Background
Statins are hypothesized to reduce the risk of cardiotoxicity associated with anthracyclines and trastuzumab. Our aim was to study the association of statin exposure with hospitalization or emergency department visits (hospital presentations) for heart failure (HF) after anthracycline‐ and/or trastuzumab‐containing chemotherapy for early breast cancer.
Methods and Results
Using linked administrative databases, we conducted a retrospective cohort study of women aged ≥66 years without prior HF who received anthracyclines or trastuzumab for newly diagnosed early breast cancer in Ontario between 2007 to 2017. Statin‐exposed and unexposed women were matched 1:1 using propensity scores. Trastuzumab‐treated women were also matched on anthracycline exposure. We matched 666 statin‐discordant pairs of anthracycline‐treated women and 390 pairs of trastuzumab‐treated women (median age, 69 and 71 years, respectively). The 5‐year cumulative incidence of HF hospital presentations after anthracyclines was 1.2% (95% CI, 0.5%–2.6%) in statin‐exposed women and 2.9% (95% CI, 1.7%–4.6%) in unexposed women (
P
value, 0.01). The cause‐specific hazard ratio associated with statins in the anthracycline cohort was 0.45 (95% CI, 0.24–0.85;
P
value, 0.01). After trastuzumab, the 5‐year cumulative incidence of HF hospital presentations was 2.7% (95% CI, 1.2%–5.2%) in statin‐exposed women and 3.7% (95% CI, 2.0%–6.2%) in unexposed women (
P
value 0.09). The cause‐specific hazard ratio associated with statins in the trastuzumab cohort was 0.46 (95% CI, 0.20–1.07;
P
value, 0.07).
Conclusions
Statin‐exposed women had a lower risk of HF hospital presentations after early breast cancer chemotherapy involving anthracyclines, with non‐significant trends towards lower risk following trastuzumab. These findings support the development of randomized controlled trials of statins for prevention of cardiotoxicity.
Glioblastoma (GBM) carries a dismal prognosis and inevitably relapses despite aggressive therapy. Many members of the Eph receptor tyrosine kinase (EphR) family are expressed by GBM stem cells (GSC), which have been implicated in resistance to GBM therapy. In this study, we identify several EphRs that mark a therapeutically targetable GSC population in treatment-refractory, recurrent GBM (rGBM). Using a highly specific EphR antibody panel and CyTOF (cytometry by time-of-flight), we characterized the expression of all 14 EphR in primary and recurrent patient-derived GSCs to identify putative rGBM-specific EphR. EPHA2 and EPHA3 coexpression marked a highly tumorigenic cell population in rGBM that was enriched in GSC marker expression. Knockdown of EPHA2 and EPHA3 together led to increased expression of differentiation marker GFAP and blocked clonogenic and tumorigenic potential, promoting significantly higher survival Treatment of rGBM with a bispecific antibody against EPHA2/A3 reduced clonogenicity and tumorigenic potential of xenografted recurrent GBM via downregulation of AKT and ERK and increased cellular differentiation. In conclusion, we show that EPHA2 and EPHA3 together mark a GSC population in rGBM and that strategic cotargeting of EPHA2 and EPHA3 presents a novel and rational therapeutic approach for rGBM. Treatment of rGBM with a novel bispecific antibody against EPHA2 and EPHA3 reduces tumor burden, paving the way for the development of therapeutic approaches against biologically relevant targets in rGBM. .
PurposeWe sought to determine to what extent the knowledge of carrying a BRCA1 or BRCA2 mutation influences the uptake of preventive surgeries in Bahamian women, including bilateral salpingo‐oophorectomy and bilateral mastectomy.Patients and methodsThe study population consisted of 78 female residents of the Bahamas for whom a BRCA1 or BRCA2 mutation had been detected between 2004 and 2014. The mean age of the 78 participants at the time of genetic testing was 46 years (age range 22–73 years). The mean time of follow‐up was 4.4 years.ResultsOf the 78 study participants, 19 women had a bilateral salpingo‐oophorectomy (24%). Seven out of 37 patients who had unilateral breast cancer chose to remove the unaffected contralateral breast (19%). Three of 13 patients with no history of breast cancer chose to have a prophylactic bilateral mastectomy (23%).ConclusionPreventive surgery is an acceptable option for a significant proportion of Bahamian women with a BRCA1 or BRCA2 mutation. It will be important to identify and reduce barriers to preventive surgery in the Bahamas in order that the benefit of getting testing can be fully realized.
Purpose of reviewCoronary artery disease (CAD) is a common comorbidity in patients with cancer. We review shared risk factors between the two diseases and cancer treatments that increase the risk of CAD. We also discuss outcomes and management considerations of patients with cancer who develop CAD.Recent findingsSeveral traditional and novel risk factors promote the development of both CAD and cancer. Several cancer treatments further increase the risk of CAD. The presence of cancer is associated with a higher burden of comorbidities and thrombocytopenia, which predisposes patients to higher bleeding risks. Patients with cancer who develop acute coronary syndromes are less likely to receive timely revascularization or appropriate medical therapy, despite evidence showing that receipt of these interventions is associated with substantial benefit. Accordingly, a cancer diagnosis is associated with worse outcomes in patients with CAD. The risk-benefit balance of revascularization is becoming more favorable due to the improving prognosis of many cancers and safer revascularization strategies, including shorter requirements for dual antiplatelet therapy after revascularization.SummarySeveral factors increase the complexity of managing CAD in patients with cancer. A multidisciplinary approach is recommended to guide treatment decisions in this high-risk and growing patient group.
Clinicians should be aware of the potential for the pharmacologic activity of SGLT2 inhibitors to persist long after the standard drug clearance period of five half-lives, the typical duration used to guide pre-operative medication recommendations.
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