Overall Survival In Breast Cancer Research Articles

Abstract PO2-02-07: Clinicopathological Features and Prognostic Role of HER2 Low in Early Breast Cancer: A real world study

Abstract Background: The definition of human epidermal growth factor receptor-2(HER2) low was proposed with the development of T-DXd, a novel antibody-drug conjugate (ADCs) targeting HER2 in the field of breast cancer (BC) treatments. However, whether HER2 low is a distinct subgroup is still an ongoing debate with mixed results. Current retrospective studies focused on HER2 low concentrated more on metastatic BC, less was known in early BC. The retrospective study was conducted based on HER2 low early BC to comprehensively analyze its clinicopathological features and prognostic roles compared with HER2 IHC0. Methods: This single institution retrospective study enrolled 999 early stage (stage I through III) HER2 negative invasive BC patients diagnosed at Chinese PLA General Hospital from January 2010 to December 2015. Tumors with HER2 immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization assay were defined as HER2 low. Clinicopathological characteristics s and survival outcomes including disease-free survival (DFS) and overall survival (OS) were compared between HER2 IHC0 and HER2 low groups. The correlations between HER2 expression and estrogen receptor (ER) status were determined by Mantel-Haenszel χ2 test. Cohen’s kappa coefficient (k) was adopted to evaluate the concordance between HER2 expression on primary tumors and matched biopsies. Results: 999 patients were eligible for inclusion criteria, among which the percentages of HER2 low in the whole cohort, HR positive group and HR negative group were 83.6%, 86.54%, 72.14% respectively. It was observed the presence of a significant higher proportion of ER level > 10% (p < 0.001), PgR positive (p < 0.001) and more patients who received endocrine therapy (p = 0.002). In HR positive group, clinicopathological features were balanced between HER2 IHC0 and HER2 low. In HR negative group, HER2 low manifested a higher proportion of invasive ductal type (p = 0.016) compared with HER2 IHC0. Survival analysis showed a significantly longer OS in HER2 low BC than HER2 IHC0. (HR: 0.458, 95%CI: 0.262-0.800, p = 0.0005). Nevertheless, the independent role was not reached in DFS. When stratified by HR status, patients with HER2 low in HR positive group demonstrated a longer OS than HER2 IHC0 (HR: 0.55, 95%CI: 0.273-1.105, p = 0.0385). The same trend was observed in HR negative group (HR: 0.385, 95%CI: 0.158-0.939, p = 0.0132). Neither the HR positive group nor the HR negative group achieved significant DFS. Besides, a positive correlation was observed between ER status and the rate of HER2 low (Mantel-Haenszel c2 test, p < 0.001, Pearson’s R = 0.159, P < 0.001). No regularity of survival differences between HER2 IHC0 and HER2 low was found in each ER level in the exploratory study. Finally, 119 patients who developed relapsed or metastatic disease were identified, with the most prevalent metastatic site being bone (31.1%), following by lung (16.80%) and lymph node (13.44%). Among 52 patients with matched biopsy samples, dynamic changes of HER2 IHC status were confirmed in both primary and relapsed statuses, with an discordance rate of 28.84% (K = 0.194, 95%CI: 0.168-0.219). conclusion: HER2 low expression breast cancer may not be regarded as a unique BC group in this real-world population due to similar clinicopathological features and prognostic roles especially in hormone-receptor positive cases. ER level was positively correlated with the rate of HER2 low population. Overall, whether HER2 low is a distinct subgroup remains to be supported and validated by more data both in clinical and molecular levels. Key words: HER2 low; Breast cancer; Clinicopathological Features; Prognosis; Molecular type Clinicopathological Features and Prognostic Role of HER2 Low in Early Breast Cancer: A real world study Citation Format: Ziqing Kong, Weihong Zhao. Clinicopathological Features and Prognostic Role of HER2 Low in Early Breast Cancer: A real world study [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 PO2-02-07.

A comprehensive analysis of the prognostic characteristics of microRNAs in breast cancer.

Both overall survival (OS) and disease-specific survival (DSS) are significant when determining a patient's prognosis for breast cancer (BC). The effect of DSS-related microRNAs on BC susrvival, however, is not well understood. Here, we spotted differentially expressed miRNAs (DEMs) in the TCGA database of BC DSS, identified eight DSS-related miRNAs, and constructed a risk model. AUC values at 1, 3, and 5years were 0.852, 0.861, and 0.868, respectively, indicating a risk model's excellent prognostic prediction ability. Then, we validated miRNA roles in BC OS and finally defined miR-551b as an independently prognostic miRNA in BC. According to function analysis, miR-551b is strongly linked with the emergence and spread of cancer, including protein ubiquitination, intracellular protein transport, metabolic pathways, and cancer pathways. Moreover, we confirmed the low expression of miR-551b in BC tissue and cells. After miR-551b inhibition or overexpression, cell function was either dramatically increased or diminished, respectively, indicating that miR-551b could regulate BC proliferation, invasion, and migration. In conclusion, we thoroughly clarified BC-related miRNAs on DSS and OS and verified miR-551b as a crucial regulator in the development and prognosis of cancer. These results can offer fresh ideas for BC therapy.

SIRT3 Expression Predicts Overall Survival and Neoadjuvant Chemosensitivity in Triple-Negative Breast Cancer.

The Sirtuin (SIRT) family consists of seven evolutionary conserved NAD-dependent deacetylases that play important roles in various cancers, including breast cancer (BC). SIRTs expression has been reported to have prognostic value in BC, but these studies used limited sample size and yielded inconsistent conclusions. This study evaluated the association of SIRT3 and other SIRT family members with survival and neoadjuvant chemotherapy outcomes. BC patients' data was obtained from the TCGA-BRCA, METABRIC and GEO databases, comprising 4336 samples. SIRTs expression and overall survival (OS) were analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. SIRT3 expression levels were compared between pathologic complete response (pCR) and non-pCR groups after neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). Protein-protein interaction networks were constructed using the STRING database. Gene set enrichment analysis (GSEA) was performed to explore potential functions of SIRT3. Through systematic analysis of SIRTs expression and OS of BC using three independent cohorts: TCGA-BRCA, METABRIC and GSE16446, we found that high SIRT3 expression was significantly associated with worse OS in TNBC in the TCGA-BRCA cohort, which was validated in the METABRIC and GSE16446 cohorts. SIRT3 expression was correlated with BC subtypes and American Joint Committee on Cancer (AJCC) T stage, but not with age-at-diagnosis, race, or tumor stage. Moreover, TNBC patients with higher SIRT3 expression had lower pCR rates after neoadjuvant chemotherapy (p = 6.40e-03) and SIRT3 expression was significantly lower in the pCR group than in the non-pCR group in TNBC (p = 4.2e-03). GSEA indicated that SIRT3 was involved in drug-related pathways such as oxidative phosphorylation, metabolism of xenobiotics by cytochrome P450, and drug metabolism. Our study suggests that SIRT3 is a potential biomarker for both OS and neoadjuvant chemosensitivity in TNBC. It may also assist in selecting suitable candidates and treatment options for TNBC patients.

The androgen receptor interacts with GATA3 to transcriptionally regulate a luminal epithelial cell phenotype in breast cancer

BackgroundThe androgen receptor (AR) is a tumor suppressor in estrogen receptor (ER) positive breast cancer, a role sustained in some ER negative breast cancers. Key factors dictating AR genomic activity in a breast context are largely unknown. Herein, we employ an unbiased chromatin immunoprecipitation-based proteomic technique to identify endogenous AR interacting co-regulatory proteins in ER positive and negative models of breast cancer to gain new insight into mechanisms of AR signaling in this disease.ResultsThe DNA-binding factor GATA3 is identified and validated as a novel AR interacting protein in breast cancer cells irrespective of ER status. AR activation by the natural ligand 5α-dihydrotestosterone (DHT) increases nuclear AR-GATA3 interactions, resulting in AR-dependent enrichment of GATA3 chromatin binding at a sub-set of genomic loci. Silencing GATA3 reduces but does not prevent AR DNA binding and transactivation of genes associated with AR/GATA3 co-occupied loci, indicating a co-regulatory role for GATA3 in AR signaling. DHT-induced AR/GATA3 binding coincides with upregulation of luminal differentiation genes, including EHF and KDM4B, established master regulators of a breast epithelial cell lineage. These findings are validated in a patient-derived xenograft model of breast cancer. Interaction between AR and GATA3 is also associated with AR-mediated growth inhibition in ER positive and ER negative breast cancer.ConclusionsAR and GATA3 interact to transcriptionally regulate luminal epithelial cell differentiation in breast cancer regardless of ER status. This interaction facilitates the tumor suppressor function of AR and mechanistically explains why AR expression is associated with less proliferative, more differentiated breast tumors and better overall survival in breast cancer.

A nomogram for predicting overall survival of breast cancer with regional lymph node metastasis in young women.

Young breast cancer (YBC) patients demonstrate a heightened propensity for regional lymph node metastasis (RLNM) in contrast to cohorts across varying age demographics. The aim of our study was to identify clinicopathologic prognostic variables in YBC patients with RLNM and construct a practical and reliable nomogram for the prediction of overall survival (OS) using the Surveillance, Epidemiology, and End Results (SEER) database. Young individuals (≤40 years) with a diagnosis of breast cancer with RLNM were recognized from the SEER database between 2010 and 2015, and further randomly split into two cohorts: the training set (n=4,497) and the validation set (n=1,927). We first performed univariate and multivariate Cox regression analyses to confirm independent survival predictors of OS. A novel prognostic nomogram was developed and evaluated using Harrell's concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). To make a clear distinction between high- and low-risk patients in terms of patient survival, Kaplan-Meier survival curves were assessed using the log-rank test. Nine risk factors were found as independent prognostic variables in predicting OS, including race, grade, histology, surgery, radiation, molecular subtype, American Joint Committee on Cancer (AJCC) stage 7th edition, T stage, and N stage. The C-index values of our nomogram were 0.786 [95% confidence interval (CI): 0.767-0.805] and 0.791 (95% CI: 0.760-0.822) in our training and validation groups, respectively. The ROC curves demonstrated sufficient discriminating ability, while the predicted and real survival rates were fairly consistent, as shown by the calibration plots. The prediction model had a higher net benefit and acceptable clinical value, as shown by the DCA curves. In YBC patients with RLNM, we successfully established a unique nomogram to forecast the 2-, 3-, and 5-year OS. Clinicians may utilize this nomogram to pinpoint patients at higher risk and provide them with appropriate customized therapies.

Molecular subtype identification and prognosis stratification based on lysosome-related genes in breast cancer

BackgroundLysosomes are known to have a significant impact on the development and recurrence of breast cancer. However, the association between lysosome-related genes (LRGs) and breast cancer remains unclear. This study aims to explore the potential role of LRGs in predicting the prognosis and treatment response of breast cancer. MethodsBreast cancer gene expression profile data and clinical information were downloaded from TCGA and GEO databases, and prognosis-related LRGs were screened for consensus clustering analysis. Lasso Cox regression analysis was used to construct risk features derived from LRGs, and immune cell infiltration, immune therapy response, drug sensitivity, and clinical pathological feature differences were evaluated for different molecular subtypes and risk groups. A nomogram based on risk features derived from LRGs was constructed and evaluated. ResultsOur study identified 176 differentially expressed LRGs that are associated with breast cancer prognosis. Based on these genes, we divided breast cancer into two molecular subtypes with significant prognostic differences. We also found significant differences in immune cell infiltration between these subtypes. Furthermore, we constructed a prognostic risk model consisting of 7 LRGs, which effectively divides breast cancer patients into high-risk and low-risk groups. Patients in the low-risk group have better prognostic characteristics, respond better to immunotherapy, and have lower sensitivity to chemotherapy drugs, indicating that the low-risk group is more likely to benefit from immunotherapy and chemotherapy. Additionally, the risk score based on LRGs is significantly correlated with immune cell infiltration, including CD8 T cells and macrophages. This risk score model, along with age, chemotherapy, clinical stage, and N stage, is an independent prognostic factor for breast cancer. Finally, the nomogram composed of these factors has excellent performance in predicting overall survival of breast cancer. ConclusionsIn conclusion, this study has constructed a novel LRG-derived breast cancer risk feature, which performs well in prognostic prediction when combined with clinical pathological features.

Transforming growth factor-induced gene TGFBI is correlated with the prognosis and immune infiltrations of breast cancer

BackgroundTransforming growth factor β (TGFβ) is a critical regulator of lung metastasis of breast cancer and is correlated with the prognosis of breast cancer. However, not all TGFβ stimulated genes were functional and prognostic in breast cancer lung metastatic progress. In this study, we tried to determine the prognosis of TGFβ stimulated genes in breast cancer.MethodsTGFβ stimulated genes in MDA-MB-231 cells and lung metastasis-associated genes in LM2-4175 cells were identified through gene expression microarray. The prognosis of the induced gene (TGFBI) in breast cancer was determined through bioinformatics analysis and validated using tissue microarray. The immune infiltrations of breast cancer were determined through “ESTIMATE” and “TIMER”.ResultsTGFBI was up-regulated by TGFβ treatment and over-expressed in LM2-4175 cells. Through bioinformatics analysis, we found that higher expression of TGFBI was associated with shorted lung metastasis-free survival, relapse-free survival, disease-free survival, and overall survival of breast cancer. Moreover, the prognosis of TGFBI was validated in 139 Chinese breast cancer patients. Chinese breast cancer patients with higher TGFBI expression had lower overall survival. Correspondingly, breast cancer patients with higher TGFBI methylation had higher overall survival. TGFBI was correlated with the score of the TGFβ signaling pathway and multiple immune-related signaling pathways in breast cancer. The stromal score, immune score, and the infiltrations of immune cells were also correlated with TGFBI expression in breast cancer.ConclusionsTGFβ-induced gene TGFBI was correlated with the prognosis and immune infiltrations of breast cancer.

Preoperative systemic inflammation response index: Clinicopathologic predictor of pathological complete response in HER2-positive breast cancer patients receiving neoadjuvant systemic therapy.

Multiple pretreatment systemic inflammatory markers (SIMs) have been reported as predictors of pathological complete response (pCR) after neoadjuvant systemic therapy (NST) in patients with breast cancer (BC). However, the most significant SIM remains to be conclusively identified, and variations among different molecular subtypes remain unknown. The objective of the study was to identify the most significant SIM in patients with human epidermal growth factor receptor 2 (HER2) positive BC, to construct a pCR-predictive nomogram combining it with other clinicopathologic factors, and to evaluate its prognostic value on survival. We retrospectively reviewed the findings for 240 patients with stage I-III HER2-positive BC who underwent NST and subsequent surgery at Kaohsiung and Taichung Veterans General Hospital from 2011 to 2021. Clinicopathologic factors were analyzed by stepwise logistic regression with backward selection. The data were used to construct a nomogram plot for determining the pCR probability. Kaplan-Meier curves and log-rank test were used to evaluate disease-free survival (DFS) and overall survival (OS). Among the pretreatment SIMs, only the systemic inflammation response index (SIRI) was significantly related to pCR, with an optimal cutoff value of 1.27 × 10 9 /L. Stepwise logistic analyses indicated that clinical N stage, HER2 immunohistochemistry score, hormone receptor status, targeted therapy regimen, and SIRI were independent predictors of pCR, with an area under the curve of 0.722. The Hosmer-Lemeshow test and calibration curve revealed that the predictive ability was a good fit to actual observations. A nomogram was constructed based on the logistic model. The external validation of the model also revealed satisfactory discrimination and calibration. Kaplan-Meier analysis showed that patients with SIRI <1.27 had longer DFS and OS. Pretreatment SIRI <1.27 is predictive of pCR, DFS, and OS in HER2-positive BC. Our nomogram could efficiently predict pCR and facilitate clinical decision-making before neoadjuvant treatment.

Treatment of Internal Mammary Nodes is Associated With Improved Overall Survival in Breast Cancer: A Meta-Analysis.

The role of internal mammary nodal irradiation (IMNI) as a component of regional nodal radiotherapy is a controversial issue in breast radiation oncology with conflicting results presented in recent landmark trials. We thus created a meta-analysis of available data to better ascertain the potential benefit of IMNI. We hypothesize that with the increased power available within a meta-analysis, IMNI will prove to improve overall survival (OS) in breast cancer. Literature search was conducted for prospective studies comparing IMNI to no IMNI. Primary endpoint was OS and secondary endpoints included local recurrence, regional recurrence, disease-free survival (DFS), breast cancer mortality (BCM), distant metastasis-free survival (DMFS), grade 2+ skin toxicity, cardiac events, and pneumonitis events. Subgroup analyses were performed for tumor location (medial/central vs. lateral), and nodal status (pN+ vs. pN0). Fixed-effect model was used if there was no heterogeneity, random-effects model otherwise. Four studies with a total of 5258 patients (IMNI: n=2592; control: n=2666) were included in the study. Pooled results showed IMNI significantly improved OS for all-comers (hazard ratio [HR]=0.89; 95% CI 0.81-0.97; P =0.008), as well as subgroups of pN+ with medial/central tumor location (HR=0.84; 95% CI 0.73-0.96; P =0.01) and pN+ with lateral tumor location (HR=0.87; 95% CI 0.77-0.99; P =0.04). There was no significant difference in OS for subgroups of pN0 and medial/central tumor location. There was no difference in local recurrence, but regional recurrence was significantly improved ( P =0.04). Endpoints of DFS (HR 0.91, 95% CI 0.84-0.99 P =0.03), BCM (HR 0.87, 95% CI 0.77-0.98, P =0.03), and DMFS (HR=0.87; 95% CI, 0.78-0.98; P =0.02) were all improved with IMNI. Grade 2+ skin toxicity, cardiac events and pneumonitis events were not significantly different between patient in the IMNI and no IMNI groups. Inclusion of IMN irradiation improves OS, DFS, BCM, and DMFS in breast cancer. Largest effect on OS was noted in the subgroup of patients with pN+ and medial/central tumor location.

Identification of prognostic biomarkers of invasive ductal carcinoma by an integrated bioinformatics approach

Background: Invasive ductal carcinoma (IDC) is the most common type of breast cancer (BC) worldwide. Nowadays, due to its heterogeneity and high capacity for metastasis, it is necessary to discover novel diagnostic and prognostic biomarkers. Therefore, this study aimed to identify novel candidate prognostic genes for IDC using an integrated bioinformatics approach. Methods: Three expression profile data sets were obtained from GEO (GSE29044, GSE3229, and GSE21422), from which differentially expressed genes (DEGs) were extracted for comparative transcriptome analysis of experimental groups (IDC versus control). Next, STRING was utilized to construct a protein interaction network with the shared DEGs, and MCODE and cytoHubba were used to identify the hub genes, which were then characterized using functional enrichment analysis in DAVID and KEGG. Finally, using the Kaplan-Meier tracer database, we determined the correlation between the expression of hub genes and overall survival in BC. Results: We identified seven hub genes (Kinesin-like protein KIF23 [KIF23], abnormal spindle-like microcephaly [ASPM]-associated protein [ASPMAP], Aurora kinase A [AURKA], Rac GTPase-activating protein 1 [RACGAP1], centromere protein F [CENPF], hyaluronan-mediated motility receptor [HMMR], and protein regulator of cytokinesis 1 [PRC1]), which were abundant in microtubule binding and tubulin binding, pathways linked to fundamental cellular structures including the mitotic spindle, spindle, microtubule, and spindle pole. The role of these genes in the pathophysiology of IDC is not yet well characterized; however, they have been associated with other common types of BC, modulating pathways such as Wnt/β-catenin, the epithelial-to-mesenchymal transition (EMT) process, chromosomal instability (CIN), PI3K/AKT/mTOR, and BRCA1 and BRCA2, playing an important role in its progression and being associated with a poor prognosis, thus representing a way to improve our understanding of the process of tumorigenesis and the underlying molecular events of IDC. Conclusions: Genes identified may lead to the discovery of new prognostic targets for IDC.

Expression and prognostic role of STAT5a across cancer types.

Studies examining the role of signal transducer and activator of transcription 5 (STAT5) in various cancers have produced controversial results. To address this controversy, we examined the prognostic role of STAT5a in cancer patients across multiple cancers. Transcription levels of STAT5a between tumors and normal tissues, obtained from public databases, were analyzed for statistical differences using Cox regression analysis with the outcome as overall survival and covariate of interest as high STAT5a expression. Meta-analysis was then conducted to summarize the hazard ratio estimate from the Cox regression analyses. We found that STAT5a was significantly under-expressed in breast, lung, and ovarian cancers, while STAT5a was significantly overexpressed in lymphoid neoplasm diffuse large B-cell lymphoma, glioblastoma, and glioma. High STAT5a expression was significantly associated with favorable survival in bladder cancer (lnHR = -0.8689 [-1.4087, -0.3292], P-value = 0.0016), breast cancer (lnHR = -0.7805 [-1.1394, -0.4215], P-value < 0.0001) and lung cancer (lnHR = -0.3255 [-0.6427, -0.0083], P-value = 0.0443). After adjusting for clinicopathological factors, high STAT5a expression remained significantly associated with favorable survival in breast cancer (lnHR = -0.6091 [-1.0810, -0.1372], P-value = 0.0114). These results suggest that higher STAT5a expression is associated with favorable overall survival in breast cancer, and therefore might have protective effects, and that STAT5a expression could be a potential prognostic biomarker, especially in breast cancer. However, the prognostic role of STAT5a is dependent on cancer type.

Risk-adjusted benchmarking of long-term overall survival in patients with HER2-positive early-stage Breast cancer: A Swedish retrospective cohort study.

The main objective of the current study was to explore the value of risk-adjustment when comparing (i.e. benchmarking) long-term overall survival (OS) in breast cancer (BC) between Swedish regions. We performed risk-adjusted benchmarking of 5- and 10-year OS after HER2-positive early BC diagnosis between Sweden's two largest healthcare regions, constituting approximately a third of the total population in Sweden. All patients diagnosed with HER2-positive early-stage BC between 01-01-2009 and 31-12-2016 in healthcare regions Stockholm-Gotland and Skane were included in the study. Cox proportional hazards model was used for risk-adjustment. Unadjusted (i.e. crude) and adjusted 5- and 10-year OS was benchmarked between the two regions. The crude 5-year OS was 90.3% in the Stockholm-Gotland region and 87.8% in the Skane region. The crude 10-year OS was 81.7% in the Stockholm-Gotland region and 77.3% in the Skane region. However, when adjusted for age, menopausal status and tumour biology, there was no significant OS disparity between the regions, neither at the 5-year nor 10-year follow-up. This study showed that risk-adjustment is relevant when benchmarking OS in BC, even when comparing regions from the same country that share the same national treatment guidelines. This is, to our knowledge, the first published risk-adjusted benchmarking of OS in HER2-positive BC.

Neoadjuvant chemotherapy response, disease-free survival, and overall survival of breast cancer in a single institution

BackgroundBreast cancer is the most common malignancy among women worldwide. Previous studies have shown factors influencing breast cancer patients' survival, including histopathological grading, stage, histopathological type, hormone receptors, and the number of mitotic images. This study aimed to determine the survival rate in breast cancer patients based on neoadjuvant chemotherapy (NAC) response and regimen. MethodsThis was an observational analytic study with a retrospective design. The population was breast cancer patients at our institution who had undergone NAC. Kaplan–Meier analysis using the log-rank method was used to determine the level of survivability (overall survival [OS] and disease-free survival [DFS]) of patients based on chemotherapy response and regimen. ResultsThe NAC overall response rate of breast cancer patients was 93.17 %, whereas the non-response rate was 6.83 %. Significant differences existed in the DFS of patients by chemotherapy response (p = 0.010). Patients with a complete response had a mean survival of 71.37 ± 2.92 months, those with progressive disease had a mean survival of 64.80 ± 15.58 months, and overall patients had a mean survival of 68.56 ± 10.452 months. Patients with a complete response had a mean recurrence time of 69.54 ± 7.48 months; this was 57.53 ± 19.06 months in those with progressive disease, for an overall time of 65.41 ± 13.81 months. No significant difference existed between the NAC regimens in OS and DFS (p = 0.901 and p = 0.798, respectively). ConclusionGenerally, the response to NAC in breast cancer was very good. The DFS rates were significantly different from the chemotherapy response but not from the NAC regimen.

Racial/ethnic and socioeconomic differences in breast cancer surgery performed and delayed surgical treatment: Mediating impact on mortality.

585 Background: Breast cancer is the most common malignancy affecting women of all racial and ethnic backgrounds in the United States (US). Although Socioeconomic status (SES), race/ethnicity, and surgical type/delays are associated with breast cancer mortality outcomes, studies on these associations have been contrasting. This study examined the racial/ethnic and SES differences in surgical treatment types and delays. Also, we quantified the extent to which these differences explained the racial/ethnic disparities in breast cancer mortality. Methods: We studied 290,066 women 40+ years old diagnosed with breast cancer between 2010 and 2017 identified from the Surveillance, Epidemiology, and End Results database. We performed logistic regression models to examine the association of SES and race/ethnicity with surgical treatment type and delays. We performed mediation analysis models to quantify the extent to which mortality differences were mediated by treatment, sociodemographic, and clinicopathologic factors. The study subjects were de-identified, and there was no patient contact; thus, the study was exempted from an Institutional Review Board's (IRB) approval. A p-value less than 0.05 indicated significant associations for the descriptive statistics, logistic and Cox proportional hazard regressions, and mediation analysis. We used Stata 17 to perform the analyses. Results: Non-Hispanic (NH) Black [Odds ratio (OR) = 1.16, 95% CI: 1.13-1.19] and Hispanic women [OR = 1.27, 95% CI: 1.24-1.31] were significantly more likely to undergo mastectomy compared to NH White women. Similarly, NH Black and Hispanic women had higher odds of delayed surgical treatment than NH Whites. Patients in the highest SES quintile, compared to those in lowest the lowest, were less likely to experience breast cancer-specific mortality (BCSM). Variations in treatment, SES, and clinicopathological factors significantly explained 70% of the excess BCSM among NH Blacks compared to their NH White counterparts. Conclusions: In conclusion, health disparity continues to be a major societal concern in the US. It affects people of all ages, socioeconomic classes, and ethnic/racial backgrounds. The findings of this study showed that racial and ethnic minorities, the majority of whom have a lower socioeconomic position, are significantly disadvantaged regarding the evaluation, quality, cost, and duration of medical care. Future studies can assess the multifactorial effects of sociodemographic factors like SES, access to health care assessment, and educational background amidst other variables as a multidimensional predictor of treatment delay and overall survival of breast cancer and other health issues among minoritized populations.

CD146 as a prognostic marker in breast cancer: A meta-analysis.

CD146, a cell adhesion molecule, was first discovered in melanoma. Since then, it has been established as a promoter of tumor progression and metastasis. Many recent clinical studies have associated CD146 overexpression with poor prognosis in various cancers. However, clinical relevance of CD146 in prognosis of breast cancer has been poorly studied. We performed meta-analysis of data of all clinical studies associated with the prognostic value of CD146 expression in breast cancer. Relevant studies were retrieved from PubMed database as per the inclusion and exclusion criteria, data were extracted independently and carefully by two reviewers with the help of standardized form, and meta-analysis was performed to correlate CD146 expression with molecular subtypes, lymph node metastasis, and overall survival in breast cancer. Our findings suggest that CD146 expression is predominantly found in triple-negative breast cancer subtype (pooled odds ratio = 2.98, 95% confidence interval [CI] =2.19-4.05, P < .00001) and breast tumors overexpressing CD146 have a higher risk of lymph node metastasis (pooled relative risk = 1.64, 95% CI = 1.44-1.87, P < .00001). Furthermore, high expression of CD146 was associated with poor prognosis in breast cancer (pooled hazard ratio = 1.51, 95% CI = 1.21-1.87, P = .0002). Overall results suggested that CD146 may be a potential prognostic marker to predict metastatic potential and disease outcomes in breast cancer and can be used as a therapeutic target.

Genetic contribution of caspase-8 variants and haplotypes to breast cancer risk and prognosis: a case-control study in Iran

PurposeMultiple genome-wide and candidate-gene association studies have been conducted to search for common risk variants of breast cancer. Recent large meta-analyses and consolidating evidence have highlighted the role of the caspase-8 gene in breast cancer pathogenesis. Therefore, this study aimed to identify common variations and haplotypes associated with risk and overall survival of breast cancer with respect to underlying susceptibility variants in the CASP8 gene region in a group of the Iranian population.MethodsIn a case-control study with a total of 1008 samples (455 cases and 553 controls), genotyping of 12 candidate polymorphisms, consisting of rs3834129, rs2037815, rs7608692, rs12990906, rs3769821, rs6435074, rs3754934, rs3817578, rs10931936, rs1045485, rs1045487, and rs13113, were performed using PCR-based methods, including ARMS-PCR, AS-PCR, RFLP-PCR, HRM-PCR, and TaqMan-PCR.Resultsrs3834129, rs3754934, rs12990906, and rs10931936 were associated with the risk and overall survival of breast cancer. Several haplotypes were also identified an associated with a higher risk of breast cancer, including a three-SNP haplotype rs3817578-rs10931936-rs1045485 [p < 0.001, OR = 1.78(1.32–2.41)]. rs3754934-C allele showed an association with a lower risk of death in all patients [p = 0.022; HR = 0.46(0.23–0.89)] and in the hormone-receptor-positive group [p = 0.038; HR = 0.37(0.14–0.95)], as well as CC genotype in the hormone-receptor-positive group [p = 0.002; HR = 0.09(0.02–0.43)].ConclusionThe present study suggests a diagnostic and prognostic role of CASP8 gene variations in breast cancer. The risky haplotypes are likely to have one or more underlying breast cancer susceptibility alleles. Understanding the mode of action of these alleles will aid individual-level risk prediction. It also may help identify at-risk patients to provide them with better surveillance.

Risk and prognosis of secondary esophagus cancer after radiotherapy for breast cancer

Although radiation therapy (RT) improves locoregional recurrence and overall survival in breast cancer (BC), it is not yet clear whether RT affects the risk of patients with BC developing second esophageal cancer (SEC). We enrolled patients with BC as their first primary cancer from nine registries in the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2018. Fine–Gray competing risk regressions were assessed to determine the cumulative incidence of SECs. The standardized incidence ratio (SIR) was used to compare the prevalence of SECs among BC survivors to that in the general population of the US. Kaplan–Meier survival analysis was applied to calculate the 10-year overall survival (OS) and cancer-specific survival (CSS) rates for SEC patients. Among the 523,502 BC patients considered herein, 255,135 were treated with surgery and RT, while 268,367 had surgery without radiotherapy. In a competing risk regression analysis, receiving RT was associated with a higher risk of developing an SEC in BC patients than that in the patients not receiving RT (P = .003). Compared to the general population of the US, the BC patients receiving RT showed a greater incidence of SEC (SIR, 1.52; 95% confidence interval [CI], 1.34–1.71, P < .05). The 10-year OS and CSS rates of SEC patients after RT were comparable to those of the SEC patients after no RT. Radiotherapy was related to an increased risk of developing SECs in patients with BC. Survival outcomes for patients who developed SEC after RT were similar to those after no RT.

Abstract P5-08-08: Ultrasound-guided injection with or without rehabilitation exercise in breast cancer survivors with sub-acromion-deltoid bursitis: a pilot randomized clinical study

Abstract BACKGROUND: Due to the increasing overall survival of breast cancer (BC) patients, a growing interest has been raised in the current literature on disabling consequences of cancer and its treatment [1,2]. In particular, after radical surgery for BC, patients might frequently be affected by functional limitation of the shoulder joint, potentially related to the immobilization, surgical scar tensions, axillary web syndrome, subpectoral prostheses or expanders, or peripheral nerve damage [3]. In this scenario, several challenges are still open in the therapeutic approach to this disabling condition and the optimal management of shoulder dysfunction in breast cancer patients is far from being fully characterized. Therefore, the aim of this study was to assess the effects of a comprehensive rehabilitation program including ultrasound-guided injection of the sub-acromion deltoid bursa (SAD) followed by a rehabilitation exercise protocol in terms of feasibility, pain relief, upper limb function, quality of life, and safety. METHODS: In this study, we recruited consecutive breast cancer women referring to a Physical Medicine and Rehabilitation in Northern Italy and suffering from SAD bursitis in the absence of tendon lesions. Patients were assessed for eligibility and subsequently randomly assigned 1:1 to two groups. Group A received ultrasound-guided percutaneous injection of the SAD bursa (lidocaine and triamcinolone acetate) followed by a rehabilitation exercise program of 5 sessions lasting 1 hour each., while Group B received ultrasound-guided percutaneous injection only. Patients were assessed at baseline (T0), after a week (T1), and after 3 months (T2). The outcomes were numerical pain rating scale (NPRS), handgrip strength (HGS) test, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the Oxford Shoulder Score (OSS), Global Perceived Effect (GPE), and safety. RESULTS: Thirty-seven patients were enrolled and randomly assigned to Group A (n=19; mean age: 56.05 ± 10.30 years; body mass index (BMI): 23.58 ± 2.79 kg/m2) and Group B (n=18; mean age: 58.39 ± 12.09 years; BMI: 22.72 ± 3.16 kg/m2). No major or minor adverse events were reported after this multidisciplinary intervention. Statistically significant within-group differences were found in both groups in terms of NPRS after the treatment (p &amp;lt; 0.05) and after the follow-up (p &amp;lt; 0.05). The between-group analysis showed significant differences in pain intensity (NRS: 2.16 ± 1.39 vs 4.78 1.77; p &amp;lt; 0.05), isometric muscle strength (25.11 3.20 vs 20.33 4.92; p&amp;lt; 0.001), shoulder function (OSS: 17.00 3.27 vs 33.11 6.471; p&amp;lt; 0.0001), and EORTC QLQ-C30 (Functional subscale: 88.74 7.71 vs 77.67 13.64; p=0.017; Symptom subscale: 11.43 8.56 vs 19.61 13.72; p=0.048; Global Health subscale: 79.36 13.72 vs 70.56 8.26; p=0.022) of the after the follow-up. However, no significant differences (p &amp;gt; 0.05) were reported at T1. CONCLUSION: Our findings showed that a comprehensive rehabilitation approach including ultrasound-guided injection combined with rehabilitation exercise might be safe, well-tolerated, and effective in breast cancer patients with SAD bursitis. These data emphasized the positive role of an interdisciplinary rehabilitation management in pain management and improving overall well-being of breast cancer patients. Further studies with larger samples and longer follow-ups are needed to confirm our data. REFERENCES: 1. Nardin S et al. Breast Cancer Survivorship, Quality of Life, and Late Toxicities. Front Oncol 2020, 10, 864. 2. D’Egidio V et al. Counseling interventions delivered in women with breast cancer to improve health-related quality of life: a systematic review. Qual Life Res 2017, 26, 2573-2592, doi:10.1007/s11136-017-1613-6. 3. Hidding JT et al. Treatment related impairments in arm and shoulder in patients with breast cancer: a systematic review. PLoS One. 2014 May 9;9(5):e96748. Citation Format: Lorenzo Lippi, Alessandro de Sire, Arianna Folli, Francesco D’Abrosca, Alessio Turco, Giuseppina Bonizzi, Nicola Fusco, Marco Invernizzi. Ultrasound-guided injection with or without rehabilitation exercise in breast cancer survivors with sub-acromion-deltoid bursitis: a pilot randomized clinical study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-08.

Myocardial Infarction-Induced INSL6 Decrease Contributes to Breast Cancer Progression.

Myocardial infarction (MI) induces early-stage breast cancer progression and increases breast cancer patients' mortality and morbidity. Insulin-like peptide 6 (INSL6) overexpression can impede cardiotoxin-induced injury through myofiber regeneration, playing a significant role in MI progression. To investigate the diverse significance of INSL6 in a variety of malignant tumors, we explored INSL6 through MI GEO dataset and multiple omics data integrative analysis, such as gene expression level, enriched pathway analysis, protein-protein interaction (PPI) analysis, and immune subtypes as well as diagnostic value and prognostic value in pancancer. INSL6 expression was downregulated in the MI group, and overall survival analysis demonstrated that INSL6 could be the prognostic biomarkers in the overall survival of breast cancer (BRCA). INSL6 expression differs significantly not only in most cancers but also in different molecular and immune subtypes of cancers. INSL6 might be a potential diagnostic and prognostic biomarker of cancers due to the high accuracy in diagnostic and prognostic value. Furthermore, we focused on BRCA and further investigated INSL6 from the perspective of the correlations with clinical characteristics, prognosis in different clinical subgroups, coexpression genes, and differentially expressed genes (DEGs) and PPI analysis. Overall survival and disease-specific survival analysis of subgroups in BRCA demonstrated that lower INSL6 expression had a worse prognosis. Therefore, INSL6 aberrant expression is associated with the progression and immune cell infiltration of the tumor, especially in KIRP and BRCA. Therefore, INSL6 may serve as a potential prognostic biomarker and the crosstalk between MI and tumor progression.

PD-L1 on Circulating Tumor Cells Indicates Poor Prognosis in Breast Cancer

Background: In breast cancer, research concerning programmed death-ligand 1 (PD-L1) on circulating tumor cells (CTCs) is limited. Besides, the best cell type for determining the prognostic and predictive values of PD-L1 has not been established. This study investigated associations between PD-L1 on tumor cells (TCs), CTCs, and tumor-infiltrating immune cells (TIICs), respectively, and prognosis and clinicopathological features in breast cancer. Methods: Twenty patients with breast cancer were recruited; one was excluded for confirmed lymphoma. The PD-L1 on TCs and TIICs was determined via immunohistochemistry; PD-L1 mRNA expression on CTCs was analyzed. The chi-squared test and Kaplan-Meier and Cox proportional hazards model analyses were applied. Results: The median follow-up time was 60 months. Of the 19 patients, 14 had &gt;1 CTC/10 mL peripheral blood. Among these, each had ≥1 CTC showing PD-L1. At baseline, there was no difference between groups with or without metastasis regarding CTCs and PD-L1 expression. Patients with high PD-L1 levels on CTCs had poor overall survival (p = 0.034). In the multivariate analysis, PD-L1 levels on CTCs and T stage were independent prognostic factors (p = 0.029, 0.010, respectively). Conclusions: High levels of PD-L1 on CTCs may prognose shorter overall survival in breast cancer.