Left Ventricular Ejection Fraction Screening and Clinical Decision-making in Metastatic HER2-positive Breast Cancer.

BACKGROUND: Antibodies against human epidermal growth factor receptor 2 (HER2) affect metastatic breast cancer cells and cardiac myocytes. Guidelines recommend evaluation of cardiac ejection fraction (EF) every 3 months despite little supporting evidence for this need. We assessed the impact of EF screening on clinical practice. PATIENTS AND METHODS: We carried out retrospective analysis of patients with HER2-positive metastatic breast cancer receiving HER2-directed therapy to assess the impact of aggressive cardiac screening on management decisions. RESULTS: Data for 128 patients were analyzed. The median number of EF screenings in the first year of therapy was 3 (range=1-8). A total of 29 patients had an asymptomatic decrease in EF. These patients had more EF screenings, more exposure to anthracyclines or left-sided radiation, were more likely to receive a cardiology consult and have an angiotensin converting enzyme inhibitor added to their therapy. Ninety patients underwent aggressive screening; this was not associated with cessation of HER2 therapy (p=0.92). CONCLUSION: Routine EF screening did not have an impact on decisions regarding HER2 therapy in patients with metastatic breast cancer. Given the known benefit of HER2 treatment, reducing the frequency of cardiac screening may be reasonable.

Younger age of menopause in women with cerebral aneurysms.

BACKGROUND: The incidence of subarachnoid hemorrhage in women surges following menopause. Estrogen fluctuations have been implicated in cerebral aneurysm formation, growth and rupture and are thought to explain the well-known gender disparity. The aim of this study was to examine the association between age at menopause, which can determine lifetime estrogen exposure, and the presence of cerebral aneurysms. METHODS: A retrospective case-control study was conducted by interviewing postmenopausal women with intradural cerebral aneurysms about their basic medical and gynecologic histories. This information was compared with the same data points collected from 4682 women contacted through random digit phone dialing in the National Institute of Child Health and Human Development-sponsored Contraceptive and Reproductive Experiences Study published in 2002. RESULTS: Among 76 consecutive postmenopausal women with cerebral aneurysms who were treated by a single physician and interviewed, multivariate logistic regression showed that later menopause age (OR 0.79, CI 0.63 to 0.996, p=0.046) was significantly associated with a lower aneurysm incidence. Premature menopause (<40 years) was seen in 26% of cases and 19% of controls (p=0.15). Each categorical increase in menopause age (<40, 40-44, 45-49, 50-54, ≥55 years) decreased the likelihood by 21%. Despite a trend towards earlier mean age at menopause in the case group, the difference was not statistically significant. CONCLUSION: There is a trend showing that an earlier age at menopause is associated with the presence of a cerebral aneurysm. This suggests that loss of estrogen earlier in a woman's life may contribute to the pathogenesis of cerebral aneurysm. These data may identify a risk factor for cerebral aneurysm pathogenesis and also a potential target for future therapies.