Cancer Outcomes Research Articles

Spatially preserved multi-region transcriptomic subtyping and biomarkers of chemoimmunotherapy outcome in extensive-stage small cell lung cancer.

Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. We analyzed tumor samples from 58 ES-SCLC patients enrolled in two multicenter single-arm phase IIIb studies evaluating front-line chemoimmunotherapy in Spain: n=32 from the IMfirst trial, and n=26 from the CANTABRICO trial. We utilized the GeoMxTM DSP system to perform multi-region transcriptomic analysis. For subtype classification, we performed hierarchical clustering using the relative expression of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y). Subtype distribution was similar between both cohorts, except for SCLC-P, not identified in the CANTABRICO_DSP cohort. A total of 44% of the patients in both cohorts had tumors with multiple co-existing transcriptional subtypes. Transcriptional subtypes or subtype heterogeneity were not associated with outcomes. Most potential targets did not show subtype-specific expression. Consistently in both cohorts, tumors from patients with long-term benefit (time to progression ³12 months) contained an IFNg-dominated mRNA profile, including enhanced capacity for antigen presentation. Hypoxia and glycolytic pathways were associated with resistance to chemoimmunotherapy. This work suggests that intratumoral heterogeneity, inconsistent association with outcome, and unclear subtype-specific target expression might be significant challenges for subtype-based precision oncology in SCLC. Pre-existing IFNg-driven immunity and mitochondrial metabolism seem correlates of long-term efficacy in this study, although the absence of a chemotherapy control arm precludes concluding that these are predictive features specific for immunotherapy.

Transforming Rectal Cancer Detection: The Role of Emerging Technologies

Rectal cancer is a common and serious disease. Early diagnosis of rectal cancer can improve the effectiveness of treatment and the prognosis of the disease. Modern medical technology not only provides doctors with a series of methods to diagnose rectal cancer, but also brings more and more new means. This is a very exciting area of research, and many scientists and doctors are pushing the boundaries of knowledge and working to develop real, tangible inventions and techniques that can improve clinical outcomes for patients. We hope that by providing an indepth analysis of the current and potential future impact of these emerging technologies on rectal cancer detection, the article will serve to inform both the scientific community and the public about the revolutionary leaps forward that are being made in this area. These technologies, as well as the new diagnostic and therapeutic approaches that they facilitate, have the potential not only to greatly improve the management and outcome of rectal cancer, but also to substantially enhance the patient experience and indeed reshape the entire patient journey. The future directions and implications of these new technologies will also be explored, including their potential of changing the outcomes of rectal cancer, the ethical consideration in their implementation, as well as the challenges and barriers to their wide adoption.

Assessing the value of incorporating a polygenic risk score with non-genetic factors for predicting breast cancer diagnosis in the UK Biobank.

Previous studies have demonstrated that incorporating a polygenic risk score (PRS) to existing risk prediction models for breast cancer improves model fit, but to determine its clinical utility the impact on risk categorisation needs to be established. We add a PRS to two well-established models and quantify the difference in classification using the net reclassification improvement (NRI). We analysed data from 126,490 post-menopausal women of "White British" ancestry, aged 40-69 years at baseline from the UK Biobank prospective cohort. The breast cancer outcome was derived from linked registry data and hospital records. We combined a PRS for breast cancer with 10-year risk scores from the Tyrer-Cuzick and Gail models, and compared these to the risk scores from the models using phenotypic variables alone. We report metrics of discrimination and classification, and consider the importance of the risk threshold selected. The Harrell's C statistic of the 10-year risk from the Tyrer-Cuzick and Gail models was 0.57 and 0.54, respectively, increasing to 0.67 when the PRS was included. Inclusion of the PRS gave a positive NRI for cases in both models (0.080 (95% confidence interval: 0.053, 0.104) and 0.051 (95% CI: 0.030, 0.073), respectively), with negligible impact on controls. The addition of a PRS for breast cancer to the well-established Tyrer-Cuzick and Gail models provides a substantial improvement in the prediction accuracy and risk stratification. These findings could have important implications for the ongoing discussion about the value of PRS in risk prediction models and screening.

N0 neck trial: Does intensification of follow-up (Ultrasound + Physical Examination) influence outcomes in early-stage oral cancer?

Aim of the studyWe previously reported a survival benefit of elective neck dissection (END) over therapeutic neck dissection (TND) in patients with clinically node-negative early-stage oral cancer. We now report the results of the second question in the same study addressing the impact of adding neck ultrasound to physical examination during follow-up on outcomes. MethodsPatients with lateralized T1/T2 oral squamous cell carcinoma (SCC) were randomized to END or TND and to follow-up with physical-examination plus neck ultrasound (PE+US) versus physical-examination (PE). The primary endpoint was overall survival (OS). ResultsBetween January 2004 and June 2014, 596 patients were enrolled. This is an intention to treat analysis of 592 analysable patients, of whom 295 were allocated to PE+US and 297 to PE with a median follow-up of 77.47 months (interquartile range (IQR) 54.51–126.48). There was no significant difference (unadjusted hazard ratio [HR], 0.92, 95% CI, 0.71–1.20, p = 0.54) in 5-year OS between PE+US (70.8%, 95% CI, 65.51−76.09) and PE (67.3%, 95% CI, 61.81−72.79). Among 131 patients with neck node relapse as the first event, the median time to relapse detection was 4.85 (IQR 2.33–9.60) and 7.62 (IQR 3.22–9.86) months in PE+US and PE arms, respectively. The N stage in the PE+US arm was N1 33.8%, N2a 7.4%, N2b/c 44.1% and N3 14.7% while in PE was N1 28.6%, N2a 9.5%, N2b/c 39.7%, N3 20.6% and unknown 1.6%. ConclusionAdding neck ultrasound to physical examination during follow-up detects nodal relapses earlier but does not improve overall survival.

Novel radiation and targeted therapy combinations for improving rectal cancer outcomes.

Neoadjuvant radiotherapy (RT) is commonly used as standard treatment for rectal cancer. However, response rates are variable and survival outcomes remain poor, highlighting the need to develop new therapeutic strategies. Research is focused on identifying novel methods for sensitising rectal tumours to RT to enhance responses and improve patient outcomes. This can be achieved through harnessing tumour promoting effects of radiation or preventing development of radio-resistance in cancer cells. Many of the approaches being investigated involve targeting the recently published new dimensions of cancer hallmarks. This review article will discuss key radiation and targeted therapy combination strategies being investigated in the rectal cancer setting, with a focus on exploitation of mechanisms which target the hallmarks of cancer.

Additional prognostic value of polymorphisms within the 3'-untranslated region of programmed cell death pathway genes in early-stage breast cancer.

The programmedcell death (PCD) pathway plays an important role in restricting cancer cell survival and proliferation. However, limited studies have investigated the association between genetic variants in the 3'-untranslated region of the PCD pathway genes and breast cancer outcomes. In this study, we genotyped 28 potentially functional single nucleotide polymorphisms (SNPs)in 23 PCD pathwaygenesin 1,177patients withearly-stagebreast cancer(EBC)from a Han Chinese population.The median follow-up period was 174 months. Among all the candidateSNPs, fourindependent SNPs (rs4900321 and rs7150025 in ATG2B, rs6753785 in BCL2L11, and rs2213181 in c-Kit) were associated with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer-specific survival (BCSS)and overall survival (OS), respectively. Further combined genotypes of these four SNPs revealed that the survival decreasedas the number of unfavorable genotypes increased(Ptrend= 1.0 × 10-6, 8.5 × 10-8, 3.6 × 10-4, and 1.3 × 10-4for iDFS, DDFS, BCSS, and OS, respectively). Receiver operating characteristiccurve analysis demonstrated that incorporating unfavorable genotypes and clinicopathological variables improved the ability to predict EBC survival (P= 0.006, 0.004, 0.029, and 0.019 for iDFS, DDFS, BCSS, and OS, respectively).Additionally, rs6753785 and rs2213181 were associated with BCL2L11and c-KitmRNA expression, respectively. Our results suggest that these four SNPs may act as novel biomarkers for EBC survival, possibly by modulating the expression of the corresponding genes.

Systematic Review on the Effectiveness and Outcomes of Nivolumab Treatment Schemes in Advanced and Metastatic Cervical Cancer.

Advanced and metastatic cervical cancer remains a formidable challenge in oncology, with immune checkpoint inhibitors such as the PD-1 inhibitor nivolumab emerging as a potential therapeutic option. This systematic review rigorously assesses the effectiveness and outcomes of various nivolumab treatment regimens within this patient cohort, drawing from clinical trials and real-world evidence up to December 2023. Following a comprehensive search across PubMed, Scopus, and Embase, four studies were deemed eligible, involving a collective total of 80 patients. One preliminary trial data were excluded from the final analysis, as well as four other proceedings and abstracts on the efficacy and safety of nivolumab on advanced cervical cancer. The patients' average age across these studies was 48 years, with an average of 38% having an Eastern Cooperative Oncology Group (ECOG) performance status of 1. Notably, 64% of all patients were positive for high-risk HPV, and 71% exhibited PD-L1 positivity, indicating a substantial target population for nivolumab. The analysis revealed a pooled objective response rate (ORR) of 48%, with a disease control rate (DCR) averaging 71%. Moreover, progression-free survival (PFS) at 6 months was observed at an average rate of 50%, reflecting the significant potential of nivolumab in managing advanced stages of the disease. The review highlights the influence of PD-L1 status on response rates and underscores the enhanced outcomes associated with combination therapy approaches. By delineating the variability in treatment efficacy and pinpointing key factors affecting therapeutic response and survival, this systematic review calls for further investigations to refine nivolumab's clinical application, aiming to improve patient outcomes in advanced and metastatic cervical cancer.

Evaluation of Stages, Treatment Protocols, and Outcomes of Colorectal Cancer among West Bank Patients.

Background: Colorectal cancer (CRC) is the second most widespread cancer among Palestinian patients. As cancer care improves in hospitals across the West Bank, services like palliative care, targeted therapy, bone marrow transplantation, and individualized therapy are still limited. This study aimed to assess the CRC stages, treatment protocols, and survival rates of patients in the West Bank. Methodology: This retrospective study collected data from the medical records of Al-Najah University Hospital (NUH), which specializes in the care of cancer patients. Patients with confirmed CRC (stages I-IV) undergoing surgical or medical treatment were included in the study. Data collection was standardized by using a data collection form to gather information from the medical records included in the study. All statistical analyses were performed using SPSS (version v27), and survival was assessed using a regression analysis of the number of days from the time of diagnosis to the most recent visit against the type of treatment (e.g., surgery, chemotherapy, radiotherapy). Results: A sample of 252 patients with CRC from NUH was collected, including 143 males and 109 females aged between 27 and 86 years, with the average age being 60.6 ± 11.4 years. The sample included 183 patients (72.6%) diagnosed with colon cancer only, 29 patients (11.5%) diagnosed with rectal cancer only, and 40 patients (15.9%) diagnosed with both. Diagnosis took place at CRC stage I for 3 patients (1.2%), stage II for 33 patients (13.1%), stage III for 57 patients (22.6%), and stage IV for 159 patients (63.1%). Surgery was the most prevailing mode of treatment for 230 patients (91.3%), while 227 patients (90.1%) received chemotherapy treatment, and 38 patients (15.1%) received radiotherapy. Of the 252 patients, 40 patients (15.8%) received FOLFOX (i.e., folinic acid, fluorouracil, oxaliplatin), and 25 patients (9.9%) received FOLFIRI (i.e., folinic acid, fluorouracil, irinotecan), while the 187 remaining patients (74.2%) were treated with capecitabine, oxaliplatin, bevacizumab, cetuximab, regorafenib, cisplatin, etoposide, gemcitabine, or a combination thereof. The sample was categorized into six outcomes: (1) death, (2) cure, (3) disease progression, (4) disease recurrence, (5) under-treatment, and (6) unknown. Mortality was high, with 104 patients (41.3%) dying within a short time after diagnosis, and may have been attributable to delayed diagnosis. Surgical treatment had a positive impact on increasing the survival years, and it was significant (p = 0.033). Conclusions: A high percentage of patients were diagnosed in advanced CRC stages. The treatment modes were adopted from general international guidelines; however, the cure rates were low, and mortality was high. More studies need to be undertaken to investigate the actual application of chemotherapy protocols, and survival would benefit from the involvement of clinical pharmacists in the chemotherapy protocol selection, dosing, frequency, and follow-up. The present study advocates for greater public awareness of CRC and attests to the merits of screening by primary care professionals, which can help to avoid this serious illness and to promote a better prognosis.

Individualized center-based analysis of urinary and sexual functional outcome after radical prostatectomy based on the prostate cancer outcome study: a post hoc pathway to patient outcome measurement analysis for quality improvement.

We evaluate differences of patient-reported outcome measurements (PROM) based urinary continence and sexual function 12 months after radical prostatectomy (RPE) based on perioperative, surgical, and patient-specific characteristics in a large European academic urology center. All men enrolled in the Prostate Cancer Outcome Study (PCO) study who were treated with RPE between 2017 and 2021 completed EPIC-26 information surveys before and 12 months after RPE. Survey data were linked to clinical data of our institution. Logistic regression analyses were performed to examine the correlation between individual surgeons, patient characteristics, patient clinical data, and their urinary continence and sexual function. In total, data of 429 men were analyzed: unstratified mean (SD) EPIC-26 domain score for urinary function decreased from 93.3 (0.7) to 60.4 (1.5) one year after RPE, respectively for sexual function from 64.95 (1.6) to 23.24 (1.1). Patients with preoperative adequate urinary function (EPIC-26 score > 80) reported significantly different mean urinary function scores between 53.35 (28.88) and 66.25 (25.15), p= 0.001, stratified by surgeons experience. On binary logistic regression analyses, only nerve sparing techniques (OR: 1,83, 95% CI: 1.01;3.21; p = 0.045) and low body mass index (OR: 0.91, CI: 0.85;0.99, p= 0.032) predicted adequate postoperative urinary function. The results show how using provider-specific data from a larger cohort study enables to develop institution-specific analysis for functional outcomes after RPE. These models can be used for internal quality improvement as well as enhanced and provider-specific patient communication and shared decision making.

Subcellular expression of MTA1, HIF1A and p53 in primary tumor predicts aggressive triple negative breast cancers: a meta-analysis based study.

The prevalence of TNBC in India is higher compared to western countries. There is a multitude of biomarkers associated with different clinical outcomes of TNBC with contradictory reports. Identification of a set of specific biomarkers from the very many number of proteins reported in the literature to predict prognosis of TNBC is an urgent clinical need. A systematic review of key molecular biomarkers in cohort studies that have been investigated for their role in breast cancer prognosis was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. A meta-analysis was used to evaluate their pooled hazard ratio (HR) and the corresponding 95% confidence interval (95% CI) statistically. Immunohistochemical characterization of the meta-analyzed markers were performed in a cohort of 200 retrospective TNBC and 100 non TNBC patient tissues. Kaplan-Meier plot were used to evaluate disease free survival (DFS), and overall survival (OS). Cox regression models were used to evaluate predictors of DFS and OS. Using a meta-analytical approach, we consolidated the biomarker signatures associated with survival outcomes in breast cancers. The promising markers that emerged for the prediction of DFS and OS included E-Cadherin, Survivin, p53, MTA1, HIF1A, CD133, Vimentin and CK5/6. Evaluation of these markers in tumor tissue revealed that subcellular localization of p53, MTA1 and HIF1A had a significant association in predicting TNBC prognosis. Kaplan Meier plot revealed that p53 (OS p = 0.007, DFS p = 0.004), HIF 1A (OS p = 0.054, DFS p = 0.009) and MTA1 (OS p = 0.043, DFS = p = 0.001) expression in the primary tumor tissue were found to be significantly correlated with poor OS and DFS, whereas expression of Survivin (DFS p = 0.024) and E Cadherin (DFS p = 0.027) correlated with DFS alone in TNBC. Univariate analysis revealed that p53, HIF1A and MTA1 could be independent prognostic markers. Our study suggests cytoplasmic over expression of HIF1A, nuclear over expression of MTA1 and mutated p53 in the primary tumor tissue of TNBC have significance as markers predicting survival of TNBC patients.

Implementation and Evaluation of a Breast Cancer Disease Model Using Real-World Claims Data in Germany from 2010 to 2020.

Breast cancer is the leading cause of cancer-related mortality among women in Germany and worldwide. This retrospective claims data analysis utilizing data from AOK Baden-Wuerttemberg, a major statutory German health insurance provider, aimed to construct and assess a real-world data breast cancer disease model. The study included 27,869 female breast cancer patients and 55,738 age-matched controls, analyzing data from 2010 to 2020. Three distinct breast cancer stages were analyzed: Stage A (early breast cancer without lymph node involvement), Stage B (early breast cancer with lymph node involvement), and Stage C (primary distant metastatic breast cancer). Tumor subtypes were estimated based on the prescription of antihormonal or HER2-targeted therapy. The study established that 77.9% of patients had HR+ breast cancer and 9.8% HER2+; HR+/HER2- was the most common subtype (70.9%). Overall survival (OS) analysis demonstrated significantly lower survival rates for stages B and C than for controls, with 5-year OS rates ranging from 79.3% for stage B to 35.4% for stage C. OS rates were further stratified by tumor subtype and stage, revealing varying prognoses. Distant recurrence-free survival (DRFS) analysis showed higher recurrence rates in stage B than in stage A, with HR-/HER2- displaying the worst DRFS. This study, the first to model breast cancer subtypes, stages, and outcomes using German claims data, provides valuable insights into real-world breast cancer epidemiology and demonstrates that this breast cancer disease model has the potential to be representative of treatment outcomes.

Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer.

Understanding the role of the tumour microenvironment (TME) in lung cancer is critical to improving patient outcome. We identified four histology-independent archetype TMEs in treatment-naive early-stage lung cancer using imaging mass cytometry in the TRACERx study (n=81 patients/198 samples/2.3million cells). In immune-hot adenocarcinomas, spatial niches of T cells and macrophages increased with clonal neoantigen burden, whereas such an increase was observed for niches of plasma and B cells in immune-excluded squamous cell carcinomas (LUSC). Immune-low TMEs were associated with fibroblast barriers to immune infiltration. The fourth archetype, characterised by sparse lymphocytes and high tumour-associated neutrophil (TAN) infiltration, had tumour cells spatially separated from vasculature and exhibited low spatial intratumour heterogeneity. TAN-High LUSC had frequent PIK3CA mutations. TAN-High tumours harboured recently expanded and metastasis-seeding subclones and had a shorter disease-free survival independent of stage. These findings delineate genomic, immune and physical barriers to immune surveillance and implicate neutrophil-rich TMEs in metastasis.

Plasma IL-1 and IL-6 Family Cytokines with Soluble Receptor Levels at Diagnosis in Head and Neck Squamous Cell Carcinoma: High Levels Predict Decreased Five-Year Disease-Specific and Overall Survival.

Activation of the acute-phase cascade (APC) has been correlated with outcomes in various cancers, including head and neck squamous cell carcinoma (HNSCC). Primary drivers of the APC are the cytokines within the interleukin-6 (IL-6) and IL-1 families. Plasma levels of IL-6 family cytokines/soluble receptors (IL-6, IL-27, IL-31, OSM, CNTF, soluble (s-)gp130, s-IL-6Rα) and IL-1 family members (IL-1RA, s-IL-33Rα) were determined at diagnosis for 87 human papillomavirus (HPV)-negative (-) HNSCC patients. We then studied the 5-year Disease-Specific Survival (DSS) and Overall Survival (OS). Increased plasma levels of IL-6 (p < 0.001/p < 0.001) (DSS/OS), IL-31 (p = 0.044/p = 0.07), IL-1RA (p = 0.004/p = 0.035), soluble (s)-IL-6Rα p = 0.022/p = 0.035), and s-gp130 (p = 0.007/p = 0.003) at diagnosis were predictors of both OS and DSS from HPV(-) HNSCC patients. The cytokine DSS/OS predictions were associated with TNM stage and smoking history, whereas the soluble receptors IL-6Rα, gp130, and IL33Rα more uniquely predicted DSS/OS. Clinically, IL-6 levels above 2.5 pg/mL yielded 75% specificity and 70% sensitivity for DSS. In conclusion, high plasma levels of IL-6, IL-31, and IL-1RA, as well as the soluble receptors IL-6Rα, gp130, and IL33Rα, predicted clinical outcome. This shows their potential as candidates for both general therapy and immune therapy stratification, as well as being future platforms for the development of new immunotherapy.

Surgical outcomes for non-small cell lung cancer in younger adults: A population-based study.

The surgical outcomes for younger patients with non-small cell lung cancer (NSCLC) remain uncertain. The aim of this study was to investigate the clinical features long-term survival outcomes in younger individuals with NSCLC following surgery. We queried the Surveillance, Epidemiology, and End Results database from 2010 to 2017, selecting all pathologically confirmed NSCLC cases that underwent cancer-directed surgery. Younger patients were defined as those aged 18-50 years, while older patients were 51-80 years. Propensity score matching (PSM) was implemented to mitigate selection bias. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared using the Kaplan-Meier method. Among the 33 586 treated surgically patients, 2223 (6.6%) were young. Compared to the older group, younger patients had a higher frequency of female gender, non-white ethnicity, carcinoid tumors, stage IV disease, pneumonectomy, and postoperative adjuvant therapies. The 5-year OS rates were significantly higher for younger patients (79.3% vs. 62.0%; p < 0.001), as were the 5-year LCSS rates (82.4% vs. 71.8%; p < 0.001). Post-PSM, younger patients consistently demonstrated significantly better OS and LCSS. Further stage-specific analysis revealed significantly improved 5-year OS rates at each stage and superior 5-year LCSS for stages I-II among younger patients. However, there was no statistically significant difference in LCSS for stages III-IV. Overall, younger patients with NSCLC treated surgically exhibit superior OS and LCSS compared to their older counterparts, although no statistically significant difference in LCSS for stages III-IV was observed between the two age groups.

Impact of ABCB1 and ABCG2 Transporter in Outcome of Gallbladder Cancer

BackgroundGallbladder cancer (GBC) is a biologically aggressive malignancy requiring appropriate biomarkers to improve its outcome. Role of ABC transporters (ABCB1 and ABCG2) has been linked to cancer aggressiveness, tumorigenesis and multidrug resistance. Herein, we studied the prognostic implication of ABCB1 and ABCG2 in GBC. MethodsFresh tissue (tumour & normal) samples collected from 54 patients who underwent R0 resection, were analysed for mRNA and protein expression of ABCB1 and ABCG2 by quantitative Real-Time PCR and western blotting respectively in this prospective study. The molecular findings were correlated with clinical-pathological parameters using χ2 and fisher exact test. The molecular changes in ABCB1 and ABCG2 was analysed for predicting overall survival (OS), disease free survival (DFS) and response to chemotherapy using Kaplan Meier log rank test and Cox regression multivariate analysis. ResultsThe mean age of the cohort was 50 ±13.2 with 26 (48.1%) patients had early stage gallbladder cancer (GBC). Overexpression of ABCB1 and ABCG2 was noted in 32/54(59%) and 40/54 (74%) cases respectively. The protein expression of ABCB1(P-glycoprotein) and ABCG2 (BCRP) was higher in 27/54 (50%) and 37/54 (59%) cases respectively. The mean OS and DFS was 20.7 ±11.5 and 19.3 ± 12.2 months at median follow up 24 months. The TNM stage, lymph node metastasis, and presence of gallstone were significant factors for predicting OS and DFS on multivariate analysis. Both ABCB1 and ABCG2 did not show any significant correlation with OS and DFS with similar incidence of late death and recurrence among over-expression and down-expression. Sub- group comparison suggests that change in expression pattern of ABCB1 and ABCG2 may not affect response to chemotherapy in GBC. ConclusionAltered expression of ABCB1 and ABCG2 may not be a useful prognostic marker for survival or response to chemotherapy in GBC. Presently, histo-pathological characteristics and associated gallstones are the important predictors for survival and recurrence in GBC.

Distinct ER and PR expression patterns significantly affect the clinical outcomes of early HER2-positive breast cancer: A real-world analysis of 871 patients treated with neoadjuvant therapy

IntroductionThe impact of distinct estrogen receptor (ER) and progesterone receptor (PR) expression patterns on tumor behavior and treatment outcomes within HER2-positive breast cancer is not fully explored. This study aimed to comprehensively examine the clinical differences among patients with HER2-positive breast cancer harboring distinct ER and PR expression patterns in the neoadjuvant setting. MethodsThis retrospective analysis included 871 HER2-positive breast patients treated with neoadjuvant therapy at our hospital between 2011 and 2022. Comparisons were performed across the three hormone receptor (HR)-specific subtypes, namely the ER-negative/PR-negative/HER2-positive (ER-/PR-/HER2+), the single HR-positive (HR+)/HER2+, and the triple-positive breast cancer (TPBC) subtypes. ResultsOf 871 patients, 21.0% had ER-/PR-/HER2+ tumors, 33.6% had single HR+/HER2+ disease, and 45.4% had TPBC. Individuals with single HR+/HER2+ tumors and TPBC cases demonstrated significantly lower pathological complete response (pCR) rates compared to those with ER-/PR-/HER2+ tumors (36.9% vs. 24.3% vs. 49.2%, p < 0.001). Multivariate analysis confirmed TPBC as significantly associated with decreased pCR likelihood (OR = 0.42, 95%CI 0.28–0.63, p < 0.001). Survival outcomes, including disease-free survival (DFS) and overall survival (OS), showed no significant differences across HR-specific subtypes in the overall patient population. However, within patients without anti-HER2 therapy, TPBC was linked to improved DFS and a trend towards better OS. ConclusionsHER2-positive breast cancer exhibited three distinct HR-specific subtypes with varying clinical manifestations and treatment responses. These findings suggest personalized treatment strategies considering ER and PR expression patterns, emphasizing the need for further investigations to unravel molecular traits underlying HER2-positive breast cancer with distinct HR expression patterns.

Atherosclerosis and the Bidirectional Relationship between Cancer and Cardiovascular Disease: From Bench to Bedside-Part 1.

Atherosclerosis, a complex metabolic-immune disease characterized by chronic inflammation driven by the buildup of lipid-rich plaques within arterial walls, has emerged as a pivotal factor in the intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked by shared risk factors and pathophysiological mechanisms, underscores the need for a comprehensive understanding of how these two formidable health challenges intersect and influence each other. Cancer and its treatments can contribute to the progression of atherosclerosis, while atherosclerosis, with its inflammatory microenvironment, can exert profound effects on cancer development and outcomes. Both cancer and cardiovascular disease involve intricate interactions between general and personal exposomes. In this review, we aim to summarize the state of the art of translational data and try to show how oncologic studies on cardiotoxicity can broaden our knowledge of crucial pathways in cardiovascular biology and exert a positive impact on precision cardiology and cardio-oncology.

Social capital in the management of breast cancer in Lagos, Nigeria.

Breast cancer is the most common cancer in women worldwide, necessitating substantial social support during diagnosis and treatment. This study examines the role of social capital in breast cancer management, focusing on the experiences of patients. The objective of the study was to explore the role of social capital in breast cancer management among women living with breast cancer in Lagos, Nigeria. Using a qualitative design, the study recruited 23 women with breast cancer receiving treatment at a teaching hospital in Lagos, Nigeria. Data were content analyzed to identify themes related to social capital. The study found that social capital, crucial for breast cancer patients' emotional and instrumental support, stems from various sources such as relatives, immediate family, spouses, places of worship, friends, and neighbors. Effective coping and management of the condition were facilitated through this support network. However, assistance from places of worship, friends, and neighbors was only accessible to those who openly acknowledged their health conditions and had established connections with these social groups. Relationships led to support only when there was a disclosure of the health condition. (1) This finding reinforces the importance of integrating social support mechanisms including family, friends, and community networks into breast cancer management programs. (2) The study identifies diverse sources of social capital, including relatives, family, spouses, places of worship, friends, and neighbors, stressing the need for tailored support networks. (3) Research reveals the link between health condition disclosure and support accessibility from groups like places of worship and friends, and it emphasizes creating stigma-free environments for patients to disclose health status comfortably. (4) The study highlights family involvement in breast cancer management as crucial for effective coping. Healthcare professionals should prioritize interventions strengthening family support systems. (5) Findings of stress community support for better breast cancer outcomes, advocating for initiatives like support groups and awareness campaigns to boost social capital and aid affected individuals. The study emphasizes the significance of involving family members in the breast cancer management process and highlights the need for support systems within families and communities to facilitate better outcomes for breast cancer patients.

Lifetime Exposure to Cigarette Smoke, B Cell Tumor Immune Infiltration, and Immunoglobulin Abundance in Ovarian Tumors.

Cigarette smoke exposure has been linked to systemic immune dysfunction, including for B cell and immunoglobulin (Ig) production, and poor outcomes in ovarian cancer patients. No study has evaluated the impact of smoke exposure across the lifecourse on B cell infiltration and Ig abundance in ovarian tumors. We measured markers of B and plasma cells and Ig isotypes using multiplex immunofluorescence on 395 ovarian cancer tumors in the Nurses' Health Study (NHS)/NHSII. We conducted beta-binomial analyses evaluating odds ratios (OR) and 95% confidence intervals (CI) for positivity of immune markers by cigarette exposure among cases and Cox proportional hazards models to evaluate hazard ratios (HR) and 95%CI for developing tumors with low (<median) or high (≥median) immune cell/Ig percentage. There were no associations between smoke exposure and B cell or IgM infiltration in ovarian tumors. Among cases, we observed higher odds of IgA+ among ever smokers (OR: 1.54, 95%CI: 1.14, 2.07) and ever smokers with no parental smoke exposure (OR: 2.03, 95%CI: 1.18, 3.49) versus never smokers. Women with parental cigarette smoke exposure versus not had higher risk of developing ovarian cancer with low IgG+ (HR: 1.51, 95%CI: 1.10, 2.09), while ever versus never smokers had a lower risk (HR: 0.74, 95%CI: 0.56,0.99). Ever smoking was associated with increased odds of IgA in ovarian tumors. IgA has been associated with improved ovarian cancer outcomes, suggesting that although smoking is associated with poor outcomes in ovarian cancer patients, it may lead to improved tumor immunogenicity.

Optimal timing for the first cystoscopic follow-up using time-to-treatment initiation analysis of oncologic outcomes in primary non-muscle invasive bladder cancer

Various guidelines recommend the first follow-up cystoscopy at 3 months; however, no data exist on the optimal timing for initial follow-up cystoscopy. We tried to provide evidence on the timing of the first cystoscopy after the initial transurethral resection of bladder tumor (TUR-BT) for patients with non-muscle invasive bladder cancer (NMIBC) using big data. This was a retrospective National Health Insurance Service database analysis. The following outcomes were considered: recurrence, progression, cancer-specific mortality, and all-cause mortality. Exposure was the time-to-treatment initiation (TTI), a continuous variable representing the time to the first cystoscopy from the first TUR-BT within 1 year. Additionally, we categorized TTI (TTIc) into five levels: < 2, 2–4, 4–6, 6–8, and 8–12 months. A landmark time of 1 year after the initial TUR-BT was described to address immortal-time bias. We identified the optimal time for the first cystoscopy using Cox regression models with and without restricted cubic splines (RCS) for TTI and TTIc, respectively. Among 26,660 patients, 16,880 (63.3%) underwent cystoscopy within 2–4 months. A U-shaped trend of the lowest risks at TTI was observed in the 2–4 months group for progression, cancer-specific mortality, and all-cause mortality. TTI within 0–2 months had a higher risk of progression (aHR 1.36; 95% confidence intervals [CI] 1.15–1.60; p < 0.001) and cancer-specific mortality (aHR 1.29; 95% CI 1.05–1.58; p = 0.010). Similarly, TTI within 8–12 months had a higher risk of progression (aHR 2.09; 95% CI 1.67–2.63; p < 0.001) and cancer-specific mortality (aHR 1.96; 95% CI 1.48–2.60; p < 0.001). Based on the RCS models, the risks of progression, cancer-specific mortality, and all-cause mortality were lowest at TTI of 4 months. The timing of the first cystoscopy follow-up was associated with oncologic prognosis. In our model, undergoing cystoscopy at 4 months has shown the best outcomes in clinical course. Therefore, patients who do not receive cystoscopy at approximately 4 months for any reason need more careful follow-up to predict a poor clinical course.