Lung adenocarcinoma (LUAD) is the most common type of lung cancer and seriously threatens the lives of many people worldwide. The difficulty in early diagnosis of lung cancer has always been a difficulty in lung cancer treatment, and basic leucine zipper nuclear factor 1 (BLZF1) has been shown to promote the occurrence and development of various cancers. This study used 505 LUAD patients in TCGA (TCGA dataset) and 60 LUAD patients in Yunnan Cancer Hospital (Clinical dataset) as research subjects to explore the role of BLZF1 in LUAD. The study found that the expression levels of mRNA and protein of the BLZF1 gene in cancer tissues were significantly higher than those in para-cancer tissues in the TCGA dataset and clinical dataset (P < 0.001). Receiver operating characteristic (ROC) curves analysis found that the AUC value of BLZF1 was 0.759 (95% CI = 0.7049-0.8140, P < 0.0001) in the TCGA dataset, and the AUC value was 0.9985 (95% CI = 0.9954-1.0000, P < 0.0001) in the clinical dataset. Moreover, the BLZF1 gene expression level in the two data sets was significantly correlated with the patient's T stage, and survival analysis showed that high BLZF1 gene expression levels were associated with decreased recurrence-free survival (RFS) (HR = 1.510, 95% Cl = 1.095-2.083, P = 0.012) and overall survival (OS) (HR = 1.472, 95% Cl = 1.099-1.973, P = 0.010). Protein-protein interaction (PPI) and enrichment analysis showed that the BLZF1 gene was closely associated with biological processes such as Golgi function, vesicle transport and cell membrane system maintenance. The expression correlation of BLZF1 with glycolysis-related genes indicated that BLZF1 may play a role in LUAD by participating in the sugar metabolism pathway. In addition, this study downregulated the expression of BLZF1 by small interfering RNA (si-BLZF1), and downregulation of BLZF1 expression significantly inhibited the proliferation, cloning, migration and invasion of LUAD cells. Therefore, BLZF1 may be involved in the occurrence and development of lung adenocarcinoma, which can be a potential diagnostic biomarker in clinical practice.

The inhibitory effects of evodiamine on GBC cells were evaluated in vitro using a cell viability assay. Cell migration capacity was assessed via wound healing and Transwell assays. Apoptosis and cell cycle distribution were analyzed by flow cytometry and Western blotting (WB). The molecular mechanisms were investigated using Quantitative polymerase chain reaction (qPCR) and WB to quantify ZEB1 gene expression. In vivo, the anti-tumor activity of evodiamine was verified in a nude mouse model. Evodiamine significantly inhibited the proliferation of GBC cells. Flow cytometry and Western blotting revealed that evodiamine induced G2/M phase arrest and promoted apoptosis. mRNA-sequencing (mRNA-seq) demonstrated that evodiamine suppressed the transcription of ZEB1 and genes in the PI3K-Akt signaling pathway. Consistent with in vitro findings, evodiamine exhibited remarkable antitumor effects in a nude mouse model. This study confirms that evodiamine inhibits GBC cell proliferation and induces apoptosis. The mechanism involves suppression of ZEB1 expression and inactivation of the PI3K-Akt signaling pathway.

Familial clustering of testicular germ cell tumour (TGCT) is well-established, whereas the risk of non-testicular cancer among relatives remains inconsistent across studies. To evaluate the overall and site-specific cancer risk among first-degree relatives and grandparents of TGCT patients compared to cancer-free controls. We enrolled 1453 subjects from two andrology centres: 628 TGCT patients, 367 oncohaematological (OH) malignancy patients, and 458 cancer-free controls undergoing vasectomy. Family cancer history was collected through standardized questionnaires documenting cancer occurrence and type in first-degree relatives and grandparents, categorizing malignancies into 16 specific groups. Positivity for family history of cancer was significantly higher in the TGCT cohort compared with controls (p<0.001), whereas no significant increase was observed in the OH cohort. Conversely, analyses based on tumour rates (total number of cancers) revealed significantly higher tumour burden in both TGCT and OH cohorts compared to controls (p<0.001). Site-specific analysis in TGCT patients' relatives showed significantly higher risk of TGCT (OR: 6.11, 1.83-20.39), pancreas (OR: 9.05, 2.17-37.66), thyroid (OR: 6.32, 1.45-27.55), uterine (OR: 4.82, 1.08-21.44) and urinary tract cancers (OR: 3.07, 1.43-6.58). Both TGCT and OH relatives showed a significant risk for breast, gastrointestinal and lung cancer. We observed notable familial clustering of cancers, not limited to TGCT but spanning several malignancies. Many of the observed associations involve cancers within the Lynch syndrome spectrum, suggesting TGCT as a potential atypical manifestation of Lynch-associated tumorigenesis. Nonetheless, the familial aggregation may also reflect gene-environment interactions and susceptibility loci related to hormone-dependent pathways, as evidenced by the elevated risks of breast and uterine cancers in TGCT families. One of the major limitations of our study, like many others relying on familial data, is the potential for recall bias in patient-reported family histories. Our study demonstrates a significant familial cancer risk in TGCT patients, underscoring the importance of detailed family history collection and the need for further studies to clarify the contributing genetic and environmental determinants.

Decomposing educational inequalities in cancer mortality: The roles of incidence and survival in Belgium, 2004-2013.

With the rising incidence and mortality rates of cancer, there is an urgent need for effective biomarkers to predict cancer occurrence and monitor its prognosis. The red blood cell distribution width to albumin ratio (RAR), a novel inflammatory biomarker, has inconclusive associations with both cancer occurrence and prognosis. This study aims to explore the relationship between RAR and cancer incidence, as well as the prognosis of cancer survivors. we included 21,452 U.S. adults from the National Health and Nutrition Examination Survey 2005 to 2016, of whom 1910 were cancer survivors. The association between RAR and cancer incidence was assessed using weighted multivariable logistic regression. The relationship between RAR and mortality in cancer survivors was evaluated using weighted multivariable Cox proportional hazards models and sensitivity analyses. The outcomes assessed were all-cause and cancer-specific mortality. After full adjustment for confounders, no significant association was found between RAR and cancer incidence. However, each unit increase in RAR was significantly associated with increased all-cause mortality (hazard ratio 2.42, 95% confidence interval [CI]: 1.93–3.03) and cancer-specific mortality (hazard ratio 2.49, 95% CI: 1.79–3.47) in cancer survivors. This positive association was consistent across all predefined subgroups. A prognostic model incorporating RAR demonstrated moderate discriminative ability, with a C-index of 0.76 and time-dependent areas under the curve for 5- and 10-year survival of 0.77 and 0.83, respectively. RAR is an independent prognostic factor for both all-cause and cancer-specific mortality in cancer survivors, suggesting its potential utility as a prognostic biomarker. The model shows moderate accuracy, warranting external validation to confirm its clinical utility.

High-quality evidence on cancer occurrence for women who have used medically assisted reproduction (MAR) is required to guide care. To compare cancer incidence in MAR-exposed women with the general population of women. This is a population-based cohort study of Australian women. MAR treatments, pregnancies, incident cancers, and deaths were ascertained using linkage between population-based administrative health datasets and statutory registries. Women aged 18 to 55 years who used MAR from 1991 to 2018 were identified and analyzed from April to November 2024. Three MAR cohorts were created: assisted reproductive therapy (ART), intrauterine insemination with ovarian stimulation (IUI/OS), and ovulation induction using clomiphene citrate (clomiphene citrate). Cancer incidence among MAR-exposed women was compared with the age-, jurisdiction-, and calendar year-matched general population. The main outcomes were cancer standardized incidence ratios (SIRs) and rate differences. A total of 417 984 MAR-exposed women were included, with 274 676 (65.7%) having ever used ART (median [IQR] age, 34 [31-38] years; median [IQR] follow-up time, 9.42 [5.08-15.42] years), 120 739 (28.9%) having ever used IUI/OS (median [IQR] age, 34 [30-38] years; median [IQR] follow-up time, 11.67 [6.25-18.42] years), and 175 510 (42.0%) having ever used clomiphene citrate (median [IQR] age, 32 [28-36] years; median [IQR] follow-up time, 9.42 [5.42-13.58] years). The overall incidence of invasive cancer was comparable with the general population for the ART (SIR, 1.00; 95% CI, 0.98-1.02) and IUI/OS (SIR, 0.99; 95% CI, 0.97-1.02) cohorts and slightly elevated for the clomiphene citrate cohort (SIR, 1.04; 95% CI, 1.00-1.07). For all cohorts, incidence of uterine cancer (SIRs, 1.23-1.83) and in situ and invasive melanoma (SIRs, 1.07-1.15) were elevated, and incidence of cervical cancer (SIRs, 0.52-0.61) and cancer of the trachea, bronchus, and lung (SIRs, 0.62-0.70) were lower. Ovarian cancer incidence was elevated for the ART (SIR, 1.23; 95% CI, 1.10-1.37) and IUI/OS (SIR, 1.18; 95% CI, 1.01-1.37) cohorts. In situ breast cancer incidence was elevated for the ART cohort only (SIR, 1.24; 95% CI, 1.12-1.38). Incidence of invasive breast cancer was not elevated. Rate differences for invasive cancers with elevated incidence were all small (<1 to 6.51 cases per 100 000 person-years). In this cohort study of cancer incidence in women who received MAR, the overall incidence of cancer was comparable with that of the general population. The incidence of certain cancers appeared elevated; however, the excess numbers of these cancers were small, and there was reduced incidence of other cancers. Causation cannot be inferred from this descriptive evidence, but findings may guide women and their health care practitioners.

Associations of cognitive function and depression with future cancer risk in middle-aged and older adults: Findings from a National China Survey.

Obesity is closely associated with the occurrence and progression of breast cancer. While body mass index (BMI) is widely used to diagnose obesity, it has certain limitations. Subcutaneous fat thickness (SFT) also serves as an indicator of body composition. However, studies on breast SFT are scarce. This study aims to investigate the relationship between BMI, breast SFT, and ultrasound features of breast cancer, as well as their associations with tumor proliferation and invasiveness. This study retrospectively analyzed the relationship between BMI and clinical and ultrasound characteristics in 1670 patients. Among them, breast SFT was measured in 470 patients using mammography and ultrasound, and the correlation between SFT and BMI was assessed. The relationship between ultrasound-measured SFT and pathological as well as ultrasound features was also analyzed. The correlation between breast SFT, BMI, and somatic gene mutations was analyzed in 234 patients. Patients with BMI ≥24 kg/m2 exhibited more malignant ultrasound features. SFT measured by mammography was correlated with SFT measured by ultrasound (r = 0.565, p < .001). Both BMI and SFT measured via mammography (r = 0.578, p < .001) and ultrasound (r = 0.485, p < .001) showed significant correlations. Breast SFT varied significantly among tumors with different shapes (p = .025), boundaries (p < .001), and posterior echo features (p < .001). The area under the curve (AUC) for breast SFT predicting irregular shape, halo, and posterior shadowing was 0.605, 0.666, and 0.632, respectively, with cutoff values of 8.65, 8.35, and 8.35 mm. Patients with breast SFT ≥8.6 mm demonstrated significantly elevated Ki67 levels (p = .004). No differences in somatic mutation frequencies were found at a threshold of 8.60 mm for fat thickness or at a BMI of 24 kg/m2. However, at BMI ≥22 kg/m2, mutation frequencies were higher. BMI and breast SFT are associated with malignant ultrasound features. While both have diagnostic value, BMI is more reliable than fat thickness for predicting cancer proliferation and invasion, with a BMI threshold of 22 kg/m2 offering higher diagnostic value than 24 kg/m2.

Circadian rhythm: An emerging force for colorectal cancer treatment.

BackgroundNon-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality with limited treatment efficacy. Small nucleolar RNAs (snoRNAs) have emerged as potential key players in tumorigenesis, but their roles in NSCLC are largely unexplored. Our previous study identified SCARNA20 as significantly downregulated in NSCLC tissues, suggesting a potential tumor-suppressive function. Thus, in order to further explore the role of SCARNA20 in NSCLC, we conducted this study to verify its function.MethodsThe biological functions of SCARNA20 were investigated in vitro using NSCLC cell lines (A549, H1299, H1437). Experiments included Cell Counting Kit-8 (CCK-8) and colony formation assays for proliferation, flow cytometry for apoptosis and cell cycle analysis, and Transwell and wound healing assays for migration and invasion. A subcutaneous xenograft mouse model was established using A549 cells overexpressing SCARNA20 to assess its impact on tumor growth in vivo. Tumor tissues were analyzed via hematoxylin and eosin (H&E) and immunohistochemical staining (Ki-67, Caspase-3). Transcriptome sequencing and bioinformatics analysis were performed to explore underlying mechanisms.ResultsOverexpression of SCARNA20 significantly inhibited NSCLC cell proliferation, colony formation, migration, and invasion in vitro. It also promoted cell apoptosis and induced cell cycle arrest, primarily at the G0/G1 phase. In the mouse xenograft model, SCARNA20 overexpression markedly suppressed tumor growth, reduced tumor weight, decreased Ki-67 expression (proliferation marker), and increased Caspase-3 expression (apoptosis marker). Transcriptome analysis revealed 2604 differentially expressed genes following SCARNA20 overexpression, which were enriched in pathways such as cytokine-cytokine receptor interaction, MAPK signaling, and TNF signaling.ConclusionsSCARNA20 acts as a tumor suppressor in NSCLC, inhibiting malignant phenotypes including cell proliferation, migration, and invasion, both in vitro and in vivo. Its mechanisms may involve promoting apoptosis, inducing cell cycle arrest, and modulating critical cancer-related pathways. SCARNA20 represents a potential novel therapeutic target for NSCLC.

We describe the occurrence of second primary lung cancers (SPLCs) and their determinant in Sweden. Nation-wide cancer registry from years 1961 to 2021 identified a total of 853 SPLCs. The incidence of SPLCs increased almost linearly from 1980 onwards, equally for women and men and approximately equally after the four main histological types. SPLC included adenocarcinoma 63.9%, squamous cell carcinoma (SCC) 19.4%, small cell carcinoma 9.6% and large cell carcinoma 9.1%. The female cumulative probability (CumP) of SPLC after first adenocarcinoma in 10 years reached 0.019, after SCC 0.015 and after small and large cell carcinoma 0.008. The respective CumP for men was 0.013, 0.012, 0.002 and 0.005. While adenocarcinoma was often followed by second adenocarcinoma, after first non-adenocarcinoma SPLCs presented in diverse histologies. Relative risk of SPLC compared with first lung cancer was overall 3.59, higher for women (4.16) than for men (2.99) and approximately equally high after adenocarcinoma and SCC. In patients diagnosed before age 55 years, the relative risk was 6.68 for all, but after female adenocarcinoma it was 9.95 compared with 6.77 for males. The highest relative risks, up to 20-fold, were found after early onset female adenocarcinoma diagnosed after defined T stages. Although SPLCs are still rare, their number is increasing rapidly and the relative risks compared with first lung cancer are substantial, qualifying selected groups of high-risk patients, such as patients with early onset adenocarcinoma for early detection by CT screening when/if such tests become available.

The concomitant occurrence of pulmonary embolism (PE) and lung cancer (LC) poses a significant mortality risk in the United States. Though both diseases are well studied across the literature individually, their combined burden remains unexplored. To evaluate the temporal trends in PE-related mortality among US adults ≥ 65 years with lung cancer from 1999 to 2020, stratified by demographic and geographic variables, by analyzing death certificates related to PE and lung cancer from the CDC WONDER database. We queried the CDC WONDER database for mortality trend analysis with multiple causes of death, having PE and LC, both as either contributing or underlying causes of death, from 1999 to 2020. AAMRs were calculated per 1,000,000 people, stratified by sex, race, geography, and metropolitan status. AAPCs and APCs with 95% CI were evaluated through Joinpoint regression. Between 1999 and 2020, there were 32,409 deaths among adults (aged ≥ 65) with PE and LC, with the majority of fatalities manifesting in medical facilities (60.52%). The overall AAMR increased significantly from 26 (95% CI: 24.3 to 27.7) in 1999 to 41.2 (95% CI: 39.4 to 42.9) in 2020, with an AAPC of 1.92 (95% CI: 1.10 to 2.76, p < 0.001). Men had higher mortality rates with an AAMR of 44.4 (95% CI: 43.8 to 45.1) than 28.4 (95% CI: 27.9 to 28.8) in females. In race/ethnicity, NH-Blacks possessed the highest AAMRs of 44.4 (95% CI: 42.9 to 45.8) among other races. In regional stratification, the Midwest region showed the highest AAMRs of 39.3 (95% CI: 38.4 to 40.1), with the highest AAMRs of 58 (95% CI: 47.5 to 68.4) in Vermont, and non-metropolitan areas had higher AAMRs of 36.06 (95% CI: 35.1 to 37) (Graphical abstract). This study highlights the potential demographic disparities in PE and LC-related mortalities among older adults, underscoring the necessity for improved interventions, early screening, public health awareness programs, and equity in healthcare access.Clinical trial registration:Not applicable, as this is a retrospective observational study that relies on publicly available data.

Gastric cancer (GC) is an epithelial malignant tumor with high morbidity and mortality. In recent years, more and more studies have strengthened our understanding of how GC develops, including the origin of GC cells, precancerous lesions, gene mutations, transcriptional changes, protein translation and the tumor microenvironment. With the concept of accurate tumor therapy gradually applied to clinical practice, these data provide more reference and basis for early prevention, early screening, early detection and accurate treatment of GC.

One of the most striking features of the adipose depot surrounding the prostate [periprostatic adipose tissue (PPAT)] is that its accumulation is independent of body mass index. Its volume varies considerably between individuals, with some patients exhibiting abundant PPATs, which have been correlated to the occurrence of aggressive prostate cancer (PCa). However, abundant PPAT is not well defined at the biological level. We used a new statistical approach to define abundant PPAT by normalizing PPAT volume to prostate volume in a cohort of 351 patients using a linear regression model. Applying this definition, we confirmed the link between abundant PPAT and PCa aggressiveness, thereby validating our approach. At the biological level, we showed that abundant PPAT exhibited extensive extracellular matrix remodeling, notably of the collagen network, decreasing the mechanical constraints in hypertrophic adipocytes, leading to inflammation-free expansion. Degradation of the most abundant collagen in adipose tissue (AT), collagen VI, was associated with increased production of endotrophin, a signaling peptide derived from AT that was also elevated in the urine of patients with abundant PPAT confirming the clinical relevance of our results. These results highlight a unique mechanism of expansion of an adipose depot and open new mechanistic avenues to explain its role in prostate-related disorders. © 2026 The Pathological Society of Great Britain and Ireland.

Abstract Objective: This study aims to evaluate age-related patterns pertaining to the anatomical sites of second primary cancers occurring within five years of an initial breast cancer diagnosis. Methods: Our analysis focuses on patients (n=68,109) whose first recorded cancer diagnosis was early-stage breast cancer, diagnosed between 2008 and 2019. Age, diagnosis dates, and all anatomical cancer sites of these 68,109 patients were extracted from the Q-Centrix Clinical Data Warehouse. The Q-Centrix Clinical Data Warehouse is a proprietary database of de-identified clinical data produced through expert-driven human abstraction. The subset sourced from the Clinical Data Warehouse includes information from 78 hospitals, health systems, and cancer centers across the country. Patients were split into 6 age groups: &amp;lt;40 (n=2,628), 40-49 (n=10,306), 50-59 (n=16,508), 60-69 (n=19,486), 70-79 (n=13,209), and 80+ (n=5,967). Five patients did not have a recorded age group in the data warehouse. The occurrence of a second cancer within 5 years of the initial breast cancer diagnosis was categorized as “Yes” or “No”. Logistic regression was used to assess the odds of a patient developing a second non-same-day cancer within 5 years in patients &amp;gt;40 years of age compared to those &amp;lt; 40 years of age. A p-value cutoff of &amp;lt;0.05 was considered significant. A second analysis was conducted on the subset of patients who developed a second non-simultaneous cancer within five years of the initial breast cancer diagnosis. Of the 68,109 patients who had breast cancer logged as their first cancer in our data warehouse, 4680 (∼7%) fit these criteria. The site of the second cancer was categorized as breast or non-breast. 29 patients in this group did not have a second cancer site stored in the data warehouse. 2 additional patients did not have their age stored in the data warehouse. These patients were dropped from the final set, bringing the total to 4,649. A logistic regression model was then run to determine the odds of the second primary site being located outside the breast versus inside the breast in patient age-groups &amp;gt;40 years of age compared to those &amp;lt;40 years of age. A p-value cutoff of &amp;lt;0.05 was considered significant. The age distribution of this group included 119 patients &amp;lt;40 years of age, 40-49 (n=561), 50-59 (n=1070), 60-69 (n=1426), 70-79 (n=1038), and 80+ (n=435). Results: The odds of developing a second non-simultaneous cancer within 5 years of an initial early-stage breast cancer diagnosis relative to the &amp;lt;40 age group was .68 in the 50-59 age group, .60 in the 60-69 age group, .55 in the 70-79 age group and .59 in the 80+ age group (p-value &amp;lt;0.05). The odds of the 40-49-year age group relative to the &amp;lt;40-year age group was not statistically significant. In the group that did develop a second cancer diagnosis within 5 years, the odds of the tumor location being outside the breast versus inside the breast were 2.05 times greater for patients aged 50-59 years. A 60-69-year-old patient was 3.49 times likelier, a 70-79-year-old patient was 4.76 times likelier, and a patient 80 years or older was 5.05 times likelier to have a second cancer site outside of the breast relative to a patient who was &amp;lt;40 years of age (p-value&amp;lt;.05). The odds of the 40-49-year age group developing a cancer located outside the breast versus inside the breast relative to the &amp;lt;40-year age group was not statistically significant. Conclusions: The odds ratios in the second analysis suggest that the odds of developing a second cancer outside the breast, relative to within the breast, within five years of an initial early-stage breast cancer diagnosis, increase progressively with patient age. Further analyses are required to determine how this relationship differs with respect to the original breast cancer diagnosis receptor type, stage, and anti-neoplastic treatment modality. Citation Format: B. Zigler, V. Wang, V. Smith. Analyzing Age-Related Patterns of Second Primary Cancer Sites Following a Primary Breast Cancer Diagnosis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-05-26.

Abstract Introduction: Despite breast and lung cancer being the most common malignancies in females, the occurrence of double primary cancers has been rarely reported in literature. It is well-established that at an earlier age of diagnosis in patients with breast cancer is linked to more aggressive phenotypes, highlighting the importance of early screening in this demographic group. There is a deficiency in the literature related to secondary thoracic malignancies among this high-risk group. Methods: This retrospective case series reviewed a cohort of eight patients with double metachronous, primary breast and lung cancers at the Sylvester Cancer Center. Data on patient demographics, diagnoses, treatment modalities, and outcomes were obtained from electronic health records. Results: All 8 patients were biologically female with a median age of 58.5 years. Racial distribution was 25% Asian, 12.5% Black and 62.5% White. 80% of White identified as the Hispanic/Latinx ethnicity. 62.5% of patients were never-smokers and 12.5 % were light, former smokers. The median age of diagnosis of breast and lung cancer was 60 years and 62.5 years, respectively. The average time between both diagnoses was 1.9 years (range 0.33 - 4 years). The majority (87.5%) of genetic profiles indicated a hormone receptor-positive mutation, with 33% of this genetic subset also showing an EGFR mutation. 75% of lung tumors were PDL-1 negative. Our review also indicates a decrease in concern for smoking. Despite no statistical significance between ethnicity and age of diagnosis of breast or lung cancer (p= .157), there was a trend demonstrating Hispanic/Latinx patients being diagnosed at an earlier age for both. There was no statistical significance between ethnicity and smoking status (p= .465), or ethnicity and time between diagnoses (p = 1). Conclusions: In this diverse, real-world cohort of patients with metachronous and synchronous lung and breast cancers, we noted interesting, hypothesis-generating observations. Trends indicated an earlier diagnosis of both breast and lung cancer in Hispanic/Latinx patients. 75% of our cohort had a dual diagnosis of breast ductal carcinoma and lung adenocarcinoma. 87.5% of individuals in our cohort displayed a hormone receptor-positive profile and 75% a PDL-1 negative prevalence. This case series confirms the importance of screening breast cancer patients with low-dose CT for early detection of lung cancer. Since double primary breast and lung cancer is rare, molecular profiling with next-generation sequencing could also provide insightful information. Citation Format: K. Sureshkumar, R. Dawar, S. Kareff. Exploring Characteristics and Outcomes of Metachronous Primary Breast and Lung Cancer in A Diverse Cohort [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-06-11.

Abstract Background: The Athena Breast Health Network (Athena) is a University of California (UC) and Sanford Health initiative integrating clinical care and research to drive improvements in breast screening. Here, we evaluated cancer occurrence and tumor type in our UC San Francisco (UCSF) Athena cohort. We assessed the association with 5-year invasive cancer risk level by the Breast Cancer Surveillance Consortium (BCSC) version 3 (BCSCv3) model and the development of aggressive or non-aggressive cancer. Methods: BCSCv3 risk scores were calculated for 10,031 consented UCSF Athena participants enrolled 2011-2022 with a median follow-up of 6.9 years. The BCSCv3 model includes age, race/ethnicity, prior breast biopsy results, breast density, first and second-degree family history, body mass index, menopausal status, and age at first live birth. Risk information was gathered prior to breast cancer diagnosis. The ‘high’ risk threshold was previously set at &amp;gt;1.67% 5-year risk by the BCSCv3 model (PMID37976443). All others were classified as ‘low’ risk.To identify those who developed invasive breast cancer after intake, we performed a cancer linkage with the San Francisco Mammography Registry and the UCSF cancer registry (complete through Dec. 2018 and Jan. 2022 respectively).Tumor aggressiveness was defined in two ways. Advanced or non-advanced cancer was classified by the AJCC prognostic pathologic stage (&amp;gt;stage II is advanced, &amp;lt;stage II is non-advanced). Faster and slower growing cancer considered tumor biology only, where one or more of the following criteria defined faster: HR-negative, HER2-positive, and/or grade 3, all other were slower growing cancers.We used logistic regressions to examine associations between BCSCv3 5-year risk score and breast cancer incidence and tumor aggressiveness. Results: Of the 10,031 participants, 2838 (28%) participants were designated as ‘high’ risk, and 7193 (72%) participants were ‘low’ risk.Overall, 213 (2%) developed breast cancer. 34 (16%) developed advanced cancer and 179 (84%) developed non-advanced cancer. Among women with breast cancer, 60 (28%) developed faster-growing cancers and 153 (72%) developed slower-growing cancers.The median 5-year BCSCv3 risk score for women with and without breast cancer was 1.73% and 1.38% respectively (p&amp;lt;0.001). The average 5-year BCSCv3 risk score for women with advanced and non-advanced cancers was 1.67% and 1.74%, respectively. The average 5-year BCSCv3 risk score for women with faster and slower growing cancers was 1.65% and 1.76%, respectively. In logistic regression analysis adjusted for age, women in the high-risk group had significantly higher odds of developing non-advanced cancer compared to healthy controls (OR = 3.08, 95% CI 1.87-5.08, p&amp;lt;0.001), whereas the association for advanced cancer was not statistically significant (OR = 1.24, 95% CI 0.56-2.77, p=0.59).Similarly, when analyzing slow vs. fast growing cancer, in logistic regression analysis adjusted for age, women in the high-risk group had significantly higher odds of developing slower-growing cancer compared to healthy controls (OR = 2.02, 95% CI 1.39-2.92, p&amp;lt;0.0001), whereas the association for faster-growing cancer was not statistically significant (OR = 1.62, 95% CI 0.88-2.99, p=0.12). Conclusions: This study confirms that higher 5-year BCSCv3 risk scores are associated with higher overall breast cancer development. Participants with the highest 5-year BCSCv3 risk scores are more likely to develop cancers with less aggressive features, suggesting the BCSCv3 model may preferentially predict less aggressive tumors. Those with the highest 5-year BCSCv3 risk may be more likely to benefit from endocrine risk reduction therapy. The Analysis using the recently developed BCSC advanced cancer model is ongoing and may offer better discrimination for those at risk for advanced cancers. Citation Format: K. Leggat-Barr, J. Tice, K. Badal, R. Sayaman, B. Parker, S. Hartman, H. Anton-Culver, H. Park, A. Ziogas, A. Petruse, A. Naiem, K. Malvin, L. Sabacan, T. Lewis, T. Glatt, S. Kapoor, A. Verma, P. Warner, E. Tsopurashvili, A. Griffin, V. Lee, J. McGuire, S. Borowsky, WISDOM Study and Athena Breast Health NetworkInvestigators and Advocate Partners, C. Kaplan, R. Hiatt, A. Stover-Fiscalini, K. Kerlikowske, Y. Shieh, L. Esserman, L. van ‘t Veer. Prediction of Breast Cancer Risk and Tumor Aggressiveness in the Athena Breast Health Network [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-01-21.

Establishment of threshold of human gut microbes and risk assessment system for colorectal cancer.

Head and neck squamous cell carcinoma (HNSCC) and esophageal SCC (ESCC) share risk factors, such as alcohol consumption, smoking, and aldehyde dehydrogenase 2 (ALDH2) gene polymorphisms. However, the involvement of these factors in the occurrence of double primary cancers remains unclear. This study aimed to examine the risk factors for double cancers. This single-center study analyzed 113 patients with HNSCC and ESCC diagnosed between 2014 and 2022, classified into four stage-based groups: Group A (early ESCC + early HNSCC), Group B (early ESCC + advanced HNSCC), Group C (advanced ESCC + early HNSCC), and Group D (advanced ESCC + advanced HNSCC). Associations among clinical factors, Lugol-voiding lesions (LVLs), and prognosis were evaluated. Genetic analyses of ALDH2, CYP2A6, and ADH1B were performed in 20 patients, and multivariate Cox analysis included tumor stage, smoking, and body mass index (BMI). Smoking was more common in Group B than in Group A (89.0% vs. 73.5%, p = 0.013) and was associated with Lugol-voiding lesions (p = 0.027). Three-year overall survival declined with advancing stage (93.3%, 74.0%, 33.3%, and 36.4% for Groups A-D; p < 0.001). Multivariate analysis identified advanced stage, smoking (HR = 1.9, p = 0.009), and low BMI (< 18.5 kg/m2, HR = 2.3, p = 0.024) as poor prognostic factors. Inactive ALDH2 correlated with drinking history, and poorly metabolizing CYP2A6 was less frequent among smokers. Heavy smoking was associated with the development of LVLs and poor prognosis in those with double primary cancers. ALDH2 and CYP2A6 may contribute to cancer risk, underscoring the importance of abstinence from alcohol and smoking in preventive healthcare.

Epigenetics shapes all aspects of cancer occurrence and progression. Among them, chromatin methylation is a particularly important regulator of oncogenic processes. The dynamic shifts in methylation can influence the development or death of tumor cells. In the therapeutic context, effectively targeting and modulating DNA, RNA, and histone methylation brings promise for the early detection, prognostic assessment, and treatment of cancer. In particular, novel methylation inhibitors or modulators powerfully kill tumor cells or improve existing therapeutic strategies through different signaling pathways, thereby improving patient prognosis and survival. The discussion of the role of methylation in early cancer screening, therapeutic resistance in tumors, approaches to treating cancer, and cancer patient prognosis, while also providing data about the clinical application of methylation-focused strategies and interventions. These efforts are shaped by an overall framework focused on the mechanisms responsible for regulating methylation and targeting biomarkers. Together, this article provides insights into how methylation-driven approaches can be leveraged for early cancer detection, overcoming therapy resistance, and tailoring personalized treatments.