Despite concerns about cognitive decline after cancer treatment, most breast cancer survivors show no increased risk of developing Alzheimer’s disease, and some may have a slightly lower risk than their cancer-free peers, according to a large retrospective study from Korea.
However, any apparent protective effect faded with time, the investigators reported online in JAMA Network Open.
Overall, this is “reassuring news for cancer survivors,” Tim Ahles, PhD, a psychologist with Memorial Sloan Kettering Cancer Center, New York City, who wasn’t involved in the study, told Medscape Medical News.
“I get this question from patients a lot,” Ahles said. And based on these findings, “it doesn’t look like a history of breast cancer and breast cancer treatment increases your risk for Alzheimer’s disease.”
Breast cancer survivors often report cancer-related cognitive impairment, such as difficulties with concentration and memory, both during and after cancer treatment. But evidence surrounding patients’ risk for Alzheimer’s disease is mixed. One large study based in Sweden, for instance, reported a 35% increased risk for Alzheimer’s disease among patients diagnosed with breast cancer after the age of 65 years, but not among younger patients. A population-based study from Taiwan, however, found no increase in the risk for dementia overall compared with cancer-free individuals but did note a lower dementia risk in patients who had received tamoxifen.
To help clarify the evidence, investigators assessed Alzheimer’s disease risk in a large cohort of patients and explored the association by treatment type, age, and important risk factors.
Using the Korean National Health Insurance Service database, the researchers matched 70,701 patients who underwent breast cancer surgery between 2010 and 2016 with 180,360 cancer-free control individuals.
The mean age of breast cancer survivors was 53.1 years. Overall, 72% received radiotherapy. Cyclophosphamide (57%) and anthracycline (50%) were the most commonly used chemotherapies, and tamoxifen (47%) and aromatase inhibitors (30%) were the most commonly used endocrine therapies.
The primary outcome of this study was the incidence of newly diagnosed Alzheimer’s disease, which was defined on the basis of at least one prescription for medications to manage dementia associated with Alzheimer’s disease (donepezil, rivastigmine, galantamine, or memantine).
During a median follow-up of about 7 years, 1229 newly diagnosed Alzheimer’s disease cases were detected in breast cancer survivors and 3430 cases in control individuals — incidence rates of 2.45 and 2.63 per 1000 person-years, respectively.
This corresponded to an 8% lower risk for Alzheimer’s disease in breast cancer survivors compared with cancer-free control individuals at 6 months (subdistribution hazard ratio [SHR], 0.92; 95% CI, 0.86-0.98). The association was especially notable in survivors older than 65 years (SHR, 0.92; 95% CI, 0.85-0.99).
Looking at individual treatment modalities, only radiation therapy was associated with significantly lower risk for Alzheimer’s disease among breast cancer survivors (adjusted HR [aHR], 0.77).
Several risk factors were associated with a significantly higher risk for Alzheimer’s disease: current smoker vs never or ex-smokers (aHR, 2.04), diabetes (aHR, 1.58), and chronic kidney disease (aHR, 3.11). Notably, alcohol use, physical activity level, and hypertension were not associated with Alzheimer’s disease risk.
However, any potential protective effect may be short-lived. The reduced risk for Alzheimer’s disease was no longer significant at 1 year (SHR, 0.94; 95% CI, 0.87-1.01), 3 years (SHR, 0.97; 95% CI, 0.90-1.05), or 5 years (SHR, 0.98; 95% CI, 0.89-1.08).
Even so, breast cancer survivors can still feel reassured by the findings.
“Concerns about chemobrain and the long-term adverse effects of breast cancer treatment on cognition are common, but our findings suggest that this treatment does not directly lead to Alzheimer’s disease,” wrote the authors, led by Su-Min Jeong, MD, with Seoul National University College of Medicine, Seoul, South Korea.
Ahles agreed. The general takeaway from this study is that there is “no strong evidence that the cancer treatment is going to increase your risk for developing Alzheimer’s,” Ahles said. When patients ask about the risk for Alzheimer’s disease, “I can say, ‘Here’s yet another new study that supports the idea that there’s no increased risk.’”
He cautioned, however, that the study doesn’t address whether people with a genetic predisposition to Alzheimer’s might develop it sooner due to cancer treatment.
“Does the cancer treatment increase your probability or nudge you along? The study doesn’t answer that question,” Ahles said.
The study reported having no commercial funding. Jeong and Ahles reported having no relevant disclosures.