Recent retrospective studies suggest that beta-adrenergic blocking drugs (BB) are associated with improved outcomes in people with a range of cancers. Although limited and discordant data suggest that BB may increase overall survival (OS) of patients with localized breast cancer (BC), there is no information on the effects of BB in women with advanced BC.

To explore the association between BB use and BC outcomes, we retrospectively reviewed the ROSE/TRIO-012, a double-blinded, multinational phase III trial that randomized 1,144 patients with HER2-negative advanced BC to first-line docetaxel in combination with ramucirumab or placebo. We compared progression-free survival (PFS), OS, Overall Response Rate (ORR), and Clinical Benefit Rate (CBR) in patients who received BB to those who did not.

153/1,144 (13%) patients received BB; 62% prior to enrolment and 38% began after enrolment. Median PFS in BB treated patients was longer than in patients who did not receive them (10.3 vs. 8.3 months; HR 0.81; 95% CI 0.66-0.99; p = 0.038 ). Patients treated with BB only after enrolment had even higher median PFS (15.5 vs. 8.3 months, p < 0.001 ). In the TNBC subset, median PFS was 13 months with BB, compared to 5.2 months without BB (HR 0.52; 95% CI 0.34-0.79; p = 0.002 ). The benefit of BB intake in PFS was independent of treatment-emergent hypertension ( p =  0.476) but associated with treatment arm ( p = 0.037 ). The test for interactions between BB and treatment arm was not significant ( p = 0.276 ). No differences were seen in OS, ORR, or CBR. A validation dataset analysis had consistent but less substantial improved outcomes for women with node positive operable breast cancer receiving BB in the BCIRG-005 trial.

In this exploratory analysis BB intake was associated with significant improvement in PFS, particularly in patients with TNBC and patients not previously exposed to BB.