Background: Evidence remains inconsistent regarding the potential influence of β-blocker (BB) use on clinical outcomes in women with breast cancer. We aimed to evaluate the association between BB and prognosis of breast cancer in an updated meta-analysis. Methods: Follow-up studies comparing the clinical outcomes of breast cancer in women with and without use of BB were included by search of PubMed, Embase, and Cochrane’s Library. A random-effect model was used to pool the results. Results: Seventeen observational studies were included. Pooled results did not support a significant association between BB use and breast cancer recurrence (risk ratio [RR] = 0.85, 95% confidence interval [CI]: 0.68–1.07, P=0.17), breast cancer related deaths (RR = 0.83, 95% CI: 0.65–1.06, P=0.14), or all-cause deaths (RR = 1.01, 95% CI: 0.91–1.11, P=0.91) in women with breast cancer. Study characteristics such as sample size, definition of BB use, follow-up durations, adjustment of menopausal status, or quality score did not significantly affect the results. Subgroup analyses showed that BB may be associated with a trend of reduced risk of all-cause deaths in women with breast cancer in prospective studies (two datasets, RR = 0.81, P=0.05), but not in retrospective studies (eight datasets, RR = 1.06, P=0.16; P for subgroup analyses = 0.02). Conclusions: Current evidence from observational studies does not support a significant association between BB use and improved prognosis in women with breast cancer.
Background. Formononetin, an active ingredient isolated from the traditional Chinese medicinal herb Astragalus membranaceus, has anticancer and chemoresistance-reducing biological activities. We evaluated the efficacy of formononetin in improving the tumoricidal effect of everolimus by suppressing the mTOR pathway in breast cancer cells. Methods. Cell survival was assessed using an MTT assay. Apoptosis was detected using flow cytometry. Proteins related to the mTOR pathway were detected and assessed using real-time PCR and Western blot analysis. Results. The results showed that formononetin enhances the efficacy of everolimus in suppressing breast cancer cell growth both in vitro and in vivo. The combination of formononetin and everolimus resulted in a 2-fold decrease in tumor volume and a 21.6% decrease in cell survival. The apoptosis ratio in cells treated with formononetin and everolimus increased by 27.9%. Formononetin and everolimus also inhibited the expression of p-mTOR and p-P70S6K and increased the expression of PTEN and p-4EBP-1. Notably, formononetin alone inhibited p-Akt expression but not everolimus. Conclusions. Formononetin enhances the tumoricidal effect of everolimus by inhibiting the activity of Akt.
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