinical stage at diagnosis, stage II were 46 (43.8%) and stage III in 59 (56.2%). In 105 patients, median number of somatic mutations was 60 (interquartile range [IQR]: 38.5, 91). CtDNA detection rate at BC diagnosis was 90.5% and all of BC which not be detected ctDNA was HER2-positive BC with clinical stage II. Median amount of ctDNA at diagnosis was 20 (IQR: 6, 44). In the number of somatic mutations, there was no difference according to BC subtypes (P=0.121) and clinical stage (P=0.700) but the amounts of ctDNA at diagnosis was different. CtDNA was much more detected in TNBC compared to HER2-positive BC (Median: 34.5 vs. 15.9; P&amp;lt; 0.001) and clinical stage III compared to clinical stage II (Median 33.2 vs. 19.5; P=0.002). After NAC, ctDNA at curative surgery was tested in 70 patients. In 70 patients, pathologic complete response(pCR) was observed in 44 patients. CtDNA was detected in ten patients (14.3%) and eight did not achieve pCR and two with pCR (Specificity of assay: 95.5%, positive predictive value: 0.80, P=0.032). Conclusions Personalized ctDNA assay can precisely detected ctDNA at diagnosis and their detection rate was associated with BC subtypes and clinical stage. In addition, ctDNA at curative surgery also can predict NAC response in EBC patients. Long term ctDNA follow up of MRD would be warranted. Citation Format: Ji-Yeon Kim, Hae Hyun Jung, Jeong Eon Lee, Seok Won Kim, Hwang-Phill Kim, Sunghoon Heo, Jongseong Ahn, Tae-You Kim, Young-Hyuck Im. Personalized circulating tumor DNA assay precisely predicts the response of neoadjuvant chemotherapy in breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-16-01.

Aim.To study the possibilities of speckle-tracking echocardiography (STE) in 3D mode in assessing the strain of the myocardium and identifying subclinical cardiotoxicity during anthracycline-containing chemotherapy in breast cancer patients with arterial hypertension.&#x0D; Materials and methods.The study included 47 patients with triple negative breast cancer (BC) with AH and normotension. All patients underwent transthoracic echocardiography with an assessment of the left ventricular (LV) ejection fraction, also used STE in three-dimensional mode with an assessment of global longitudinal (GLS), circular (GCS), radial (GRS) strain and a new strain parameter strain area (GAS).&#x0D; Results.In patients with BC for a more accurate assessment of LV systolic function, it is advisable to use 3D echocardiography. In BC patients with AH, the initial parameters of LV strain were statistically significantly worse than in patients with normotension and further deterioration was observed after chemotherapy. To determine the sensitivity and specificity of the strain parameters from the 3D-STE data, an ROC analysis was performed. The most diagnostically significant parameter of strain, as a marker of cardiotoxicity, was the global area strain (GAS), which with a cut-off value -14.0% showed a sensitivity equal to 81.5% and a specificity of 73.3%, but the value this parameter of LV deformation requires further study.&#x0D; Conclusion.In BC patients with AH and normotension it is advisable to use the STE in 3D mode to analyze the strain and systolic function of the LV during antitumor treatment. The method is promising for identifying subclinical cardiotoxicity, but further research is needed to develop diagnostic criteria.