Breast Cancer Survivors May Face Lower Alzheimer Risk, Especially With Radiation

Compared with women without breast cancer, most survivors of breast cancer have a decreased risk for Alzheimer disease (AD), according to the findings of a study published in JAMA Network Open.

Many breast cancer survivors report difficulty concentrating and with memory during and after their cancer treatment.

To assess whether breast cancer affects AD risk, researchers from the Seoul National University College of Medicine and Sungkyunkwan University School of Medicine sourced data for this study from the Korean National Health Insurance Service (K-NHIS) database, which covers 97% of the population in South Korea. Patients (n=70,701) who underwent surgery for breast cancer between 2010 and 2016 were matched in a 1:3 ratio with individuals who were cancer-free (n=180,360) and evaluated for AD through 2020.

The mean ages of the survivor and control groups were 53.1 and 53.3 years, respectively (P <.001). A body mass index (BMI) of 25 kg/m² or higher was observed in 30.9% of survivors and 30.5% of control individuals (P =.03). Dyslipidemia was present in 18.1% and 17.4% (P < .001), hypertension in 22.1% and 21.7% (P =.01), and diabetes in 6.7% and 6.4% of the survivor and control groups, respectively (P =.03).

Cancer survivors had received cyclophosphamide (56.8%), anthracycline (50.1%), tamoxifen (47.0%), and aromatase inhibitors (30.0%).

During follow-up, the incidence rate of AD was 2.45 per 1000 person-years among breast cancer survivors and 2.63 per 1000 person-years among control individuals.

In the fully adjusted model, AD risk was significantly lower among breast cancer survivors than control individuals (adjusted subdistribution hazard ratio [aSHR], 0.92; 95% CI, 0.86-0.98).

Stratified by age, lower risk for AD was observed among breast cancer survivors aged 65 years and older (aSHR, 0.92; 95% CI, 0.85-0.99) but not among younger survivors with no significant age interaction (P =.96).

In the subgroup analyses, the lower risk for AD among breast cancer survivors was only observed among those who received radiation therapy (adjusted hazard ratio [aHR], 0.77; 95% CI, 0.68-0.87), whereas higher risk for AD was observed among those with:

• chronic kidney disease (aHR, 3.11; 95% CI, 1.98-4.88),
• current smokers (aHR, 2.04; 95% CI, 1.53-2.72),
• diabetes (aHR, 1.58; 95% CI, 1.36-1.82), and
• those with an income in the lowest quartile (aHR, 1.24; 95% CI, 1.08-1.43).

In the unadjusted landmark analyses, a lower risk for AD among breast cancer survivors was observed at 6 months (subdistribution hazard ratio [SHR], 0.91; 95% CI, 0.85-0.97), 1 year (SHR, 0.92; 95% CI, 0.86-0.98), and 3 years (SHR, 0.93; 95% CI, 0.96-0.99) but not at 5 years (SHR, 0.93; 95% CI, 0.85-1.02). These trends were attenuated in adjusted analyses at all time points after 6 months (aSHR, 0.92; 95% CI, 0.86-0.99). No age interactions were observed all (P ≥.42).

The researchers wrote, “Understanding the potential protective association of breast cancer on AD can enhance surveillance strategies for AD among these survivors.”

The major limitation in this study was the significant group differences at baseline.

“[B]reast cancer survivors had an 8% lower risk of AD compared with age-matched controls without cancer. Breast cancer treatment with radiation was associated with a lower risk of AD. Landmark analyses suggest that a longer survival period might attenuate this association,” the researchers concluded.