Abstract Background: Male breast cancer (MBC) is rare, but its incidence is increasing worldwide. Evidence regarding survival differences compared with female breast cancer (FBC) is limited. This study aimed to characterize sex-specific survival patterns in Korean breast cancer and to identify key contributing factors using explainable artificial intelligence (XAI) methods. Methods: This study utilized data from the Korean Clinical Data Utilization for Research Excellence (K-CURE), a nationwide registry of all breast cancer cases in Korea. Patients diagnosed between 2012 and 2021 were analyzed by sex. Overall survival (OS) and breast cancer-specific survival (BCSS) were assessed using multivariable Cox proportional hazards models. XAI techniques, including SHAP and LIME, were applied to identify sex-specific contributors to survival. Results: Among 200,222 patients (846 males, 199,376 females), males showed significantly poorer OS and BCSS than females (p<.001). This disparity persisted after adjustment (male OS HR ≈1.30-1.40; BCSS HR ≈1.40-1.50). Distant stage was associated with the highest mortality risk in both sexes (male HR ≈9-12; female HR ≈10-24). Distinct sex-specific patterns were observed. In males, metabolic indicators showed opposite associations with survival: higher hemoglobin was linked to lower mortality (HR ≈0.88), whereas higher fasting blood sugar was associated with increased mortality risk (HR ≈1.04). In females, hormone and targeted therapies were associated with reduced mortality (HR ≈0.30-0.55). XGBoost models achieved moderate predictive performance for both outcomes (OS AUC ≈0.85; BCSS AUC ≈0.87). SHAP and LIME analyses consistently supported these patterns, suggesting that metabolic profiles contributed more to risk estimation in males, whereas tumor stage and treatment factors were relatively more influential in females. Conclusion: These findings indicate that sex differences in breast cancer survival arise not only from differences in overall risk profiles but also from distinct prognostic factors specific to each sex. In males, metabolic indicators were more closely associated with survival, whereas in females, tumor stage and treatment factors had greater relevance. Overall, these results reflect differing underlying mechanisms by sex and highlight the need for tailored, sex-specific management strategies in breast cancer care. Citation Format: Seohyun Ahn, Juyeon Hwang, Sun-Young Kong, Jin Ho Park, So-Youn Jung, Hyun-Jin Kim. Sex-specific survival patterns in korean breast cancer: Explainable AI insights from K-CURE Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3562.

HER2-low breast cancer, defined as immunohistochemistry (IHC) 1 + or 2 + without ERBB2 amplification, has uncertain long-term prognostic significance compared with HER2-zero breast cancer (IHC 0), particularly according to hormone receptor (HR) status. Recent therapeutic advances targeting HER2-low disease have increased interest in understanding its biological and prognostic characteristics in early breast cancer. However, despite increasing recognition of HER2-low breast cancer as a distinct therapeutic entity, its prognostic significance in early-stage breast cancer remains controversial, with inconsistent findings reported across studies, particularly according to HR status. In this study, we aimed to evaluate the prognostic relevance of HER2-low expression in early-stage breast cancer, stratified by HR status. We retrospectively analyzed data from 7,281 patients with HER2-negative early breast cancer treated between 2005 and 2023 at a single institution. Clinicopathological characteristics and long-term survival outcomes were compared between the HER2-low and HER2-zero subgroups according to HR status. Long-term overall survival (OS) and breast cancer-specific mortality were assessed according to HR status using survival analyses. HER2-low tumors demonstrated more luminal-like biological characteristics, including higher hormone receptor positivity, lower histologic grade, and lower Ki-67 expression, although they also showed relatively higher tumor and greater nodal stage involvement. However, HER2-low status was not associated with improved OS in the overall cohort. Among HR-positive patients, survival outcomes were comparable between HER2-low and HER2-zero tumors. Among HR-negative patients, HER2-low expression demonstrated a trend toward poorer survival outcomes; however, this association did not remain statistically significant after multivariable adjustment. A significant interaction between HER2 status and Ki-67 expression was observed in HR-negative disease, with HER2-low tumors demonstrating particularly poor outcomes among patients with low Ki-67 expression. HER2-low expression demonstrates distinct prognostic implications according to HR status, supporting the biological heterogeneity of HER2-negative breast cancer. These findings suggest that the prognostic impact of HER2-low expression is modified by both HR status and proliferative activity, identifying a potentially high-risk subgroup of HR-negative, HER2-low tumors with low Ki-67 expression. Further studies are warranted to clarify the biological mechanisms underlying the differential prognostic effects of HER2-low expression across HR subgroups.

Reliable biomarkers associated with pathological complete response (pCR) following neoadjuvant chemotherapy (NAC) remain limited. We therefore conducted an exploratory longitudinal metabolomic study to identify candidate plasma metabolites associated with treatment response in patients with breast cancer undergoing NAC. Thirty patients were prospectively enrolled between July and November 2021. Of these, 20 with complete longitudinal plasma samples were included in the final analysis. Plasma samples were collected longitudinally from diagnosis through surgery. Targeted metabolomic profiling was performed using the AbsoluteIDQ® p400 HR kit. Of the 408 measured metabolites, 213 were consistently detected across all samples and included in the analysis. Among the 20 patients analyzed, 8 achieved pCR and 12 did not. Seven candidate metabolites showed nominally significant differences between the pCR and non-pCR groups at diagnosis. Because HER2 receptor expression differed significantly between the groups (p = 0.04), longitudinal analyses were performed using HER2-adjusted linear mixed-effects models. Distinct metabolite trajectories were observed between response groups, and PC(42:0) and PC(32:5) remained significantly associated with treatment response after Benjamini–Hochberg false discovery rate (FDR) correction. This exploratory longitudinal metabolomic study identified PC(42:0) and PC(32:5) as candidate metabolites showing distinct longitudinal patterns according to NAC treatment response. No metabolites remained significant at diagnosis after FDR correction. These findings should be considered hypothesis-generating and warrant validation in larger prospective cohorts.

Abstract Purpose: Breast cancer remains the most common malignancy among women, with about 20% driven by HER2 overexpression. Although HER2-targeted therapies have improved outcomes, acquired resistance and recurrence persist. Clinical HER2 Immunohistochemistry(IHC) often fails to reflect actual HER2 abundance, as seen in both IHC-negative/high-protein and IHC 3+/low-protein cases. Thus we conducted an integrated proteogenomic analysis to define HER2 heterogeneity and identify recurrence-associated signatures. Methods: Total of 62 patients with a median age of 41.5 years (range, 25-60) were included from National Cancer Center in Korea, and breast tumor tissues analyzed using an integrated proteogenomic workflow combining whole-exome sequencing, whole-transcriptome, global proteomics, phosphoproteomics, and PRM-based HER2 quantification. Differential genomic and proteomic features between the 46 non-recurrence and 15 recurrence patients were compared and validated in TCGA and CPTAC cohorts. Results: Description between clinical IHC and quantitative HER2 measurement were observed in 10% of low HER2 and in 25% of high HER2 cases. Recurrent patients revealed frequent TP53 mutations, MYC amplification, and ERBB2 hotspot variants (E192* and D844*) in genomic profiling. DEGs analyses integrating RNA and proteomic expression identified a shared set of recurrence-associated genes, including ATXN7L3BM GPRC5A and GPRC5A and WNT5A, which collectively reflected pathways related to extracellular matrix remodeling, metastatic, signaling, metabloic reprogramming, and transcriptional regulation. METABRIC comparison showed similar patterns of ERBB2/MYC amplification, TP53 loss, and genomic instability observed in recurrent tumors. Mutational signature analysis indicated dominant contributions from aging-related, APOBEC-driven, and homologous recombination-defective processes. Copy-number signature profiling further identified five recurrent genomic subtypes (CNV48 A-E), including chromothripsis-like and loss of heterozygosity patterns shared with TCGA and METABRIC HER2-positive tumors. Conclusions: These findings indicate that recurrence risk in HER2-positive breast cancer is determined more by initial tumor stage than by HER2 IHC status. This underscores the clinical value of quantitative proteogenomic assessment as a complementary tool to improve risk stratification beyond conventional HER2 testing. This work was supported by grant from the National Cancer Center. (Grant No. 2510692-1) Citation Format: Eunjoo Lee, Seung Min Park, Kyung-Hee Kim, So-Youn Jung, Gi Yeon Lee, Eun-Gyeong Lee, Min-Chae Kang, Jong Bae Park, Kong Sun-Young. Integrated proteogenomics reveals molecular predictors of recurrence beyond HER2 IHC in HER2-positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7920.

Abstract Purpose Patient-derived organoids (PDOs) are useful cancer models because they reflect important features of each patient’s tumor. In Korea, however, researchers have not had enough PDO samples with clear clinical information. To improve this situation, the National Cancer Center created a platform to collect organoids from different cancers and provide reliable models that can be used for research. Methods Tumor specimens were obtained through surgical resection, image-guided biopsy, and malignant body fluids. All samples were processed using a unified workflow covering tissue handling, enzymatic dissociation, organoid culture, and criteria for long-term growth. PDOs that continued to grow for more than five passages were classified as successfully established. Quality checks included STR profiling, mycoplasma testing, and histologic and genomic evaluation to ensure accuracy and safety. Clinical and pathological information was linked to each PDO, and biobanking procedures were used for long-term storage. Selected models were evaluated in drug-response assays using a 384-well screening format. Results The platform currently maintains 122 PDO models across multiple cancer types, including oral (n = 33), pancreatic (n = 20), tongue (n = 16), gastric (n = 16), ovarian (n = 9), gallbladder (n = 8), biliary tract (n = 8), breast (n = 5), liver (n = 4), and colorectal cancers (n = 3). These PDOs preserved key histopathologic, genetic, and phenotypic characteristics of their matched tumors and were successfully cryopreserved for long-term use. Drug-response profiling of 42 PDOs with 46 therapeutic agents revealed substantial inter-tumoral variability, and several investigational compounds demonstrated notable antitumor activity. In representative cases, ex vivo cytotoxic responses corresponded with clinical treatment outcomes, underscoring the translational relevance of the platform. Conclusions This PDO platform provides a centralized and high-quality resource that reflects the biological and clinical diversity of human cancers. By supporting systematic drug screening, mechanistic studies, and biomarker-based precision approaches, the platform offers essential infrastructure to advance translational oncology research and promote the development of personalized therapeutic strategies in Korea. This research was supported by the Bio&Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. RS-2025-19542979) Citation Format: JUBI HEO, LEE Choong-Jae, Eun Joo LEE, Sung Weon Choi, Sang-Jae Park, Sang Myung Woo, Sang Yoon Park, Myong Cheol Lim, So-Youn Jung, Bo Hyun Kim, Jung Won Chun, Joohyun Hong, Wonyoung Choi, Sun-Young Kong, . Multi-cancer patient-derived organoid platform for translational cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7532.

Adipocytes are essential stromal components of the tumor microenvironment (TME) in breast cancer that play pivotal roles in cancer progression and chemoresistance. In close proximity to tumor cells, they undergo phenotypic reprogramming into cancer-associated adipocytes (CAAs), characterized by multilocular lipid droplets, increased mitochondrial content, and elevated expression of uncoupling protein 1 (UCP1). Although these features superficially resemble those of beige adipocytes, they do not recapitulate classical thermogenic programming, reflecting a unique metabolic adaptation driven by the TME. Here, we identified tumor necrosis factor receptor-associated protein 1 (TRAP1), a mitochondrial paralog of HSP90, as a central regulator of the transition of adipocytes into CAAs. TRAP1 was highly upregulated in CAAs and was required to drive a tumor-associated adipocyte secretory program, including the adipokine complement factor D (CFD). Genetic and pharmacological TRAP1 inhibition destabilized the mitochondrial electron transport chain, reduced cellular respiration, and activated the energy sensor AMPK. This subsequently suppressed mTOR and PPARγ signaling, effectively abrogating adipocyte reprogramming and diminishing pro-tumorigenic adipokine secretion. Crucially, this CAA-secreted CFD promoted cancer cell survival and chemoresistance via C3aR-AKT/ERK signaling, and blocking this TRAP1-mediated crosstalk profoundly sensitized breast tumors to chemotherapy in vivo. Collectively, these findings identify TRAP1 as a master regulator of adipocyte transdifferentiation within the TME, offering a novel strategy to restrict tumor growth and overcome drug resistance in breast cancer.

Abstract Background: The ubiquitin-proteasome system (UPS) and autophagy cooperate to maintain protein homeostasis, yet how these pathways interact to regulate breast cancer stem cells (BCSCs) remains unclear. PSMD2, a 19S regulatory subunit of the proteasome, has been linked to poor outcomes in several cancers, but its role within the autophagy-proteostasis network in ER+ breast cancer has not been defined. Here, we examined how PSMD2 influences CSC maintenance and drug response through UPS-autophagy crosstalk and explored how its suppression alters autophagy regulation and CSC vulnerability in ER+ breast cancer. Methods: Stable PSMD2 knockdown (ShPSMD2) lines were generated in ER+ breast cancer cells (MCF-7, ZR-75-1). Autophagy was modulated using hydroxychloroquine (HCQ). Western blotting assessed CSC-related markers (SOX2, OCT4, NANOG), EMT markers (E-cadherin, N-cadherin, Vimentin), and autophagy proteins (LC3B-II, p62, p-mTOR). Functional assays, including MTT viability, colony formation, migration, and invasion, were performed to evaluate PSMD2-dependent phenotypes. Mammosphere and viability assays assessed CSC formation and HCQ sensitivity. Tumor growth and metastasis were tested using mammary fat-pad and tail-vein xenografts in NSG mice. Results: PSMD2 depletion reduced CSC frequency, mammosphere formation, and colony formation, with decreased stemness markers (SOX2, OCT4, NANOG) and reversal of EMT features, shown by lower N-cadherin, Vimentin, and Snail. Loss of PSMD2 resulted in LC3B-II and p62 accumulation with mTOR suppression, indicating impaired autophagy turnover and disrupted proteostasis. PSMD2-deficient cells displayed reduced migration and invasion and were more sensitive to HCQ-induced cytotoxicity. HCQ treatment further lowered PSMD2 protein levels in a dose-dependent manner, implying feedback destabilization of the proteasome under lysosomal stress. This correlated with loss of CD44+/CD24- CSC-like populations and reduced sphere-forming ability. In xenografts, PSMD2 knockdown suppressed tumor growth and lung, liver metastasis, suggesting that PSMD2 is a critical node linking proteostasis to metastatic progression. Conclusions: PSMD2 depletion disturbs UPS-autophagy coordination, leading to loss of proteostasis and CSC depletion in ER+ breast cancer. This insight reveals PSMD2 as a key regulator of proteolytic balance and a potential target for autophagy-based therapeutic strategies. Citation Format: Yejoo Lee, Ju Hee Kim, So-Youn Jung, Wonshik Han. PSMD2 Suppression Disrupts Autophagy Turnover and Creates an Autophagy-Dependent Vulnerability in ER+ Breast Cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2203.

Background: This study aims to examine the association between a plant-based diet index (PDI) and the risk of breast cancer in Korean women. Additionally, we aim to assess whether the associations differ by menopausal status and in estrogen receptor (ER) and progesterone receptor (PR) status. Methods: In this case-control study, we included 395 breast cancer patients and 395 age-matched controls from the National Cancer Center Hospital. The overall PDI, healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI) were calculated based on dietary intake assessed using a 106-item semi-quantitative food frequency questionnaire. Logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between plant-based diets and breast cancer, adjusting for potential confounders. Results: We found that PDI was inversely associated with breast cancer, while uPDI was positively associated. However, hPDI was not significantly associated with breast cancer after multivariable adjustment. In analyses stratified by menopausal status, PDI showed an inverse association with breast cancer in premenopausal women, while uPDI was positively associated with breast cancer in both pre-and postmenopausal women. Additionally, when stratified by ER and PR status, we observed that both PDI and uPDI showed stronger associations in the ER+/PR+ group, whereas hPDI remained non-significant in both the ER+/PR+ and ER-/PR-groups. Conclusion: A higher PDI was associated with lower odds of breast cancer, supporting the recommendation to increase plant-based food intake and reduce animal food intake as part of dietary guidance for breast cancer prevention.

One of the key challenges in cancer treatment and precision oncology is the use of multi-omics data and their integration into matched clinical information. Although several analytical portals have been developed, most platforms do not support user-uploaded data or the integrated analysis of clinical and multi-omics datasets. To address these limitations, we developed the Korea Cancer Omics Research (K-CORE) portal, a user-friendly analytical platform designed to integrate and analyze multi-omics and clinical data. K-CORE supports various omics levels and a wide range of analytical tools. To validate the utility and reproducibility of the K-CORE, we designed synthetic datasets that reflected real-world omics data distributions. The analytical results from K-CORE were compared side by side with those from widely used R packages such as maftools and edgeR. In conclusion, K-CORE offers a practical and intuitive platform for the multidomain integration of clinical and omics data, supporting the advancement of precision oncology. Nevertheless, as analytical technologies and precision oncology continue to evolve, continuous maintenance and user feedback will become essential for future platform improvements.

BACKGROUND/OBJECTIVES: Dietary supplement use is common among breast cancer survivors, but studies on Asian populations remain limited. This study investigated dietary supplement use among Korean breast cancer survivors, distinguishing between vitamin/ mineral (VM) and non-vitamin/non-mineral (NVNM) supplements. SUBJECTS/METHODS: This cross-sectional study included 1,136 stage I-III breast cancer survivors from 12 Korean hospitals, who survived more than 6 mon post-surgery. The participants completed a questionnaire on post-diagnostic dietary supplement use. Stepwise logistic regression was applied, calculating odds ratios (ORs) and 95% confidence intervals (CIs) to identify the demographic and clinical factors associated with VM and NVNM use. RESULTS: Seventy percent of survivors reported supplement use, with 25% using a single product. The most common VM supplements were multivitamins/minerals, vitamin D, and vitamin C, while the most common NVNM supplements included omega-3 fatty acids, probiotics, and ginseng. Survivors with higher education and greater physical activity were more likely to use VM supplements (ORs [95% CIs], 2.74 [1.76-4.25] for college graduates or above vs. middle school or below; 1.38 [1.02-1.88] for the most active group vs. the least active group). NVNM use was associated with higher education, greater physical activity levels, and a history of smoking (ORs [95% CIs], 2.29 [1.46-3.58] for college graduates or above vs. middle school or below; 1.52 [1.13-2.06] for the most active group vs. the least active group; 2.00 [1.23-3.25] for ever smokers vs. never smokers). Survivors who had undergone chemotherapy were also more likely to use NVNM supplements than those who had not (OR [95% CI], 1.37 [1.02-1.84]). CONCLUSION: Seventy percent of Korean breast cancer survivors used dietary supplements in this study. VM use was associated with higher education and physical activity, while higher NVNM use was associated with higher education, greater physical activity, a history of smoking, and chemotherapy.

Genetic testing and counseling have become increasingly prevalent in breast cancer treatment with the advancement of precision oncology. Understanding patients’ information-seeking experiences is essential for providing better genetic cancer services. However, these experiences are insufficiently understood. This qualitative study explored the information-seeking experiences during genetic testing and counseling of patients at high risk for hereditary breast cancer. Four focus group interviews were conducted with 17 breast cancer patients who had undergone genetic testing and counseling. Participants were purposively recruited from the National Cancer Center’s outpatient clinic in South Korea. Data were audio-recorded, transcribed verbatim, and analyzed inductively using thematic analysis, complemented by a deductive approach informed by Lambert and Loiselle’s Health Information-Seeking Behavior (HISB) framework. Three main themes, derived from 24 codes and seven subthemes, captured the characteristics of HISB: (1) type of information sought—stage-specific information needs, (2) amount of information sought—varied preferences for information amount based on coping with information load and uncertainty, and (3) preferred methods of information delivery—desire for clear, reliable, and supportive communication from providers. These findings highlight the need for personalized information delivery at each stage: core decision content before testing, and results-contingent plans after testing—all tailored to individual preferences and coping capacity for information load and uncertainty. This study underscores the critical role of empathic and clear communication from HCPs supported by supplementary materials in facilitating informed decision-making and improving outcomes for patients at high risk for hereditary breast cancer.

Purpose:Despite a nationwide breast cancer screening program in Korea, spatial disparities in stage at diagnosis persist. This study aimed to examine disparities in breast cancer incidence by stage and their association with area-level risk factors. Materials and Methods:We conducted a population-based ecological study using data from the Korea National Cancer Incidence Database (2005-2018). Among 230,214 women diagnosed with breast cancer, 215,803 with known stage were included. Stage-specific incidence across 250 municipalities was estimated for three periods (2005-2008, 2009-2013, and 2014-2018). For 2014-2018, associations with the area deprivation index (ADI), obesity rate, alcohol consumption rate, cancer screening rate, and mammography unit availability were assessed using Bayesian hierarchical models. Results:Of 215,803 patients, 59.0% had localized-stage, 35.5% regional-stage, and 5.5% distant-stage. Localized-stage incidence was higher in affluent areas, whereas distant-stage incidence was higher in deprived areas. In multivariable models, lower ADI (β = -0.058; 95% credible interval [CrI]: -0.098, -0.019), lower obesity rate (β=-0.066; 95% CrI: -0.091, -0.041), and higher mammography availability (β=0.014; 95% CrI: 0.001, 0.027) were significantly associated with higher localized-stage incidence. Conversely, higher ADI (β=0.103; 95% CrI: 0.017, 0.188) and higher alcohol consumption (β=0.227; 95% CrI: 0.115, 0.338) were significantly associated with increased distant-stage incidence. Conclusion:Spatial disparities in stage-specific breast cancer incidence in Korea were associated with area-level deprivation, healthcare resources, and health-related behaviors. Integrating spatial perspectives into cancer control strategies may help promote more equitable early detection and contribute to improve breast cancer outcomes.

Breast cancer survivors are living longer. However, the risk of second primary cancer (SPC) remains a concern. The aim of this study was to identify risk factors for synchronous SPC (sSPC) and metachronous SPC (mSPC) among patients who survive breast cancer and evaluate causes of death. This population-based cohort study used data from the South Korean Cancer Public Library Database, which integrates the national cancer registry with insurance claim and health screening data. Female patients diagnosed with primary breast cancer between 2012 and 2019 were included in the study. SPCs were defined as new histologically distinct malignancies occurring six months or more (mSPC) or less than six months (sSPC) after breast cancer diagnosis. Cox proportional hazards models were used to identify risk factors for SPC. Cumulative incidence and causes of death were examined by cancer stage and age. Among 15,430 women with breast cancer who met the eligibility criteria, 497 developed sSPC and 812 developed mSPC. In multivariable models, an age ≥70 vs <40 years was associated with a higher risk of both sSPC (hazard ratio [HR], 3.58; 95% confidence interval [CI], 2.01-6.36; P < 0.001) and mSPC (HR, 3.18; 95% CI, 2.06-4.91; P < 0.001). Fasting blood sugar ≥140 mg/dL was associated with sSPC (HR, 1.61; 95% CI, 1.06-2.45; P = 0.02), but not with mSPC. Cumulative-incidence curves showed a higher prevalence of thoracic and gastrointestinal mSPC in older and lower-income strata, consistent with Cox results. Although smoking was more prevalent in low-income groups, it was not an independent predictor. Cause-of-death analyses indicated that SPCs more often accounted for death in older survivors and in those with early-stage index breast cancer. The results of this study identify metabolic and socioeconomic factors as key predictors of SPC in patients who survive breast cancer. Tailored survivorship strategies are needed for high-risk subgroups, including older patients and those with low incomes or poor metabolic profiles.

BACKGROUND/OBJECTIVES:Isoflavones are estrogen-like compounds found in plants and their health effects remain equivocal. We investigated dietary isoflavone intake and its associated factors in Korean breast cancer survivors, with a comparison to cancer-free women. SUBJECTS/METHODS:The usual dietary intake of breast cancer survivors (n = 981, mean age 52 yrs) in 9 hospitals between 2012 and 2019 was assessed using 3-day food records or food frequency questionnaires (FFQs). They were age-matched to 2,943 cancer-free women who completed FFQs as part of a nationwide study conducted between 2012 and 2016. We used the flavonoid database of common Korean foods and the Phenol-Explorer database to estimate isoflavone intake. The contribution of each food or food group to the total isoflavone intake was calculated. The adjusted least-squares means of dietary isoflavone intake according to lifestyle and clinical factors were calculated using generalized linear models. RESULTS:Breast cancer survivors had a higher mean dietary isoflavone intake (23.59 mg/day) than cancer-free women (17.81 mg/day). Major food sources, including tofu, soybeans, and doenjang, contributed to over 70% of the isoflavone intake in both groups. When we estimated dietary isoflavone intake according to lifestyle characteristics, isoflavone intake increased with higher scores of adherence to the American Cancer Society dietary guidelines but decreased with increasing body mass index in both groups. Among cancer-free women, dietary isoflavone intake was higher among those who had never smoked and among dietary supplement users. Among breast cancer survivors, dietary isoflavone intakes did not vary with clinical characteristics, including time since surgery and estrogen receptor status. CONCLUSION:Breast cancer survivors were more likely to consume isoflavones than age-matched cancer-free women. Dietary isoflavone intake was associated with healthy lifestyle characteristics in women both with and without breast cancer. Further research is needed to understand the role of the higher isoflavone intake among breast cancer survivors compared to cancer-free women on their prognosis.

The advent of next-generation sequencing (NGS) has significantly enhanced hereditary cancer comprehensive germline genetic testing. While initial efforts targeted BRCA1 and BRCA2, NGS now reveals a broader range of cancer susceptibility genes, highlighting diverse genetic variations. The variability of pathogenic variants (PVs) across ethnic groups underscores the critical importance of population-specific studies. This study evaluates PVs frequency and their clinical relevance in Korean hereditary cancer patients, providing detailed insights into the genetic characteristics in this population. We analyzed real-world data from 5,893 patients who underwent genetic testing at the National Cancer Center in Korea between 2006 and 2023. Genetic testing included either BRCA1/2 test (n=2,342) or NGS panel testing (n=3,551), with the type of test determined by the physician’s clinical decision and insurance reimbursement criteria. We collected demographic characteristics, personal and family history and analyzed the impact of these factors on PV carrier status. The median age of the patients was 51.3 years (range: 4-92), with 96.3% female. The distribution of diagnosed cancers was as follows: breast cancer (55.8%), ovarian cancer (37.2%), thyroid cancer (2.4%), pancreatic cancer (2.4%), endometrial cancer (2.4%), colorectal cancer (1.9%), prostate cancer (1.7%), lung cancer (0.8%), gastric cancer (0.8%), other cancers (2.8%) and multi-organ cancers (n=677). Among 43.6% patients with a family history of cancer, 87.1% reported a first-degree relative (FDR), 40.5% a second-degree relative (SDR), and 5.2% a third-degree relative (TDR).PVs were observed in 184/1,612 (11.4%) breast cancer, 202/732 (27.5%) ovarian cancer in BRCA1/2 test and 221/1,681(13.1%) breast cancer, 333/1,463 (22.8%) ovarian cancer in NGS panel testing. In patients who underwent NGS panel testing, 606 individuals represented 626 PVs. The genes most commonly affected included BRCA1 (35.8%), BRCA2 (27.3%), RAD51D (4.2%), ATM (3.8%), PALB2 (3.5%), MUTYH (3.0%), CHEK2 (2.4%), MSH2 (2.4%), BRIP1 (2.2%), MLH1 (2.1%), MSH6 (1.9%) and PMS2 (1.8%).In breast and ovarian cancer, multiple organ involvement emerged as a significant risk factor for suspected germline PVs (p <0.01). PV of breast cancer patients was significantly associated with family history of 50.9% with FDR, 13.8% with SDR, and 1.7% with TDR. Our study identified overall 16.6% prevalence of germline PVs in Korean patients and there is a notable finding involving genes other than BRCA1/2, which highlights the broader spectrum of genetic alterations, suggesting the need for greater awareness and preparedness in hereditary cancer.This study was supported by grant from the National Cancer Center. (grant number NCC-2410821). Ha-Eun Lee, Sang-Yoon Park, Seeyoun Lee, So-Youn Jung, Myong Cheol Lim, Han-Sung Kang, Jun-Ha Jang, Sun-Young Kong. Real-World data of germline variants in 5,893 Korean hereditary cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2271.

PURPOSE:In the past 15 years, numerous decision aids (DAs) have been developed to assist families affected by hereditary cancer syndromes in decision-making for managing inheritance and cancer risk. We identified the range and characteristics of DAs, focusing on their development stage according to guideline recommendations, their outcomes, and effectiveness. METHODS:A comprehensive search was conducted in MEDLINE, EMBASE, Cochrane, CINAHL, and PsycINFO, along with manual searches. Eligible articles reported DAs for supporting families affected by hereditary cancer syndromes, published in English from inception to July 2024. Quality was assessed using the Mixed-Methods Appraisal Tool. RESULTS:From 15,066 records, 32 studies with a moderate risk of bias, reporting 23 unique DAs, were identified. Most DAs targeted women (69.6%) with hereditary breast and ovarian cancer syndrome (73.9%) in North America and Europe (81.3%), primarily supporting decisions on cancer risk-reduction strategies (56.5%) and genetic testing/counseling (47.8%). Only 4 DAs were consistent with guideline-recommended development process, including prototype development, alpha- and beta-testing. Development and alpha-testing outcomes included user experience, understandability, and psychological impact. Beta-testing evaluated decision-making capacity, quality of the decision-making process, psychological impact, and impact on decisions. DAs consistently improved decision-making capacity and quality of the decision-making process but showed variable effects on psychological outcomes and actual decision in risk management. CONCLUSION:DAs are underdeveloped for genetic, racial, or gender minorities, according to guideline-recommended development process. Future research should develop DAs for broader populations and clarify their effectiveness, particularly regarding psychological outcomes.

Perception of patient’s causal attribution is crucial for developing effective prevention strategies and improving overall health management approaches. Causal attributions of cancer patients have been well investigated in Western populations, while relatively few studies have conducted on East Asian populations. This study aimed to explore the perceptions of causal attributions among Korean cancer patients who underwent genetic testing. Patients who met the criteria of hereditary cancer underwent germline genetic testing were recruited at the National Cancer Center in Korea between July 2023 and October 2024 (CRIS No. KCT0009460). Causal attributions were assessed through an open-ended item included in the Korean version of the Brief Illness Perception Questionnaire (BIPQ-K): “Please list in rank-order the three most important factors that you believe caused your illness.” Responses were considered valid if they answered more than once in the three factors. Of the 958 cancer patients analyzed (97.9% female; mean age±SD, 52.7±9.9 years), breast cancer (531, 55.4%), ovarian cancer (390, 40.7%), other types of cancer (51, 5.3%), and multiple organ cancers (80, 8.4%) were included. First cancer diagnosis age less than the age of 40 were 194 (20.3%) patients and family history of cancer within second-degree relatives were observed in 748 (78.1%) patients. Their genetic testing results frequency were as following: pathogenic variants (PV), 196 (20.5%); variants of uncertain significance (VUS), 357 (37.3%); benign variants (BV), 405 (42.3%). The top five perceived risk factors were stress (718, 74.9%), dietary habits (385, 40.2%), genetics or family history (177, 18.5%), lack of weight management (167, 17.4%), and sleep habits (152, 15.9%). In the PV group, genetics or family history was reported more frequently compared to the VUS and BV groups (39.3% vs. 13.1%; p<0.001). Korean cancer patients tended to overattribute stress as a cause of cancer than Western population, and this tendency was similar in PV group. Additionally, 10 respondents attributed their cancer to COVID-19 or COVID-19 vaccination, reflecting the influence of health anxieties during the COVID-19 pandemic period. The association between clinical and demographic characteristics and causal attributions will be analyzed. This work was supported by the grant of the Korean Cancer Survivors Healthcare R&D Project through the National Cancer Center, funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. RS-2023-CC139201). Min-Chae Kang, Mi-Ae Jang, Sang-Yoon Park, So-Youn Jung, Seeyoun Lee, Jun-Kyu Kim, Boyoung Park, Sun-Young Kong. Causal attribution in Korean cancer patients who underwent genetic testing: What caused my cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1017.

OBJECTIVE:Understanding how patients with cancer attribute their illness is crucial for improving public health interventions and support strategies. This scoping review explores perceived causal attributions among women with breast and gynecological cancers, focusing on quantitative studies. It further examines regional and temporal patterns and identifies gaps in public awareness. METHODS:A literature search was conducted in four electronic databases: PubMed, EMBASE, CINAHL, and APA PsycINFO. Eligible studies focusing on women diagnosed with breast or gynecological cancers and their perceived causal attributions were included. Filters were applied for language (English, Korean), publication type (original article), and time-period (1949-2025). Data were extracted, categorized, and analyzed descriptively. RESULTS:Our search identified 3072 studies, of which 41 met the inclusion criteria. Psychological risk factors, particularly stress, were the most frequently reported top-ranked causal attributions (50.0%), followed by biological risk factors (23.8%), while behavioral risk factors were under-recognized. The Western population was more focused on biological risk factors, whereas non-Western population more frequently reported psychological and environmental factors. Moreover, studies published after 2015 reported an increased emphasis on psychological risk factors, while attributions to fate or chance diminished significantly. CONCLUSION:The persistent over-attribution of psychological risk factors and under-recognition of behavioral risk factors highlight the need for targeted education and campaigns. Cultural and societal influences shape these perceptions, emphasizing the importance of evidence-based education to improve cancer awareness and prevention strategies.