title: Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival.
abstract: Laboratory models show that the beta-blocker, propranolol, can inhibit norepinephrine-induced breast cancer cell migration. We hypothesised that breast cancer patients receiving beta-blockers for hypertension would show reduced metastasis and improved clinical outcome. Three patient subgroups were identified from the medical records of 466 consecutive female patients (median age 57, range 28-71) with operable breast cancer and follow-up (>10 years). Two subgroups comprised 43 and 49 hypertensive patients treated with beta-blockers or other antihypertensives respectively, prior to cancer diagnosis. 374 patients formed a non-hypertensive control group. Metastasis development, disease free interval, tumour recurrence and hazards risk were statistically compared between groups. Kaplan-Meier plots were used to model survival and DM. Beta-blocker treated patients showed a significant reduction in metastasis development (p=0.026), tumour recurrence (p=0.001), and longer disease free interval (p=0.01). In addition, there was a 57% reduced risk of metastasis (Hazards ratio=0.430; 95% CI=0.200-0.926, p=0.031), and a 71% reduction in breast cancer mortality after 10 years (Hazards ratio=0.291; 95% CI=0.119-0.715, p=0.007). This proof-of-principle study showed beta-blocker therapy significantly reduces distant metastases, cancer recurrence, and cancer-specific mortality in breast cancer patients suggesting a novel role for beta-blocker therapy. A larger epidemiological study leading to randomised clinical trials is needed for breast and other cancer types including colon, prostate and ovary.
authors.affiliation: Department of Cellular Pathology, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK and The John van Geest Cancer Research Centre School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS UK.
authors.forename: Desmond G
authors.initials: DG
authors.lastname: Powe
authors.affiliation: Institute of Immunology, University of Witten/Herdecke, DE-58448, Witten, Germany.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Voss
authors.affiliation: Institute of Immunology, University of Witten/Herdecke, DE-58448, Witten, Germany.
authors.forename: Kurt S
authors.initials: KS
authors.lastname: Zänker
authors.affiliation: School of Molecular Medical Sciences, University of Nottingham, Nottingham, NG7 2UH, UK.
authors.forename: Hany O
authors.initials: HO
authors.lastname: Habashy
authors.affiliation: School of Molecular Medical Sciences, University of Nottingham, Nottingham, NG7 2UH, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
authors.affiliation: School of Molecular Medical Sciences, University of Nottingham, Nottingham, NG7 2UH, UK.
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.affiliation: Institute of Immunology, University of Witten/Herdecke, DE-58448, Witten, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Entschladen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists