Analysis Of Breast Cancer Patients Research Articles

Activation of the γ-secretase/NICD-PXR/Notch pathway induces Taxol resistance in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is currently the only subtype lacking efficient targeted therapies. Taxol is the primary chemotherapeutic agent for TNBC. However, Taxol resistance often develops in the treatment of TNBC patients, which importantly contributes to high mortality and poor prognosis in TNBC patients. Recent preclinical studies have shown that the inhibition of Notch pathway by γ-secretase inhibitors can slow down the progression of TNBC. Our studies in bioinformatic analysis of breast cancer patients and TNBC/Taxol cells in vitro showed that there was high correlation between the activation of Notch pathway and Taxol resistance in TNBC. Increased γ-secretase activity (by the overexpression of catalytic core PSEN-1) significantly reduced Taxol sensitivity of TNBC cells, and enhanced biological characteristics of malignancy in vitro, and tumour growth in vivo. Mechanistically, increased γ-secretase activity led to the accumulation of NICD in the nucleus, promoting the interaction between NICD and PXR to activate PXR, which triggered the transcription of PXR downstream associated drug resistance genes. Furthermore, we showed that pharmacological inhibition of γ-secretase with γ-secretase inhibitors (Nirogacestat and DAPT) can reverse Taxol resistance in vivo and in vitro. Our results for the first time demonstrate that the activation of γ −secretase/NCD-PXR/Notch pathway is one of important mechanisms to cause Taxol resistance in TNBC, and the blockades of this pathway may represent a new therapeutic strategy for overcoming Taxol resistance in TNBC.

Real-World Analysis of Breast Cancer Patients Qualifying for Adjuvant CDK4/6 Inhibitors

BackgroundAdjuvant CDK4/6 inhibitors abemaciclib and ribociclib improved disease-free survival (DFS) added to endocrine therapy in hormone receptor (HR)-positive HER2-negative early breast cancer (EBC), in monarchE (NCT03155997) and NATALEE (NCT03701334) trials respectively. We assessed the proportion and outcome of EBC patients qualifying for adjuvant CDK4/6 inhibitors in the real-world. MethodsConsecutive female patients with HR-positive HER2-negative EBC between 1997 and 2017 from the Australian Capital Territory and South-East New South Wales Breast Cancer Treatment Group registry were analyzed. Patients eligible for abemaciclib had ≥4 axillary nodes involved or 1-3 nodes plus primary >5 cm or grade 3. Ribociclib eligibility was defined as node-positive and node-negative with primary >5 cm or >2 cm grade 3. ResultsOf 3840 patients, 671 (17.5%) were abemaciclib-eligible and 1587 (41.3%) ribociclib-eligible . The 5-year DFS was 77% and 94% in abemaciclib-eligible and noneligible registry patients respectively (HR 2.6, 95% CI 2.26-3.05, P < .001). The 5-year DFS was 86% and 97% in ribociclib-eligible and noneligible registry patients respectively (HR 1.92, 95% CI 1.67-2.19, P < .001). Compared with monarchE trial patients, abemaciclib-eligible registry patients were older (median 55 years in registry vs. 51 years in trial), with lower nodal burden (≥4 nodes in 44% in registry vs. 60% in trial). There were more stage III cancers in NATALEE trial patients (60%) than ribociclib-eligible registry patients (24%). ConclusionsMany women with EBC will qualify for adjuvant CDK4/6 inhibitors (17.5% abemaciclib, 41.3% ribociclib) with resource and workforce implications. In the real-world setting, a greater proportion of adjuvant CDK4/6-eligible patients have lower stage disease, therefore the absolute benefit from treatment may be smaller than estimated by the trials.

An analysis of breast cancer patients with ultrasound BI-RADS 3 lesions after minimally invasive excision in clinicopathological features and influencing factors of residual tumor

Objectives: To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision. Methods: In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People's Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group (n=39) and non-tumor residual group (n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results: The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor (OR=16.852, 95%CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions: BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.

General analysis of breast cancer patients tested for BRCA mutations and evaluation of acute radiotherapy toxicity.

The objective of our study is to evaluate breast cancer patients with BRCA1 or BRCA2 gene mutations and compare them with patients without these mutations. Specifically, we aim to assess the acute side effects of radiotherapy in both groups. Data were collected from four participating centers, comprising information from 73 patients who underwent known mutation analysis and had complete data. Patients were monitored on a weekly basis throughout their treatment for acute toxicity, which was evaluated using the Radiation Therapy Oncology Group (RTOG) acute toxicity criteria. The median age of the 73 patients included in our study was 43. Among them, 17 had BRCA1-positive mutations and 19 had BRCA2-positive mutations. Invasive ductal carcinoma was present in 67 patients, all of whom underwent surgery. Of the patients, 57 received conventional radiotherapy doses, while 16 received hypofractionated radiotherapy doses. During follow-up, metastasis occurred in three patients. In BRCA-positive patients, those under 40 years of age (p<0.001), with high nodal positivity (p=0.008), grade 2-3 (p=0.022), and lymphovascular invasion (p=0.002) were significantly more frequent compared to BRCA-negative patients (p<0.001). The median survival was 35.8 months. Grade 1 dysphagia developed in seven BRCA-negative patients and four BRCA-positive patients, with no significant difference observed between the two groups (p=0.351). There was also no statistical difference observed in the occurrence of grade 2-3 skin reactions, with 11 BRCA-negative patients and eight BRCA-positive patients experiencing these side effects. Our study supports existing literature by identifying an association between the presence of BRCA mutations and young age, nodal status, grade, and lymphovascular invasion. Additionally, we found no significant difference in the occurrence of radiotherapy toxicity between BRCA-positive and BRCA-negative patients. These findings suggest that radiotherapy can be safely administered to BRCA-positive patients after breast-conserving surgery or mastectomy. Keywords for our study include breast cancer, BRCA mutation, radiotherapy, and side effects.

Genomic analysis of breast cancer patients from Kerala: A novel BRCA1 mutation detected.

Breast cancer is the most common cancer among females, with an incidence of 6,41,000 cases annually. The genetic makeup of the individuals, ethnicity, geographical location, lifestyle, and BMI are some well-described factors associated with breast cancer. It is well known that pathogenic variants in BRCA1 and BRCA2 are associated with a majority of hereditary breast cancer. Genome-wide association studies (GWAS) have identified more than 80 germline susceptibility loci responsible for hereditary breast cancer. In the present study, analysis of 94 genes associated with hereditary cancer was performed using next generation sequencing (NGS) in twelve patients having breast cancer and suspected with hereditary association. Four out of twelve (33%) patients harbored pathogenic mutation of the BRCA1 gene. Two patients was identified p. E23Vfs*17 mutation in BRCA1, one patient had p.Glu1580Gln in BRCA1, and a novel frameshift variant p.T1456Ifs*9(c.4367Cdel) in one patient. In the present study, out of four detected mutations in the BRCA1 gene, three were known and one was a novel BRCA1 mutation. It is advised to perform NGS-based genome sequencing to identify the genetic predisposition in breast cancer patients.

An Overview of Psychological Analysis of Breast Cancer Patients undergoing Modified Radical Mastectomy and Breast Conservation Surgery and its impact on Objectified Body Consciousness at a Tertiary Care Cancer Centre in South India

BackgroundBreast cancer is the most common cancer among females, and surgery plays a central role in its treatment. Surgical treatments may have a negative psychological impact on women's mental health regarding their body image. The purpose of this study was to compare the psychological health insights pertaining to objectified body consciousness scores before and after the surgery and also to observe whether these scores were comparable across the surgery types. Materials and MethodsThis retrospective analysis of prospectively maintained data included 706 breast carcinoma patients who underwent either Breast Conservation Surgery or Modified Radical Mastectomy at tertiary care Cancer Centre, between the years 2020 to 2021. A validated questionnaire of Objectified Body Consciousness was used to obtain responses at diagnosis and at 6 months postsurgery and final scores were calculated for both instances. Two sample t-tests/analysis of variance and Chi-square tests were used to compare continuous and categorical variables respectively. ResultsOut of total 706 breast cancer patients, 402 patients underwent Breast Conservation Surgery and 304 underwent Modified radical mastectomy procedure. A statistically significant change was seen in the mean Objectified Body Consciousness Score (14.22 ± 15.44) for all patients when compared preoperatively(72.72 ± 11.38) and postoperatively(60.15 ± 17.58). This change was higher in the Modified Radical Mastectomy group(29.38 ± 11.53). Also, statistically significant rise in scores was seen with increasing age. ConclusionWe could affirmatively conclude in our study that younger breast cancer patients and all patients who underwent a Modified Radical Mastectomy, had more psychological apprehension with the body image postsurgery, signifying these groups should be encouraged by healthcare professionals to reach out for counselling at the earliest.

Survival outcomes and clinicopathological factors analysis of breast cancer patients. A single-institution cohort from 2012 to 2020 in a Mexican population.

e13104 Background: In Mexico, The Instituto Mexicano del Seguro Social (IMSS) is a tripartite contribution which provides care to more than 74 million beneficiaries, which represents more than 50% of the general population of the country. Although Mexican breast cancer statistics have been reported, it is imperative to know the updated statistics on the epidemiology in our Institution. The aim of this study is to describe the survival outcomes and the clinical-pathological characteristics of patients with breast cancer. Methods: Records of breast cancer patients treated at the Oncology Hospital from Centro Medico Nacional Siglo XXI of IMSS, from January 2012 to December 2020 were included. We analyzed clinical and demographic characteristics of the population, as well as survival outcomes at 5-years. Results: A cohort of 5,264 patients was included. Median follow up was 54.9 months. Forty-three percent (n = 2,274) were diagnosed in early-stage breast cancer (I–IIA), 43.1% (n = 2,269) in stages IIB-III, and 7% (n = 383) in stage IV. The most common immunophenotype was hormone receptor (HR) positive, HER2-negative (70.8%, n = 3,726). HER2-positive represents 19.3% (n = 1011), among HR-positive were 12.4% (n = 650) and HR-negative, 6.9% (n = 361). 527 patients (10.1%) were triple negative. At 5-years, disease-free survival was 74.9% (95% CI, 73.5 to 76.3) and overall survival was 90.4% (95% CI, 89.4 to 91.3). High histologic grade (HR 1.51; 95% CI, 1.33 to 1.7; p &lt; 0.001) and lymphovascular invasion (HR 1.84; 95% CI, 1.62 to 2.1; p &lt; 0.001) were associated with higher risk of recurrence. Adjuvant chemotherapy was significantly associated to a 42% reduction in the risk of recurrence, HR 0.58 (95% CI, 0.49 to 0.69; p &lt; 0.0001), and 54% in the risk of death, HR 0.46 (95% CI, 0.33 to 0.63; p &lt; 0.0001) in stage III. Lobular histology was also associated with worse survival, HR 1.41 (95% CI, 1.069 to 1.859; p = 0.015). Conclusions: An update of breast cancer Mexican patients treated at IMSS is presented. We highlight the impact of adjuvant treatment and pathological risk factors for recurrence and death. This work can contribute to evaluate areas for improvement in management and outcomes in our population.

Prognostic Model and Influencing Factors for Breast Cancer Patients

Breast cancer is a common disease that affects women's life and health. Survival analysis of breast cancer patients can help doctors and patients understand the prognosis of patients and provide guidance for clinical treatment. In this study, experiments were conducted based on SEER breast cancer patient data, and feature selection was performed first, followed by the construction of prognostic models using four survival analysis methods. the C-Index, BS, and IBS indexes of the RSF model were 0.8535, 0.0853, and 0.0512, respectively, which had the best predictive effect in the prognostic model for breast cancer patients. Based on the SHAP method to analyze the important factors affecting the prognosis of breast cancer patients, the results showed that tumor stage, TNM stage, grade and age have a great impact on the prognosis of breast cancer patients.

PO-1255 Toxicity analysis of breast cancer patients treated with VMAT and 3D-CRT

PO-1255 Toxicity analysis of breast cancer patients treated with VMAT and 3D-CRT

Dose coverage and breath-hold analysis of breast cancer patients treated with surface-guided radiotherapy

BackgroundSurface-guided radiotherapy (SGRT) is used to ensure a reproducible patient set-up and for intra-fraction motion monitoring. The arm position of breast cancer patients is important, since this is related to the position of the surrounding lymph nodes. The aim of the study was to investigate the set-up accuracy of the arm of patients positioned using SGRT. Moreover, the actual delivered dose was investigated and an extensive breath-hold analysis was performed.Methods84 patients who received local or locoregional breast radiation therapy were positioned and monitored using SGRT. The accuracy of the arm position, represented by the clavicle position, was studied on the anterior–posterior kV-image. To investigate the effect of changes in anatomy and patient set-up, the actual delivered dose was calculated on cone-beam CT-scans (CBCT). A deformable registration of the CT to the CBCT was applied to deform the structures of the CT onto the CBCT. The minimum dose in percentage of the prescribed dose that was received by 98% of different CTV volumes (D98) was determined. An extensive breath-hold analysis was performed and definitions for relevant parameters were given.ResultsThe arm position of 77 out of 84 patients in total was successful, based on the clavicle rotation. The mean clavicle rotation was 0.4° (± 2.0°). For 89.8% of the patients who were irradiated on the whole-breast D98 was larger than 95% of the prescribed dose (D98 > 95%). D98 > 95% applied for 70.8% of the patients irradiated on the chest wall. Concerning the lymph node CTVs, D98 > 95% for at least 95% of the patients. The breath-hold analysis showed a mean residual setup error of − 0.015 (± 0.90), − 0.18 (± 0.82), − 0.58 (± 1.1) mm in vertical, lateral, and longitudinal direction, respectively. The reproducibility and stability of the breath-hold was good, with median 0.60 mm (95% confidence interval (CI) [0.66–0.71] mm) and 0.20 mm (95% CI 0.21–0.23] mm), respectively.ConclusionsUsing SGRT we were able to position breast cancer patients successfully, with focus on the arm position. The actual delivered dose calculated on the CBCT was adequate and no relation between clavicle rotation and actual delivered dose was found. Moreover, breath-hold analysis showed a good reproducibility and stability of the breath-hold.Trial registration CCMO register NL69214.028.19.

Survival analysis of breast cancer patients using machine learning models

Survival analysis of breast cancer patients using machine learning models

Construction of a prognostic score model for breast cancer based on multi-omics analysis of study on bone metastasis.

Breast cancer (BRCA) is the most common type of cancer and the second leading cause of cancer-related death in women all over the world. Metastasis to bone is an indicator of poor prognosis in BRCA patients. This study aimed to develop a prognostic score model for predicting bone metastasis in patients with BRCA. BRCA-related RNA sequencing datasets and corresponding clinical information were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) were screened using Limma package of R software. A risk score based predictive model was constructed based on the key genes identified through univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) Cox regression. The gene expression profiles in BRCA patients were analyzed by gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA). Random survival forest (RSF) analysis of BRCA patients with bone metastasis was conducted to identify the key DEGs. Based on DEG analysis, a total of 677 genes were identified as genes related to bone metastasis in BRCA. By univariate Cox regression and LASSO regression, 28 DEGs were identified as signature genes to develop the prognostic model. A risk score for each patient was created by incorporating the expression values of each specific gene and weighting them with the corresponding estimated regression coefficients. Patients were divided into a low-risk and a high-risk group based on the median risk score. Overall survival (OS) was significantly lower in the high-risk group. The receiver operating characteristic (ROC) curve and multi-omics analysis indicated that the model had high training/testing accuracy and a good clinical predictive value. We used extra data from GEO database to verify the robustness of the prognostic model, and the lower OS in high-risk group and area under the curve (AUC) value indicated the model had strong predictive efficacy for prognosis of BRCA. A prognostic prediction model was constructed based on 28 key DEGs identified through multi-omics analysis of studies on bone metastasis. The model may provide a promising method for distinguishing the high-risk BRCA patients and help on decision making in addition to prognosis prediction for BRCA patients.

Survival analysis of breast cancer patients after diagnosis of second primary malignancies, focusing on the second primary hematologic malignancy.

Although the overall survival (OS) of breast cancer patients is increasing with improved detection and therapies, so is the risk of breast cancer patients developing subsequent malignancies. We investigated the OS of breast cancer survivors according to sites of second primary malignancies (SPM). The OS of the second primary hematologic malignancy (SPHM) was then compared with that of metastatic breast cancer (MBC). We retrospectively analyzed patients diagnosed with primary breast cancer between 1998 and 2019. Only those with SPM were eligible for analysis. First, the OS of patients with SPM diagnosed as the first event after the diagnosis of breast cancer was analyzed. Next, the OS of patients with SPHM, with or without breast cancer relapse, was compared with that of patients with MBC, matched using the propensity score. Patients diagnosed with SPM without breast cancer relapse as the first event had a significantly better OS than did patients with MBC, but the OS of those with SPHM as the first event did not differ significantly from that of patients with MBC (hazard ratio [HR], 1.558; 95% confidence interval [CI], 0.856-2.839; P = 0.147). The OS of patients with SPHM with or without breast cancer relapse was worse than that of the MBC group after propensity score matching (HR, 1.954; 95% CI, 1.045-3.654; P = 0.036). Prognosis of SPM diagnosed as the first event was statistically better than that of MBC, except in case of SPHM. Patients with SPHM, with or without MBC, showed poor OS before and after propensity score matching.

Disparities in Time to Treatment for Breast Cancer.

This study aimed to identify the demographic/socioeconomic factors associated with disparities in time to breast cancer treatment. We conducted an analysis of breast cancer patients from the National Cancer Database, 2008-2019. Time intervals from diagnosis to surgery, radiation, and chemotherapy were compared based on age, sex, race, and socioeconomic status. A total of 715,210 patients with breast cancer were included. Overall, Hispanic patients had the longest times to surgery, radiation, and chemotherapy compared to non-Hispanic patients (surgery 73.3 vs. 53.8 days, radiation 177.2 vs. 136.9 days, chemotherapy 83.0 vs. 66.5 days, all p<0.01). Similarly, black patients, those who were uninsured, and those with lower income (<$63,000) had the longest times to treatment. We identified several racial/socioeconomic disparities in time to treatment. Further investigation into the causes of these disparities is of increasing importance to address inequities in breast cancer care.

Can Montgomery tubercles impact aesthetic 3D nipple-areolar complex tattooing? An anatomical, quantitative analysis of breast cancer patients

PurposeWe aimed to establish a relationship between the amount of Montgomery tubercles (MTs) per nipple-areolar complex (NAC) given patient characteristics such as age, BMI, menopausal status, race/ethnicity, and NAC size to better inform current 3D NAC tattooing practices. MethodsPreoperative photographs of patients pursuing breast reconstruction after mastectomy in 2010 through 2018 were reviewed. The number of MTs on each native NAC was quantified. The impact of patient factors on the quantity of MTs was evaluated via Pearson correlation and bivariate analyses. ResultsTwo hundred and eleven patients (399 breasts) were reviewed. On average, patients had 5.0 ± 5.2 MTs (range, 0–25 MTs). Number of MTs did not correlate with patient age, BMI, or NAC size. Premenopausal females were more likely than postmenopausal females to have a greater number of MTs per breast (p-value = 0.0183). ConclusionsPostmastectomy patients desiring a more “youthful” NAC may consider additional MTs when pursuing 3D NAC tattooing.

Near-Maximum Rib Dose is the Most Relevant Risk Factor for Ipsilateral Spontaneous Rib Fracture: A Dosimetric Analysis of Breast Cancer Patients after Radiotherapy

<h3>Purpose/Objective(s)</h3> Spontaneous rib fracture (SRF) is a common late complication in treated breast cancer patients. This study evaluated the incidence and risk factors of ipsilateral SRF after radiotherapy (RT) in breast cancer patients. In addition, we identified dosimetric parameters that were significantly associated with ipsilateral SRF. <h3>Materials/Methods</h3> We retrospectively reviewed 2,204 patients with breast cancer who underwent RT between 2014 and 2016, and were followed up with bone scans. We evaluated clinical risk factors for ipsilateral SRF. Dose-volume histogram analysis was also performed for patients (n = 538) whose dosimetric data were available. All ipsilateral ribs were manually delineated, and dosimetric parameters of the ribs were converted into the equivalent dose in 2 Gy fractions (EQD2). <h3>Results</h3> Ipsilateral SRF occurred in 14.5% of patients 3 years after RT. The median time to develop ipsilateral SRF was 15 months. In multivariate analysis of all patients, a hypofractionated dose scheme and abnormally low bone density were significant clinical risk factors for ipsilateral SRF. In dosimetric analysis, near-maximum rib dose (D2cc) best predicted ipsilateral SRF. The cutoff value of D2cc was EQD2 52 Gy, as determined by receiver operating characteristic analysis. In multivariate analysis including dosimetric variables, D2cc EQD2 ≥ 52 Gy was the only significant risk factor for ipsilateral SRF. <h3>Conclusion</h3> Our data demonstrated that near-maximum rib dose was the best dosimetric parameter to predict ipsilateral SRF in RT-treated breast cancer patients. Additionally, we suggest that the dose for the rib be constrained to D2cc EQD2 < 52 Gy to minimize the risk of ipsilateral SRF.

Prognostic factors for cancer-specific survival in 220 patients with breast cancer: A single center experience.

Hospital-based breast cancer survival studies are scarce in western Iran. Furthermore, the relationship between breast cancer survival and clinical parameters has been extensively studied, but many of the findings come from developing countries. This paper aims to estimate the survival of hospital-based breast cancer patients and its predictor factors. This retrospective analysis was conducted on 578 patients with primary breast cancer who underwent surgery between 2004 and 2020. Information was collected from medical reports by the Hospital information system in Imam Reza Hospital, Kermanshah, Iran. One-, 2-, 5-, and 10-year breast cancer-specific survival has been calculated using the Kaplan-Meier process. Crude and adjusted Hazard Ratios (HR) were calculated using the Cox proportional regression model. One-, 2-, and 5-year overall breast cancer survival were 219 (99.54%), 196 (89.09%), 159 (72.27%), and 70 (31.81%), respectively. Univariate analysis of breast cancer patients with tumor-related variables revealed that factors such as age, menopause status, lymph node metastasis, number of lymph nodes, organ metastasis, and stage of disease were significantly associated with disease-specific survival (p<.05). Multivariate analysis demonstrated that metastasis (HR=41.77, 95% CI: 15.3-114.15) and lymph node metastasis (HR=5.26, 95% CI: 1.9-14.6) were significantly related to survival. The findings demonstrate that survival is relatively low and is consistent with late-stage disease diagnosis. It is believed that this is due to a poor level of awareness, lack of screening programs, and subsequent late access to treatment.

High levels of unfolded protein response component CHAC1 associates with cancer progression signatures in malignant breast cancer tissues.

The aberrant mRNA expression of a UPR component Cation transport regulator homolog 1 (CHAC1) has been reported to be associated with poor survival in breast and ovarian cancer patients, however, the expression of CHAC1 at protein levels in malignant breast tissues is underreported. The following study aimed at analyzing CHAC1 protein expression in malignant breast cancer tissues. Evaluation of CHAC1 expression in invasive ductal carcinomas (IDCs) with known ER, PR, and HER2 status was carried out using immunohistochemistry (IHC) with CHAC1 specific antibody. The Human breast cancer tissue microarray (TMA, cat# BR1503f, US Biomax, Inc., Rockville, MD) was used to determine CHAC1 expression. The analysis of CHAC1 IHC was done to determine its expression in terms of molecular subtypes of breast cancer, lymph node status, and proliferation index using Qu-Path software. Survival analysis was studied with a Kaplan-Meier plotter. Immunohistochemical analysis of CHAC1 in breast cancer tissues showed significant up-regulation of CHAC1 as compared to the adjacent normal and benign tissues. Interestingly, CHAC1 immunostaining revealed high expression in tumor tissues with high proliferation and positive lymph node metastasis suggesting that CHAC1 might have an important role to play in breast cancer progression. Furthermore, high CHAC1 expression is associated with poor overall survival (OS) in large breast cancer patient cohorts. As a higher expression of CHAC1 was observed in tissue cores with high Ki67 index and positive lymph node metastasis it may be concluded that enhanced CHAC1 expression correlates with proliferation and metastasis. The further analysis of breast cancer patients' survival data through KM plot indicated that high CHAC1 expression is associated with a bad prognosis hinting that CHAC1 may have a possible prognostic significance in breast cancer.

Intraoperative sentinel lymph node evaluation in patients with node-positive breast cancer status post neoadjuvant systemic therapy - An institutional experience

Recent studies have shown the feasibility and utility of sentinel lymph node (SLN) biopsy in patients with biopsy proven node-positive breast cancer after neoadjuvant chemotherapy. We reviewed our experience in intraoperative SLN evaluation in such cases and its effect on axillary management. A retrospective analysis of breast cancer patients (2015–2018) with a biopsy-proven positive axillary lymph node, who received neoadjuvant systemic therapy and underwent intraoperative SLN assessment was performed. Intraoperative SLN assessment results were compared with final pathology. Its accuracy and effect on axillary management is summarized. We identified 106 patients with positive axillary lymph node and neoadjuvant systemic therapy between the ages of 28 and 75 years who had SLN biopsy and lumpectomy (33) or mastectomy (73). Three or more SLNs were identified in 91 cases (86 %). The previously biopsied lymph node was identified as one of the sentinel lymph nodes in 93 cases (88 %). There is a high concordance rate between frozen section diagnosis and final diagnosis on sentinel lymph nodes. No false positive case and seven false negative frozen section diagnosis cases (diagnosed as negative on frozen section and positive on permanent sections) were identified. False-negative frozen section diagnosis correlated with low-volume nodal disease and obscuring tumor bed changes. Almost half of the positive lymph nodes were converted to negative after neoadjuvant chemotherapy. SLN biopsy with intraoperative frozen section evaluation after neoadjuvant systemic therapy in node-positive patients is an effective way to minimize axillary surgery.

Near-maximum rib dose is the most relevant risk factor for ipsilateral spontaneous rib fracture: adosimetric analysis of breast cancer patients after radiotherapy.

Spontaneous rib fracture (SRF) is acommon late complication in treated breast cancer patients. This study evaluated the incidence and risk factors of ipsilateral SRF after radiotherapy (RT) in breast cancer patients. In addition, we identified dosimetric parameters that were significantly associated with ipsilateral SRF. We retrospectively reviewed 2204patients with breast cancer who underwent RT between 2014 and 2016, and were followed up with bone scans. We evaluated clinical risk factors for ipsilateral SRF. Dose-volume histogram analysis was also performed for patients (n = 538) whose dosimetric data were available. All ipsilateral ribs were manually delineated, and dosimetric parameters of the ribs were converted into the equivalent dose in 2 Gy fractions (EQD2). Most of the patients with SRF (87.3%) were asymptomatic, and the remaining symptomatic patients complained of mild tenderness or chest wall discomfort; these symptoms all resolved within 6months without any treatment. Ipsilateral SRF occurred in 14.5% of patients 3years after RT. The median time to develop ipsilateral SRF was 15months. In dosimetric analysis, near-maximum rib dose (D2cc) best predicted ipsilateral SRF. The cut-off value of D2cc was EQD2 52 Gy, as determined by receiver operating characteristic analysis. In multivariate analysis including dosimetric variables, D2cc EQD2 ≥ 52 Gy was the only significant risk factor for ipsilateral SRF. Our data demonstrated that near-maximum rib dose was the best dosimetric parameter to predict ipsilateral SRF in RT-treated breast cancer patients. In addition, our results suggest that patients who received RT with exceeding rib dose cut-off value and had ipsilateral SRF on bone scan be recommended routine follow-up without additional imaging tests.