By Linda Carroll

(Reuters Health) – Most older women who get chemotherapy for breast cancer do not experience problems with cognition in the first two years after diagnosis and treatment, a new study finds.

But researchers did find one small subset of women who suffered some declines in attention, mental processing speed and decision making, according to the results published in the Journal of Clinical Oncology.

Among those who did experience declines, most carried a genetic mutation, APOE4, that has been linked to a heightened risk for Alzheimer’s disease, said the study’s lead author, Dr. Jeanne Mandelblatt, a professor of oncology and medicine at Georgetown University’s Lombardi Comprehensive Cancer Center in Washington, DC.

“It suggests to us that there might be a chemotherapy and APOE4 interaction,” Mandelblatt said. “So, these women may have had an underlying susceptibility to cognitive problems.”

Mandelblatt and her colleagues followed 344 newly diagnosed patients with early-stage breast cancer and 347 healthy women as a comparison group for two years. The cancer survivors and controls were 60 to 98 years old at the beginning of the study.

Both groups of women were given cognitive tests at the outset to evaluate attention, processing speed, executive functioning, verbal learning and memory. The patients were retested after breast cancer chemotherapy or hormonal treatments and then participants were tested again 12 months and 24 months later.

Most of the cancer patients showed no declines in cognition compared with the control group. But those who had the APOE4 mutation and received chemotherapy did show declines in all tested areas. Over time this subgroup also saw improvements in verbal learning and memory, but the declines in attention, processing speed and executive functioning persisted.

Mandelblatt cautioned against taking the APOE4 results too far, however. “While this was a very large study, only about 30 percent of women treated for breast cancer received chemotherapy,” she explained. “And only about 20-25 percent were APOE4 positive. The subset with both (characteristics) is small, which is why I think this very provocative finding, while important, needs to be (confirmed in other studies).”

For women worried about the potential cognitive effects of cancer treatment, the overall findings might be most useful to those whose tumor characteristics suggest that chemotherapy’s usefulness in prolonging survival “might be a bit of a tossup,” Mandelblatt said.

“This is an important study,” said Tracy Vannorsdall, an assistant professor of psychiatry and behavioral medicine at Johns Hopkins Medicine in Baltimore, Maryland. “We know breast cancer occurs more frequently in older women. But there are far fewer studies in older women showing how diseases and treatments affect them. There’s been a need for this kind of study.”

The new findings “will allow providers to have a more informed conversation with their patients about how treatments might affect cognition,” said Vannorsdall, who wasn’t involved in the study. “They may also help researchers find out who will be at greater risk and also whether there are interventions that might help improve cognition and daily functioning.”

Still, before doctors change their practices, “I think there’s going to need to be more data,” Vannorsdall said.

One piece of good news for those with the APOE4 mutation: “they were no different from the other groups after two years in terms of learning and memory,” Vannorsdall noted.

The study overall will be encouraging to older women with breast cancer, said Dr. Jules Cohen, a clinical associate professor of medicine at Stony Brook University in New York. Cohen, who wasn’t involved in the new research, has been studying the impact of chemotherapy on brain function in both people and animal models.

“The fact that they detected a relatively low rate of cognitive decline is encouraging,” Cohen said. “It’s assumed that the older you are, the more toxicity you will experience from chemotherapy. So sometimes we in oncology may be hesitant to give chemotherapy to older patients and the patients may suffer higher rates of relapse and lower rates of cure if they don’t get the treatment.”

Cohen would also like to see more studies on the topic. “I would say that the issue is not completely settled yet,” he added. “One issue with studies like this is the nature of the tests. It’s possible that the standardized tests are not sensitive enough to capture smaller or more nuanced changes in cognition.”

SOURCE: Journal of Clinical Oncology, online October 3, 2018.