medwireNews: Statin use is not associated with improved survival outcomes in patients with early-stage HER2-positive breast cancer, suggests a post-hoc analysis of the APHINITY trial.
“These results must be interpreted with caution due to the exploratory nature of the analysis and the associated limitations,” say Christian Maurer (University Hospital and German Cancer Research Center Heidelberg) and co-workers.
They explain in Breast Cancer Research and Treatment that “[p]reclinical models suggest that the mevalonate pathway, which can be targeted with statins, acts as an escape mechanism of survival and growth in HER2-[positive breast cancer] resistant to anti-HER2 therapies.”
And so, examining the association between statin use and outcomes in this patient population is warranted, continue the investigators.
They conducted a post-hoc analysis of the phase 3 APHINITY trial, which investigated the addition of pertuzumab versus placebo to adjuvant trastuzumab plus chemotherapy in 4804 patients with early HER2-positive breast cancer.
A total of 423 (8.8%) participants were taking statins at baseline or initiated them within a year of random assignment in the trial. They were significantly older than participants who were not statin users (median age 62 vs 50 years), more frequently postmenopausal (91.1 vs 47.6%), and had a higher BMI (median 27.3 vs 24.4 kg/m2).
Statin users were also significantly more likely than nonusers to have smaller tumors (≤1.9 cm, 46.1 vs 39.5%) and to be diagnosed with hyperlipidemia (83.0 vs 3.4%), hypertension (64.1 vs 18.4%), diabetes (24.6 vs 3.9%), and coronary heart disease (4.0 vs 0.6%).
On the other hand, anthracycline-containing chemotherapy regimens were used significantly less often among statin users than nonusers (71.4 vs 78.6%).
Multivariate analysis adjusting for age, menopausal status, BMI, nodal and hormone receptor status, presence of comorbidities, and treatment arm showed no significant association between statin use and invasive disease-free survival, distant relapse-free interval, or overall survival, with respective nonsignificant hazard ratios of 1.11, 1.21, and 1.16.
The researchers note that in univariate analysis, statin use “was associated with a trend to worse [overall survival],” but add that “[i]t should come as no surprise that patients who take statins under the assumption of a concomitant disease could have a higher risk of death during the course of a clinical trial follow-up.”
Furthermore, “[i]n a competing risk analysis with the event of interest being death due to [breast cancer], statin treatment was not associated with outcome,” they continue.
In conclusion, Maurer et al say: “Only a prospective, randomized study would be able to clarify whether the prognosis of patients with early breast cancer could be improved by statins. However, considering the high costs and complexity of running such a trial, it remains questionable whether this will ever happen.
“So far, apart from the current known indications for statin use, adding statins for early HER2-positive breast cancer is not recommended.”
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Breast Cancer Res Treat 2025; doi:10.1007/s10549-025-07699-2
