Dementias in Older Women With Early‐Stage HER2 ‐Negative Breast Cancer Treated With Anthracycline Plus Taxane Versus Taxane‐Based Chemotherapy Regimens

Vollständiger Abstract

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ABSTRACT Background Anthracycline plus taxane (ATAX) regimens are associated with improved survival in HER2‐negative breast cancer (HBC) compared to taxane‐based (TAX) regimens. However, anthracyclines are known for their cardiotoxicity, which could increase the risk of neurocognitive deficits, raising concerns about neurocognitive safety, particularly in older adults. Limited evidence exists comparing neurocognitive outcomes between these two regimens. Objective To compare the incidence of Alzheimer's disease and related dementias (ADRD) between ATAX and TAX regimens in neoadjuvant (Trial #1) and adjuvant (Trial #2) settings among older women with early‐stage HBC. Methods Using SEER‐Medicare data (2010–2021), we identified women aged ≥ 66 years with newly diagnosed HBC and no prior neurocognitive conditions between 2011 and 2021. Patients were longitudinally tracked, and their eligibility for each regimen was evaluated. We applied the clone‐censor‐weight method and used weighted pooled logistic regression to estimate the 10‐year risks of ADRD, Alzheimer's disease (AD), and vascular dementia (VD). Results We identified 14 079 and 9321 eligible individuals in Trial #1 and Trial #2, respectively. For ADRD outcome, the 10‐year risk difference (RD) was −6.91% (95% CI: −15.60% to 0.91%) for HR+/HER2‐ cohort and −2.14% (95% CI: −9.57% to 5.46%) for TNBC cohort in Trial #1. The 10‐year RD was −1.42% (95% CI: −9.33% to 6.98%) for HR+/HER2‐ cohort and −2.91% (95% CI: −9.54% to 7.86%) for TNBC cohort in Trial #2. Conclusion Our findings suggest that ATAX regimens were not associated with increased risks of ADRD, AD, and VD compared to TAX regimens in older women with HBC. However, the risks of AD and VD should be interpreted with caution due to sparse events. These findings may support the continued use of ATAX regimens in this population, while also informing more personalized, risk‐adapted treatment strategies.