Coronary artery disease detected by coronary computed tomography angiography in adult survivors of childhood Hodgkin lymphoma.

BACKGROUND: Survivors of Hodgkin lymphoma (HL) have significant cardiovascular risk and require long-term surveillance. The current study assessed the prevalence of coronary artery disease (CAD) by coronary computed tomography angiography (CCTA) in adult survivors of childhood HL. METHODS: Thirty-one survivors of HL, 13 of whom (42%) were treated with radiotherapy (RT) only and 18 of whom (58%) were treated with multimodal therapy, underwent CCTA, echocardiography, electrocardiography (ECG), and treadmill stress testing. Obstructive CAD was defined as ≥50% occlusion of the left main or ≥70% occlusion of the left anterior descending, left circumflex, or right coronary arteries on CCTA. Echocardiograms with resting wall motion abnormalities or an ejection fraction <50%; ECGs with Q waves, ST abnormalities without Q waves, or T-wave abnormalities without Q waves; and a J-point depression of ≥1 mm with a horizontal or downsloping ST segment on stress testing were considered abnormal. RESULTS: The prevalence of disease in participants (median age, 40 years [range, 26 years-55 years]; median time from cancer diagnosis, 24 years [range, 17 years-39 years]) was 39%, with 39 plaques detected among 12 survivors. Three participants (10%) treated with RT only had 4 obstructive lesions; 9 patients (29%; 5 of whom were treated with RT only and 4 of whom were treated with multimodal therapy) had nonobstructive lesions. Approximately 15% of lesions involved the left main, 21% involved the proximal left anterior descending, 18% involved the proximal right coronary, and 13% involved the proximal left circumflex arteries. Of the 12 participants found to have CAD by CCTA, 7 had a positive ECG, 1 had a positive echocardiogram, and 1 had a positive stress test. CONCLUSIONS: CCTA identified CAD in a substantial percentage of survivors of HL and may be an effective screening modality for this population.

Triple-Negative Breast Cancer: Breast Tumors With an Identity Crisis.

ABSTRACT: Triple-negative breast cancer (TNBC) is pathologically defined by lack of expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 amplification and portends an aggressive clinical course with worse outcomes compared with other breast cancers. Until recently, standard treatment options consisted of sequential cytotoxic chemotherapies for both early and metastatic disease. Advances in sequencing technology have led to the identification of 4 main subtypes of TNBC based on recurrent genetic alterations, transcriptional patterns, and molecular features: basal-like 1 (BL1), basal-like 2 (BL2), mesenchymal (M), and luminal androgen receptor (LAR). Frequent alterations found in DNA damage response pathways, germline and somatic BRCA1/2 genes, PI3K signaling pathways, and the presence of androgen receptors and infiltrating immune cells could serve as actionable targets to optimize treatments and improve outcomes for patients with TNBC. Recent approvals for immune checkpoint inhibitors and the antibody-drug conjugate, sacituzumab govitecan-hziy, for advanced TNBC illustrate the advances in treatment that can result from these molecular discoveries. This review will explore the molecular subtypes of TNBC and their distinct characteristics, as well as highlight the molecular features and potential "drivers" that have been identified as promising targets for new treatment strategies.

Targeting the PI3K/AKT/mTOR Pathway in Hormone-Positive Breast Cancer.

Approximately 70% of invasive breast cancers have some degree of dependence on the estrogen hormone for cell proliferation and growth. These tumors have estrogen and/or progesterone receptors (ER/PR+), generally referred to as hormone receptor positive (HR+) tumors, as indicated by the presence of positive staining and varying intensity levels of estrogen and/or progesterone receptors on immunohistochemistry. Therapies that inhibit ER signaling pathways, such as aromatase inhibitors (letrozole, anastrozole, exemestane), selective ER modulators (tamoxifen), and ER down-regulators (fulvestrant), are the mainstays of treatment for hormone-receptor-positive breast cancers. However, de novo or acquired resistance to ER targeted therapies is present in many tumors, leading to disease progression. The PI3K/AKT/mTOR pathway is implicated in sustaining endocrine resistance and has become the target of many new drugs for ER+ breast cancer. This article reviews the function of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway and the various classes of PI3K pathway inhibitors that have been developed to disrupt this pathway signaling for the treatment of hormone-receptor-positive breast cancer.

Comorbidities Drive Outcomes for Both Malignancy-Associated and Non-Malignancy-Associated Hemophagocytic Syndrome.

BACKGROUND: Secondary hemophagocytic syndrome (SHPS) is a syndrome that develops as a result of infection, autoimmunity, or underlying malignancy. We studied novel predictors of mortality among adults with SHPS. PATIENTS AND METHODS: SHPS were identified from the Nationwide Inpatient Sample for 2009 to 2011 using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), codes. Charlson comorbidity index (CCI) was used for comorbidity assessment, excluding malignancy. Patient- and hospital-related factors on mortality were assessed by chi-square test or analysis of variance. P values were 2 sided, and the level of significance was .05. RESULTS: A total of 276 patient hospitalizations with SHPS were identified. Forty-four had an associated malignancy, 38 (86%) of which were hematologic. Median age was 42 years (range, 18-89 years). A total of 66% (n = 182) had a CCI of 0, 13% (n = 27) had a CCI of 1, and 21% (n = 57) had a CCI of 2 or more. On bivariate analysis, inpatient mortality rate was significantly higher in malignancy-associated hemophagocytic syndrome (HPS) (odds ratio [OR], 2.07; P = .04), age ≥ 50 years (OR, 3.46; P < .01), CCI ≥ 2 (OR, 3.04; P < .01), and Medicare patients (OR, 2.32; P < .01). In multivariate analysis, CCI ≥ 2 remained an independent predictor of survival in the overall study cohort (OR, 3.52; 95% confidence interval, 1.51-8.18; P < .01). CONCLUSION: Malignancy-associated HPS, CCI ≥ 2, age > 50 years, and Medicare patients were associated with a worse in-hospital mortality. In multivariate analysis, greater comorbidity burden appeared to be the single most important predictor of mortality. This suggests that outcomes for adults with HPS are predicated by the extent of organ dysfunction at diagnosis.