Prognostic Factor In Breast Cancer Research Articles

Effects of an educational physical activity intervention in young women with newly diagnosed breast cancer: Findings from the Young and Strong Study.

Obesity and inactivity are poor prognostic factors in breast cancer, but less is known regarding physical activity (PA) and weight patterns in young breast cancer survivors. The Young and Strong Study was a cluster-randomized trial evaluating education and support interventions for young women (age <45 years) with newly diagnosed breast cancer. Sites were randomized 1:1 to a Young Women's Intervention (YWI) or a contact-time control physical activity intervention (PAI). Changes in PA and weight were compared between groups using general estimating equations to evaluate clustered binary and Gaussian data. A total of 467 patients enrolled between July 2012 and December 2013 across 54 sites. Median age at diagnosis was 40years (range, 22-45). At baseline, median body mass index (BMI) was 25.4kg/m2 (range, 16.1-61.1), and participants reported a median of 0minutes (range, 0-2190) of moderate/vigorous PA/week. PA increased significantly over time in both groups (p<.001), with no difference between groups at any time point. BMI increased modestly but significantly (p<.001) over time in both groups. Provider attention to PA was observed in 74% of participants on PAI and 61% on YWI (p=.145) and correlated with PA at 12months (median 100min/week of PA in participants with provider attention to PA vs. 60min/week in those without, p=.016). In a cohort of young women with breast cancer, rates of obesity and inactivity were high. PA and BMI increased over time and were not impacted by an educational PA intervention. Findings provide important information for developing lifestyle interventions for young breast cancer survivors.

Evaluation of HER2 Gene Amplification using CISH in Patients with HER2 2+ (equivocal) Breast Carcinoma based on Immunohistochemistry in Imam Khomeini Cancer Institute from 2016 to 2018

Background: Human epidermal growth factor 2 (HER2) is known to be an important prognostic factor in breast cancer. Numerous studies have shown HER2+ breast cancers have reduced overall survival and recovery time, as well as the efficacy of anti-HER2 therapies along with chemotherapy in improving disease outcomes. For this reason, it is recommended that all patients with breast cancer should be evaluated for HER2 status. This study aimed to assess the HER2 gene amplification by the CISH method in evaluating the HER2 status in patients with immunohistochemistry (IHC) 2+ (equivocal) results. Methods: This retrospective cross-sectional study examined HER2 status based on the Chromogenic in situ hybridization (CISH) method in 280 breast carcinoma samples with an initial 2+ (equivocal) score in IHC. The relationship between HER2 amplification and hormone receptors (estrogen and progesterone) and Ki67 level was also investigated. Results: In sixty samples (21.4%), the HER2 gene was amplified based on the CISH method. The majority (215, 76.8%) of the samples were negative and 5 (1.8%) samples were indeterminate. No significant relationship was observed between HER2 amplification, estrogen receptor (p=0.143), and ki.67 protein level (p=0.977). There was a significant inverse relationship between HER2 amplification and progesterone receptor positivity (p=0.007). Conclusion: These results demonstrate that CISH is a helpful method to assess HER2 status in equivocal breast cancer and is positive (amplified) in about 21.4% of them.

The Firmicutes/Bacteroidetes Ratio as a Risk Factor of Breast Cancer

The gut microbiome can reflect the health condition of the entire body. Firmicutes and Bacteroidetes, the major phyla of the colon, can influence diseases related to obesity which are also risk factors for breast cancer. Therefore, the Firmicutes/Bacteroidetes (F/B) ratio was analyzed in patients with breast cancer. Bacterial extracellular vesicles were extracted from the serum of patients with breast cancer and healthy controls. Phyla Firmicutes and Bacteroidetes were analyzed using microbiome sequencing. Prognostic factors for breast cancer and serological test results were analyzed for correlations with the F/B ratio. The F/B ratio was three times lower in patients with breast cancer than in healthy controls. In addition, the risk factor for breast cancer, such as fasting serum glucose, was found to be related to the F/B ratio. The F/B ratio can be used as a risk factor of breast cancer and as a clue to explain underlying mechanisms affecting the development of breast cancer.

Abstract P1-01-06: Differences in breast tumor response to neoadjuvant chemotherapy by race- Is obesity the key?

Abstract Background: Breast cancer treatment includes neoadjuvant chemotherapy (NAC), offered to patients with locally advanced breast cancer and who may benefit from down-staging before conservation therapy. NAC allows for evaluation of treatment response with pathologic complete response (pCR) acting as a marker of survival. Black women receive NAC more frequently as they often present with more advanced stage tumors and the triple negative subtype. Furthermore, Black women without pCR following NAC are at greater risk of mortality. Obesity is a prognostic factor for breast cancer. Non-Hispanic Black women have the greatest prevalence of obesity in most states. Patients with higher Body Mass Index (BMI) have previously been shown to have lower rates of chemotherapy response. Data on racial and ethnic differences in pCR rates are limited and whether obesity is a confounding factor requires investigation. Methods: Retrospective review of patients diagnosed with non-metastatic breast cancer who completed NAC and had surgery at Ohio State University James Comprehensive Cancer Center between January 1, 2005, and December 31, 2019, were analyzed. Clinical stage was calculated based on tumor size and nodal status. Operative treatment received was recorded to determine pathologic stage and chemotherapy response. The study endpoint, pCR, was assessed after definitive surgery. BMI categories were based on World Health Organization classification and obese defined as 30kg/m2. For the data analysis, we included self-reported Black and White women, excluding patients classified as “Other” race. Preliminary analyses included the distribution of sample descriptive characteristics. Differences by race and demographic characteristics were compared using Pearson’s chi-square test for categorical variables and t-test or Wilcoxon rank-sum test for continuous variables. Univariate analysis and multivariable logistic regression for pCR by age, race, BMI, menopausal status, insurance status and employment status were performed. Results: A final sample of 882 met criteria (11.7% Black and 88.3% white women, 1% Hispanic ethnicity). Median age of diagnosis is 51, with median 147.4 months of follow-up. 64% of the sample had clinical stage 2 disease, 22% were triple negative, 62% Her-2 positive subtypes. For tumor characteristics 67% of Black women and 59% white women had high grade tumor. Black women also had more triple negative disease (30% vs. 21%), more advanced stage at presentation (27% vs. 21%). More white women were employed and had private insurance compared to Black women, who predominantly had public insurance. The median BMI was higher among Black women (31.5) than white women (28.6). 52% of white women vs. 47% Black had mastectomy over lumpectomy. 67% of white women had radiation vs. 61% of Black women. Overall, 33% of Black and white women had pCR, with 67% having no pCR. Race and BMI were not significant predictors of PCR rates on univariate or multivariable analysis. Age &amp;lt; 40 is the only variable associated with pCR (OR 1.645, [95 CI 1.117-2.420] p-value: 0.012). Conclusions: BMI was not a significant predictor of pCR in this limited retrospective review. However, further exploration with a larger sample evaluating differences in pCR by BMI can lead to a better understanding of the association between obesity and pCR. Though race was not significant in predicting pCR, there is also room for further research considering socioeconomic disparities and obesity rates by race. Table 1. Table 1. Predictors for pCR. Table 1. Multivariable logistic regression for pCR adjusted by age, race, BMI, menopause status, insurance status, employment status. Univariate analysis for predictors of pCR performed for race and BMI. Citation Format: Ruvarashe Rumano, Michael Grimm, Marilly Palettas, Julie Stephens, Nicole Williams, Sagar Sardesai, Dionisia Quiroga, Bhuvaneswari Ramaswamy, Electra Paskett, Bridget Oppong. Differences in breast tumor response to neoadjuvant chemotherapy by race- Is obesity the key? [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 P1-01-06.

Abstract P1-05-10: Referral pathways for breast cancer diagnosis and treatment in Mexico: a physicians’ survey

Abstract Background: Clinical stage at diagnosis is one of the most relevant prognostic factors for breast cancer (BC). In Mexico, more than half of BC patients are diagnosed at stage III-IV due to delays in referral, diagnosis, and treatment. The median time between symptom presentation and treatment initiation is 7 months; with the longest delay occurring between the first consultation and treatment start. The cause of this delay is not well defined. Our objective is to investigate if physicians in Mexico are aware of referral pathways in their respective institutions for patients with clinical suspicion and confirmation of BC. Methods: Physicians were asked to answer an anonymous and voluntary survey that included 20 questions aimed at collecting general sociodemographic data, their plan of action when BC is suspected or diagnosed, and the perception of delays and barriers in breast cancer care. The survey was promoted on exclusive social networks of Mexican health professionals. Results: In total, 802 surveys were collected. Of these, 98% were physicians, with the highest proportion (50%) being gynecologists, family, and general practitioners. The average age was 41 years, and 36% reported practicing in the public sector, 35% in the private sector, and 29% in both sectors. When faced with clinical signs and symptoms suggestive of BC, 41% of physicians in the public sector would request a breast imaging study and refer to another specialist. In contrast, 39% of specialists in the private sector preferred to request a breast imaging study and reevaluate the results. Specialties to which physicians refer patients when suspicious in public and private sectors were gynecology 41% and 29%, surgical oncology 24% and 36%, and medical oncology 17% and 19%, respectively. In the case of a confirmed BC diagnosis, physicians preferred to refer patients to oncologic surgery in 40% and 45%, medical oncology in 40% and 32%, and gynecology in 9% and 10%, respectively. Of the healthcare professionals that were surveyed, 36% in the public sector and 67% in the private sector ignored the existence of referral pathways for BC clinical suspicion and confirmation in their institution. Regarding the time interval from the onset of symptoms to treatment initiation, 64% of the private practice physicians estimated a waiting time of &amp;lt; 30 days. In contrast, only 22% considered this time interval in the public sector, 30% answered between 31-90 days, and 17% replied &amp;gt; 90 days. Most respondents from the private sector considered factors associated with the patient as the main cause for this delay. Respondents from the public sector added to this opinion that factors related to the public health services were a contributor to the delays (Table 1). Lack of knowledge about the referral pathways was significantly associated with perceiving greater delays in care (p &amp;lt;0.001). Conclusion: The results of this study indicate that there is no consensus among healthcare professionals in Mexico about an action plan when breast cancer is suspected or diagnosed. Although a proportion of the respondents acknowledge the presence of established referral pathways, long waiting times and delays persist between the first evaluation and the start of treatment. Associated factors include the saturation and limited resources of public health services. The development of a universal program and its promotion among all health professionals is imperative to improve BC care in Mexico. Table 1. Factors associated of delay in the care of clinical suspicion and confirmation of BC. Citation Format: Daniela Vazquez-Juarez, Raul Andrade-Moreno, Cynthia Villareal Garza. Referral pathways for breast cancer diagnosis and treatment in Mexico: a physicians’ survey [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 P1-05-10.

Identification of GZMA as a Potential Therapeutic Target Involved in Immune Infiltration in Breast Cancer by Integrated Bioinformatical Analysis.

Granzyme A (GZMA) is a potential prognostic target for various cancer types. However, its therapeutic significance in breast cancer with immune infiltration remains controversial. We analyzed GZMA expression and its prognostic value in breast cancer with immune cell infiltration. Data was obtained from patients with breast cancer registered at The Cancer Genome Atlas. A correlation was performed between GZMA expression and patient's clinicopathological features such as age, pathologic stage, metastasis stage, overall survival (OS), disease-specific survival (DSS), and progress free interval (PFI). Kaplan-Meier analyses and Cox proportional hazard regression model were used to examine the predictive significance of GZMA expression for breast cancer. The co-expression pattern of GZMA was assessed by the LinkedOmics web portal. The relationship between GZMA expression and immune cells was analyzed using the TIMER database. The correlation between GZMA and lymphocytes and immunomodulators was established with the TISIDB database. There was a lower GZMA expression in breast cancer tissue than in normal tissue. Interestingly, GZMA expression was associated with age, pathologic stage, and the Tumour, Node, and Metastasis stage. Overexpression of GZMA was also associated with better OS, DSS, and PFI. Based on the Cox regression analysis, GZMA was identified as an independent favorable prognostic factor for breast cancer. Our findings demonstrated a strong association between GZMA and T-cell checkpoints (PD-1, PD-L1, and cytotoxic T lymphocyte-associated antigen (CTLA-4)) in breast cancer. Moreover, we evaluated the interactions between GZMA expression and markers of dendritic and CD8+ T cells using quantitative immunofluorescence. We discovered that increased infiltration of dendritic and CD8+ T cells was associated with GZMA expression in breast cancer. GZMA expression is associated with a favorable prognosis in breast cancer and is significantly correlated with immune cell infiltration. GZMA may be considered a promising therapeutic target for patients with breast cancer.

Abstract PD12-08: PD12-08 Randomized trial of exercise and nutrition on pathological complete response among women with breast cancer receiving neoadjuvant chemotherapy: the Lifestyle, Exercise and Nutrition Early after Diagnosis (LEANer) Study

Abstract Background: Neoadjuvant chemotherapy is available to women with locally advanced breast cancer where chemotherapy is given prior to surgery. By examining resected tissue following neoadjuvant chemotherapy pathological complete response (pCR) can be determined. pCR is a favorable prognostic factor associated with longer survival compared to residual disease after neoadjuvant chemotherapy. Physical activity and diet may improve some side effects during treatment, but less is known about their effect on chemotherapy completion and more specifically on pCR in the neoadjuvant setting. Utilizing data from a randomized trial of diet and physical activity with a primary endpoint of chemotherapy completion in women with newly diagnosed breast cancer initiating chemotherapy, we evaluated the effect of a lifestyle intervention on pCR among the subset of women in the trial who received neoadjuvant chemotherapy. Methods: The Lifestyle, Exercise and Nutrition Early after Diagnosis (LEANer) Study enrolled 173 women with Stage I-III breast cancer who were randomized to usual care (n = 86) or a yearlong, 16-session, in-person or telephone-administered diet and physical activity intervention (n = 87) delivered by registered dietitians. Among study participants, 73 women received neoadjuvant chemotherapy and of these, 72 (98.6%) had complete follow-up pCR data (intervention = 40; usual care = 32). pCR, dates, doses and reason for dose-adjustments/delays of chemotherapy were abstracted from electronic medical records and confirmed with treating oncologists. A Chi-square test was used to examine the effect of the intervention versus usual care on pCR. Results: The 72 women receiving neoadjuvant chemotherapy with complete follow-up pCR data in LEANer were 49.4±11.6 years old, had a body mass index of 30.0+6.7 kg/m2, and 37.0% and 49.3% had stage I or II breast cancer, respectively. Just over half (52.1%) of women had ER/PR positive cancers and 32.9% of tumors were HER2 positive, with no statistically significant differences in tumor type by study arm. 92.7% of the women randomized to intervention adhered to all of the counseling sessions during their neoadjuvant chemotherapy and had statistically significant improvements in mean physical activity (161 minute increase versus 40 minute increase, p-value = &amp;lt; 0.001) and fiber intake (0.21 gram/day increase versus -5.17 g/day decrease, p-value = 0.020), as well as median fruit and vegetable intake (0.6 serving/day increase versus -0.5 serving/day decrease, p-value = 0.041) compared to usual care. There was a benefit of the intervention on pCR compared to usual care (52.5% with pCR in the intervention arm versus 28.1% with pCR in the usual care arm, p-value = 0.037). The intervention effect on pCR did not appear to be impacted by chemotherapy completion (relative dose intensity of 92% in intervention versus 90% in usual care) or chemotherapy dose delays as these were similar in the two study arms. In mediation analyses, results suggested that the changes in physical activity mediated, at least partially, the intervention effect on pCR. Conclusions: A primarily telephone-based diet and physical activity intervention led to improved pCR compared to usual care among the subset of women with breast cancer in the LEANer Study who received neoadjuvant chemotherapy. As pCR is an important prognostic factor for breast cancer, additional lifestyle interventions focusing on the neoadjuvant treatment setting with pCR as the primary outcome are necessary to confirm the potential benefits of lifestyle changes on pCR. Citation Format: Leah Ferrucci, Tara B. Sanft, Maura Harrigan, Brenda Cartmel, Fangyong Li, Michelle Zupa, Courtney McGowan, Leah Puklin, Thai Hien Nguyen, Anna M. Tanasijevic, Marian L. Neuhouser, Dawn Hershman, Karen Basen-Engquist, Beth Jones, Tish Knobf, Anees B. Chagpar, Andrea L.M. Silber, Jennifer A. Ligibel, Melinda L. Irwin. PD12-08 Randomized trial of exercise and nutrition on pathological complete response among women with breast cancer receiving neoadjuvant chemotherapy: the Lifestyle, Exercise and Nutrition Early after Diagnosis (LEANer) 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 PD12-08.

Quality Indicators Compliance and Survival Outcomes in Breast Cancer according to Age in a Certified Center

Age as a breast cancer (BC) prognostic factor remains debatable. Several studies have investigated clinicopathological features at different ages, but few make an age group direct comparison. The European Society of Breast Cancer Specialists quality indicators (EUSOMA-QIs) allow a standardized quality assurance of BC diagnosis, treatment, and follow-up. Our objective was to compare clinicopathological features, compliance to EUSOMA-QIs and BC outcomes in three age groups (≤45 years, 46-69 years, and ≥70 years). Data from 1580 patients with staged 0-IV BC from 2015 to 2019 were analyzed. The minimum standard and desirable target on 19 mandatory and 7 recommended QIs were studied. The 5-year relapse rate, overall survival (OS), and BC-specific survival (BCSS) were also evaluated. No meaningful differences in TNM staging and molecular subtyping classification between age groups were found. On the contrary, disparities in QIs compliance were observed: 73.1% in ≤45 years and 46-69 years women vs. 54% in older patients. No differences in loco-regional or distant progression were observed between age groups. Nevertheless, lower OS was found in older patients due to concurrent non-oncological causes. After survival curves adjustment, we underscored evidence of undertreatment impacting BCSS in ≥70 years women. Despite a unique exception-more invasive G3 tumors in younger patients-no age-specific differences in BC biology impacting outcome were found. Although increased noncompliance in older women, no outcome correlation was observed with QIs noncompliance in any age group. Clinicopathological features and differences in multimodal treatment (not the chronological age) are predictors of lower BCSS.

Concordance of immunohistochemistry for predictive and prognostic factors in breast cancer between biopsy and surgical excision: a single-centre experience and review of the literature

PurposeAccurate evaluation of breast cancer on bioptic samples is of fundamental importance to guide therapeutic decisions, especially in the neoadjuvant or metastatic setting. We aimed to assess concordance for oestrogen receptor (ER), progesterone receptor (PR), c-erbB2/HER2 and Ki-67. We also reviewed the current literature to evaluate our results in the context of the data available at present.MethodsWe included patients who underwent both biopsy and surgical resection for breast cancer at San Matteo Hospital, Pavia, Italy, between January 2014 and December 2020. ER, PR, c-erbB2, and Ki-67 immunohistochemistry concordance between biopsy and surgical specimen was evaluated. ER was further analysed to include the recently defined ER-low-positive in our analysis.ResultsWe evaluated 923 patients. Concordance between biopsy and surgical specimen for ER, ER-low-positive, PR, c-erbB2 and Ki-67 was, respectively, 97.83, 47.8, 94.26, 68 and 86.13%. Cohen’s κ for interobserver agreement was very good for ER and good for PR, c-erbB2 and Ki-67. Concordance was especially low (37%) in the c-erbB2 1 + category.ConclusionOestrogen and progesterone receptor status can be safely assessed on preoperative samples. The results of this study advise caution in interpreting biopsy results regarding ER-low-positive, c-erbB2/HER and Ki-67 results due to a still suboptimal concordance. The low concordance for c-erbB2 1 + cases underlines the importance of further training in this area, in the light of the future therapeutic perspectives.

Systemic Inflammatory Response as a Prognostic Factor in Breast Cancer. Part II. Hematological Markers of Inflammation

Chronic inflammation is one of the recognized factors contributing to the onset and progression of malignant neoplasms. At the systemic level, a chronic inflammatory process is accompanied by an increased levels of inflammatory mediators and a change in hematological parameters of peripheral blood. According to numerous clinical studies, the change in the ratio of blood cell populations in cancer patients is an independent prognostic factor in malignant tumors of various localizations. This review is devoted to hematological parameters of the systemic inflammatory response (SIR) in breast cancer (BC). The review presents the characteristics of blood cells used for calculations of hematological indices (neutrophils, lymphocytes, monocytes, platelets); approaches for assessing SIR using these indices (NLR, PLR, LMR, etc.); comparative analysis of data on the association of the hematological indices with the clinical and morphological features of BC, patient survival and tumor response to chemotherapy. The data indicating the benefit of SIR hematological markers investigation during monitoring after treatment are summarized. Complex algorithms, including clinical, morphological and hematological factors, which are proposed to improve the quality of prognosis assessment, are considered. The information accumulated to date suggests that hematological indices reflecting SIR activity in BC patients can serve as additional independent prognostic factors. The development of the prognostic algorithms that are informative for certain clinical groups of BC patients is a promising area of research.

Outcomes and bioethical implications of lymphadenectomy in mastectomized patients: Importance and indication of ultrasound-guided fine-needle aspiration biopsy

Lymph node involvement is the main prognostic factor in breast cancer. Mastectomized patients usually undergo lymphadenectomy (LA) of micrometastatic sentinel lymph nodes (SLNs) despite the evidence of AMAROS trial to replace this therapy with radiotherapy in select cases. We demonstrate the ability of ultrasonography to detect non-metastatic or micrometastatic SLNs. Method: 132 patients who underwent mastectomy were evaluated. Ultrasound-guided fine-needle aspiration biopsy (FNAB) was indicated for suspicious lymph nodes. LA and SNL biopsy (SLNB) were performed in patients with positive and negative FNAB, respectively. LA was performed in cases of positive FNAB or positive SLNB except in the presence of isolated tumor cells and micrometastatic SLNs. The tumor burden after LA in patients with negative FNAB and positive SLNB was measured, and the presence of two or fewer positive SLNs was considered a low burden. Results: Sensitivity of FNAB for detecting positive lymph nodes in patients with a high tumor burden was 93% in our series, specificity was 84%. Positive (PPV) and negative predictive value (NPV) were respectively 60% and 79%. Conclusions: LA could have been avoided in 90% of mastectomized patients with negative FNAB and a low tumor burden who met the AMAROS criteria with a high NPV (79%).

Prognostic Impact of Smoking on Bevacizumab Combination Chemotherapy for Advanced Breast Cancer.

Smoking has been a proven carcinogenic risk factor for various cancers, including breast cancer. Furthermore, smoking has been recognized as a prognostic factor of breast cancer. Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) used in combination with chemotherapy to treat breast cancer. We, herein, investigated the effect of smoking on the prognosis of unresectable breast cancer patients who received bevacizumab plus weekly paclitaxel. From April 2011 to June 2022, 131 patients received bevacizumab plus weekly paclitaxel for unresectable breast cancer. At their first visit to our hospital, smoking status (i.e., period of smoking and amount of smoking per day) was evaluated by interview, and packs-years were calculated. Time to treatment failure (TTF) was significantly longer in the high packs-years group than the low packs-years group (p=0.010, log-rank). The log-rank test showed that the high packs-years group had a significantly longer overall survival than the low packs-years group (p=0.049, log-rank). Multivariate analysis of TTF revealed that progesterone receptor (p=0.005, HR=0.408) and packs-years (p=0.007, HR=0.391) were independent factors. A history of smoking may impact prognosis of combination chemotherapy with bevacizumab for advanced breast cancer treatment.

Prognostic factors of breast cancer among South Algerian women

Prognostic factors of breast cancer among South Algerian women

Prognostic factors of breast cancer among South Algerian women

Prognostic factors of breast cancer among South Algerian women

Integrated transcriptome and network analysis identifies EZH2/CCNB1/PPARG as prognostic factors in breast cancer.

Breast cancer (BC) has high morbidity, with significant relapse and mortality rates in women worldwide. Therefore, further exploration of its pathogenesis is of great significance. This study selected therapy genes and possible biomarkers to predict BC using bioinformatic methods. To this end, the study examined 21 healthy breasts along with 457 BC tissues in two Gene Expression Omnibus (GEO) datasets and then identified differentially expressed genes (DEGs). Survival-associated DEGs were screened using the Kaplan-Meier curve. Based on Gene Ontology (GO) annotation, survival-associated DEGs were mostly associated with cell division and cellular response to hormone stimulus. The enriched Kyoto Encyclopedia of Gene and Genome (KEGG) pathway was mostly correlated with cell cycle and tyrosine metabolism. Using overlapped survival-associated DEGs, a survival-associated PPI network was constructed. PPI analysis revealed three hub genes (EZH2, CCNB1, and PPARG) by their degree of connection. These hub genes were confirmed using The Cancer Genome Atlas (TCGA)-BRCA dataset and BC tissue samples. Through Gene Set Enrichment Analysis (GSEA), the molecular mechanism of the potential therapy and prognostic genes were evaluated. Thus, hub genes were shown to be associated with KEGG_CELL_CYCLE and VANTVEER_BREAST_CANCER_POOR_PROGNOSIS gene sets. Finally, based on integrated bioinformatics analysis, this study identified three hub genes as possible prognostic biomarkers and therapeutic targets for BC. The results obtained further understanding of the underground molecular mechanisms related to BC occurrence and prognostic outcomes.

Relationship Between Serum 25-Hydroxy Vitamin D Level and Breast Cancer Prognostic Factors

Vitamin D deficiency plays an important role in the development of various diseases, including cancer. Regarding the high prevalence of breast cancer and vitamin D deficiency in Iran, this study aimed to investigate the relationship between vitamin D deficiencies and prognostic factors in breast cancer. This descriptive-analytical cross-sectional study was performed from March 2015 to March 2017 at Imam Reza hospital in Kermanshah city, Iran. 145 breast cancer patients with pathologic confirmation and before the neoadjuvant or adjuvant treatments were included by simple and convenient sampling. Serum 25(OH) D levels were measured in all patients before receiving treatment. The collected data were analyzed by using SPSS software (version. 20), and the relationship between the levels of 25(OH) D and the studied factors was assessed by inferential statistical tests in each group. The results showed that there was a statistically significant direct relationship between serum vitamin D levels and some factors, including age, ER, and PR, but a significant inverse relationship was observed between serum vitamin D levels and the level of ki67 and metastasis. There was no statistically significant relationship between the mean serum level of vitamin D and tumor grade and P53 receptor, but high levels of vitamin D were associated with low-grade tumors and P53 negativity. According to the findings, lower levels of vitamin D can be associated with higher levels of ki67 and P53, higher-grade breast cancer, a higher rate of metastases, as well as lower percentage of hormone receptor positivity.

Low expression of NR1H3 correlates with macrophage infiltration and indicates worse survival in breast cancer.

Background: Nuclear receptor NR1H3 is a key regulator of macrophage function and lipid homeostasis. Here, we aimed to visualize the prognostic value and immunological characterization of NR1H3 in breast cancer. Methods: The expression pattern and prognostic value of NR1H3 were analyzed via multiple databases, including TIMER2, GEPIA2 and Kaplan-Meier Plotter. TISIDB, TIMER2 and immunohistochemical analysis were used to investigate the correlation between NR1H3 expression and immune infiltration. GO enrichment analysis, KEGG analysis, Reactome analysis, ConsensusPathDB and GeneMANIA were used to visualize the functional enrichment of NR1H3 and signaling pathways related to NR1H3. Results: We demonstrated that the expression of NR1H3 was significantly lower in breast cancer compared with adjacent normal tissues. Kaplan-Meier survival curves showed shorter overall survival in basal breast cancer patients with low NR1H3 expression, and poorer prognosis of relapse-free survival in breast cancer patients with low NR1H3 expression. NR1H3 was mainly expressed in immune cells, and its expression was closely related with infiltrating levels of tumor-infiltrating immune cells in breast cancer. Additionally, univariate and multivariate analysis indicated that the expression of NR1H3 and the level of macrophage infiltration were independent prognostic factors for breast cancer. Gene interaction network analysis showed the function of NR1H3 involved in regulating of innate immune response and macrophage activation. Moreover, NR1H3 may function as a predictor of chemoresponsiveness in breast cancer. Conclusion: These findings suggest that NR1H3 serves as a prognostic biomarker and contributes to the regulation of macrophage activation in breast cancer.

A novel cuproptosis-related prognostic 2-lncRNAs signature in breast cancer.

Background: Cuproptosis, a newly defined regulated form of cell death, is mediated by the accumulation of copper ions in cells and related to protein lipoacylation. Seven genes have been reported as key genes of cuproptosis phenotype. Cuproptosis may be developed by subsequent research as a target to treat cancer, such as breast cancer. Long-noncoding RNA (lncRNA) has been proved to play a vital role in regulating the biological process of breast cancer. However, the role of lncRNAs in cuproptosis is poorly studied. Methods: Based on TCGA (The Cancer Genome Atlas) database and integrated several R packages, we screened out 153 cuproptosis-related lncRNAs and constructed a novel cuproptosis-related prognostic 2-lncRNAs signature (BCCuS) in breast cancer and then verified. By using pRRophetic package and machine learning, 72 anticancer drugs, significantly related to the model, were screened out. qPCR was used to detect the differentially expression of two model lncRNAs and seven cuproptosis genes between 10 pairs of breast cancer tissue samples and adjacent samples. Results: We constructed a novel cuproptosis-related prognostic 2-lncRNAs (USP2-AS1, NIFK-AS1) signature (BCCuS) in breast cancer. Univariate COX analysis (p < .001) and multivariate COX analysis (p < .001) validated that BCCuS was an independent prognostic factor for breast cancer. Overall survival Kaplan Meier-plotter, ROC curve and Risk Plot validated the prognostic value of BCCuS both in test set and verification set. Nomogram and C-index proved that BCCuS has strong correlation with clinical decision-making. BCCuS still maintain inspection efficiency when patients were splitting into Stage I-II (p = .024) and Stage III-IV (p = .003) breast cancer. BCCuS-high group and BCCuS-low group showed significant differences in gene mutation frequency, immune function, TIDE (tumor immune dysfunction and exclusion) score and other phenotypes. TMB (tumor mutation burden)-high along with BCCuS-high group had the lowest Survival probability (p = .005). 36 anticancer drugs whose sensitivity (IC50) was significantly related to the model were screened out using pRRophetic package. qPCR results showed that two model lncRNAs (USP2-AS1, NIFK-AS1) and three Cuproptosis genes (FDX1, PDHA1, DLAT) expressed differently between 10 pairs of breast cancer tissue samples and adjacent samples. Conclusion: The current study reveals that cuproptosis-related prognostic 2-lncRNAs signature (BCCuS) may be useful in predicting the prognosis, biological characteristics, and appropriate treatment of breast cancer patients.

The expression of HER2/neu in patients with lung cancer and its associated factors.

Lung cancer is the most common cause of cancer-related death worldwide in both sexes. Evidence suggests the role of genetic factors in lung cancer. Studying of such factors can help understand the cancer prognosis. Overexpression of the human epidermal growth factor receptor-2 (HER2/neu) protein is considered an important prognostic factor in breast cancer, but its role has not been confirmed in lung cancer. Therefore, the present study aimed to investigate the role of its expression in patients with lung cancer. In this cross-sectional study, patients aged >18 years who were referred to Afzalipoor Hospital, Kerman, Iran, from 2016 to 2017, and were diagnosed with lung cancer were enrolled into the study if they had a pathological sample of their cancerous lung. Their demographics were recorded, and the sample was sectioned and stained to measure HER2/neu gene expression according to DAKO instructions using heat-induced antigen retrieval (HIER) enzyme marker. The samples of 100 patients with lung cancer were evaluated (84% men and 16% women) with a mean age of 61.34 years (standard deviation of 12.51 years). HER2/neu expression was significantly associated with the type of cancer and was highest in adenocarcinoma and zero in small cell carcinoma (P < 0.001), but not with patients' sex, age, smoking status and family history of cancer (P > 0.05). These results emphasized the overexpression of HER2/neu in different types of lung cancer, which can be used further for therapeutic purposes. The results showed that HER2/neu was overexpressed not only in adenocarcinoma but also in other types, like squamous cell carcinoma. Therefore, all subtypes of non-small cell lung carcinoma should be considered for anti-HER2 therapies, and further research is required for small cell lung carcinoma.

Correlation study between apparent diffusion coefficients and the prognostic factors in breast cancer

To analyse the correlation between apparent diffusion coefficients (ADC) derived from intratumoural and peritumoural regions with prognostic factors and immune-inflammatory markers in breast cancer (BC). In this retrospective study, 89 patients (age range, 28-66 years; median, 45 years) with a diagnosis of invasive BC who underwent routine blood tests and multiparametric magnetic resonance imaging (MRI) were enrolled. The study cohort was stratified according to tumour maximum cross-section ≥20 mm, lymph node metastasis (LNM), time-signal intensity curve (TIC) type, and receptor status. Minimum, maximum, mean, and heterogeneity values of tumour ADC (ADCtmin, ADCtmax, ADCtmean, and ADCheter), maximum values of peritumoural ADC (ADCpmax), and the ratio of peritumoural-tumour ADC (ADCratio) were obtained on the ADC maps. Linear regression analyses were performed to investigate the correlation between immune-inflammatory markers, prognostic factors and ADC values. HER-2 was positively associated with ADCtmax, ADCtmean, and ADCpmax values (β=0.306, p=0.004; β=0.283, p=0.007; β=0.262, p=0.007, respectively), while platelet-to-lymphocyte ratio (PLR) was positively associated with ADCpmax and ADCratio values (β=0.227, p=0.020; β=0.231, p=0.020, respectively). Among ADC parameters, ADCpmax showed the highest predictive values for evaluating the presence of LNM (AUC, 0.751; sensitivity, 70.4%; specificity, 77.1%). The ADCpmax value could provide additional assistance in predicting prognostic factors of BC.