Beta-blockers (BB) are highly utilized as antihypertensive agents. Preclinical studies indicate BB use may modulate key biochemical pathways resulting in favorable breast cancer prognosis. However, this prognostic benefit has not been well elucidated in HER2-positive advanced breast cancer (ABC). The aim of this study was to evaluate the association between BB use and overall survival (OS) / progression-free survival (PFS) in patients with HER2+ ABC using targeted HER2-therapies within the phase III clinical trials CLEOPATRA, MARIANNE, EMILIA and THERESA.
The study was a pooled post-hoc analysis of individual-participant data (IPD). Cox proportional hazards analysis was used to assess the association between concomitant BB use and survival outcomes. Analyses were stratified by study and treatment and adjusted for age, race, body mass index, plasma albumin concentration levels, ER and PR status, performance status, presence of visceral disease and brain metastases and presence of cardiovascular disease and diabetes.
IPD was available from 2596 patients with HER2+ ABC of which 712 had pre-existing cardiovascular disease, and 249 (9.5%) were concomitantly using BB. Adjusted analysis indicated that individuals with concomitant BB use had worse OS (HR [95%CI] = 1.27 [1.04-1.55]; P= 0.017) compared to individuals not using BB. Similarly, OS in individuals with pre-existing cardiovascular disease (1.28 [1.02-1.61]; P=0.034) was not improved with BB use. Statistical significance was not observed between PFS and concomitant BB use.
Within high-quality large IPD, concomitant BB use was associated with worse OS. The association was independent of cardiovascular disease and other known prognostic factors. The study’s findings trend against the contemporary perception of BB use in cancer. Future research will have a role in identifying the cause, which is currently unknown, but possibly related to pre-existing cardiovascular disease severity, HER2+ ABC pathology, HER2 therapy-specific effects or BB use in HER2+ ABC.