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This article is a survey of 476 consecutive cases of tumor death for heart involvement. The somewhat selected group of cases (from a Veterans Administration hospital) shows an incidence of cardiac metastasis of 19.1 per cent. The bulk of tumors metastasizing to the heart were bronchogenic carcinoma, malignant melanoma, malignant lymphoma, and carcinoma of the pancreas and esophagus. Electrocardiographic changes were frequent and correlated fairly closely with the anatomic extent of the disease. The related literature is reviewed.M YOCARDIAL involvement by neoplasms arising elsewhere in the body is no longer considered rare. A survey of the literature discloses a gradually rising incidence of myocardial metastasis as this subject is more closely explored. It has recently been estimated that more than 500 instances of tumor metastasis to the heart are now recorded, and more than 20 of these were diagnosed before death

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BACKGROUND: Over the last 40 years, the incidence of breast cancer in young women in the U.S. has been relatively low and stable, but the absolute number of young women with breast cancer is increasing because of the growing population. Some epidemiological studies have shown that breast cancer diagnosed before age 40 have significantly worse overall 5-year survival. Disease free survival is also inferior in young women, and they have more aggressive cancers in general. This study aims to validate these findings using genomic analysis of large databases. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA; n= 1095) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n=1894) were used for analysis. We divided the database into the Young (<40 yo) and Non-Young (>40 yo) cohorts, based on age at diagnosis. The following analysis will give the TCGA and METABRIC results in each category, respectively. RESULTS: There were 8.9% (98) and 6% (116) patients who were found to be Young. In the Young cohort, 69.5% (64) and 37.9% (44) were ER(+), whereas 77.9% (742) and 79.5% (1415) in the Non-Young cohort were ER(+). Further, 60.8% (56) and 31.9% (37) were PR(+) in the Young cohort, compared to 68.4% (641) and 54.4% (972) in the Non-Young cohort. Her2(+) cancers were noted in 22.2% (12) and 25% (29) in the Young cohort, whereas 22.6% (152) and 11.6% (207) were Her2(+) in the Non-Young cohort. Our group developed a pipeline to calculate PAM50 from the RNA-Seq dataset. Utilizing this calculated PAM50 in TCGA, we found that there were less Luminal A and B patients in the Young cohort, 41.6% (42) and 17.8% (18) compared to 49.7% (377) and 22.9% (174) in the Non-Young cohort. This was also the case in METABRIC where 17.2% (20) and 9.5% (11) were Luminal A and B, compared to 36.9% (659) and 25.2% (450) in the Non-Young group. In contrast, there were more basal-like subtypes in the Young group, 17.8% (18) and 28.4% (33), as compared to the Non-Young group, 16.1% (122) and 9.3% (166). These results agree with previous epidemiological studies that showed that hormone receptor positive tumors increase and basal-like subtypes decrease with age. The number of Stage I patients was lower in Young patients 13.5% (13) and 25.3% (22), than in Non-Young patients 17.3% (169) and 34.4% (453). Similarly, there were less Stage II patients in the Young 54.2% (52) and 58.6% (51) compared to 58.3% (569) and 56.9% (749) in the Non-Young. This reverses in Stage III where the incidence is increased in the Young at 31.2% (30) and 16.1% (14) compared to 22.4% (219) and 7.7% (101) in the Non-Young. Young patients had a lower median disease-free survival than Non-Young patients (NA vs 214.7 mo, p=0.027); however, there was no statistical significance in median survival. Young patients had a lower median disease-specific survival than non-young patients of 221.1 months vs 282.6 months (p=0.00123) in METABRIC. CONCLUSION: We used large datasets to examine survival in very young breast cancer patients (<40 yo) vs older patients and found that young patients are likely to have unfavorable subtypes, higher stage, and a lower overall survival and DFS as compared to their older counterparts. Further analysis with genomics is needed. Citation Format: Young JS, Kawaguchi T, Yan L, Qi Q, Liu S, Takabe K. Young breast cancer patients (<40 yo) have unfavorable subtypes, higher stage and worse survival [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-05-14.

INTRODUCTION: Young breast cancer patients have more aggressive subtypes and higher mortality rates. This study investigates the biologic, immunologic, and oncogenic differences between Young (≤40 yo) and Non-Young (>40 yo) patients with breast cancer. MATERIALS/METHODS: The Cancer Genome Atlas (TCGA; n=1095) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n=1894) were used for analysis. Gene Set Enrichment Analysis (GSEA) was performed on breast cancer patients in TCGA. We calculated mutation load using both TCGA and METABRIC. We also calculated the Cytolytic Activity Score (CYT), Mutant-Allele Tumor Heterogeneity (MATH), T-Cell Receptor (TCR)-Richness, and Ki67 mRNA expression in TCGA. RESULTS: There were 97 and 116 Young patients and 994 and 1788 Non-Young patients in the TCGA and METABRIC databases respectively. Young patients had a lower DFS (p=0.012) in TCGA. Young patients had a lower DSS (p<0.001) in METABRIC. There were less Stage I (13.5% vs 17.3%) and II (54.2% vs 58.3%) patients and more Stage III (31.2% vs 22.4%) patients in the Young group. There were more basal-like subtypes in the Young in TCGA (17.8% vs 16.1%) and METABRIC (28.4% vs 9.3%). Mutation load in TCGA was lower in the Young (p=0.030), but not significantly different in the METABRIC database. MATH, which reflects tumor heterogeneity, was not significantly different between the groups. These results were unexpected since Young patients have a higher proportion of basal-like subtype which is known to be rich in mutations and more immunogenic. In TCGA, Young patients were found to have higher amounts of activated dendritic cells (p=0.049). In METABRIC, Young patients had higher amounts of Plasma cells (p=0.016), CD4 memory-activated T-cells (p<0.001), NK resting cells (p=0.015), and M1 Macrophages (p=0.002). We also found that regulatory T-cells (p=0.029), activated NK cells (p=0.016), M2 Macrophages (p<0.001), and resting Mast cells (p=0.006) were lower in the Young. This unexpectedly showed that anti-tumor immune cells were more enriched in Young patients. Indeed, the CYT, which reflects tumor killing activity, and TCR-Richness, which reflects T-cell function, were both significantly higher in Young patients (p=0.034, p=0.004, respectively), which was opposite from what we expected due to its biological aggressiveness. GSEA was then used to analyze the TCGA database to clarify gene sets that are enriched in Young patients. Of the 50 Hallmark gene sets analyzed, 4 gene sets were found to be enriched in Young patients; G2M Checkpoint (p=0.002), Hallmark MYC Targets V1 (p=0.004), HALLMARK E2F Targets (p=0.035), and Hallmark Unfolded Protein Response (p=0.038). Ki67 which reflects cell proliferation was significantly higher in Young vs Non-Young patients (p=0.004). CONCLUSIONS: Both TCGA and METABRIC cohorts demonstrated that Young patients have more basal-like subtype and significantly worse survival. Our results support the notion that Young patients have more aggressive cancer not because of mutations, tumor heterogeneity or immune cell infiltrations, but because of aggressive oncogene expressions. Citation Format: Young JS, Asaoka M, Katsuta E, Kawaguchi T, Qi Q, Liu S, Yan L, Takabe K. Young breast cancer patients demonstrate worse survival associated with aggressive oncogene expression but not with mutation load, tumor heterogeneity or pro-tumor immune cell infiltrations [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 P3-06-15.