Corrigendum to \u201cThe Role of PAX7 in Breast Cancer Prognosis and Its Mechanistic Involvement in the Wnt/\u03b2\u2010Catenin Pathway\u201d

BackgroundAccurate prognosis and identification of cancer subtypes at molecular level are important steps towards effective and personalised treatments of breast cancer. To this end, many computational methods have been developed to use gene (mRNA) expression data for breast cancer subtyping and prognosis. Meanwhile, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been extensively studied in the last 2 decades and their associations with breast cancer subtypes and prognosis have been evidenced. However, it is not clear whether using miRNA and/or lncRNA expression data helps improve the performance of gene expression based subtyping and prognosis methods, and this raises challenges as to how and when to use these data and methods in practice.ResultsIn this paper, we conduct a comparative study of 35 methods, including 12 breast cancer subtyping methods and 23 breast cancer prognosis methods, on a collection of 19 independent breast cancer datasets. We aim to uncover the roles of miRNAs and lncRNAs in breast cancer subtyping and prognosis from the systematic comparison. In addition, we created an R package, CancerSubtypesPrognosis, including all the 35 methods to facilitate the reproducibility of the methods and streamline the evaluation.ConclusionsThe experimental results show that integrating miRNA expression data helps improve the performance of the mRNA-based cancer subtyping methods. However, miRNA signatures are not as good as mRNA signatures for breast cancer prognosis. In general, lncRNA expression data does not help improve the mRNA-based methods in both cancer subtyping and cancer prognosis. These results suggest that the prognostic roles of miRNA/lncRNA signatures in the improvement of breast cancer prognosis needs to be further verified.

Background: Early-onset breast cancer is typically defined as a diagnosis of disease before age 40-45. Prior studies have shown interesting associations between race and obesity on the incidence and prognosis of breast cancer. Data from the SEER program at the National Cancer Institute has shown increased mortality amongst African American women (0.2%) compared to Non-Hispanic White (NHW) women (0.1%) who were diagnosed with breast cancer at age 45 years or younger. This is despite a similar risk of diagnosis between racial groups of this age range (1.27%, 1.27%). Other large studies have shown that African American patients tended to present with more advanced disease had worse clinical outcomes. Our study sought to determine the impact of race and obesity on the diagnosis and prognosis of early onset breast cancer amongst the patient population at Georgetown University Hospital (GUH). Methods: We compiled a database of all new patients, 652 in total, seen at Lombardi Cancer Center at Medstar GUH from 10/2020- 6/2022. We reviewed patient charts in the EMR and documented age at diagnosis, race, ethnicity, stage at diagnosis, and BMI. The BMI was categorized by underweight (BMI < 18.5), healthy weight (BMI 18.5-24.9), overweight (BMI 25-25.9), obese (BMI 30-34.9), and morbidly obese (BMI ≥ 35). Stage at diagnosis was determined by comparing the pathology report with the NCCN guidelines version 4.2022. We identified 136 patients who were diagnosed at GUH at age 45 years old or younger and compared our findings to SEER data from 2017-2019. Results: Out of 136 patients who met our age criteria, 131 had racial data available: 29 AA (0.22), 68 NHW (0.52), 4 Hispanic (0.03), 30 Other (0.23). Out of the 34 patients with advanced disease (stage 3 and 4) 16 were NHW (0.47), 4 were AA (0.12), 2 were Hispanic (0.06) and 12 were Other (0.35). 131 patients had BMI data available: 5 underweight (0.04), 56 healthy weight (0.43), 41 overweight (0.31), 21 obese (0.16), and 8 morbidly obese (0.06). 18 patients with advanced disease were overweight or obese, out of which 11 were NHW (0.61), 3 were AA (0.16), 3 were Other (0.16), and 1 was Hispanic (0.06). Conclusion: In contrast with the SEER data, our study found that the patient population at GUH had a much higher proportion of Non-Hispanic White (NHW) patients who were diagnosed with advanced disease compared to African American (AA) patients. It also found a higher proportion of NHW patients amongst those who were diagnosed with advanced stage disease and were overweight or obese compared to AA patients. This data suggests that in our patient population, Non-Hispanic White women who were overweight or obese at the time of diagnosis of early onset breast cancer (≤ 45 years old) were more likely to be diagnosed with advanced stage disease than women in other demographic groups. It is possible that this discrepancy is related to racial variations in receptor status. Further investigation is required to correlate these associations in clinical practice with other known demographic variables and disease-specific risk factors in order to better understand how they impact the diagnosis and prognosis of early-onset breast cancer. Citation Format: Austin Kordic, Amanda Reyes, Nadia Ashai. Evaluating the Impact of Race and Body Mass Index on the Diagnosis and Prognosis of Early Onset Breast Cancer [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 P4-03-42.

The relationship between the expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 and breast cancer prognosis was studied. Two breast cancer cell lines (MDA-MB-231 and MCF-7) and one human normal breast cell line (HS578Bst) were investigated. Fluorescence real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to detect cellular mRNA and protein MMP-2 and MMP-9 expression levels. Breast cancer tissue samples from 80 patients and tumor-adjacent normal tissue samples from 40 patients were collected, and MMP-2 and MMP-9 expression in these samples were examined using immunohistochemistry (IHC). The relationship of MMP-2 and MMP-9 expression levels with breast cancer patient clinicopathological parameters and prognosis was analyzed. RT-PCR and western blot results showed that MMP-2 and MMP-9 mRNA and protein expression levels were significantly higher in MDA-MB-231 and MCF-7 cells than in HS578Bst cells. A high expression of MMP-2 and MMP-9 was found in 83.75% (67/80) and 78.75% (63/80) of breast cancer tissue samples, respectively. MMP-2 and MMP-9 expression in breast cancer tissues were significantly different from that in tumor-adjacent normal tissues (p<0.01). MMP-2 and MMP-9 expression levels in breast cancer tissues were correlated with lymph node metastasis and tumor staging. Single factor survival analysis showed that MMP-2 and MMP-9 were factors influencing breast cancer prognosis. MMP-2 and MMP-9 are highly expressed in breast cancer tissues and are closely related to lymph node metastasis and tumor staging. MMP-2 and MMP-9 can be used as reference indices for guiding breast cancer prognosis and treatment.

ObjectiveTo identify the relationship between telomere length and the prognosis of breast cancer with different status of estrogen receptor (ER).MethodsWe collected single nucleotide polymorphisms (SNPs) associated with telomere length and breast cancer prognosis from the MRCIEU GWAS database and the dataset of a large meta-analysis conducted by the Breast Cancer Association Consortium (BCAC), respectively. The relationship was identified using inverse-variance weighted (IVW), MR-Egger, weighted median, penalized weighted median, and maximum likelihood methods. IVW, MR-Egger, and MR-PRESSO methods were used to perform sensitivity analysis to assess the accuracy of the results.ResultsTelomere length was negatively associated with the prognosis of total breast cancer (odds ratio [OR]=1.84, 95% confidence interval [CI]=1.08-3.14, IVW method), especially with ER- breast cancer (OR=1.89, 95% CI=1.11-3.22, IVW method). No similar relationship was found between telomere length and the prognosis of ER+ breast cancer (OR=0.99, 95% CI=0.62-1.58, IVW method). The findings from other methods were consistent with the results shown by the IVW method. The Mendelian randomization assumptions did not appear to be violated. Sensitivity analysis indicated that the result was robust, and no bias was observed in the study.ConclusionTelomere length is associated with the prognosis of total breast cancer, especially with ER- breast cancer. There is no significant correlation between telomere length and the prognosis of ER+ breast cancer. These findings add to the evidence that long telomere could predict a poor prognosis of ER- breast cancer.

Simple SummaryWhile most systematic reviews have focused on the association between dietary factors and breast cancer incidence, this current study focuses on the association between comprehensive dietary factors and breast cancer prognosis among breast cancer survivors by systematic review and meta-analysis. We reviewed a total of 63 cohort studies to assess the association between dietary factors and breast cancer prognosis by subgroup analysis with prediagnostic or postdiagnostic dietary intake, menopausal status, and dietary or supplementary micronutrient intake. We found that unhealthy dietary patterns, including the intake of beer and saturated fat, exacerbated the risk of breast cancer prognosis; however, the supplementation of most vitamins was desirable for breast cancer prognosis. Therefore, this study’s systematic review and meta-analysis provide useful dietary information for the development of dietary guidelines/recommendations to improve prognosis among breast cancer survivors.Few studies have summarized the association between dietary factors and breast cancer (BC) prognosis among breast cancer survivors (BCS). Therefore, we carried out a systematic review and meta-analysis to determine the associations between dietary factors and BC prognosis among BCS. We performed a literature search in PubMed and Embase to investigate the association between dietary factors and BC prognosis. We applied a random-effects model to compute the hazard ratio/relative risk and their 95% confidence intervals and heterogeneity (Higgins I2) and to generate forest plots using STATA. Among the 2279 papers identified, 63 cohort studies were included in the systematic review and meta-analysis. Our main finding was that higher consumption of beer and saturated fat negatively affected BC prognosis. However, the intake of lignans, fiber, multivitamins, and antioxidants was negatively associated with the risk of mortality. Furthermore, we performed subgroup analyses by menopausal status and dietary or supplementary micronutrient intake. Most trends were similar to the main findings; in particular, the vitamin C, vitamin D, and vitamin E supplements decreased the risk of mortality. This study’s current systematic review and meta-analysis provide comprehensive dietary information for the development of dietary guidelines/recommendations to improve prognosis among BCS.

BackgroundAlthough the rapid development of diagnosis and treatment has improved prognosis in early breast cancer, challenges from different therapeutic response remain due to breast cancer heterogeneity. DEAD-box helicase 27 (DDX27) had been proved to influence ribosome biogenesis and identified as a promoter in gastric and colorectal cancer associated with stem cell-like properties, while the impact of DDX27 on breast cancer prognosis and biological functions is unclear. We aimed to explore the influence of DDX27 on stem cell-like properties and prognosis in breast cancer.MethodsThe expression of DDX27 was evaluated in 24 pairs of fresh breast cancer and normal tissue by western blot. We conducted Immunohistochemical (IHC) staining in paraffin sections of 165 breast cancer patients to analyze the expression of DDX27 and its correlation to stemness biomarker. The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database were used to analyze the expression of DDX27 in breast cancer. Kaplan–Meier survival analysis were used to investigate the implication of DDX27 on breast cancer prognosis. Western blot, CCK-8 assay, Transwell assay and wound-healing assay were carried out to clarify the regulation of DDX27 on stem cell-like properties in breast cancer cells. Gene Set Enrichment Analysis (GSEA) was performed to analyze the potential molecular mechanisms of DDX27 in breast cancer.ResultsDDX27 was significantly high expressed in breast cancer compared with normal tissue. High expression of DDX27 was related to larger tumor size (p = 0.0005), positive lymph nodes (p = 0.0008), higher histological grade (p = 0.0040), higher ki-67 (p = 0.0063) and later TNM stage (p < 0.0001). Patients with high DDX27 expression turned out a worse prognosis on overall survival (OS, p = 0.0087) and disease-free survival (DFS, p = 0.0235). Overexpression of DDX27 could enhance the expression of biomarkers related to stemness and promote stem cell-like activities such as proliferation and migration in breast cancer cells.ConclusionDDX27 can enhance stem cell-like properties and cause poor prognosis in breast cancer, also may be expected to become a potential biomarker for breast cancer therapy.

Immunoediting is crucial in cancer development and progression. This study compared the characteristics and prognosis of post-transplant breast cancer (PTBC) patients receiving immunosuppressants and general breast cancer patients. Data from the Asan Medical Center Breast Cancer (AMCBC), kidney transplantation, and liver transplantation databases recorded during 1989-2013 were retrospectively analyzed. Four controls of AMCBC cohort per one case of PTBC cohort were selected based on tumor size, lymph node metastasis, and age. After a median of 61 and 90.8months after liver and kidney transplantation, respectively, 8 and 16 patients were diagnosed with breast cancer, respectively (p=0.178). Mean age at breast cancer diagnosis was 51.9 (±8.7) and 45.2 (±4.5) years in liver and kidney transplantation patients, respectively. Age at diagnosis was significantly younger in kidney transplantation patients than in general breast cancer patients (45.2±4.5 vs. 48.5±10.1years; p=0.008). Cancer was detected via asymptomatic screening in 41.7% of the PTBC cohort but 30.6% of the control cohort (p=0.241). In the PTBC cohort, 7 (29.2%) patients had stage 0 breast cancer compared with 1704 (9.7%) in the control cohort (p=0.022); 22 (91.7%) patients had lymph node-negative cancer compared with 11,704 (66.8%) in the control cohort (p=0.01). Estrogen receptor, progesterone receptor, and HER2 positivity did not differ between cohorts. Immunosuppressant use was not a poor prognostic factor for breast cancer patients. Age at breast cancer diagnosis was younger in patients who received kidney transplants; the subtype and prognosis of breast cancer were comparable with that in the general cohort. Immunosuppressants do not adversely affect breast cancer prognosis.

Clinicopathological characteristics and prognosis of breast cancer with special histological types: A surveillance, epidemiology, and end results database analysis

Background:Breast cancer is the most commonly diagnosed malignancy and a major cause of cancer-related deaths in women globally. Identification of novel prognostic and pathogenesis biomarkers play a pivotal role in the management of the disease.Methods:Three data sets from the GEO database were used to identify differentially expressed genes (DEGs) in breast cancer. Gene Ontology (GO) enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway analyses were performed to elucidate the functional roles of the DEGs. Besides, we investigated the translational and protein expression levels and survival data of the DEGs in patients with breast cancer from the Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine, Human Protein Atlas, and Kaplan Meier plotter tool databases. The corresponding change in the expression level of microRNAs in the DEGs was also predicted using miRWalk and TargetScan, and the expression profiles were analyzed using OncomiR. Finally, the expression of novel DEGs were validated in Chinese breast cancer tissues by RT-qPCR.Results:A total of 46 DEGs were identified, and GO analysis revealed that these genes were mainly associated with biological processes involved in fatty acid, lipid localization, and regulation of lipid metabolism. Two novel biomarkers, ADH1A and IGSF10, and 4 other genes (APOD, KIT, RBP4, and SFRP1) that were implicated in the prognosis and pathogenesis of breast cancer, exhibited low expression levels in breast cancer tissues. Besides, 14/25 microRNAs targeting 6 genes were first predicted to be associated with breast cancer prognosis. RT-qPCR results of ADH1A and IGSF10 expression in Chinese breast cancer tissues were consistent with the database analysis and showed significant down-regulation.Conclusion: ADH1A, IGSF10, and the 14 microRNAs were found to be potential novel biomarkers for the diagnosis, treatment, and prognosis 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.

Background: Patients with germline TP53 pathogenic variants (Li-Fraumeni syndrome - LFS) have an increased risk of breast cancer, which is the most common type of cancer in premenopausal women with LFS. These women are also at risk of other second malignancies, including radiotherapy-induced malignancies. On the other hand, little is known about the prognosis of breast cancer in patients with LFS or if the disease behavior differs from non-hereditary BC. The objective of this study was to characterize the phenotype and prognosis of early BC in patients with LFS compared to a matched cohort of patients without germline pathogenic variants (PV) related to BC. Methods: This retrospective study evaluated patients with early BC treated in an academic cancer center from Dec 1999 to Mar 2022. The LFS cohort included consecutive patients with BC who harbored a PV or likely PV of TP53. The matched control cohort (2:1) included patients with BC with no germline PV in a panel test. Primary endpoint was disease-free survival (DFS). Since LFS is associated with an increased risk of new primary malignancies, only locoregional and distant BC recurrence were considered as events in the DFS analysis. Secondary endpoints included response to systemic therapy, sites of recurrence, and breast cancer-related deaths. Results: Forty-six patients with LFS were evaluated; the control cohort included 91 matched patients. In the LFS cohort, 14 different PV or likely PV were identified, with TP53 p.R337H being the most common (n=32). Median age was 40 years in both groups. In the LFS cohort, 35% of the pts had HER2-positive BC compared to 21% in the control cohort. Primary tumors greater than 5 cm were observed in 15% of pts in the LFS cohort and 25% of pts in the control cohort. Positive lymph nodes were observed in 11% and 14%, respectively. Among 15 pts with LFS who received neoadjuvant chemotherapy, all (100%) had a response, with 5 (33%) complete responses. Thirty-five patients in the control group received neoadjuvant chemotherapy: 83% responded, with 11 (31%) presenting a complete response. With a median follow-up of 43 months, 5-year DFS rates were 82.6% (95% CI 65.1 – 91.9%) in the LFS cohort and 91.5% (95% CI 79.1 – 96.6%) in the control cohort (P=0.427). Rates and sites of recurrence, new primary BC, and deaths are detailed in the table. Conclusions: In addition to a higher risk of new primary breast cancer, LFS patients with early breast cancer had numerically higher rates of locoregional and distant recurrence in comparison with a matched cohort. Nevertheless, further studies are required to understand if these differences are due to tumor behavior particularities or to differences in therapeutic management. Recurrence and death events Citation Format: Vanessa Petry, Renata Colombo Bonadio, Daniela Jafet, Roberta Campos, Luiz Senna, Allyne Cagnacci, Laura Testa, Maria Candida Villares Fragoso, Maria del Pilar Estevez Diz. A matched cohort study of the prognosis of early breast cancer in patients with Li-Fraumeni syndrome [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 P3-05-12.

[Purpose] It is important to make early decisions about treatment changes in treatment-resistant groups. The aim of this study is to extract non-responders among preoperative chemotherapy using 18F-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) in primary breast cancer. We hypothesized that early evaluation of FDG PET after the first course of docetaxel (DTX) would predict treatment resistant group by the relationship between changes on FDG accumulation and tumor diameter on magnetic resonance imaging (MRI). [Patients and Methods] Thirty-seven of 41 patients were evaluated. Clinical stage was T1-4, N0-3, and M0 between August 2007 and December 2010. Four courses of DTX were administered followed by 4 courses of fluorouracil/epirubicin/cyclophosphamide (FEC) followed by surgery. FDG-PET evaluation was performed by the maximum standardized uptake value (SUVmax). FDG-PET scans were performed at baseline, at 15 days after the first course of DTX (C1D15), and at 15 days after 4 courses of DTX (C4D15). Tumor reduction rate was measured on MRI at baseline and at C4D15 according to Response Evaluation Criteria in Solid Tumors (RECIST). ROC analysis was performed by between SUVmax of C1D15 and MRI of C4D15. Changes of SUVmax C1D15 were divided into high and low group by ROC analysis. Core needle biopsy (CNB) was performed to evaluate the treatment effect pathologically after 4 courses of DTX (C4CNB). The pathological treatment effect of surgical specimens after 4 courses of FEC (C4FEC) was also examined. The difference in progression-free survival (PFS) rate or overall survival (OS) rate between the low and high SUVmax of C1D15 change rate was calculated using Kaplan-Meier survival curves and compared by log-rank test. The protocol of the study was approved by the Ethics Committee of the Gunma Prefectural Cancer Center (ECGPCC), and all patients gave their written informed consent before enrollment (No. 19011). The observational study was also approved by ECGPCC (No. 30087). [Results] There were ER+HER2-:17, ER+HER2+:4, ER-HER2-:11, and ER-HER2+:5 cases. SUVmax change rate C1D15 correlated with the SUVmax change rate C4D15 and tumor shrinkage rate on MRI C4D15 in univariate (SUVmax C4D15: γ=.567, p&amp;lt;.001, MRI C4D15: γ=.748, p&amp;lt;.001) and in multivariate analysis (SUVmax C4D15: γ=414, p=.002, MRI C4D15: γ=.616, p&amp;lt;.001). The SUVmax change rate C1D15 correlated with pathological effect of C4CNB (γ=.392, p=.032) and of surgical specimen C4FEC (γ=.440, p=.006) in univariate analysis. From ROC analysis based on SUVmax C1D15 and MRI C4D15 (AUC=.924, 95% CI: .828-1.000, p&amp;lt;.001), the SUVmax C1D15 were divided into two groups with high and low SUVmax changes. The mean SUVmax in the low group (&amp;lt;30%) (n=15) was 15.8% (±9.7). The mean SUVmax in the high group (≥30%) (n=22) was 50.8% (±11.7). The mean of MRI change rate of C4D15 was 20.4% (±5.4) in the low SUVmax change group and 69.2% (±5.8) in the high SUVmax change group, showing a significant difference between the two groups (p&amp;lt;.001). The low SUVmax change group showed shorter PFS than the high SUVmax group (median 80.9 vs 93.7 months, p=.050), but there was no difference in OS (p=.719). [Conclusion] Changes less than 30% of 18F-FDG uptake after the first course of DTX may reflect the treatment resistance and poor prognosis in primary breast cancer. Citation Format: Tomoko Hirakata, Yasuhiro Yanagita, Tomomi Fujisawa, Teruhiko Kinoshita, Hiroyuki Horikoshi, Nariyuki Oya, Tsukasa Akiyoshi, Misa Iijima, Takeshi Miyamoto, Keiko Yanai, Hiroshi Matsumoto, Kenichi Inoue, Rie Horii, Takaaki Fujii, Ken Shirabe. Changes in 18F-FDG-PET uptake after the first course of DTX reflect response to preoperative chemotherapy and prognosis in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-23.

G protein-coupled estrogen receptor (GPER), or GPR30, is a membrane receptor reported to mediate non-genomic estrogen responses. Tamoxifen is a partial agonist at GPER in vitro. Here, we investigated if GPER expression is prognostic in primary breast cancer, if the receptor is treatment-predictive for adjuvant tamoxifen, and if receptor subcellular localization has any impact on the prognostic value. Total and plasma membrane (PM) GPER expression was analyzed by immunohistochemistry in breast tumors from 742 postmenopausal lymph node-negative patients subsequently randomized for tamoxifen treatment for 2-5 years versus no systemic treatment, regardless of estrogen receptor (ER) status, and with a median follow-up of 17 years for patients free of event. PM GPER expression was a strong independent prognostic factor for poor prognosis in breast cancer without treatment-predictive information for tamoxifen. In the tamoxifen-treated ER-positive and progesterone receptor (PgR)-positive patient subgroup, the absence of PM GPER (53 % of all ER-positive tumors) predicted 91 % 20-year distant disease-free survival, compared to 73 % in the presence of GPER (p = 0.001). Total GPER expression showed positive correlations with ER and PgR and negative correlation with histological grade, but the correlations were biphasic. On the other hand, PM GPER expression showed strong negative correlations with ER and PgR, and strong positive correlation with HER2 overexpression and high histological grade. GPER overexpression and PM localization are critical events in breast cancer progression, and lack of GPER in the PM is associated with excellent long-term prognosis in ER-positive and PgR-positive tamoxifen-treated primary breast cancer.

Aim: To explore the role of RanBP9 in breast cancer. Materials & methods: Oncomine, TIMER, GEPIA, UALCAN, c-BioPortal databases and tissue microarray analysiswere used in this study. Results: The expression level of RanBP9 is elevated in breast cancer tissues, which is associated with poor prognosis in breast cancer patients. RanBP9 exhibits genetic alterations and a decreased methylation level in cancer tissues. RanBP9 mayalso regulate cell cycle progression and is linked to tumor purity and the infiltrating levels of immune cells. Conclusions:RanBP9 may correlate with prognosis and immune infiltration in breast cancer, laying the foundation for future studies on the potential role of RanBP9 in breast cancer.

173 Background: Statin treatment has not yet been evaluated in relation to breast cancer (BC) prognosis in diabetes mellitus (DM) patients. Reported decreased survival following BC in women with metabolic syndrome, led us to investigate whether specific statin therapy may lead to improved BC survival. Reported associations between elevated C-reactive protein (CRP) levels at the time of diagnosis with worse cancer prognosis, and CRP-lowering properties of statin treatment in non-cancer patients, led us to investigate whether statin use is associated with lower CRP levels at the time of BC diagnosis and with improved BC outcomes. Methods: All DM patients newly diagnosed with BC between 2003 and 2007 (Roswell Park Cancer Institute) were retrospectively reviewed (n = 225). BC pathology, outcomes, existing comorbidities and drug therapy were documented. Follow up began at BC diagnosis and ended with first confirmed recurrence and/or death, or last date of follow-up. Hazard ratios (HR) and 95% confidence intervals (CI)s representing the association between statins, BC and a defined event were computed with Cox proportional hazards model. CRP plasma levels were determined by enzyme-linked immunosorbent assay in specimens donated at the time of BC diagnosis. A total of 98 study patients, DM+BC, and their matched controls, BC only (n = 196) were analyzed. Results: After a median follow up of 30 months, patients receiving statins for cholesterol management were found to have better disease-free survival (HR 0.27, 95% CI: 0.10, 0.71, X2 = 7.31, p = 0.06), and lower overall mortality (HR 0.23, 95% CI: 0.08, 0.66, X2 = 7.80, p = 0.05) compared to patients not receiving any cholesterol management medication. CRP levels have ranged between 0.2 and 21 mg/L and clinically relevant levels ( &gt; 3mg/L) were noted in the study group. Conclusions: This study explored for the first time the association between statin therapy and BC prognosis in DM. We observed improved outcomes in statin-treated patients. While we currently analyze statin therapy in relationship with baseline CRP levels and BC prognosis, our existing findings suggest that statins have the potential to improve BC outcomes potentially through lowering overall inflammation.