Alzheimer's Gene Tied to 'Chemo Brain' in Breast Cancer Survivors
Many older breast cancer patients might worry that they will be struck by "chemo brain" after their treatments, but a new study suggests that only those who carry a gene linked to Alzheimer's face that risk.
Researchers found that breast cancer survivors carrying the APOE4 gene who underwent chemotherapy were more likely to experience long-term impairment in brain function.
But the study did not prove that the gene caused the cognitive (thinking) problems known as chemo brain. And the declines observed were small, the study authors added.
"It was only a small group who had cognitive problems after chemotherapy treatment, and those women were distinct in having that APOE4 gene," said lead researcher Dr. Jeanne Mandelblatt. She is a professor of oncology at Georgetown Lombardi Comprehensive Cancer Center, in Washington, D.C.
These results are good news for the large majority of breast cancer survivors. Most women who received chemotherapy or hormone therapy didn't experience long-term thinking or memory declines related to either their cancer or their treatment, the findings showed.
"Our study suggests that, for most older breast cancer patients, chemotherapy and hormonal treatments do not have major adverse effects on cognitive function, at least as measured by our current tests," Mandelblatt said.
Experts have long been concerned that older people might be at increased risk for thinking and memory problems related to cancer treatment, Mandelblatt said.
Aging is already related to dementia and Alzheimer's disease, she noted, and seniors also face a number of other health problems that affect their ability to think.
For the study, researchers recruited 344 breast cancer patients between the ages of 60 and 98. These women were compared with 347 healthy women of similar ages, to see whether breast cancer or its treatments spurred any sort of intellectual decline.
Both groups of women were given a battery of 13 cognitive tests at the beginning of the study, before cancer patients received any treatment. They were re-tested one and two years later.
Tests showed that women treated with hormone therapy suffered no long-term cognitive problems, whether or not they carried the APOE4 gene.
But breast cancer patients with the APOE4 gene did experience a notable decline in thinking and memory if they received chemotherapy, the researchers reported.
"The APOE4 gene is a very strong genetic risk factor for Alzheimer's disease," Mandelblatt said. "There's probably some interaction between chemotherapy and something this gene controls, but we're very careful to say this finding needs to be replicated. We also need to take this into the laboratory so we can understand better the mechanisms and pathways."
Only 20 percent to 25 percent of people are APOE4-positive, Mandelblatt said, and fewer than 30 percent of older breast cancer patients receive chemotherapy.
And she emphasized that the mental declines observed were not large.
"The types of cognitive changes we observed even in this group who were at genetic risk, these changes were reasonably mild and not of the magnitude you see in Alzheimer's disease," Mandelblatt said. "We don't want women to worry that they're going to have severe memory problems. These were mild declines in cognitive abilities."
So, it's too soon to include the APOE4 gene in discussions about breast cancer treatment, Mandelblatt stressed.
"It needs more research before we can make a recommendation like that," Mandelblatt concluded. "The primary consideration for women in choosing their treatment is to survive their cancer. If their cancer is more advanced, they're going to want to choose the most aggressive treatment so they survive their disease."
One cancer expert agreed.
The current trend is to use chemotherapy less often in treating breast cancer patients, given recent findings that show it's often not needed, said Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society.
"On the other side of the equation, women whose breast cancer has recurred may require chemotherapy, and there may not be an option to avoid it even with the presence of this gene," Lichtenfeld said.
More research and discussion are needed before treatment guidelines are changed to take into account the APOE4 gene, Lichtenfeld said.
"It's very rare we immediately change course on what we do," Lichtenfeld said. "We certainly need perhaps more research and certainly more discussion before routinely testing women for the presence of that gene."
The study was published Oct. 4 in the Journal of Clinical Oncology.
The U.S. National Institute on Aging has more about genetics and Alzheimer's disease.
SOURCES: Jeanne Mandelblatt, M.D., MPH, professor, oncology, Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C.; Len Lichtenfeld, M.D., deputy chief medical officer, American Cancer Society; Oct. 3, 2018, Journal of Clinical Oncology