The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer

Purpose: Androgen receptor (AR) expression occurs in up to 86% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers. In vitro, AR inhibitors enhance antitumor activity of trastuzumab, an anti-HER2 antibody, in trastuzumab-resistant HER2+ cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety of enzalutamide, an AR-signaling inhibitor, in patients with advanced HER2+ AR+ breast cancer previously treated with trastuzumab. Methods: Eligible patients had measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group status 64 1, no history of brain metastases, and previously received 65 1 anti-HER2 regimen for advanced disease. Patients received 160\ua0mg oral enzalutamide daily and 6\ua0mg/kg intravenous trastuzumab every 21\ua0days until disease progression or unacceptable toxicity. Primary end point was clinical benefit rate at 24\ua0weeks (CBR24); secondary end points included progression-free survival (PFS) and safety. Results: Overall, 103\ua0women were enrolled [median age 60\ua0years (range 34\u201383)]; 62% had received 65 3\ua0lines of prior anti-HER2 therapy. CBR24, comprising patients with confirmed partial responses (5%) and durable stable disease at 24\ua0weeks (19%), was 24% in the efficacy evaluable set (n = 89). CBR24 did not seem related to AR-expression levels or hormone receptor status. Median PFS was 3.4\ua0months (95% confidence interval 2.0\u20133.8). Overall, 97 (94%) patients experienced treatment-emergent adverse events (TEAEs), with fatigue most common (34%). Dyspnea (4%) and malignant neoplasm progression (3%) were the only TEAEs grade 65 3 reported in 65 3\ua0patients. 22 patients (21%) reported serious TEAEs. Four patients (4%) experienced fatal, non-drug-related TEAEs. Conclusions: Enzalutamide plus trastuzumab was well tolerated, and a subset of patients in this heavily pretreated population had durable disease control. Determination of biomarkers is needed to identify patients most likely to benefit from this combination. ClinicalTrials.gov number: NCT0209196

Mapping high-risk clusters and identifying place-based risk factors of mental health burden in pregnancy

Purpose: Despite affecting up to 20% of women and being the leading cause of preventable deaths during the perinatal and postpartum period, maternal mental health conditions are chronically understudied. This study is the first to identify spatial patterns in perinatal mental health conditions, and relate these patterns to place-based social and environmental factors that drive cluster development. Methods: We performed spatial clustering analysis of emergency department (ED) visits for perinatal mood and anxiety disorders (PMAD), severe mental illness (SMI), and maternal mental disorders of pregnancy (MDP) using the Poisson model in SatScan from 2016 to 2019 in North Carolina. Logistic regression was used to examine the association between patient and community-level factors and high-risk clusters. Results: The most significant spatial clustering for all three outcomes was concentrated in smaller urban areas in the western, central piedmont, and coastal plains regions of the state, with odds ratios greater than 3 for some cluster locations. Individual factors (e.g., age, race, ethnicity) and contextual factors (e.g., racial and socioeconomic segregation, urbanity) were associated with high risk clusters. Conclusions: Results provide important contextual and spatial information concerning at-risk populations with a high burden of maternal mental health disorders and can better inform targeted locations for the expansion of maternal mental health services

Evaluation of Harms Reporting in U.S. Cancer Screening Guidelines

BACKGROUND: Cancer screening should be recommended only when the balance between benefits and harms is favorable. This review evaluated how U.S. cancer screening guidelines reported harms, within and across organ-specific processes to screen for cancer. OBJECTIVE: To describe current reporting practices and identify opportunities for improvement. DESIGN: Review of guidelines. SETTING: United States. PATIENTS: Patients eligible for screening for breast, cervical, colorectal, lung, or prostate cancer according to U.S. guidelines. MEASUREMENTS: Information was abstracted on reporting of patient-level harms associated with screening, diagnostic follow-up, and treatment. The authors classified harms reporting as not mentioned, conceptual, qualitative, or quantitative and noted whether literature was cited when harms were described. Frequency of harms reporting was summarized by organ type. RESULTS: Harms reporting was inconsistent across organ types and at each step of the cancer screening process. Guidelines did not report all harms for any specific organ type or for any category of harm across organ types. The most complete harms reporting was for prostate cancer screening guidelines and the least complete for colorectal cancer screening guidelines. Conceptualization of harms and use of quantitative evidence also differed by organ type. LIMITATIONS: This review considers only patient-level harms. The authors did not verify accuracy of harms information presented in the guidelines. CONCLUSION: The review identified opportunities for improving conceptualization, assessment, and reporting of screening process-related harms in guidelines. Future work should consider nuances associated with each organ-specific process to screen for cancer, including which harms are most salient and where evidence gaps exist, and explicitly explore how to optimally weigh available evidence in determining net screening benefit. Improved harms reporting could aid informed decision making, ultimately improving cancer screening delivery. PRIMARY FUNDING SOURCE: National Cancer Institute