Carcinoma In Women Research Articles

Reproductive life and differentiated thyroid carcinoma in women: reciprocal influences on their respective outcome.

To analyze the reciprocal influences between female reproductive life and DTC management. Data on pregnancy outcome in DTC patients indicate that after conceiving, these women may need an increased L-T4 dose to maintain suppressed serum TSH levels. Nevertheless, this does not determine major harm in terms of pregnancy outcome. Analogously, the most recent findings obtained with the propensity score matching approach have confirmed that pregnancy does not significantly affect DTC clinical course and eventually tumor prognosis. A recent metanalysis and a large case-control study excluded a significant effect of radioactive iodine treatment (RAIT) on several reproductive variables in DTC patients, providing reassuring evidence that the current recommendations on RAIT for women of childbearing age are sufficiently well tolerated and do not affect fertility nor pregnancy rate. Overall, the most recent studies have provided sufficiently reassuring evidence that the occurrence of pregnancy and DTC management are of no reciprocal harm for adverse outcome in affected women of childbearing age. Thus, female DTC patients should be managed according to the individual response to treatment before pregnancy. When DTC diagnosis is made after conception, delaying surgery does not represent a harm in most patients.

Human Papillomavirus Genotypes Distribution in High-Grade Cervical Lesions and Invasive Cervical Carcinoma in Women Living in Mauritania: Implications for Cervical Cancer Prevention and HPV Prophylactic Vaccination.

Cervical cancer related to high-risk human papillomavirus (HR-HPV) is the second female cancer in Mauritania (Northwest Sahelian Africa). We assessed the distribution of HPV genotypes in Mauritanian women with high-grade cervical intraepithelial neoplasia (CIN2/3) or invasive cervical cancer (ICC). A prospective study was conducted in the Centre Hospitalier National, Nouakchott, Mauritania, to collect cervical biopsies among women suspected of CIN2/3 or cancer. HPV DNA detection and genotyping were carried out from formalin-fixed, paraffin-embedded biopsies using multiplex PCR (Human Papillomavirus Genotyping Real-Time PCR Kit, Bioperfectus Technologies Co., Taizhou, China). Fifty biopsies were included from women (mean age: 56.7 years) suffering from CIN2/3 (28.0%) and ICC (72.0%) which corresponded to 32 (64.0%) squamous cell carcinomas (SCC) and 4 (8.0%) adenocarcinomas (ADC). HPV DNA detection was successful in 47 (94.0%) samples. The most prevalent HR-HPV genotypes were HPV-45 (40.4%), HPV-16 (38.3%), HPV-39 and HPV-52 (23.4%), HPV-33 (17.0%), HPV-18 (14.9%), HPV-35 (4.2%), and HPV-56 (2.1%). The majority (93.6%) of HPV-positive biopsies contained at least one HPV type covered by the 9-valent Gardasil-9® vaccine, and 40.9% were infected by multiple vaccine HPV genotypes. To eradicate cervical cancer in Mauritania, prophylactic HPV vaccination must be combined with primary molecular screening of cervical HR-HPV infection.

Fatal Bladder Carcinoma in Woman with Human Immunodeficiency Virus: A Case Report

Background: Chronic human immunodeficiency virus (HIV) infection is associated with an increased incidence of Non-Acquired Immunodeficiency Syndrome (non-AIDS) defining cancers. To date, only a limited number of cases of bladder cancer have been linked with HIV infection in women. We sought to describe the clinical characteristics of HIV-associated bladder cancer. Methods: A 54-year-old female patient presented with symptoms of an occlusive syndrome. Medical examination was followed by a CT scan. The imaging revealed a significant finding. There was a noticeable process within the bladder. Further evaluation and management were recommended. Results: Spontaneous urinary cytology revealed the presence of malignant cells. An endoscopy was performed under spinal anesthesia, uncovering a large sessile tumor with necrotic areas located on the ventral aspect and dome of the bladder. Due to the severity of the condition, a palliative resection was carried out. Subsequent histological examination identified the tumor as a high-grade urothelial carcinoma, with evidence of muscle invasion. This diagnosis confirmed the aggressive nature of the disease, highlighting the necessity for further medical management and intervention. Conclusion: Bladder cancers in HIV-infected patients are rare but can occur in relatively young individuals with a low nadir CD4 cell count. These cancers often exhibit aggressive pathological features and can be fatal.

Cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy for treating previously treated advanced endometrial cancer in Sweden

Objective Pembrolizumab plus lenvatinib was recently approved for the treatment of advanced or recurrent endometrial carcinoma in women with disease progression on or following prior treatment with a platinum‑containing therapy in any setting, and who are not candidates for curative surgery or radiation (KEYNOTE-775/Study-309; NCT03517449). The objective was to assess the cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy from a Swedish healthcare perspective. Materials and methods A lifetime partitioned-survival model with three health states (progression free, progressed disease, death) was constructed. Chemotherapy was represented by paclitaxel or doxorubicin. Overall survival, progression-free survival, time on treatment, and utility data were obtained from KEYNOTE-775 (database lock: March 1, 2022). Costs (in 2020 Swedish Krona [SEK]) included drug acquisition and administration, health state, end of life, adverse event management, subsequent treatment, and societal (scenario analysis). Outcomes were calculated as quality-adjusted life-years (QALY) and life-years. Model results were presented as incremental cost-effectiveness ratios for all-comers, patients with proficient mismatch repair tumors, and deficient mismatch repair tumors. Deterministic and probabilistic sensitivity analyses were conducted. Results Pembrolizumab plus lenvatinib is a cost-effective treatment when compared with chemotherapy, with estimated deterministic and probabilistic incremental cost-effectiveness ratios of SEK 795,712 and 819,757 per QALY gained. Pembrolizumab plus lenvatinib was associated with a large incremental QALY and life-year gain per person versus chemotherapy over the model time horizon (1.49 and 1.76). Limitations Time-to-event data were incomplete and semiparametric and parametric curves were utilized for lifetime extrapolation. Willingness-to-pay thresholds, costs, and utility weights vary by country, which would vary the treatment’s cost effectiveness in different countries. Conclusions This partitioned survival analysis suggests that pembrolizumab plus lenvatinib is cost effective compared with chemotherapy in Sweden for women with advanced or recurrent endometrial carcinoma following previous systemic therapy. Results were robust to mismatch repair status and to changes in parameters/assumptions.

A novel PD-1/PD-L1 pathway-related seven-gene signature for the development and validation of the prognosis prediction model for breast cancer.

Breast cancer (BC/BRCA) is the most common carcinoma in women. The average 5-year survival rate of BC patients with stage IV disease is 26%. A considerable proportion of patients still do not receive effective therapy. It is an unmet need to identify novel biomarkers for BC patients. Herein, we evaluated whether the programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) status is associated with the clinical outcomes of BC, based on data from The Cancer Genome Atlas (TCGA). Clinical and transcriptome data of BC patients were obtained from TCGA dataset, and prognostic genes in BC patients were identified, as well as the PD-1/PD-L1 pathway mainly associating with the BC patients. Following the execution of the consensus clustering algorithm, BC patients were segregated into two clusters, and subsequent investigation of the potential mechanisms between them was carried out. A comparison of ferroptosis and N6-methyladenosine (m6A) was conducted between the two groups with the greatest difference in prognosis. Based on least absolute shrinkage and selection operator (LASSO) analysis, a signature associated with the PD-1/PD-L1 pathway was developed, and the prognosis outcome and the predictive accuracy of the signature model were further assessed. Prognostic genes in BC patients were studied using TCGA data and it was found that the PD-1/PD-L1 pathway was most associated with the BC patients. Then, a low-risk (C1) group and a high-risk (C2) group of BC patients were constructed based on a PD-1/PD-L1 pathway-related signature. The functional analyses suggested that the underlying mechanisms between these groups were mainly associated with immune-related pathways. We found that ferroptosis and m6A were significantly different between the two groups. A PD-1/PD-L1 pathway-related gene signature was further developed to predict survival of BC patients, including 7 genes [mitogen-activated protein kinase kinase 6 (MAP2K6), NF-kappa-B inhibitor alpha (NFKBIA), NFKB Inhibitor Epsilon (NFKBIE), Interferon gamma (IFNG), Toll/interleukin-1 receptor domain-containing adapter protein (TIRAP), IkappaB kinase (CHUK), and Casein kinase 2 alpha 3 gene (CSNK2A3)]. The receiver operating characteristic (ROC) curves were analyzed to further assess the prognostic values of these 7 genes. The 1-, 3-, and 5-year values of the areas under the curve (AUCs) for overall survival were 0.651, 0.658, and 0.653 in this seven gene signature model, respectively. PD-1/PD-L1 pathway-related subtypes of BC were identified, which were closely associated with the immune microenvironment, the ferroptosis status, and m6A in BC patients. The gene signature involved in the PD-1/PD-L1 pathway might help to make a distinction and predict prognosis in BC patients.

Abstract B012: Pedigree and multi-omics analyses implicate nucleotide excision repair genes, XPA, ERCC6, and ERCC8, in susceptibility to breast cancer

Abstract Background: The majority of low- and moderate-risk [odds ratios (OR) ≤ 3] susceptibility genes for peri- and post-menopausal breast cancer (≥50 years of age), particularly those with minor allele frequency (MAF) of <30%, have not yet been identified and/or validated. We used a hypothesis-driven integrative approach to identify breast cancer susceptibility genes by analyzing pedigree and multi-omics (genomics, transcriptomics, mutation landscape) data. Methods: We conducted pedigree analysis in 31 families with DNA repair disorders, xeroderma pigmentosum (XP), trichothiodystrophy (TTD), Cockayne syndrome (CS), XP/TTD and XP/CS. These disorders can be caused by mutations in genes involved in the nucleotide excision repair (NER) pathway such as XPA-XPG, ERCC6 and ERCC8. We estimated the frequency of hereditary breast cancer, defined as the presence of at least two cases of premenopausal breast cancer (diagnosed <50 years of age) or one case of premenopausal breast cancer and one case of ovarian cancer in one side of the family, in our study. Furthermore, we conducted individual analysis of four genome-wide association studies (GWAS) datasets (totaling 2961 cases and 4335 controls), individual and meta-analysis of two gene expression microarray datasets (98 cases and 163 controls), and targeted analysis of The Cancer Genome Atlas (TCGA) (522 breast cancers). All analyses involved invasive ductal breast carcinoma in women diagnosed at ≥50 years of age. Results: In an XP family with causative mutations in XPA, there were four cases of premenopausal breast cancer (including heterozygote mutation carriers), one case of ovarian cancer, and one case of prostate cancer. Comprehensive sequencing failed to identify a BRCA1 or BRCA2 mutation in this family. Overall, 7 of 31 (22.6%) families with DNA repair disorders had a family history that was compatible with hereditary breast cancer. Hence, we selected a panel of NER genes as candidates for association studies with breast cancer. Our candidate-gene association analysis of GWAS datasets suggested an increased risk of breast cancer with ERCC6 (main effect:1.29 ≤ OR ≤ 2.91, 0.005 ≤ p ≤ 0.04, 11.8 ≤ MAF ≤ 29.7%) and implicated its interaction with ERCC8 (joint effect:3.03 ≤ OR ≤ 5.31, 0.01 ≤ pinteraction ≤ 0.03). Our transcriptomics analysis identified significant upregulation of ERCC6 (p=7.95 × 10–6) and ERCC8 (p=4.67 × 10–6) in breast cancer. Our analysis of TCGA breast tumor data showed similar mutation frequency of ERCC6 (1.8%) and ERCC8 (0.3%) as known breast cancer susceptibility genes such as BLM (1.9%) and LSP1 (0.3%). Conclusion: Our integrative analyses suggest that ERCC6 may be a previously unreported low- to moderate-risk breast cancer susceptibility gene, which may also interact with ERCC8. ERCC6 and ERCC8 code for the main components of the transcription-coupled (TC) repair sub-pathway of the NER. TC-NER protects against genotoxic agents, such as free radicals and reactive oxygen species. Our results provide a deeper biologic insight and leads for prevention of common breast cancer. Citation Format: Roxana Moslehi, Amiran Dzutsev. Pedigree and multi-omics analyses implicate nucleotide excision repair genes, XPA, ERCC6, and ERCC8, in susceptibility to breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B012.

Development of prognostic model and multivariate analysis for breast cancer survival patients using SEER database

Background: Many studies employed machine learning (ML) to forecast the prognosis of breast cancer (BC) patients and discovered that the ML model showed high individualized forecasting ability. Breast cancer is the most frequent kind of carcinoma in women globally and ranks as the leading cause of death in women. Objectives: This study intends to use the Surveillance, Epidemiology, and End Results dataset to categorize breast carcinoma cases’ alive and dead conditions. Deep learning and machine learning have been extensively utilized in clinical studies to address various categorization problems due to their ability to manage massive data sets in an organized manner. Pre-processing the data allows it to be visualized and analyzed for making critical choices. This study describes a realistic machine learning-based strategy for categorizing the SEER breast cancer dataset. Materials and methods: We employed classification and machine learning algorithms to classify breast cancer mortality. Four well-known classification ML algorithms were employed in this study. To identify risk factors, we employed multivariate analysis using the data set. Results: The decision tree performed the best accuracy (0.914) among all the models. T4 stage (β=1.4, p<0.001, OR=4.22, 95% CI (2.06-8.64), N2 stage (β=0.39, p=0.008, OR= 1.49, 95% CI (1.111-1.997) found to be major risk factors for breast cancer mortality using multivariate analysis. Conclusion: The significant prognostic variables affecting the breast carcinoma survival rates reported in the current research are relevant and might be turned into decision support systems in the medical realm.

Knowledge and awareness toward human papillomavirus vaccination among Saudi female nursing students.

Human Papillomavirus is a sexually transmitted agent, causing cervical cancer. In Saudi Arabia, cervical cancer is ranked as the ninth most common carcinoma in women. HPV vaccine is an effective prevention method against HPV high-risk types such as HPV 18 and 16. Research on HPV vaccine knowledge and awareness is limited due to the lack of extensive data reportage on HPV and cervical cancer cases among Saudi women. This study was aimed to determine the knowledge and awareness of human papillomavirus vaccination among Saudi nursing female students. This study was cross-sectional and included (n = 114) participants. The study used an online survey, which included demographical variables and the HPV knowledge scale. The data were collected from October 10, 2023, until January 3, 2024. Descriptive data, Mann-Whitney Z-tests and nonparametric tests were used to analyze the study's findings. The study participants' mean age was 20.8 years (SD 1.6). Most students (72%) did not receive the HPV vaccine. The overall mean HPV knowledge was 10.0 (SD 7.08). The HPV knowledge subscales showed poor levels of knowledge of HPV infection, screening, and vaccines: 5.15 (SD 3.87), 1.39 (SD 1.34), and 2.06 (SD 1.87), respectively. In conclusion, Saudi Arabia having a predominantly youthful population, it is crucial to implement educational programs that improve the understanding and awareness of HPV infection among nursing students and other health professionals. There is a necessity to establish impactful awareness campaigns and integrate interventional research to inform health professionals and the public about the disease and dispel misunderstandings and cultural beliefs about HPV and HPV vaccines to prevent cervical cancers among young females.

Clinicopathologic and genetic analysis of invasive breast carcinomas in women with germline CHEK2 variants

PurposeGermline pathogenic variants in checkpoint kinase 2 (CHEK2) are associated with a moderately increased risk of breast cancer (BC). The spectrum of clinicopathologic features and genetics of these tumors has not been fully established.MethodsWe characterized the histopathologic and clinicopathologic features of 44 CHEK2-associated BCs from 35 women, and assessed responses to neoadjuvant chemotherapy. A subset of cases (n = 23) was additionally analyzed using targeted next-generation DNA sequencing (NGS).ResultsMost (94%, 33/35) patients were heterozygous carriers for germline CHEK2 variants, and 40% had the c.1100delC allele. Two patients were homozygous, and five had additional germline pathogenic variants in ATM (2), PALB2 (1), RAD50 (1), or MUTYH (1). CHEK2-associated BCs occurred in younger women (median age 45 years, range 25–75) and were often multifocal (20%) or bilateral (11%). Most (86%, 38/44) were invasive ductal carcinomas of no special type (IDC-NST). Almost all (95%, 41/43) BCs were ER + (79% ER + HER2-, 16% ER + HER2 + , 5% ER-HER2 +), and most (69%) were luminal B. Nottingham grade, proliferation index, and results of multiparametric molecular testing were heterogeneous. Biallelic CHEK2 alteration with loss of heterozygosity was identified in most BCs (57%, 13/23) by NGS. Additional recurrent alterations included GATA3 (26%), PIK3CA (226%), CCND1 (22%), FGFR1 (22%), ERBB2 (17%), ZNF703 (17%), TP53 (9%), and PPM1D (9%), among others. Responses to neoadjuvant chemotherapy were variable, but few patients (21%, 3/14) achieved pathologic complete response. Most patients (85%) were without evidence of disease at time of study (n = 34). Five patients (15%) developed distant metastasis, and one (3%) died (mean follow-up 50 months).ConclusionAlmost all CHEK2-associated BCs were ER + IDC-NST, with most classified as luminal B with or without HER2 overexpression. NGS supported the luminal-like phenotype and confirmed CHEK2 as an oncogenic driver in the majority of cases. Responses to neoadjuvant chemotherapy were variable but mostly incomplete.

Vulvar squamous cell carcinoma in women 80 years and older: Treatment, survival and impact of comorbidities

BackgroundDespite being a disease of mainly older women, little is known about the clinical management of older women with vulvar squamous cell carcinoma (VSCC). We evaluated their daily clinical management compared with younger women, and established the prevalence of comorbidities and its impact on overall survival (OS). MethodsAll Dutch women diagnosed with VSCC from 2015 to 2020 (n = 2249) were selected from the Netherlands Cancer Registry. Women aged ≥80 years (n = 632, 28%) were defined as “older” patients, women <80 years were considered as “younger”. Chi-square tests were performed to evaluate differences in treatment by age group and comorbidities. Differences in OS were evaluated using Kaplan-Meier Curves and log-rank test. ResultsThe vast majority of both older (91%) and younger (99%) patients with FIGO IA VSCC received surgical treatment of the vulva. Older FIGO IB-IV VSCC patients were less likely to undergo groin surgery than younger patients (50% vs. 84%, p < 0.01). Performance of surgical treatment of the vulva and groin(s) was not associated with the number of comorbidities in older patients (p = 0.67 and p = 0.69). Older patients with ≥2 comorbidities did have poorer OS compared to women with one or no comorbidities (p < 0.01). ConclusionThe vast majority of older patients underwent vulvar/local surgery. Older patients less often received groin surgery compared to younger patients. The majority of older patients had at least one comorbidity, but this did not impact treatment choice. The poorer survival in older VSCC patients may therefore be due to death of competing risks instead of VSCC itself.

Incidence and outcomes of incidental endometrial carcinoma in women undergoing hysterectomy for pelvic organ prolapse (2147)

Incidence and outcomes of incidental endometrial carcinoma in women undergoing hysterectomy for pelvic organ prolapse (2147)

Overall survival of breast cancer patients in association with ESR1 polymorphism

Breast cancer (BC) is the most common carcinoma in women. Genetic polymorphism in estrogen receptor-α (ESR1) gene is involved in alteration in receptor expression, function and evolving as important determinant of breast cancer susceptibility. The present study aimed to evaluate single nucleotide polymorphism (SNP) in breast carcinoma to find out co-relation with overall survival (OS) of breast carcinoma patients. In present study, overall survival of two hundred breast cancer patients with single nucleotide polymorphism was studied in detail. OS was evaluated by Kaplan-Meier method and then analysed with the log-rank test. The cox regression method was used for analyzing data of survival, hazard ratio estimation and its confidence interval value. The significant association of OS was observed with AG genotype of rs9340799 and rs373404617 (Log-rank χ2 = 18.1658, DF = 2, p = 0.0351; χ2 = 5.7632, DF = 2, p = 0.0560 respectively). The genotypes of ESR1 SNP rs9340799 and rs373404617 were predictive of good outcomes of breast cancer. This study suggests that overall survival studies are helpful in investigating progression or regression of the disease which is required for perfect management of breast carcinoma. Future directions include genetic and proteomic-based approaches for breast carcinoma development and progress.

Critical Analysis of Advanced High-Grade Serous Epithelial Ovarian Cancer in Women: An Experience of 100 Cases from a Regional Cancer Center in Northeast India.

Debabrata BarmonOvarian cancer is the sixth most common cancer in women worldwide. Patients with ovarian carcinoma mostly present at an advanced stage with serous type of epithelial ovarian cancers, which is the most lethal of all pelvic malignancies. This study aims to critically analyze high-grade serous epithelial ovarian carcinomas in women from the Northeastern region of India and compare our data with Western literature to modify treatment strategies and improve survival outcomes. This hospital-based retrospective analysis involved data from the records of 100 women with high-grade epithelial ovarian cancer treated primarily with neoadjuvant chemotherapy followed by interval debulking surgery in the department of gynecologic oncology at a tertiary level regional cancer institute from January 2018 to December 2019. The demographic, clinical and pathological profile, and survival outcome were evaluated using descriptive statistics. The overall survival of the study population was calculated using Kaplan-Meier curves using SPSS software (version 24). The majority of women belonged to 41 to 55 years age group. At first presentation to the hospital, 89 and11% patients were in stage III and stage IV of disease, respectively. Clinically, 95% of women had ascites, and 18% had metastasis to lymph nodes. Distant metastasis to lungs and liver was present in 10 and 3% of cases, respectively. A substantial percentage (98%) of women had raised serum Ca125 > 1000 at baseline, ranging from 1,745 to 10,987 IU/mL. Almost two-thirds of the cases had partial-to-complete response to neoadjuvant chemotherapy (78%). In most of the women (72%), there was no residual disease at interval debulking surgery (R0), though 28% women had R1& R2 resection. The median overall survival time was 36 months. High-grade serous ovarian cancer is commonly seen in older age group, but its occurrence in younger population has also been observed. Early diagnosis is crucial in decreasing morbidity and mortality among these patients. Therefore, efforts should be made to identify risk factors for malignancy. Assessing each parameter of statistical information reflecting its own profile may be important for calculating the risk for the development of ovarian cancer, which can help in implementing preventive measures in the future.

Retrospective Analysis of the Risk of Breast Carcinoma Following Recurrent In vitro Fertilization Treatments

ABSTRACT Background: Breast cancer is one of the most common cancers affecting women globally, with risk factors including genetic predisposition, environmental influences, and hormonal exposure. The use of in vitro fertilization (IVF) has been associated with high doses of hormonal treatments, raising concerns about the potential increase in breast cancer risk due to these treatments. This study aims to evaluate the incidence of breast carcinoma following recurrent IVF treatments. Methodology: This retrospective cohort study involved 62 women who underwent three or more IVF cycles at a single fertility clinic. Participants were selected based on their comprehensive medical records from the clinic’s database, excluding those with known genetic predispositions to breast cancer. The study cohort was compared with a control group of 62 women who did not undergo IVF but were matched for age and socioeconomic status. Breast cancer incidence was identified through cross-referencing participant records with national cancer registries. Results: Of the 62 women in the IVF group, 8 (12.9%) developed breast carcinoma compared to 4 (6.5%) in the control group. The median time from the first IVF treatment to the cancer diagnosis was 7 years. Statistical analysis using Cox proportional hazards models revealed a hazard ratio of 2.1 for developing breast carcinoma among IVF participants compared to controls, although this was not statistically significant (95% confidence interval: 0.8–5.4; P = 0.12). Conclusion: The findings suggest a higher incidence of breast carcinoma in women undergoing recurrent IVF treatments compared to those who did not undergo such treatments, although the results did not reach statistical significance. The study highlights the need for further research with larger cohorts to robustly determine the relationship between IVF treatments and breast cancer risk. Enhanced screening and monitoring for breast cancer may be advisable for women undergoing repeated IVF cycles.

Establishment of a novel cytokine-related 8-gene signature for distinguishing and predicting the prognosis of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a common carcinoma in women, and the prognosis of TNBC is the worst. Using data from The Cancer Genome Atlas (TCGA) database, we analyzed the functional roles of cytokine-related genes in TNBC. The clinical and transcriptome data of TNBC patients were downloaded from TCGA database. A systematical analyses of the data from TCGA database were conducted to screen the prognostic genes and identify the main cytokine-related pathways related to TNBC. We identified 499 prognostic genes in TNBC patients from TCGA database and the cytokine-related pathways closely related to TNBC. TCGA-TNBC patients were divided into the high-risk cluster (C1) group and the low-risk cluster (C2) group based on the cytokine-related genes. The C1 group patients exhibited tumor metastasis and an advanced tumor stage. The functional analysis revealed that the upregulated differentially expressed genes (DEGs) in the C1 group were mainly associated with the extracellular matrix (ECM)-receptor interaction, stem cell proliferation, focal adhesion, and cyclic adenosine monophosphate (cAMP) signaling pathway, while the downregulated DEGs in the C1 group were mainly associated with cytokine and cytokine receptors, T-helper 17 (Th17) cell differentiation, and primary immunodeficiency. The immune activity of C1 group was lower than that of C2 group, and the identified half-maximal inhibitory concentration scores of 3 chemotherapy drugs (i.e., doxorubicin, methotrexate, and paclitaxel) were lower in C2 group than C1 group. More importantly, we constructed a novel prognostic signature and identified the following 8 genes: CCL25, CXCL13, IL12RB2, IL21, TNFRSF13C, TNFRSF8, CCL7 and GDF5. The status of the cytokine-related pathway was closely related to tumor classification and immune activity in the TNBC patients. The gene signature of the cytokine-related genes showed an good performance in predicting the prognosis of TNBC patients, and could predict the prognosis of TNBC patients.

Clinicopathological and prognosis significance of RIPK1 in patients with cervical squamous cell carcinoma: a retrospective cohort study.

Cervical cancer is one of the most common types of carcinoma in women and has high morbidity and mortality rates worldwide. Recurrent and metastatic disease remains difficult to treat. Receptor interacting protein kinase 1 (RIPK1) is a key molecule in mediating apoptosis, necroptosis, and inflammatory pathways downstream of death receptors and pattern recognition receptors. This study sought to explore the clinicopathological and prognosis significance of RIPK1 expression in cervical squamous cell carcinoma (CSCC). The data of 100 CSCC patients who underwent curative surgery from 2019 to 2020 were retrospectively included in this study. We collected the clinicopathological information of the patients and detected RIPK1 protein expression using immunohistochemistry. The Chi-square test and a 1-way analysis of variance were used to make comparisons between groups stratified by RIPK1 expression. A Pearson linear correlation analysis was used to evaluate the association between RIPK1 expression and the clinicopathological characteristics of the patients. A Cox regression analysis and Kaplan-Meier curves were used to analyze overall survival (OS) and progression-free survival (PFS). A multivariable regression analysis was conducted to identify the risk factors for an impaired prognosis in CSCC. RIPK1 was found to be overexpressed in the CSCC tissues. RIPK1 expression was significantly associated with age, the preoperative serum squamous cell carcinoma antigen (SCC-Ag) level, lymph node metastasis, invasion depth, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, PFS, and OS (P<0.05). The PFS and OS differed significantly among patients with RIPK1 expression (P<0.05). The multivariate analysis showed that RIPK1 was not independent risk factors for PFS and OS in CSCC patients (P>0.05). The expression of RIPK1 was significantly upregulated in CSCC and was associated with the clinicopathological features of CSCC. RIPK1 might serve as a novel marker that can be used to predict the prognosis of CSCC patients and as a biological target for the treatment of CSCC.

Does concomitant hysterectomy impact menopausal symptoms in premenopausal BRCA1/2 pathogenic carriers undergoing risk reducing salpingo-oophorectomy?

Prevention of high-grade serous carcinoma in women with a pathogenic variant in the BRCA1/2 genes includes prophylactic bilateral salpingo-oophorectomy (PBSO). There is debate on whether concomitant hysterectomy should be offered, with benefits including decreased risk of endometrial carcinoma and the option to use estrogen-alone menopausal hormone therapy (MHT), which is thought to be associated with better menopause-specific quality of life and lower breast cancer risk. The objective is to determine if BRCA1/2 mutation carriers undergoing premenopausal PBSO with concomitant hysterectomy have improved MENQOL compared with those women with an intact uterus.

Comparison of T1/2 Tongue Carcinoma with or without Radial Forearm Flap Reconstruction Regarding Post-Therapeutic Function, Survival, and Gender.

Flap reconstruction is commonly used in advanced tongue carcinoma in order to compensate for the loss of tongue tissue and function. Surprisingly, a large number of reconstructed early-stage tongue cancer can be found. Survival or functional benefits in these cases remain unclear. A retrospective data analysis of 384 surgically treated tongue carcinoma patients was conducted aiming to find epidemiologic and survival differences between patients with (n = 158) or without flap reconstruction (n = 226). A prospective functional analysis was performed on 55 early-stage tongue cancer patients, 33 without and 22 with radial-forearm flap reconstruction, focusing on post-therapeutic swallowing function as the primary endpoint, speech as the secondary endpoint, xerostomia, quality of life, and mouth opening. Consistent with the current literature, we demonstrated the significantly more frequent use of flap grafts in advanced tongue carcinomas. For the first time, we depicted a higher female ratio in the reconstructed group (p = 0.02). There were no significant differences in survival or functional outcomes between the groups. The none-reconstructed group showed more frequent use of adjuvant C/RT despite presenting fewer N+ stages. The higher female ratio in the reconstruction group is plausible due to the anatomically smaller oral cavity and relatively larger carcinoma in women. A higher presence of close margins in the none-reconstruction group may explain the more frequent use of adjuvant C/RT. Since we found no survival or functional differences between the groups, we propose a critical approach toward flap reconstruction in T1/2 tongue carcinoma. At the same time, proportional aspects and adequate resection margins should be taken into account.

Human papillomavirus-associated cancer incidence by disaggregated Asian American, Native Hawaiian, and other Pacific Islander ethnicity.

Asian Americans and Native Hawaiians and other Pacific Islanders have suboptimal human papillomavirus (HPV) vaccination and cancer screening rates. Asian Americans and NHPIs are often aggregated, masking disparities characterized by varying colonization and immigration patterns and cultural and religious beliefs between populations and ethnicities. We examined the incidence of HPV-associated cancers across disaggregated Asian American and NHPI ethnicities. Using the Surveillance, Epidemiology, and End Results Detailed Asian/Pacific Islander database, we calculated 1990 to 2014 sex-specific, age-standardized HPV-associated cancer incidence of cervical carcinoma, oropharyngeal squamous cell carcinoma (SCC), vulvar SCC, vaginal SCC, anal SCC, and penile SCC by ethnicity: Asian Indian and Pakistani, Chinese, Filipino, Japanese, Kampuchean, Korean, Laotian, Native Hawaiian, other Pacific Islander, and Vietnamese. Trends by calendar period (1990 to 1996, 1997 to 2002, 2003 to 2008, 2009 to 2014) were estimated using Joinpoint regression. The most common HPV-associated cancer was cervical carcinoma in women and oropharyngeal SCC in men. During 1990 to 2014, cervical carcinoma incidence per 100 000 ranged from 4.5 (Asian Indian and Pakistani) to 20.7 (Laotian). Cervical carcinoma incidence only statistically significantly declined for Asian Indian and Pakistani, Filipino, Korean, Laotian, and Vietnamese women (range = 19.9% to 44.1% decline per period). Among men, oropharyngeal SCC incidence per 100 000 ranged from 1.1 (Chinese) to 5.1 (Native Hawaiian). Oropharyngeal SCC incidence only statistically significantly increased (31.0% increase per period) for Japanese men. Heterogeneity across ethnicities were observed for other cancer sites. HPV-associated cancer incidence varied widely between Asian Americans and NHPIs and by ethnicity, underscoring the need for improved data capture of ethnic groups in research and more tailored interventions to better address health disparities between Asian American and NHPI populations.

Immunoprofiling of BRAFV600E in Precancerous and Cancerous Lesions of Breast by Immunohistochemistry and its Association with Clinicopathological Features

Introduction: Breast carcinoma in women is one of the few causes of morbidity and mortality which concerns the health providers. The molecular basis of breast carcinoma in recent years has provided the insight for the genesis of carcinoma, the prognostic, and predictive utility for targeted therapies. Aim: A study has been planned with the aim to know immunoprofiling of BRAFV600E in precancerous and cancerous lesions of the breast by Immunohistochemistry (IHC) and its association with clinicopathological features. Materials and Methods: The subjects will be divided in two groups of 45 cases each: Precancerous breast lesions; and Invasive ductal carcinoma. The tissue of these cases will undergo IHC of BRAFV600E. The comparison of expression is to be brought out and the clinicopathological association of immunoexpression of BRAFV600E will also be studied.