Korean Breast Cancer Society

Hypoxia, a condition characterized by low oxygen availability, plays a significant role in cancer biology and tumor behavior. The interplay between hypoxia-related prognostic genes and immune cell infiltration is pivotal in shaping the clinical outcomes of HER2-enriched breast cancer. Therefore, this study aimed to identify prognostic hypoxic genes affecting the infiltration of immune cells in HER2-enriched breast cancer. Gene expression and overall survival data of HER2-enriched breast cancer were accessed from the Cancer Genome Atlas (TCGA). After data pre-processing, the genes filtered based on hypoxia signature were acquired from the Molecular Signatures Database (MSigDB). Through Cox regression, univariate and multivariate survival analyses were applied. In relation to immune infiltration analysis, TIMER.02 was utilized to find a correlation between selected genes and infiltrates. The gene expression of 58 HER2-enriched samples was investigated. Relate to univariate analysis, 14 genes were selected as the most influential genes in HER2-enriches patients’ survival, among which 5 genes, NDST1, GBE1, BNIP3L, IGFBP3, and KIF5A, had the most significant effect in multivariate analysis. Subsequently, the role of 11 hypoxia genes was confirmed as effective genes in immune cell infiltration, and finally, evaluating genes in terms of their effect on the number of infiltrated immune cells showed that the GBE1 gene (HR = 1.8, 95% CI = 1.01–3.32, P = 0.049) is probably one of the crucial hypoxic genes affecting immune cell infiltration on HER2-enriched breast cancer patients. The results indicated that out of the 14 hypoxia-related genes that contribute to the survival of HER2-enriched patients, 11 were found to influence the infiltration of immune cells. Notably, GBE1 emerged as a significant gene, impacting both patient survival and the most immune cell infiltration. Hence, further studies are warranted to elucidate its precise mechanisms and explore its potential as a therapeutic target in cancer immunotherapy.

IntroductionBreast cancer-related lymphedema (BCRL) is a debilitating condition that affects a significant proportion of breast cancer survivors, profoundly impacting their quality of life. While many studies have investigated the risk factors for BCRL occurrence, the determinants of its severity remain underexplored.MethodsThis retrospective observational study evaluated the risk factors associated with BCRL severity among patients treated at the Motamed Cancer Institute, Tehran, Iran. Female patients with unilateral BCRL aged 25–75 years were included. Data were collected over a 10-year period and analyzed for demographic, clinical, and pathological variables. Lymphedema severity was assessed using established clinical staging criteria and categorized into early-stage (stages 1 and 2a) and advanced-stage (stages 2b and 3) groups. Also, presence of fibrosis and non-pitting edema were other indicators of BCRL severity. Statistical analyses included univariate and multivariate logistic regression to identify predictors of advanced-stage BCRL.ResultsA total of 500 participants were analyzed, with a mean age of 41.16 ± 10.20 years and BMI of 28.72 ± 4.78 kg/m². Advanced-stage BCRL was significantly associated with older age (p = 0.00), higher number of excised lymph nodes (p = 0.04), and radiotherapy (p = 0.00). Multivariate analysis identified radiotherapy as the strongest independent predictor of advanced-stage BCRL (OR: 2.12, 95% CI: 1.22–3.67, p = 0.007). Other variables, including tumor grade, molecular subtypes, and type of surgery, did not independently predict BCRL severity.ConclusionAdvanced-stage BCRL is influenced by multiple factors, particularly radiotherapy and the extent of lymph node dissection. These findings underscore the importance of strategies to mitigate risk among breast cancer survivors, especially those undergoing radiotherapy. Further research is warranted to explore targeted interventions for reducing BCRL severity.

Abstract Background: Triple-negative breast cancer (TNBC) is defined by lack of estrogen and progesterone receptors and absence of HER2 amplification. Compared with other breast cancer subtypes, TNBC is more aggressive with more frequent metastasis especially involving visceral and central nervous system. Currently, the only available standard adjuvant treatment is chemotherapy. However, mortality rate remains high despite chemotherapy. To improve treatment, it is crucial to develop novel strategies to predict and overcome drug resistance. Our pervious study showed that CD44/CD24 expressions were associated with drug sensitivity and CD44+/CD24+ TNBC was shown to be resistant to docetaxel. In this study, we aimed to investigate the regulatory mechanism involved in CD24-mediated taxane resistance in TNBC. Methods: In this study, we used flow cytometry to determine the CD24 expressions in 7 TNBC cell lines. Western blot was used to demonstrate the levels of CD24 and LC3B-II (a marker for cellular autophagy activity) expressions in TNBC cell lines. CD24 expressions in TNBC cell lines were manipulated by target-specific shRNA and gene overexpression approaches. Cell apoptosis assay was used to determine docetaxel drug sensitivity in cells with manipulated CD24 expression. Using the same assay, autophagy inhibitors were used to further evaluate the involvement of autophagy in CD24-mediated drug resistance. To investigate the possible regulatory mechanism, autophagy related signaling pathway Akt/mTOR was studied in CD24 modified TNBC cells. Results: In this study, the relationship between CD24 expression and autophagy activities in TNBC was evaluated. LC3B-II protein expression was used to determinate autophagy activities. We have shown that TNBC cell lines with high CD24 expressions are associated with increased LC3B-II expression. Suppression of autophagy in CD24 high TNBC cells improves drug sensitivities toward docetaxel. We further demonstrated that knocking down CD24 in TNBC cells suppressed LC3B-II expression and improved docetaxel sensitivity. In addition, gene overexpression of CD24was found to enhance docetaxel resistance in TNBC cells. Our study has also shown that docetaxel increases the activation of Akt/mTOR signaling pathway in drug-resistant TNBC cells. Knocking down CD24 increased Akt/mTOR activation, and decreased the expression of PP2A and LC3B-II in TNBC. Conclusions: CD24 expression is associated with docetaxel sensitivity and autophagy activity in TNBC cells. Drug sensitivity of CD44+CD24+/high TNBC cells is regulated through autophagy related signaling pathway. Taken together, CD24 mediated TNBC drug resistance is at least partially through autophagy activity. Citation Format: Lihong Huo, Xinyu Deng, Xiang Huang, Helena R Chang. Role of autophagy in CD24-mediated TNBC drug resistance [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-03-16.

This study aimed to investigate awareness, attitudes, and perspectives on precision medicine among health professionals in Korea and to identify issues that need to be addressed before implementing precision medicine. Mixed methods research was applied. For qualitative research, a semi-structured focus group interview was conducted with six health professionals. For quantitative research, a self-reported survey was administered. A total of 542 health professionals participated in the survey, and 526 completed the entire questionnaire. Health professionals showed positive attitudes toward precision medicine. About 95–96% of respondents agreed that precision medicine will be effective in treatment and precise diagnosis, and 69.9% reported that they would participate as study subjects. Meanwhile, they expressed concerns regarding educating patients and health professionals in precision medicine and developing research and data sharing infrastructure. Also, they emphasized the importance of developing precision medicine in an equitable way. Despite varying levels of awareness of precision medicine, the health professionals expressed a willingness to engage in precision medicine research, and recommended that health professionals work closely with policymakers to design precision medicine in a way that can be effectively adopted. Health professionals showed had a positive, but cautious, attitude toward precision medicine. The results of this study suggest areas to be addressed before ushering in precision medicine in Korea.

Diabetes is an established risk factor for developing cancer. A limited body of evidence also suggests that cancer can increase the risk of developing new cases of diabetes, but the evidence is inconclusive. To evaluate whether the development of cancer is associated with increasing risk of subsequent diabetes. This cohort study included a nationally representative sample of the Korean general population observed for up to 10 years (January 1, 2003, to December 31, 2013). A total of 524 089 men and women 20 to 70 years of age without diabetes and with no history of cancer at baseline were included. Incident cancer (time-varying exposure). Incident type 2 diabetes using insurance claim codes. During 3 492 935.6 person-years of follow-up (median follow-up, 7.0 years) in 494 189 individuals (50.0% female; mean [SD] age, 41.8 [12.5] years), 15 130 participants developed cancer and 26 610 participants developed diabetes. After adjustment for age, sex, precancer diabetes risk factors, metabolic factors, and comorbidities, the hazard ratio (HR) for diabetes associated with cancer development was 1.35 (95% CI, 1.26-1.45; P < .001). The excess risk for diabetes was highest in the first 2 years after cancer diagnosis, but it remained elevated throughout follow-up. By cancer type, development of pancreatic (HR, 5.15; 95% CI, 3.32-7.99), kidney (HR, 2.06; 95% CI, 1.34-3.16), liver (HR, 1.95; 95% CI, 1.50-2.54), gallbladder (HR, 1.79; 95% CI, 1.08-2.98), lung (HR, 1.74; 95% CI, 1.34-2.24), blood (HR, 1.61; 95% CI, 1.07-2.43), breast (HR, 1.60; 95% CI, 1.27-2.01), stomach (HR, 1.35; 95% CI, 1.16-1.58), and thyroid cancer (HR, 1.33; 95% CI, 1.12-1.59) was associated with a significantly increased risk of diabetes. In this large Korean cohort, cancer development increased the risk of subsequent diabetes. These data provide evidence that cancer is associated with an increased risk of diabetes in cancer survivors independent of traditional diabetes risk factors. Physicians should remember that patients with cancer develop other clinical problems, such as diabetes, with higher frequency than individuals without cancer, and should consider routine diabetes screening in these patients.

Purpose: A better predictive model for occult invasive disease in ductal carcinoma in situ (DCIS) patients is essential to guide the tailored use of sentinel node biopsies. We hypothesized that recent improvement of contrast-enhanced breast magnetic resonance imaging (MRI) could provide more accurate information on the presence of occult invasion in DCIS patients. Methods: From a prospectively maintained database, we identified 143 DCIS patients diagnosed with needle biopsies in whom MRI images were available. Results: Sixty-five patients (45.5%) were upstaged to invasive carcinoma after curative surgery. Ultrasonographic lesion size, mass-appearance on mammography, type of needle used, and the presence of suspicious microinvasive foci were associated with increased likelihood of upstaging. Among the features of MRI, only mass-appearance was significantly associated with the presence of invasive disease (p=0.002). However, up to 50% of masses in MRI cases had massappearance on mammography as well. Other morphologic and pharmacokinetic features of MRI, such as shape, margin, and patterns of enhancement and washout, did not have a significant association. Conclusion: Among various morphologic and pharmacokinetic parameters of contrast-enhanced MRI, only mass-appearance was associated with occult invasive disease. Our results show the limitations of current contrast-enhanced MRI in predicting invasive disease in patients with preoperative diagnoses of DCIS.