Prognostic Factor In Breast Cancer Research Articles

Real-world outcomes for Chinese breast cancer patients with tumor location of central and nipple portion.

BackgroundThe association between tumor location and breast cancer prognosis has been controversial. We sought to explore the relationship between tumors located in central and nipple portion (TCNP) and Chinese breast cancer.Patients and methodsA total of 1,427 breast cancer patients were recruited. There were 328 cases of TCNP and 1,099 cases of tumors in the breast peripheral quadrant (TBPQ). The chi-square test was used to compare different variables between TCNP and TBPQ groups. A one-to-one propensity score matching (PSM) was applied to construct a matched sample consisting of pairs of TCNP and TBPQ groups. Kaplan–Meier curves were used for survival analysis of disease-free survival (DFS), breast cancer-specific survival (BCSS) and overall survival (OS). The Cox proportional hazards regression model was applied to identify prognostic risk factors.ResultsThe median follow-up time was 58 months. Compared to TBPQ, TCNP patients had significantly larger tumor size, more frequent metastasis to lymph nodes (LN) and more proportions of TNM stage II–III. DFS, OS and BCSS rates were markedly lower in the TCNP group as compared to the TBPQ group before and after PSM (all p < 0.05). Multivariate Cox analysis showed that TCNP was an independent prognostic factor for breast cancer. Subgroup analysis indicated that for breast molecular subtypes and TNM stage II-III breast cancer, TCNP were related to worse prognosis. Multivariate logistic regression revealed that TCNP was an independent contributing factor for LN metastasis.ConclusionIn Chinese breast cancer, compared to TBPQ, TCNP is associated with more LN metastasis and poorer prognosis.

CD47 expression and tumor-associated immune cells in breast cancer and their correlation with molecular subtypes and prognostic factors.

Breast cancer is the most common malignancy in women and a heterogeneous disease at the molecular level. Since most breast cancer cases are not of a special type, it is suggested that tumor-associated macrophages and tumor-infiltrating lymphocytes, which are involved in tumor growth, invasion, angiogenesis, and metastasis, may be important factors that should be evaluated together with standard criteria to determine the prognosis of cancer and assist in treatment decisions and outcome stratification. In this study, CD47 expression, which is involved in macrophage-mediated immune escape, tumor-infiltrating lymphocytes, and tumor-associated macrophages were evaluated in breast cancer molecular subgroups and correlated with prognostic factors. The immunohistochemistry of CD47, CD163, and CD3 was analyzed on the tissue microarrays of 278 invasive breast cancer cases. The CD47, CD163, and CD3 expressions were found to be correlated with various clinicopathological parameters in breast cancer. High levels of CD47, CD163, and CD3 expressions had a significant correlation with the ER status and PR status, Ki-67 proliferation index, and molecular subtype (P<0.05). The CD47 expression had a significant correlation with the CD3 and CD163 expressions (p=0.021 and p=0.001, respectively). Our results suggest that CD47, CD163, and CD3 may be among the prognostic factors of breast cancer. The combined use of CD47, CD163, and CD3 can be a new prognostic factor for patients with breast cancer, especially as a therapeutic target in hormone receptor-negative breast cancer cases and those with a high proliferation index.

Hsa_circ_0097922 promotes tamoxifen resistance and cell malignant behaviour of breast cancer cells by regulating ACTN4 expression via miR-876-3p.

An increasing number of findings have verified the critical roles of circular RNAs (circRNAs) in human cancers, and chemotherapy resistance is a poor prognostic factor for breast cancer (BC). This study is designed to explore the function of hsa_circ_0097922 in the tamoxifen resistance of breast cancer. Hsa_circ_0097922, microRNA-876-3p (miR-876-3p), and alpha-actinin 4 (ACTN4) level were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell survival, proliferation, apoptosis, migration and invasion were detected by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry, wound healing and Transwell assays. Protein levels of proliferating cell nuclear antigen (PCNA), B-cell lymphoma-2 (Bcl-2), cleaved caspase 3, matrix metalloproteinase 9 (MMP9), and ACTN4 were determined using western blot assay. Using bioinformatics software, the binding between miR-876-3p and hsa_circ_0097922 or ACTN4 was predicted, followed by confirmation by RNA immunoprecipitation (RIP) and RNA pull-down assays. A xenograft tumour model in vivo analysed the biological role of hsa_circ_0097922 on BC tumour growth and drug resistance. Hsa_circ_0097922 and ACTN4 were increased, and miR-876-3p was decreased in tamoxifen resistance BC cells. Moreover, hsa_circ_0097922 knockdown can block BC cell malignant behaviour and tamoxifen resistance in vitro. Mechanically, hsa_circ_0097922 acted as a sponge of miR-876-3p to regulate ACTN4 expression. Hsa_circ_0097922 silencing increased the drug sensitivity of BC in vivo. Hsa_circ_0097922 might regulate BC cell malignant behaviour and tamoxifen resistance partly by regulating the miR-876-3p/ACTN4 axis, hinting at a promising therapeutic target for the BC treatment.

Pathological significance of GLUT-1 expression in breast cancer cells in diabetic and obese patients: The French Guiana study

The prevalence of obesity and type 2 diabetes is higher in French Guiana compared to mainland France. These metabolic disorders are associated with an increased risk of cancer. One of the factors involved is hyperinsulinemia that promotes the action of glucose transporter 1 (GLUT-1). The objective of this study is to characterize the expression of GLUT-1 in breast cancers cells in diabetic and obese patients compared to those who are not and to describe the clinical and histological prognostic factors of breast cancer in this population. We conducted a monocentric study between 2014 and 2020. Patients were classified into three groups: diabetes, obesity, and control group. The GLUT-1 expression was assessed by immunohistochemistry. In total, 199 patients were included in this study. The median age was 53.5 years, and the median tumor size was 2.8 cm. Luminal A was the most frequent molecular type (58.1%), followed by the triple-negative type (19.9%). The breast cancer in our population was characterized by a younger age at diagnosis, more aggressive molecular types, and larger tumor size. Thus, we suggest the advancement of the age of breast cancer screening in this territory. Overexpression of GLUT-1 was observed in 60.4% of cases and in all carcinoma in situ lesions. GLUT-1 overexpression was associated with more aggressive cancers. This overexpression is correlated with high histological grade, high proliferation index, and aggressive molecular types. Our study found no difference in GLUT-1 expression between the diabetic or obese patients and the control group.

Evaluation of the Relationship Between Axillary Lymph Node Involvement with Frequently Evaluated Prognostic Factors in Breast Cancer

Evaluation of the Relationship Between Axillary Lymph Node Involvement with Frequently Evaluated Prognostic Factors in Breast Cancer

Presence of peritumoral edema on T2w MRI: a poor non-invasive prognostic marker in breast cancer patients

BackgroundThe purpose of the study was to assess the correlation between peritumoral edema (PE) seen on magnetic resonance imaging (MRI) in breast cancer and the established pathological prognostic factors like tumor histology and molecular subtype, grade, Ki67 index, lymphovascular invasion (LVI) and nodal stage. The breast MRI and pathological data of post-surgery specimen of 126 breast cancer patients over a period of 18 months were retrospectively studied. Those who received neoadjuvant therapy, had non-invasive, locally advanced, inflammatory and bilateral breast cancers were excluded. Patients were divided into two groups based on finding of peritumoral edema on T2w MRI images: Group A with PE (n = 88) and Group B without PE (n = 38). Pathological results for the two groups were analyzed and compared using Chi square test. p values of < .05 were considered as significant.ResultsStatistically significant correlation was found between the PE and molecular subtype (p value of < .01), high grade (p value of .001) and High Ki-67 index (p value of .001). No significant correlation was present for the histological type and LVI pathological nodal stage (pN).ConclusionsWe concluded that presence of PE on MRI is associated with poor pathological prognostic factors in breast cancer. It can serve as an additional non-invasive marker to assess prognosis in breast cancer patients especially in those receiving neoadjuvant therapy where the whole tumor may not be available for pathological analysis post-therapy.

CNN-Based Approaches with Different Tumor Bounding Options for Lymph Node Status Prediction in Breast DCE-MRI.

Simple SummaryBreast cancer represents the most frequent cancer in women in the world. The state of the axillary lymph node is considered an independent prognostic factor and is currently evaluated only with invasive methods. Deep learning approaches, especially the ones based on convolutional neural networks, offer a valid, non-invasive alternative, allowing extraction of large amounts of the quantitative data that are used to build predictive models. The aim of our work is to evaluate the influence of the peritumoral parenchyma through different bounding box techniques on the prediction of the axillary lymph node in breast cancer patients using a deep learning artificial intelligence approach.Background: The axillary lymph node status (ALNS) is one of the most important prognostic factors in breast cancer (BC) patients, and it is currently evaluated by invasive procedures. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), highlights the physiological and morphological characteristics of primary tumor tissue. Deep learning approaches (DL), such as convolutional neural networks (CNNs), are able to autonomously learn the set of features directly from images for a specific task. Materials and Methods: A total of 155 malignant BC lesions evaluated via DCE-MRI were included in the study. For each patient’s clinical data, the tumor histological and MRI characteristics and axillary lymph node status (ALNS) were assessed. LNS was considered to be the final label and dichotomized (LN+ (27 patients) vs. LN− (128 patients)). Based on the concept that peritumoral tissue contains valuable information about tumor aggressiveness, in this work, we analyze the contributions of six different tumor bounding options to predict the LNS using a CNN. These bounding boxes include a single fixed-size box (SFB), a single variable-size box (SVB), a single isotropic-size box (SIB), a single lesion variable-size box (SLVB), a single lesion isotropic-size box (SLIB), and a two-dimensional slice (2DS) option. According to the characteristics of the volumes considered as inputs, three different CNNs were investigated: the SFB-NET (for the SFB), the VB-NET (for the SVB, SIB, SLVB, and SLIB), and the 2DS-NET (for the 2DS). All the experiments were run in 10-fold cross-validation. The performance of each CNN was evaluated in terms of accuracy, sensitivity, specificity, the area under the ROC curve (AUC), and Cohen’s kappa coefficient (K). Results: The best accuracy and AUC are obtained by the 2DS-NET (78.63% and 77.86%, respectively). The 2DS-NET also showed the highest specificity, whilst the highest sensibility was attained by the VB-NET based on the SVB and SIB as bounding options. Conclusion: We have demonstrated that a selective inclusion of the DCE-MRI’s peritumoral tissue increases accuracy in the lymph node status prediction in BC patients using CNNs as a DL approach.

Prognostic Value of the Serum HER2 Extracellular Domain Level in Breast Cancer: A Systematic Review and Meta-Analysis.

Simple SummaryWe performed a systematic review and meta-analysis evaluating the predictive value of the serum HER2 extracellular domain (sHER2 ECD) for breast cancer prognosis. Our review investigated 40 studies (12,229 patients) that assessed the impact of the sHER2 ECD levels on breast cancer prognosis and explored the clinical significance of sHER2 ECD levels in different treatment modalities. Our findings indicated that an elevated sHER2 was an unfavorable prognostic factor in breast cancer. More interestingly, sHER2 ECD was found to be a promising biomarker for predicting adverse clinical outcomes of trastuzumab-based treatment but did not affect the efficacy of tyrosine kinase inhibitors. In addition, the baseline cutoff value of sHER2 ECD in different treatment stages of breast cancer remains to be further explored. Overall, our study suggested that sHER2 ECD levels have important prognostic value in breast cancer and may be helpful for clinicians to select the appropriate anti-HER2 therapy for HER2-positive breast cancer, providing more evidence for guiding clinical practice.An elevated serum HER2 extracellular domain is associated with poor prognosis in breast cancer, but the relationship between sHER2 and the efficacy of different modalities remains controversial. Herein, we aimed to evaluate the prognostic value of serum HER2 extracellular domain (sHER2 ECD) in breast cancer and to identify its correlation with the efficacy of different treatment regimens. A systematic search of the PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases was conducted to identify studies exploring the association between HER2 ECD level and clinical outcomes among patients with breast cancer. Using the random effects models, pooled hazard ratios (HRs), and odds ratios (ORs) with 95% confidence intervals (CI), were calculated for progression-free survival (PFS), overall survival (OS), disease-free survival (DFS), and the objective response rate (ORR). Heterogeneity was further evaluated by subgroup and sensitivity analysis. Overall, 40 studies comprising 12,229 patients were included in this systematic review and meta-analysis. Elevated HER2 ECD levels were associated with worse PFS (HR 1.74, 95% CI 1.40–2.17; p < 0.001), and this effect was observed in patients treated with chemotherapy (HR 1.81, 95% CI 1.37–2.39; p < 0.001), endocrine therapy (HR 1.91, 95% CI 1.57–2.32; p < 0.001), and trastuzumab (HR 1.74, 95% CI 1.31–2.30; p < 0.001). However, this association was not present in patients treated with tyrosine kinase inhibitors (TKIs) (HR 1.44, 95% CI 0.85–2.43, p = 0.17). The HRs/ORs for an elevated HER2 ECD level for DFS, OS, and ORR were 2.73 (95% CI 2.17–3.42; p < 0.001), 2.13 (95% CI 1.77–2.57; p < 0.001), and 0.80 (95% CI 0.49–1.31; p = 0.381), respectively. An elevated sHER2 ECD was an unfavorable prognostic factor in breast cancer but did not affect the efficacy of tyrosine kinase inhibitors such as lapatinib. Detection of sHER2 ECD may be helpful for clinicians selecting the appropriate anti-HER2 therapy for patients with HER2-positive breast cancer.

DUSP4 Silencing Enhances the Sensitivity of Breast Cancer Cells to Doxorubicin through the Activation of the JNK/c-Jun Signalling Pathway.

Doxorubicin (Dox) has limited efficiency in breast cancer (BC) due to drug-acquired resistance. The epithelial–mesenchymal transition (EMT) plays a major role in the survival and drug resistance of cancer cells. It was suggested that the JNK pathway was implicated in the response to Dox by regulating EMT. DUSP4/or MKP-2 is a well-known regulator of the JNK pathway and was found to be highly expressed in BC. However, its functional significance is not yet fully understood. In the present study, the possible involvement of MKP-2 in Dox-induced EMT was investigated in breast cancer cells. Immunohistochemistry for tissues obtained from BC patients (n = 108) revealed 71.3% of tissues stained positively for MKP-2 while only 28.7% stained negatively. However, MKP-2 protein expression exhibited no significant relationship between BC prognostic factors, such as histological grade, histological type, hormonal status, and Ki-67 marker, its expression was significantly correlated with age 40 or below. In MDA-MB-231 cells, Dox-induced phosphorylation of JNK was sufficiently enhanced in MKP-2 silenced cells. This resulted in the attenuation of Dox-induced EMT, cell cycle arrest, and ultimately accelerated apoptosis. It was confirmed that the acquisition of Dox sensitivity by MKP-2 silencing largely depends on the stimulation of the JNK pathway. Indeed, results showed that overexpressing MKP-2 in non-tumorigenic MCF-12A cells dramatically inhibited Dox-induced JNK activation and, subsequently, cell death. The present study, to our knowledge, is the first to provide evidence for the potential role of MKP-2 in chemoresistance to Dox through modulating the JNK pathway and enhancing EMT.

2D shear wave elastography in evaluation of prognostic factors in breast cancer.

To evaluate the reproducibility of the 2D shear wave elastography (2D-SWE) method and to identify the prognostic factors of breast lesions. In this prospective study, 44female patients were consecutively included from January 2020 to September 2021. All patients showing visible masses at B-mode ultrasound underwent to clinical evaluation, followed by qualitative and quantitative 2D-SWE by two different operators with over 15-year and 2-year experience, respectively. Subsequently, patients underwent to surgical treatment after core needle biopsy. Reproducibility of qualitative and quantitative 2D-SWE was evaluated by Cohen's kappa and intraclass correlation coefficient (ICC). Clinical, imaging, and histopathological data and 2D-SWE evaluations were analysed with Spearman's rank correlation test. The mean age of the patients was 55years ± 12. The mean histological and ultrasound tumour size of were 23.1mm ± 13.2 and 17.2mm ± 10.2, respectively. The interobserver agreement showed a good reproducibility limited to the qualitative evaluation colour maps (Cohen's kappa = 0.603) and to the quantitative evaluation E ratio (ICC = 0.771). Correlation analysis between the ultrasound and 2D-SWE values and the clinical-pathological parameters showed a significant relationship between E ratio and Elston-Ellis grading (P < 0.030) and between tumour size and Elston-Ellis grading (P < 0.041). The 2D-SWE has shown good reproducibility among operators with different experience. It could be a promising tool in the evaluation of some prognostic factors in ultrasound visible breast cancer.

The Diagnostic Value of the Modified mSIS Score in Predicting Sentinel Axillary Lymph Node Positivity in Patients with Early-Stage Breast Cancer

Axillary lymph node metastasis is the most important prognostic factor in breast cancer. No method exists to diagnose the metastasis of the axillary lymph nodes before surgery. Sentinel lymph node biopsy is a procedure for axillary staging. Hematological parameters and systemic inflammation play a role in cancer metastasis. This study aims to evaluate the modified Systemic Inflammation Score (mSIS) score predicting sentinel axillary lymph node positivity in early breast cancer patients and to determine if there is a need to modify it. This is a retrospective study conducted in Ankara City Hospital General Surgery Department from March 2019 to July 2021. One hundred fifty-nine patients were analyzed according to age, albumin parameters, Thrombocyte, Lymphocyte and Monocyte count, histopathological type of cancer, and lymph node metastasis status. The collected information was entered into SPSS 24.0 program. Lymph node metastasis was detected in 51 of these 159 patients. Results showed no significant difference between the lymph node metastasis group and no lymph node metastasis group after applying the mSIS score to each group. This result is due to normal albumin levels in early breast cancer patients. Platalet lymphocyte ratio (PLR) is associated with lymph node metastasis in breast cancer. PLR is applied to mSIS score instead of albumin.The new modified early-stage breast cancer SIS(mebcSIS) was established as follows: Score 0: LMR ≥ 5.7 and PLR &lt; 141, Score 1: LMR &lt; 5.7 or PLR ≥ 141, Score 2: LMR &lt; 5.7 or PLR ≥ 141. The relationship between mebcSIS and LNM was statistically significant (p = 0.003). There is a positive correlation between mebcSIS score and lymph node metastasis in early breast cancer patients.

Breast Cancer Subtypes and Prognosis: Answers to Subgroup Classification Questions, Identifying the Worst Subgroup in Our Single-Center Series

PurposeMany studies report the triple negative breast cancer (TNBC) as the worst subgroup, as such patients do not benefit from anti-hormonal therapy and human epidermal growth factor receptor 2 (HER2) antagonists. While HER2 overexpression was a poor prognostic factor in breast cancer before trastuzumab (Herceptin) was available, TNBC is often reported as the worst BC subgroup since targeted therapy is currently not possible. Since the patience-specific experiences and the current literature did not always align, we aimed to determine the BC subgroup with the shortest survival in our center.MethodsThe records of patients with BC who were admitted to Trakya University Faculty of Medicine Department of Medical and Radiation Oncology between July 1999 and December 2019 were reviewed. Patients were divided into four main groups (Luminal A, Luminal B, TNBC, and HER2-enriched) according to the St Gallen International Consensus Panel and four subgroups in accordance with estrogen receptor, progestin receptor and HER2 positivity. Patient characteristics, treatment characteristics and clinical outcomes of the four main subgroups were evaluated. Survival curves were generated using the Kaplan–Meier method, and the significance of survival differences among the selected variables was compared by using the Log rank test. Factors affecting disease-free survival (DFS) and overall survival (OS) were analyzed by Cox regression analysis.ResultsStatistical analysis was performed on 2017 patients, after excluding patients with phyllodes tumor, carcinoma-in-situ and missing information from a total of 2474 patients with BC. There were 952 (47.1%) patients in the Luminal A group, 236 (34.1%) in the Luminal B group, 236 (11.7%) in the TNBC group and 142 (7.1%) patients in the HER2 enriched group. HER2-enriched patients had the shortest survival (p < 0.001), with 113.70 ± 7.17 months of DFS and 125.45 ± 3.03 months of OS. For patients who received Herceptin, DFS was 101.50 ± 6.4 months and OS was 118.14 ± 6.16. Patients who did not receive Herceptin had 92.79 ± 18 months of DFS and 94.44 ± 15.23 months of OS.ConclusionThe HER2-enriched subgroup had the worst prognosis despite receiving targeted therapy. While the duration of DFS and OS had no significant difference between TNBC and Luminal A-B subgroups, HER2 enriched subgroup had significantly shorter survival when compared to any other subgroup. HER2-enriched subgroup had a 10-fold greater risk of death compared to the Luminal A subgroup.

Long-term Survival and Prognostic Factors of Breast Cancer.

Breast cancer survival rate is an important index for assessment of treatment effect in reducing the mortality. Weaimed to determine the fifteen-year survival rate for breast cancer at a referral center in Iran and its correlated factors. This survival study enrolled patients with breast cancer who referred to Motamed Cancer Institute (MCI) from 1998 to2016. The survival rate was calculated using the Kaplan-Meier method. The relationship of demographic, clinical and therapeuticfactors with overall survival (OS) was studied using Cox's proportional hazard model. Totally, 3443 patients were studied. Their mean age and follow-up period were 47.7 (±11.43) years and 61.66 (±52.1)months, respectively. The median follow-up time was 48.4 months (range: 1-413 months), 49.7% of the patients had high schoolor higher education, and 71.3% presented in the early stage of the disease. Death occurred in 505 (14.7%) of the patients. Theoverall 2-, 5-, 7-, 10- and 15-year survival rates were 93%, 82%, 78%, 74%, and 66%, respectively. Lymph node involvement(HR=2.07; 95% CI: 1.38-3.09), tumor size≥5 cm (HR=2.83; 95% CI: 1.59-2.04), being single/divorced/widowed (HR=1.65;95% CI: 1.13-2.4), and education level<high school diploma (HR=1.57; 95% CI: 1.13-2.17) were independent predictors ofbreast cancer survival. The five-year breast cancer survival rate in this study was higher than reported by some other studies in Iran, whichcould be due to the multidisciplinary treatment approach in MCI. Tumor size and lymph node involvement as indicators ofdelayed diagnosis may affect breast cancer survival, even though their true effect due to lead-time bias should be considered. Thecorrelation of education level with survival confirms the importance of awareness and the need to establish strategies for earlydiagnosis in Iranian women.

Evaluation of the relationship between serum levels of 25-hydroxyvitamin D and prognostic factors in breast cancer.

&lt;b&gt; Introduction:&lt;/b&gt; Breast cancer is the most frequent invasive malignancy in women worldwide. There is a modifiable risk factor (such as serum vitamin D level) for this cancer. We decided to conduct this study since the influence of serum vitamin D levels on breast cancer is still controversial. &lt;/br&gt;&lt;/br&gt; &lt;b&gt; Methods and materials:&lt;/b&gt; In this analytical cross-sectional study, 103 patients who were diagnosed with breast cancer were included. Patients&apos; demographic, clinical and pathological features were all recorded. After the laboratory provided the serum vitamin D level, it was included in the checklist. Serum vitamin D level was categorized into 3 groups: &lt;10 ng/ml, 1030 ng/ml and &gt;30 ng/ml. The chi-square test was used to assess the relationship between vitamin D levels and clinicopathological features of the patients in SPSS software. The results were considered statistically significant at P-value &lt; 0.05. &lt;/br&gt;&lt;/br&gt; &lt;b&gt; Results:&lt;/b&gt; The mean age of the patients was 47.97 8.8 years. The mean serum vitamin D level was 28.72 19.9 ng and it was divided into three groups: 1) deficient (10 ng), which included 20 (19.4%) patients, 2) insufficient (10-30 ng), which included 48 (46.6%) patients, and 3) normal (&gt;30 ng), which included 35 (34%) patients. Low vitamin D level (&lt;320 ng/ml) was mainly detected in premenopausal cases (P-value = 0.001) with poor prognosis high grade of the disease (P-value = 0.001), positive nodal involvement (P-value = 0.025) and positive Ki-67 (P = 0.021). Furthermore, patients with lower serum vitamin D levels interact in fewer outdoor activities (P-value = 0.007), sleep less during the day (P-value = 0.001) and sleep later at night (P-value = 0.009). &lt;/br&gt;&lt;/br&gt; &lt;b&gt;Conclusion:&lt;/b&gt; Decreased serum 25(OH) D levels were linked with a higher histological grade of the tumor and lymph node involvement. Low serum 25(OH) D levels were also related to prognostic factors such as high Ki67 expression and the presence of negative hormone receptors (ER and PR). Our data support negative correlations between vitamin D levels and the risk of breast cancer with poor prognostic characteristics, based on observational research.

Evaluation of prognostic role of tumour budding in breast carcinoma and its correlation with known clinicopathological parameters

Tumour budding (TB) consists of a small group of cells (upto 5) which have detached from the tumour bulk. TB has been studied in many malignancies including head and neck, colorectum, oesophagus, etc. However there are very few studies to determine its role in Breast cancer. This study was designed to study the role of tumour budding as a prognostic factor in Breast cancer. To study the grade of TB in Invasive Breast Carcinoma and correlate it with known clinicopathological parameters to determine its usefulness as a prognostic factor. In this retrospective observational study, 40 cases of modified radical mastectomy from July 2019 to December 2020 were evaluated for the tumour budding. Ethical clearance was not required as it was a secondary data collection study which did not relate to patient’s privacy, clinical examination or treatment. Significance and correlation was studied between the grade of TB and known clinicopathological parameters using Chi-square test. Out of the 40 cases evaluated, 20 cases (50%) were of High grade TB (&amp;#62;/=10/10HPF), while 20 cases (50%) were of Low grade TB (&amp;#60;10/10HPF). Majority patients were of age group 40-60 years (60%), with primary carcinoma (52.5%) and invasive ductal type (72.5%). Higher TB was observed with Lymphnode positive cases (p=0.002), in higher TNM stage (p=0.006) and with lymphovascular invasion (p=0.000). As higher grade tumour budding was associated with positive lymphnode status, higher tumour stage and presence of lymphovascular invasion, it can be considered as an indicator of poor prognosis in cases of breast carcinoma especially in resource poor institutes which are not equipped with sophisticated IHC and Molecular markers.

Lactate score predicts survival, immune cell infiltration and response to immunotherapy in breast cancer.

Background: Tumor-derived lactate can modulate the function of infiltrating immune cells to establish an immunosuppressive microenvironment that favors tumor progression. However, possible effects of lactate-related genes (LRGs) on the tumor microenvironment (TME) of breast cancer (BRCA) are still unknown. Methods: LRGs were comprehensively screened from lactate metabolism-related pathways. We correlated the expression of these LRGs with immune cell infiltrating characteristics in the TME and clinicopathological features of patients. We also established a lactate score for quantifying lactate metabolism patterns of cancers and to predict of recurrence-free survival (RFS). Results: We successfully constructed a lactate score that was an independent prognostic factor in BRCA. A low lactate score, which was associated with immune activation with increased CD8+ T cells infiltration levels, indicated an inflamed TME. Consistently, higher expression levels of inhibitory immune checkpoints, including PD-L1, LAG3, CTLA4, and TIM3, as observed from high lactate score subgroup, suggested an immune-desert phenotype as well as poor prognosis. Moreover, a low lactate score predicted the increased chemotherapeutic drug sensitivity and enhanced anti-PD-1 immunotherapy responses. Conclusion: The present study analyzed the potential roles of LRGs in the TME diversity and prognosis. These results will help to improve our understanding of the characteristics of TME immune cell infiltration and guide the development of more effective immunotherapy strategies.

Effect of Pyroptosis-Related Genes on the Prognosis of Breast Cancer

BackgroundsPyroptosis, a newly pattern of specific programmed cell death, has been reported to participate in several cancers. However, the value of pyroptosis in breast cancer (BRCA) is still not clear.MethodsHerein, we analyzed the data of BRCA from both The Cancer Genome Atlas (TCGA) and GSEA MSigDB database. Based on the obtained pyroptosis-related genes (PRGs), we searched the interactions by STRING. After that, we performed clustering analysis by ConsensusClusterPlus. The PRGs with significant prognostic value were then screened through univariate cox regression and further evaluate by constructing a risk model by least absolute shrinkage and selection operator (LASSO) Cox regression. The immune and sensitivity to drugs were also predicted by comprehensive algorithms. Finally, real-time quantitative PCR (qPCR) was performed on two of the screened signature PRGs.ResultsA total of 49 PRGs were obtained from public database and 35 of them were significantly differentially expressed genes (DEGs). Cluster analysis was then performed to explore the relationship between DEGs with overall survival. After that, 6 optimal PRGs (GSDMC, IL-18, CHMP3, TP63, GZMB and CHMP6) were screened out to construct a prognostic signature, which divide BRCA patients into two risk groups. Risk scores were then confirmed to be independent prognostic factors in BRCA. Functional enrichment analyses showed that the signature were obviously associated with tumor-related and immune-associated pathways. 79 microenvironmental cells and 11 immune checkpoint genes were found disparate in two groups. Besides, tumor immune dysfunction and exclusion (TIDE) scores revealed that patients with higher risk scores are more sensitive to immune checkpoint blockade treatment. Patients in the low-risk group were more sensitive to Cytarabine, Docetaxel, Gefitinib, Paclitaxel, and Vinblastine. Inversely, patients in the high-risk group were more sensitive to Lapatinib. Finally, we found that, CHMP3 were down-regulated in both BRCA tissues and cell lines, while IL-18 were up-regulated.ConclusionPRGs play important roles in BRCA. Our study fills the gaps of 6 selected PRGs in BRCA, which were worthy for the further study as predict potential biomarkers and therapeutic targets.

Impact of body mass index on pathological complete response and survival of breast cancer patients receiving neoadjuvant chemotherapy.

High body mass index (BMI) is regarded as a poor prognostic factor in breast cancer (BC). However, its association with pathological complete response (pCR) and survival after neoadjuvant chemotherapy (NAC) remains controversial. We wanted to assess the prognostic impact of BMI in this setting. Single-center, retrospective review of 314 BC patients undergoing NAC from 2010 to 2018. Patients were categorized as underweight/normal weight (UW/NW) (BMI < 25) or overweight/obese (OW/OB) (BMI ≥ 25). The relationship between BMI and other traditional clinical-pathological prognostic variables with the pCR rate was investigated using logistic regression analysis. The effect on event-free survival (EFS) and overall survival (OS) was estimated by the Cox proportional hazards regression analysis. One hundred and twenty-two patients were UW/NW while 192 were OW/OB. Multivariate analysis revealed that hormonal receptors negative, HER2 positive, and clinical tumor stage (cT) 1-2 were independent predictor factors for pCR. Multivariate analysis confirmed tumor grade G3 and lack of pCR as independent adverse prognostic factors for EFS, while factors associated with worse OS were cT3-4, hormone receptors negative, and lack of pCR. Non-significant differences in pCR, EFS, or OS were observed between the two baseline BMI categories. In our experience, BMI is not associated with pCR, EFS, or OS in BC patients receiving NAC. Achieving pCR is the most consistent factor associated with EFS and OS. Prospective and well-designed studies taking into account other important biological and anthropometric factors are needed to determine the exact role of BMI in this setting.

Impact of Marital Status on Prognosis of Patients With Invasive Breast Cancer: A Population-Based Study Using SEER Database.

ObjectiveThis study aimed to investigate the prognostic roles of marital status in patients with invasive breast cancer. Method: We extracted the data of patients with invasive breast cancer who were diagnosed during 2010–2015 and had complete staging and molecular typing from the Surveillance, Epidemiology, and End Results (SEER)-18 database. Kaplan–Meier curve method and Cox regression analysis were performed to investigate the differences in breast cancer–specific survival (BCSS) and overall survival (OS) in the total population and various subgroups with different marital statuses.ResultsAmong the 324,062 patients with breast cancer in this study, 55.0%, 40.0%, and 5.0% were married, unmarried, and unknown, respectively; 51.8%, 32.2%, 10.5%, and 5.5% were patients with Stages I, II, III, and IV breast cancer, respectively. The 5-year BCSS and OS of married patients were 92.6% and 88.1%, respectively, higher than those of unmarried patients (88.3% and 78.1%, P < 0.001). After adjustment for sex, age, T and N stages, histological grade, insurance status, race, year of diagnosis, and molecular subtypes, married status was an independent predictor of better BCSS [hazard ratio (HR) = 0.775, 95% confidence interval (CI) = 0.753–0.797, P < 0.001) and OS (HR = 0.667, 95% CI = 0.653–0.681, P < 0.001). After multivariate analysis of various subgroups of sex, age, stage, histological grade, insurance status, race, and molecular subtype, married status was an independent predictor of better BCSS in all subgroups except for Grade IV, age < 35 years, and uninsured subgroups. Marital status was an independent predictor of better OS in all subgroups except the subgroup with age <35 years.ConclusionsIn conclusion, marital status was an independent prognostic factor for breast cancer. The unmarried patients with breast cancer had a worse prognosis, except for the subgroup with age <35 years. Hence, unmarried patients with breast cancer and age ≥35 years may need additional psychosocial and emotional support to achieve more prolonged survival, besides active treatment of primary disease.

Non-invasive predictors of axillary lymph node burden in breast cancer: a single-institution retrospective analysis

PurposeAxillary staging is an important prognostic factor in breast cancer. Sentinel lymph node biopsy (SNB) is currently used to stage patients who are clinically and radiologically node-negative. Since the establishment that axillary node clearance (ANC) does not improve overall survival in breast-conserving surgery for patients with low-risk biological cancers, axillary management has become increasingly conservative. This study aims to identify and assess the clinical predictive value of variables that could play a role in the quantification of axillary burden, including the accuracy of quantifying abnormal axillary nodes on ultrasound.MethodsA retrospective analysis was conducted of hospital data for female breast cancer patients receiving an ANC at our centre between January 2018 and January 2020. The reference standard for axillary burden was surgical histology following SNB and ANC, allowing categorisation of the patients under ‘low axillary burden’ (2 or fewer pathological macrometastases) or ‘high axillary burden’ (> 2). After exploratory univariate analysis, multivariate logistic regression was conducted to determine relationships between the outcome category and candidate predictor variables: patient age at diagnosis, tumour focality, tumour size on ultrasound and number of abnormal lymph nodes on axillary ultrasound.ResultsOne hundred and thirty-five patients were included in the analysis. Logistic regression showed that the number of abnormal lymph nodes on axillary ultrasound was the strongest predictor of axillary burden and statistically significant (P = 0.044), with a sensitivity of 66.7% and specificity of 86.8% (P = 0.011).ConclusionIdentifying the number of abnormal lymph nodes on preoperative ultrasound can help to quantify axillary nodal burden and identify patients with high axillary burden, and should be documented as standard in axillary ultrasound reports of patients with breast cancer.