Hui Huang

Importance: Breast cancer mortality in the US declined between 1975 and 2019. The association of changes in metastatic breast cancer treatment with improved breast cancer mortality is unclear. Objective: To simulate the relative associations of breast cancer screening, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer with improved breast cancer mortality. Design, Setting, and Participants: Using aggregated observational and clinical trial data on the dissemination and effects of screening and treatment, 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models simulated US breast cancer mortality rates. Death due to breast cancer, overall and by estrogen receptor and ERBB2 (formerly HER2) status, among women aged 30 to 79 years in the US from 1975 to 2019 was simulated. Exposures: Screening mammography, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer. Main Outcomes and Measures: Model-estimated age-adjusted breast cancer mortality rate associated with screening, stage I to III treatment, and metastatic treatment relative to the absence of these exposures was assessed, as was model-estimated median survival after breast cancer metastatic recurrence. Results: The breast cancer mortality rate in the US (age adjusted) was 48/100 000 women in 1975 and 27/100 000 women in 2019. In 2019, the combination of screening, stage I to III treatment, and metastatic treatment was associated with a 58% reduction (model range, 55%-61%) in breast cancer mortality. Of this reduction, 29% (model range, 19%-33%) was associated with treatment of metastatic breast cancer, 47% (model range, 35%-60%) with treatment of stage I to III breast cancer, and 25% (model range, 21%-33%) with mammography screening. Based on simulations, the greatest change in survival after metastatic recurrence occurred between 2000 and 2019, from 1.9 years (model range, 1.0-2.7 years) to 3.2 years (model range, 2.0-4.9 years). Median survival for estrogen receptor (ER)-positive/ERBB2-positive breast cancer improved by 2.5 years (model range, 2.0-3.4 years), whereas median survival for ER-/ERBB2- breast cancer improved by 0.5 years (model range, 0.3-0.8 years). Conclusions and Relevance: According to 4 simulation models, breast cancer screening and treatment in 2019 were associated with a 58% reduction in US breast cancer mortality compared with interventions in 1975. Simulations suggested that treatment for stage I to III breast cancer was associated with approximately 47% of the mortality reduction, whereas treatment for metastatic breast cancer was associated with 29% of the reduction and screening with 25% of the reduction.

OBJECTIVES: To determine the relationship between age and aortic dilatation in patients with Marfan syndrome and to define the rate of progression of aortic dilatation in these patients. DESIGN: All patients were evaluated in a multidisciplinary clinic to establish a firm diagnosis of Marfan syndrome. Aortic dimensions were measured by echocardiography and patients with Marfan syndrome were followed up with annual physical and echocardiographic examinations to detect any change in aortic diameter over the subsequent four years. PATIENTS: One hundred and fifty-seven patients were referred to the clinic for assessment, of whom 40 exhibited diagnostic features of Marfan syndrome. Only 24 of these patients had previously been diagnosed with Marfan syndrome, while 17 other patients, previously diagnosed with Marfan syndrome, had insufficient clinical features to justify the diagnosis. RESULTS: Among the 40 patients (19 male, 21 female) with Marfan syndrome (mean age, 28 +/- 15 years), the prevalence of cardiovascular abnormalities was 90%. Aortic root dilatation was present in 78% of patients, aortic regurgitation in 28%, mitral valve prolapse in 65% and mitral regurgitation in 35%. Mean aortic root diameter in the Marfan patients (21.4 +/- 4.0 mm/m2 body surface area) markedly exceeded that of age and sex matched controls without Marfan syndrome (14.9 +/- 2.2 mm/m2) and that of first-degree relatives without Marfan syndrome (15.3 +/- 2.9 mm/m2). The occurrence of aortic dilatation in Marfan syndrome was variable, with patients as young as 20 years exhibiting severe dilatation. All patients with Marfan syndrome exhibiting aortic dilatation were advised to take beta-adrenergic blocking drugs, unless contraindicated, in an effort to retard the rate of aortic dilatation. Among 33 patients followed up for at least one year, 14 (42%) exhibited an increase in aortic diameter of at least 2 mm, while 16 of 23 patients (70%) followed up for at least three years exhibited similar progression of aortic dilatation. The overall mean rate of dilatation in the Marfan patients was 1.9 mm per year. Nine patients developed aortic dilatation of more than 50 mm diameter during four years' follow-up and required surgical repair of the aorta. Each of these patients is well at between three months' and four years' follow-up. CONCLUSIONS: Aneurysmal dilatation of the aorta is a common complication of Marfan syndrome and may become manifest at an early age. Furthermore, aortic dilatation can progress rapidly, even in the absence of symptoms. Individuals with Marfan syndrome should have annual echocardiographic examinations to monitor aortic root dimensions, and those exhibiting rapid progression of aortic dilatation or an aortic root diameter in excess of 50 mm, should be considered for elective composite graft repair of the aorta.