Prognosis Of Different Subtypes Research Articles

Abstract PO2-08-02: Evaluation of predictive and prognostic value of androgen receptorexpression in breast cancer subtypes treated with neoadjuvantchemotherapy

Abstract Background Neoadjuvant chemotherapy is the standard treatment for local advanced breast cancer administered to shrink tumors and destroy undetected metastatic cells, thereby facilitating subsequent surgery. Previous studies have shown that AR may be used as a prognostic predictor in breast cancers, but its role in neoadjuvant therapy and the relationship with prognosis of different molecular subtypes of breast cancer need to be further explored. Methods We retrospectively evaluated 1231 breast cancer patients with complete medical records at Tianjin Medical University Cancer Institute and Hospital who were treated with neoadjuvant chemotherapy between January 2018 to December 2021. All the patients were selected for prognostic analysis. The follow-up time ranged from 12 to 60 months. We first analyzed the AR expression in different subtypes of breast cancer and its correlation with clinicopathological features. Meanwhile, the association of AR expression and pCR of different breast cancer subtypes was investigated. Finally, the effect of AR status on the prognosis of different subtypes of breast cancer after neoadjuvant therapy was analyzed. Results The positive rates of AR expression in HR +/HER2-, HR +/HER2 +, HR-/HER2 + and TNBC subtypes were 82.5%, 86.9%, 72.2% and 34.6%, respectively. Histological grade III (P = 0.014, OR = 1.862, 95% CI 1.137 to 2.562), ER positive expression (P = 0.002, OR = 0.381, 95% CI 0.102 to 0.754) and HER2 positive expression (P = 0.006, OR = 0.542, 95% CI 0.227 to 0.836) were independent related factors for AR positive expression. AR expression status was associated with pCR rate after neoadjuvant therapy only in subtype of TNBC. AR positive expression was independent protective factor for recurrence and metastasis in HR +/HER2- (P = 0.033, HR = 0.653, 95% CI 0.237 to 0.986) and HR +/HER2 + breast cancer (P = 0.012, HR = 0.803, 95% CI 0.167 to 0.959), but was independent risk factors for recurrence and metastasis in TNBC (P = 0.015, HR = 4.551, 95% CI 2.668 to 8.063). AR positive expression is not an independent predictor of HR-/HER2 + breast cancer. Conclusions AR expressed the lowest in TNBC, but it could be a potential marker for the prediction of pCR in neoadjuvant therapy. AR negative patients had a higher pCR rate. AR positive expression was an independent risk factor for pCR in TNBC after neoadjuvant therapy (P = 0.017, OR = 2.758, 95% CI 1.564 to 4.013). In HR +/HER2- subtype and in HR +/HER2 + subtype, the DFS rate in AR positive patients and AR negative patients was 96.2% vs 89.0% (P = 0.001, HR = 0.330, 95% CI 0.106 to 1.034) and was 96.0% vs 85.7% (P= 0.002, HR = 0.278, 95% CI 0.082 to 0.940), respectively. However, in HR-/HER2 + and TNBC subtypes, the DFS rate in AR positive patients and AR negative patients was 89.0% vs 95.9% (P = 0.102, HR = 3.211, 95% CI 1.117 to 9.224) and 75.0% vs 93.4% (P < 0.001, HR = 3.706, 95% CI 1.681 to 8.171), respectively. In HR +/HER2- and HR +/HER2 + breast cancer, AR positive patients had a better prognosis, however in TNBC, AR-positive patients have a poor prognosis Citation Format: Jin Zhang. Evaluation of predictive and prognostic value of androgen receptorexpression in breast cancer subtypes treated with neoadjuvantchemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-08-02.

Long-Term Prognosis of Different Subtypes of Left Ventricular Noncompaction Cardiomyopathy Patients: A Retrospective Study in China.

Left ventricular noncompaction (LVNC) is a heterogeneous cardiomyopathy that can be classified into different subtypes based on morphologic and functional features. However, the prognosis of the dilated and isolated subtypes of non-pediatric LVNC remains unknown. We retrospectively studied 101 patients with LVNC diagnosed at Peking Union Medical College Hospital from 2006 to 2022 using the Jenni criteria of transthoracic echocardiography. The patients were grouped into those with dilated LVNC (n = 64) or isolated LVNC (n = 37), and 88 patients (54 with dilated LVNC and 34 with isolated LVNC) were followed up successfully. The primary outcome was major adverse cardiovascular events (a composite of cardiovascular mortality, heart failure, severe ventricular arrhythmia, and systolic embolism). The median follow-up time was 5.24 years. The incidence of major adverse cardiovascular events was 43.2%; patients with dilated LVNC had a higher risk (adjusted hazard ratio, 4.43; 95% confidence interval, 1.24-15.81; p = 0.02) than those with isolated LVNC. None of the isolated LVNC patients had cardiovascular deaths or severe ventricular arrhythmias. The risk of systemic embolism was similar between patients with dilated and isolated LVNC. Our findings indicate that transthoracic echocardiography is a useful tool for classifying LVNC into subtypes with distinct clinical outcomes. Dilated LVNC is associated with a poor prognosis, while the isolated subtype is probably a physiological condition.

Analysis of prognosis in different subtypes of invasive lobular carcinoma using the Japanese National Cancer Database-Breast Cancer Registry.

Many studies have shown that the prognosis of invasive lobular carcinoma (ILC) is better than that of invasive ductal carcinoma (IDC). However, both disorders exhibit different prognoses according to molecular subtype, and the prognosis of ILC subtypes might depend on their hormone receptor positivity rate. This study clarified the prognosis of ILC and IDC in each subtype and examined the effectiveness of adjuvant chemotherapy (CT) in luminal ILC. We planned the analysis using data from the Breast Cancer Registry in Japan. Because it was presumed that there are differences in characteristics between ILC and IDC, we created matched cohorts using exact matching to compare their prognoses. We compared the prognosis of ILC and IDC for each subtype. We also compared the prognosis of luminal ILC between the CT and non-CT groups. For all subtypes, the disease-free survival (DFS) and overall survival (OS) of ILC were poorer than those of IDC. In the analysis by each subtype, no statistically significant difference was found in DFS and OS in luminal human epidermal growth factor 2 (HER2), HER2, and triple-negative cohorts; however, luminal ILC had significantly poorer DFS and OS than luminal IDC. The CT effects on the prognosis of luminal ILC were greater in more advanced cases. Luminal ILC had a poorer prognosis than luminal IDC, contributing to the worse prognosis of ILC than that of IDC in the overall cohort. Different therapeutic approaches from luminal IDC are essential for a better prognosis of luminal ILC.

Evaluation of predictive and prognostic value of androgen receptor expression in breast cancer subtypes treated with neoadjuvant chemotherapy

BackgroundNeoadjuvant chemotherapy is the standard treatment for local advanced breast cancer administered to shrink tumors and destroy undetected metastatic cells, thereby facilitating subsequent surgery. Previous studies have shown that AR may be used as a prognostic predictor in breast cancers, but its role in neoadjuvant therapy and the relationship with prognosis of different molecular subtypes of breast cancer need to be further explored.MethodsWe retrospectively evaluated 1231 breast cancer patients with complete medical records at Tianjin Medical University Cancer Institute and Hospital who were treated with neoadjuvant chemotherapy between January 2018 to December 2021. All the patients were selected for prognostic analysis. The follow-up time ranged from 12 to 60 months. We first analyzed the AR expression in different subtypes of breast cancer and its correlation with clinicopathological features. Meanwhile, the association of AR expression and pCR of different breast cancer subtypes was investigated. Finally, the effect of AR status on the prognosis of different subtypes of breast cancer after neoadjuvant therapy was analyzed.ResultsThe positive rates of AR expression in HR + /HER2-, HR + /HER2 +, HR-/HER2 + and TNBC subtypes were 82.5%, 86.9%, 72.2% and 34.6%, respectively. Histological grade III (P = 0.014, OR = 1.862, 95% CI 1.137 to 2.562), ER positive expression (P = 0.002, OR = 0.381, 95% CI 0.102 to 0.754) and HER2 positive expression (P = 0.006, OR = 0.542, 95% CI 0.227 to 0.836) were independent related factors for AR positive expression. AR expression status was associated with pCR rate after neoadjuvant therapy only in subtype of TNBC. AR positive expression was independent protective factor for recurrence and metastasis in HR + /HER2- (P = 0.033, HR = 0.653, 95% CI 0.237 to 0.986) and HR + /HER2 + breast cancer (P = 0.012, HR = 0.803, 95% CI 0.167 to 0.959), but was independent risk factors for recurrence and metastasis in TNBC (P = 0.015, HR = 4.551, 95% CI 2.668 to 8.063). AR positive expression is not an independent predictor of HR-/HER2 + breast cancer.ConclusionsAR expressed the lowest in TNBC, but it could be a potential marker for the prediction of pCR in neoadjuvant therapy. AR negative patients had a higher pCR rate. AR positive expression was an independent risk factor for pCR in TNBC after neoadjuvant therapy (P = 0.017, OR = 2.758, 95% CI 1.564 to 4.013). In HR + /HER2- subtype and in HR + /HER2 + subtype, the DFS rate in AR positive patients and AR negative patients was 96.2% vs 89.0% (P = 0.001, HR = 0.330, 95% CI 0.106 to 1.034) and was 96.0% vs 85.7% (P = 0.002, HR = 0.278, 95% CI 0.082 to 0.940), respectively. However, in HR-/HER2 + and TNBC subtypes, the DFS rate in AR positive patients and AR negative patients was 89.0% vs 95.9% (P = 0.102, HR = 3.211, 95% CI 1.117 to 9.224) and 75.0% vs 93.4% (P < 0.001, HR = 3.706, 95% CI 1.681 to 8.171), respectively. In HR + /HER2- and HR + /HER2 + breast cancer, AR positive patients had a better prognosis, however in TNBC, AR-positive patients have a poor prognosis.

Prognostic disparities in young patients based on breast cancer subtype: A population-based study from the SEER database.

Triple-negative breast cancer (TNBC) is associated with younger age and worse long-term survival. However, the characteristics and prognosis of different subtypes of breast cancer (BC) in young (<40 years) patients have not yet been elucidated. The present population-based study explored the clinical and pathological characteristics of young TNBC patients and investigated their long-term survival. We enrolled patients from the Surveillance, Epidemiology, and End Results database younger than 40 years of age with primary BC. Cases were defined as patients with TNBC (hormone receptor [HR]-/human epidermal growth factor receptor 2 [HER2]-), and controls were patients with other subtypes of BC (HR-/HER2+, HR+/HER2-, and HR+/HER2+). Demographic, pathological, and radiotherapy, chemotherapy, and surgery data were extracted and the overall survival was the primary endpoint. We enrolled 14,234 young patients with BC in the present study, of whom 2798 (19.7%) had TNBC and 11,436 (80.3%) had another BC subtype. A higher proportion of TNBC patients than non-TNBC patients had a more advanced tumor-node-metastasis stage (II-IV 80.5% vs 73.1%, P < .001), and smaller proportions underwent radiotherapy (50.0% vs 53.3%, P = .002) and surgery (91.8% vs 92.9%, P < .001). TNBC was associated with significantly lower 5-year survival rates than other subtypes among patients with regional node positivity (0, 1-3, 4-9, ≥10: 54.2% vs 57.7%, 44.2% vs 55.9%, 31.0% vs 52.0%, and 27.7% vs 38.8%, P < .001) and those with different lymph node ratios (low, intermediate, high: 50.9% vs 56.0%, 34.6% vs 53.6%, and 24.8% vs 44.8%, P < .001). Our research is the first to investigate the relevant characteristics of young TNBC patients in comparison with those of young non-TNBC patients based on the surveillance, epidemiology, and end results database. We found that young TNBC patients have a higher pathological stage and worse long-term survival than young patients with other BC subtypes. These findings have implications in identifying young patients with TNBC for aggressive therapy and further investigations should be performed to explore new multimodal treatments for such patients.

Abstract P4-02-25: Analysis of prognosis in different subtypes of invasive lobular carcinoma using a National Cancer Database Breast Cancer Registry of Japan

Abstract [Introduction] Invasive lobular carcinoma (ILC) has different pathological and clinical features from invasive ductal carcinoma (IDC). ILC has more likely to be hormone receptor (HR) positive, and several studies reported that the prognosis of ILC was better than IDC. However, ILC also has different prognosis according to the subtypes as IDC does, and better prognosis of ILC might depend on their high HR positivity. Additionally, there are many reports that chemotherapy (CT) does not improve the prognosis of ILC due to the high positivity of HR. Therefore, we compared the prognosis of ILC and IDC in the same subtypes and considered necessity of CT for luminal ILC. ILC usually constitutes small population of invasive breast cancer. Thus, we have planed the analysis by using the Breast Cancer Registry (BCR) run on the National Cancer Database (NCD) in Japan. [Methods] 318,338 breast cancer patients were registered in BCR between 2004 and 2012. We selected 250,736 patients who were diagnosed as ILC or IDC. Patients with distant metastasis, those who did not receive surgery, and those who received preoperative therapy, and those who had bilateral breast cancer were excluded, and it resulted in 207,428 patients. Of these cases, the cases with 10-year follow-up data were 136,654, and we examined 5,705 ILC and 130,949, IDC. Because it was presumed that there are differences in pathological and clinical characteristics between ILC and IDC, we have planned to make the matched cohorts by using exact matching for comparing their prognosis. To evaluate the prognosis of each subtype, we compared DFS and OS for IDC and ILC in each subtype. To evaluate the effect of CT in luminal ILC, we corrected the data of luminal ILC with pT2N0M0 or pT1-2N1M0 patients and compared DFS and OS between endocrine therapy (ET) only group and ET+CT group. DFS was defined as the time from surgery to local or distant recurrence or death from any cause. OS was defined as the time between the surgery and the death from any cause. Peason’s Chi squared test was used to identify the characteristics. Survival curves were constructed by Kaplan-Meier method and were compared by log-rank test. [Results] We made the matched cohort by using exact matching and we identified 5,633 ILC and 5,633 IDC for prognosis analysis. In overall subtypes, the 10-year DFS of ILC was poor than those of IDC (76.56% vs 79.14%, p=0.04). In the analysis by each subtype, there was no statistical difference in DFS for luminal HER2, HER2, and TN cohorts, however luminal ILC had statistically significant poor DFS than luminal IDC (78.04% vs 81.17%, p&amp;lt; 0.01). The analysis of 10-year OS showed similar results, and there were no differences in the OS of luminal HER2, HER2 and TN cohorts between ILC and IDC. However, ILC had worse OS than IDC in luminal cohort (85.95% vs 89.13%, p&amp;lt; 0.01). To evaluate the effect of CT in luminal ILC, we made the matched cohort and we identified 95 luminal IDC and 95 luminal ILC in pT2N0 cohort, and 83 luminal IDC and 83 luminal ILC in pT1-2N1 cohort for the analysis. In pT2N0 cohort, the 10-year DFS was 82.12% in ET+CT group and 87.35% in ET only group (p=0.99). The OS of the ET+CT and the ET only group was 93.48% and 94.04% (p=0.88). In pT1-2N1 cohort, the ET only group had 54.17% and the ET+CT group had 77.03% of DFS (p=0.34). The OS in the ET only group and the ET+CT group was 61.96% and 94.81% (p=0.01). [Discussion] Although luminal HER2, HER2 and TN cohorts had no differences in prognosis between ILC and IDC, luminal ILC had a poor prognosis than luminal IDC. Therefore, luminal ILC needs stronger approach to improve their prognosis. And it was suggested that chemotherapy is effective for recurrent high-risk luminal ILC such as those with positive lymph node metastasis. [Conclusion] ILC had worse prognosis than IDC in luminal cohort, however it was comparable in luminal HER2, HER2, TN cohorts. A new strategy of treatments for luminal ILC might be needed to improve their prognosis. Citation Format: Yayoi Adachi, Sota Asaga, Hiraku Kumamaru, Yutaka Yamamoto, Shigeru Imoto, Hiromitsu Jinno. Analysis of prognosis in different subtypes of invasive lobular carcinoma using a National Cancer Database Breast Cancer Registry of Japan [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-25.

Clinicopathological characteristics of mixed neuroendocrine-non-neuroendocrine neoplasms in gastrointestinal tract.

In 2019, the World Health Organization (WHO) classification system updated the definition of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), previously known as mixed adenoneuroendocrine carcinomas (MANECs). The clinicopathological characteristics of this new definition remains to be clarified. We analyzed the clinical data of 43 patients diagnosed with MiNENs in Wuhan Union Hospital from 2011 to 2020 according to the definition of MiNENs proposed in 2019. Among the 43 patients with MiNENs, the top two most common sites were stomach and colon, and 69.8% were males. Nearly half (21/43) of the patients were diagnosed at TNM stage III, and about 53.5% (23/43) of patients were the neuroendocrine neoplasm dominant type. Among the non-neuroendocrine tumor components of 43 MiNENs patients, adenocarcinoma accounted for 95.3% (41/43) and squamous cell carcinoma accounted for 4.7% (2/43)；95.3% (41/43) of the neuroendocrine neoplasm components were neuroendocrine carcinoma (NEC) and 4.7% (2/43) were neuroendocrine tumor (NET). Approximately 60.5% (26/43) neuroendocrine components had a Ki-67 index ≥55%. In addition, we further compared the prognosis of different subtypes of the MiNENs based on the neuroendocrine neoplasm component and non-neuroendocrine neoplasm component, and the results showed that there was no significant difference in survival between different subtypes of MiNENs (P>0.05). MiNENs can exhibit diverse clinicopathological characteristics, and there is no significant difference in prognosis among MiNENs subtypes, indicating that the definition of MiNENs can well summarize the prognosis of this type of tumor.

Clinical Features, Diagnostic Test Performance, and Prognosis in Different Subtypes of Chronic Pulmonary Aspergillosis

ObjectiveThe aim of this study was to describe clinical features in different subtypes of chronic pulmonary aspergillosis (CPA)-simple aspergilloma (SA), chronic cavitary pulmonary aspergillosis (CCPA), chronic fibrosing pulmonary aspergillosis (CFPA), aspergillus nodule (AN), and subacute invasive aspergillosis (SAIA), respectively, and identify long-term prognosis of CPA.MethodsWe reviewed patients diagnosed with different subtypes of CPA from 2002 to 2020 at Nanjing Jinling Hospital, China. We analyzed the clinical and survival information of five different subgroups. A Cox regression model was used to explore proper antifungal duration and long-term survival factors of CCPA and SAIA.ResultsA total of 147 patients with CPA were included, consisting of 11 SA, 48 CCPA, 5 CFPA, 12 AN, and 71 SAIA. The most common underlying pulmonary disease was pulmonary tuberculosis (n = 49, 33%), followed by bronchiectasis (n = 46, 31.3%) and chronic obstructive pulmonary disease (COPD) or emphysema (n = 45, 30.6%), while in SAIA and CFPA groups, the most common was COPD or emphysema (45.1 and 100%). Cough (85%), expectoration (70.7%), hemoptysis (54.4%), and fever (29.9%) were common symptoms, especially in CCPA, CFPA, and SAIA groups. The common imaging manifestations included cavitation (n = 94, 63.9%), fungal ball (n = 54, 36.7%), pleural thickening (n = 47, 32.0%), and bronchiectasis (n = 46, 31.3%). SAIA and CFPA groups had a lower value of hemoglobin (HB) and serum albumin (ALB) with higher C-reactive protein and erythrocyte sedimentation rate. The positive rate of sputum culture, serum galactomannan (GM), and bronchoalveolar lavage fluid GM was 32.7% (36/110), 18.4% (18/98), and 48.7% (19/39), respectively. There were 64.6% (31/48) patients with CCPA and 25.4% (18/71) patients with SAIA who received surgery and the 5-year cumulative survival rate was 92.1 and 66.6%, respectively. SAIA, old age, male, low body mass index (BMI), COPD or emphysema, multiple distribution, low serum ALB, and positive sputum culture were adverse prognosis factors for SAIA and CCPA group, and BMI ≤ 20.0 kg/m2 was independently associated with increased mortality (hazard ratio (HR) 5.311, 95% CI 1.405–20.068, p = 0.014). Multivariable Cox regression indicated that surgery (HR 0.093, 95% CI 0.011–0.814, p = 0.032) and antifungal duration >6 months (HR 0.204, 95% CI 0.060–0.696 p = 0.011) were related to improved survival.ConclusionThe clinical features and laboratory test performance are different among SA, CCPA, CFPA, AN, and SAIA. Low BMI was an independent risk factor for survival. Selective surgery and antifungal duration over 6 months were associated with improved survival.

The expression of HOXC10 is correlated with tumor-infiltrating immune cells in basal-like breast cancer and serves as a prognostic biomarker.

BackgroundHomeobox gene C10 (HOXC10) plays a vital role in the occurrence and development of several cancers, but its effects and underlying mechanism in the prognosis of different subtypes of breast cancer remain unclear.MethodsFirst, we evaluated and compared the expression levels of HOXC10 cancer to normal tissues in the Oncomine and Tumor Immune Estimation Resource (TIMER) databases. Second, the correlation between HOXC10 and the survival of patients with different types of cancer, including breast cancer, was analyzed in the PrognoScan, Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan-Meier plotter databases. Finally, the relationship between HOXC10 and immune-infiltration levels or gene marker sets of immune cells in basal-like breast cancer (BLBC) was investigated in the TIMER and GEPIA databases.ResultsThe expression of HOXC10 was elevated in breast cancer tissues. High HOXC10 expression indicated a poor prognosis for breast cancer patients, and expression affected the survival time of lymph-node positive or grade III breast cancer patients. In BLBC, the median overall survival (OS) of patients with high HOXC10 expression was significantly shorter than that of patients with low HOXC10 expression. HOXC10 was positively correlated with the immune infiltration of macrophages in BLBC. Breast cancer patients with low HOXC10 expression in different enriched immune-cell subgroups had a favorable prognosis.ConclusionsThe level of HOXC10 expression increased significantly in breast cancer, and elevated HOXC10 was positively correlated with immune-cell infiltration and poor prognosis in BLBC. These findings shed light on the important role of HOXC10 in breast cancer. HOXC10 should be recognized as a prognostic biomarker for determining prognosis and immune infiltration in BLBC patients.

High FAS expression correlates with a better prognosis and efficacy of taxanes and target regents in breast cancer.

FAS can serve as both an oncogene and a suppresser in different malignancies, and the prognostic value of FAS remains controversial. The Oncomine database, KM-Plotter and bc-GenExMiner platform were adopted to analyze the prognostic value of FAS in breast cancer. Breast cancer tissue microarrays were further used to verify these data. The Cell Miner Tool was used to predict the value of FAS mRNA expression in predicting the efficacies of clinical drugs. We found that both FAS mRNA and protein expression level significantly reduced in breast carcinoma. In addition, high FAS expression indicates a better metastatic relapse-free survival. Interestingly, FAS was associated with a better prognosis in different subtypes of breast cancer patients, namely, only in grade II and III, lymph nodal positive or p53 wild-type patients. The data from the Cell Miner Tool revealed that FAS mRNA expression was correlated with the efficacy of the first-line chemotherapeutic taxane agents and target drugs including olaparib and everolimus. FAS expression correlates with a better prognosis in breast cancer and may provide an effective clinical strategy to predict the sensitivity of taxanes and targeted drugs.

Role of LATS1/2 in Prognosis of Advanced Gastric Cancer and Its Relationship With the Tumor Immune Microenvironment.

Background: Gastric cancer (GC) remains a refractory cancer particularly in Eastern Asia. Large tumor suppressor kinases 1/2 (LATS1/2) are core members of the Hippo pathway. The role of LATS1/2 in the prognosis of different subtypes of advanced gastric cancer and its relationship with the tumor immune microenvironment in GC remain unknown. Exploring the role of LATS1/2 in GC might provide potential immunotherapeutic approaches for treating GC.Methods: Four hundred and ninety surgically resected primary GC samples were assessed for LATS1/2, CD8, FOXP3, and CD163. Correlations between LATS1/2 expression and immune-related markers were investigated and the prognoses of patients with different GC subtypes were analyzed.Results: CD8 and CD163 appeared to be favorable and adverse prognostic factors, respectively. LATS1/2 and FOXP3 did not predict patients' overall survival. However, in microsatellite-stable GC patients, high LATS1/2 and FOXP3 expression and low CD8 expression predicted poor prognoses. Furthermore, high LATS1/2 expression was significantly correlated with decreased CD8 and increased FOXP3. Combined analysis of LATS1/2, CD8, and FOXP3 had better prognostic accuracy than did each marker individually.Conclusions: Different biological molecules can predict the prognoses of different types of GC patients. LATS1/2, core kinases in the Hippo pathway, are closely related to CD8 and FOXP3. Further understanding the mechanisms of LATS1/2 in CD8+ T cells and FOXP3+ Treg cells provides further theoretical basis and potential targets for GC immunotherapy.

Predicting the invasiveness of lung adenocarcinomas appearing as ground-glass nodule on CT scan using multi-task learning and deep radiomics.

BackgroundDue to different treatment method and prognosis of different subtypes of lung adenocarcinomas appearing as ground-glass nodules (GGNs) on computed tomography (CT) scan, it is important to classify invasive adenocarcinomas from non-invasive adenocarcinomas. The purpose of this paper is to build and evaluate the performance of deep learning networks on the differentiation the invasiveness of lung adenocarcinoma appearing as GGNs.MethodsThis retrospective study included 886 GGNs from 794 pathological confirmed patients with lung adenocarcinoma for training and testing the proposed networks. Three deep learning networks, namely XimaNet (deep learning-based classification model), XimaSharp (classification and nodule segmentation model), and Deep-RadNet (deep learning and radiomics combined classification model, i.e., deep radiomics) were built. Three classification tasks, namely task 1: classification of AAH/AIS and MIA, task 2: classification of MIA and IAC, and task 3: classification of non-invasive adenocarcinomas and invasive adenocarcinomas (AAH/AIS&MIA and IAC) were conducted to evaluate the model performance. The Z-test was used to compare the model performance.ResultsThe AUC for classification of AAH/AIS with MIA were 0.891, 0.841 and 0.779 for Deep-RadNet, XimaNet and XimaSharp respectively. The AUC for classification of MIA with IAC were 0.889, 0.785 and 0.778 for three networks and AUC for classification of AAH/AIS&MIA with IAC were 0.941, 0.892 and 0.827 respectively. The performance of deep_RadNet was better than the other two models with the Z-test (P<0.05).ConclusionsDeep-RadNet with the visual heat map could evaluate the invasiveness of GGNs accurately and intuitively, providing a theoretical basis for individualized and accurate medical treatment of patients with GGNs.

Identification of tumor microenvironment-related genes in lower-grade gliomas by mining TCGA database.

BackgroundLower-grade gliomas (LGGs) are ubiquitous and fatal branches of brain neoplasm. Finding biomarkers related to diagnosis and treatment is essential for the treatment of LGG. It is possible to reveal the potential links between tumor microenvironment and overall survival (OS) in LGG by mining the mRNA expression profile from the TCGA database. Our primary purpose was to explore key genes that can be applied for diagnosis or treatment in LGG microenvironment.MethodsBased on the ESTIMATE algorithm, the immune and stromal scores were calculated to measure the extent of infiltration of immune cells and stromal cells, respectively. The LGG samples from TCGA database were assigned into high- or low-score groups per the immune and stromal scores and differentially expressed genes (DEGs) were selected by comparing gene expression levels in the two groups. Functional enrichment analysis and protein-protein interaction (PPI) networks were performed to analyze DEGs. Finally, selected DEGs were validated using another independent LGG cohort from CGGA dataset.ResultsThe results indicated that immune/stromal scores correlated with LGG prognosis. Furtherly, survival analysis conducted for each subtype shown that immune/stromal scores were only significantly associated with the prognosis of astrocytoma, IDH-wildtype, and there was no significant statistical difference in the other subtypes. Functional enrichment analysis and protein-protein interaction (PPI) networks further showed that the upregulated DEGs were primarily involved in immune response, plasma membrane, and cytokine binding. Accordingly, a series of genes that have significant impacts on prognosis and are significantly associated with the tumor microenvironment were obtained.ConclusionsBased on the ESTIMATE algorithm, we first explored the relationship between immune/stromal scores and prognosis in different subtypes of LGG and the result shown that the scores were only strongly associated with the prognosis of astrocytoma, IDH-wildtype. Furtherly, a comprehensive bioinformatics analysis of the gene expression profiles of astrocytoma, IDH-wildtype patients was conducted, CASP8, TRIM6, TRIM38, PARP9, NMI, EPSTI1, DTX3L and AGBL2 were identified as tumor microenvironment-related genes, may be involved in the occurrence, development, and invasion of LGG.

Lip Infantile Hemangiomas Involving the Vermillion Border Have Worse Outcomes and Prognosis to Oral Propranolol Than Lesions Confined to One Side of the Vermillion

Oral propranolol has been widely used for problematic infantile hemangiomas (IHs). Lip IHs present a high risk of disfigurement and associated psychosocial dysfunction and require early treatment. Lips are compound parts that consist of the upper and lower lips and include the mucosal and cutaneous lips histologically. The present retrospective study aimed to determine the response and prognosis of different subtypes of lip IHs to the use of systemic propranolol. The data from 81 patients with lip IHs treated with systemic propranolol (2mg/kg/day) were reviewed. Localized and segmental lip IHs were evaluated separately. The outcomes and prognosis of localized hemangiomas were further evaluated stratified by different features: 1) upper and lower lip; and 2) crossing the vermilion border. The lesions involving the upper lips and those involving the lower lips had the same outcomes and prognosis. Lesions involving the vermillion border required longer treatment and had poorer outcomes and prognosis compared with lesions confined to 1 side of the vermilion. After oral propranolol treatment, IHs localized to upper lip had the same outcomes and prognosis as IHs localized to the lower lip. Lip IHs involving the vermillion border had worse outcomes and prognosis than lesions confined to 1 side of the vermillion.

P.015 Long-term progression and prognosis in different subtypes of Parkinson’s disease: validation of a new multi-domain subtyping method

Background: Parkinson’s disease (PD) varies in clinical manifestations and course of progression from person to person. Identification of distinct PD subtypes is of great priority to develop personalized care approaches. We aimed to compare long-term progression and prognosis between different PD subtypes. Methods: Data on 421 individuals with de novo early-onset PD was retrieved from Parkinson’s Progression Markers Initiative (PPMI). Using a newly developed multi-domain subtyping method (based on motor phenotype, RBD, autonomic disturbance, early cognitive deficit), we divided PD population into three subtypes at baseline: “mild motor-predominant”, “Diffuse malignant” and “Intermediate”. Rate of global progression (mixed motor and non-motor features) and developing dementia were compared between the subtypes. Results: Patients with “diffuse malignant” PD experienced 0.5 z-score further worsening of global composite outcome (p=0.017) and 2.2 further decline in MOCA score (p=0.001) after 6-years of follow-up. Hazard for MCI/dementia was significantly higher in “diffuse malignant” (HR=3.2, p&amp;lt;0.001) and “intermediate” (HR=1.8, p&amp;lt;0.001) subtypes. Individuals with “diffuse malignant” PD had the lowest level of CSF amyloid-beta (p=0.006) and SPECT striatal binding ratio (p=0.001). Conclusions: This multi-domain subtyping is a valid method to predict subgroups of PD with distinct patterns of long-term progression at drug-naïve early-stage with potential application in real-life clinical practice.

Abstract P2-08-47: Evaluation of stromal tumor-infiltrating lymphocytes (sTIL) and tertiary lymphoid structures (TLS) in early breast cancer patients with triple negative breast cancer(TNBC) included in a prospective study of neoadjuvant chemotherapy (NAC) with Epirubicin and cyclophosphamide (EC) and carboplatin-paclitaxel (PC) (BSMO 2014-01)

Abstract Background: BSMO 2014-01 is a completed prospective phase 2 study evaluating the efficacy of neoadjuvant EC and PC. One of the secondary endpoints was the correlation of sTIL with response, pCR and survival. We also assessed the relationship between sTIL and TLS in the diagnostic biopsies. Methods: Stromal TIL (sTIL) were evaluated on H&amp;E stained tumor biopsies before the start of the NAC according to the criteria described by Salgado et al(1). Scores were defined as "low" or "high" if lymphocytic infiltration in the stroma around the tumor was ≤ 10% or &amp;gt; 10%. TLS are ectopic lymph node-like structures recently identified in breast cancer. TLS were counted using a dual IHC stain for CD3 (T cells) and CD20 (B cells) and categorized as "little" if the TLS occupied &amp;lt; 10% or "moderate to abundant" if they occupied ≥ 10% of the adjacent tissue. The correlation between sTIL and pathologic parameters was analyzed using the chi-square test; DFS and OS between the groups was estimated by using the log-rank test. Results: So far we could quantify the number of sTIL in 38 out of 63 TNBC pts treated with neoadjuvant EC-PC. Twenty eight pts had a high sTIL score and 10 pts had a low sTIL score. The high-sTIL group (19/28) achieved a numerical higher pathologic complete remission (pCR) rate than the low-sTIL group (5/10) (p=0.3); both groups had a comparable disease free survival of 28.6 mths and 26.7 mths respectively (p=0.7). The overall survival was similar:29 mths and 27.8 mths respectively (p=0.8). Stromal TLS were identified in 10 out 23 samples available for this analysis and we could demonstrate a positive correlation between high levels of sTIL and high levels of moderate to abundant TLS(CD3) in the adjacent tissue in six out of the ten samples in which TLS were present (p=0.1). Conclusion: These preliminary results could not confirm the results published by Denkert et al earlier this year(2). A trend for correlation of the presence of high sTIL with moderate to abundant levels of TLS was found. Analysis on the remaining samples of all patients included in the study and correlation with outcome is ongoing and these completed results will be presented. (1)Assessing Tumor-infiltrating lymphocytes in solid tumors. Hendry S, Salgado R et al. Adv Anat Pathol 2017; 235-251. (2)Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer. Denkert C et al. Lancet Oncol 2018; 40-50. Citation Format: Fontaine C, Van den Eynden G, de Wind R, Boisson A, Renard V, Van den Bulck H, Vuylsteke P, Glorieux P, Dopchie C, Decoster L, De Grève J, Awada A, Wildiers H, Willard-Gallo K. Evaluation of stromal tumor-infiltrating lymphocytes (sTIL) and tertiary lymphoid structures (TLS) in early breast cancer patients with triple negative breast cancer(TNBC) included in a prospective study of neoadjuvant chemotherapy (NAC) with Epirubicin and cyclophosphamide (EC) and carboplatin-paclitaxel (PC) (BSMO 2014-01) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-47.

Prognosis in different subtypes of metaplastic breast cancer: a population-based analysis.

Metaplastic breast cancer (MpBC) is a rare histological subtype of breast cancer recognized as a unique pathologic entity in 2000. However, the pathogenesis, optimal therapy, and prognosis of MpBC and the potential effect of systemic treatments on different subtypes of MpBC are not well defined. A retrospective population-based study was performed to identify breast cancer patients with MpBC and other triple-negative breast cancers (TNBC) between 2010 and 2014 using the surveillance, Epidemiology, and End Results (SEER) database. Chi-square test was used to analyze characteristics between subgroups. Kaplan-Meier analysis and Multivariate Cox regressions were used to evaluate overall survival (OS) of MpBC, TNBC, and MpBC subgroups. Competing risk analysis and multivariate regression model of competing risk were used to assess breast cancer-specific survival (BCSS) of MpBC and TNBC RESULTS: We identified a study cohort of 22,433 patients (1112 MpBC and 21,321 TNBC). MpBC correlated with older population, larger tumor size and less lymph node involvement, and TNBC phenotype. Patients with MpBC especially with triple-negative subtype (TN-MpBC) had worse survival than the overall TNBC population. However, the prognosis of MpBC without triple-negative subtype (non-TN MpBC) was not different from that of TNBC. In Kaplan-Meier analysis, chemotherapy was not associated with significant difference in OS of TN-MpBC. In non-TN MpBC group, the 3-year OS was 79.8% for patients receiving chemotherapy and 70.5% in patients without chemotherapy, and chemotherapy was associated (P = 0.033) with improved OS. Within the MpBC patients, radiotherapy was significantly (HR 1.544; 95% CI 1.148-2.078; P = 0.004) associated with improved OS and (HR 1.474; 95% CI 1.067-2.040; P = 0.019) BCSS. Patients with TN-MpBC had worse prognosis than TNBC and chemotherapy was not associated with improved survival. In contrast, non-TN MpBC may derive survival benefit from chemotherapy and radiotherapy.

Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy

Tumour-infiltrating lymphocytes (TILs) are predictive for response to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) and HER2-positive breast cancer, but their role in luminal breast cancer and the effect of TILs on prognosis in all subtypes is less clear. Here, we assessed the relevance of TILs for chemotherapy response and prognosis in patients with TNBC, HER2-positive breast cancer, and luminal-HER2-negative breast cancer. Patients with primary breast cancer who were treated with neoadjuvant combination chemotherapy were included from six randomised trials done by the German Breast Cancer Group. Pretherapeutic core biopsies from 3771 patients included in these studies were assessed for the number of stromal TILs by standardised methods according to the guidelines of the International TIL working group. TILs were analysed both as a continuous parameter and in three predefined groups of low (0-10% immune cells in stromal tissue within the tumour), intermediate (11-59%), and high TILs (≥60%). We used these data in univariable and multivariable statistical models to assess the association between TIL concentration and pathological complete response in all patients, and between the amount of TILs and disease-free survival and overall survival in 2560 patients from five of the six clinical trial cohorts. In the luminal-HER2-negative breast cancer subtype, a pathological complete response (pCR) was achieved in 45 (6%) of 759 patients with low TILs, 48 (11%) of 435 with intermediate TILs, and 49 (28%) of 172 with high TILs. In the HER2-positive subtype, pCR was observed in 194 (32%) of 605 patients with low TILs, 198 (39%) of 512 with intermediate TILs, and 127 (48%) of 262 with high TILs. Finally, in the TNBC subtype, pCR was achieved in 80 (31%) of 260 patients with low TILs, 117 (31%) of 373 with intermediate TILs, and 136 (50%) of 273 with high TILs (p<0·0001 for each subtype, χ2 test for trend). In the univariable analysis, a 10% increase in TILs was associated with longer disease-free survival in TNBC (hazard ratio [HR] 0·93 [95% CI 0·87-0·98], p=0·011) and HER2-positive breast cancer (0·94 [0·89-0·99], p=0·017), but not in luminal-HER2-negative tumours (1·02 [0·96-1·09], p=0·46). The increase in TILs was also associated with longer overall survival in TNBC (0·92 [0·86-0·99], p=0·032), but had no association in HER2-positive breast cancer (0·94 [0·86-1·02], p=0·11), and was associated with shorter overall survival in luminal-HER2-negative tumours (1·10 [1·02-1·19], p=0·011). Increased TIL concentration predicted response to neoadjuvant chemotherapy in all molecular subtypes assessed, and was also associated with a survival benefit in HER2-positive breast cancer and TNBC. By contrast, increased TILs were an adverse prognostic factor for survival in luminal-HER2-negative breast cancer, suggesting a different biology of the immunological infiltrate in this subtype. Our data support the hypothesis that breast cancer is immunogenic and might be targetable by immune-modulating therapies. In light of the results in luminal breast cancer, further research investigating the interaction of the immune system with different types of endocrine therapy is warranted. Deutsche Krebshilfe and European Commission.

Diagnosis and Clinical Analysis of Primary Thyroid Lymphoma.

Objective To summarize our experiences in the diagnosis and prognosis of different subtypes of primary thyroid lymphoma (PTL). Methods The clinical data of 27 PTL patients who were treated in our hospital from January 1998 to December 2014 were retrospectively analyzed. The pathological types of these patients included B cell lymphoma unclassifiable (BCLU) (n=5),mucosa-associated lymphiod tissue lymphoma (MALT) (n=9),diffuse large B cell lymphoma (DLBCL) (n=12),and T cell lymphoma (n=1). Results Of all these 27 cases,the most common clinical symptom was painless swelling of the neck (n=21,77.8%). Of 7 patients who had received preoperative fine needle biopsy,lymphoma was suspected in 2 cases (28.6%). Among these 7 cases,the positive rate of suspicious lymphoma was 66.7% in 3 DLBCL patients,0 in 3 MALT patients,and 0 in 1 BCLU paitent. Also,25 patients underwent intraoperative frozen pathological examination,which revealed lymphoma or suspicious lymphoma in 16 cases (64.0%); in these patients,the positive rate was 66.7% for BCLU,77.8% for MALT,58.3% for DLBCL,and 0 for T-cell lymphomas. The overall survival was (89.3±12.4) months,and the overall 5-year survival rate was 61.6%. The estimated survival in symptomatic group was 31.6 months,which was significantly shorter than that in asymptomatic group (97.9 months) (P=0.032). Other factors including age,sex,tumor size,tumor stage,international prognostic index,tracheal compression,lactate dehydrogenase,residual tumor,and pathological type showed no significant effect on survival(all P>0.05). Conclusions DLBCL has the highest fine needle biopsy positive rate,MALT has the highest frozen pathological positive rate,and intraoperative frozen pathology has more malignant results than the preoperative fine needle biopsy in the diagnosis. The accompanying lymphoma symptoms may be an adverse prognostic factor.

Prognostic significance of tumor subtypes in women with breast cancer according to stage: A population-based study.

1070 Background: Tumor subtypes (TS) are an important prognostic tool in breast cancer patients (pts). However, with contemporary therapies the prognosis of different subtypes is unclear. Recently, the AJCC proposed to incorporate TS among other variables in the 8th edition of the staging manual. The aim of this study was to analyze differences in overall survival (OS) by TS according to stage compared with other factors. Methods: We evaluated women with microscopically confirmed invasive breast cancer between 2010 and 2013 with known estrogen receptor (ER) and progesterone receptor (PR) (together hormone receptor [HR]) status and human epidermal growth factor receptor 2 (HER2) status reported to the SEER program. Pts with other primary either before or after breast cancer were excluded. Pt characteristics were compared between TS. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. Results: We included 166,054 pts. Median age was 60 years (range 18-108). Median follow-up was 21 months (range 1-48). TS distribution was: 72.5% HR+/HER2-, 10.8% HR+/HER2+, 4.8% HR-/HER2+ and 12% triple negative (TN). Pts with HR+/HER2- tumors were older, had lower grade and presented with earlier stage (all p &lt; 0.0001). OS at 3 years for each subtype according to stage is shown in the table (p for interaction &lt; 0.0001). These differences in OS by TS continued to be significant for each stage in multivariate analysis adjusted for age, race, grade, histology and marital status. Conclusions: In this cohort, we observed significant differences in pt characteristics according to TS. Although HR+/HER2- tumors had better clinicopathologic features, the HR+/HER2+ group had the best OS in most stages. OS was significantly different by TS in each of the 4 stages and these results remained significant in the multivariate model. Pts with TN stage 1 tumors had similar OS as pts with HR+/HER2+ stage 2 tumors. Our results support the incorporation of TS as part of the staging variables in breast cancer. [Table: see text]