Protein gene may protect from ‘chemobrain’: Study

SINGAPORE — Researchers are a step closer to understanding why some breast cancer patients develop cognitive impairment after chemotherapy and whether some high-risk patients could benefit from early intervention.

A local study has found that early-stage breast cancer patients with a variation of the brain-derived neurotrophic factor (BDNF) gene are less likely to get “chemofog” or “chemobrain” — cognitive impairment, such as memory loss and difficulty in decision-making and multi-tasking, after chemotherapy..

Such cognitive changes “affect patients’ quality of life, prevent them from returning to work or school, and inhibit their social activities”, said Associate Professor Alexandre Chan, who co-led the study with PhD candidate Terence Ng. Both are from the National University of Singapore’s Department of Pharmacy.

“Hence, gaining a better understanding of how ‘chemobrain’ occurs and how to prevent it is crucial,” said Assoc Prof Chan.

The BDNF gene is responsible for producing a protein that controls the growth and function of nerve cells in the brain and spinal cord. Previous studies have linked the gene to cognitive impairment in patients with Alzheimer’s disease and other neuropsychological disorders, but this is the first time the BDNF gene is associated with cognitive changes in cancer patients. The discovery was reported in the international scientific journal Neuro-Oncology in August.

In this study, 145 early-stage breast cancer patients from the National Cancer Centre Singapore (NCCS) and KK Women’s and Children’s Hospital were asked to assess their self-perceived cognitive function. Based on their scores, they were separated into two groups: Those with cognitive impairment after chemotherapy (54 patients) and those without. There was a higher proportion of patients with the variation in their BDNF gene — a change in position of an amino acid in the gene — in the group without cognitive impairment.

Using statistical analysis, researchers found that patients with the gene variation had 74 per cent lower odds of developing self-perceived cognitive impairment. They were also less likely to experience impairment in verbal fluency and/or multitasking ability.

“This novel discovery can certainly help researchers better understand the underlying mechanisms that lead to the development of this chemotherapy-induced side effect,” said Assoc Prof Chan. “More importantly, this will provide us with information on whether certain patients who are at high risk for cognitive impairment post-chemotherapy may benefit from early intervention.”

The study, conducted from December 2011 to April 2014, followed an earlier study co-led by Assoc Prof Chan, which found that almost one-third (29.3 per cent) of 99 breast cancer patients reported cognitive impairment after chemotherapy.

Breast cancer is currently the top-ranked cancer among females in Singapore, representing 29.2 per cent of all cancer diagnosed among females between 2010 and 2014.

More than 90 per cent of patients with stage 1-4 breast cancer will undergo chemotherapy, said Dr Raymond Ng, a senior consultant medical oncologist at the NCCS, who was involved in the study.

Mr Terence Ng, who was the study’s lead investigator, said the exact cause of chemobrain remains unknown, but studies have identified numerous biological, clinical and demographic factors that may contribute to it, such as age, anxiety, baseline intelligence and depression.

The types and dose intensity of chemotherapy regimens may also contribute to cognitive changes, he added.

There’s still some way to go before the study findings can result in treatments for cognitive impairment. The team is now collecting additional patient samples for further studies to validate their findings. More studies on the impact of the gene variation among breast cancer patients are needed.

While chemobrain has been observed in patients with other types of cancer, including colorectal cancer and prostate cancer, more studies are needed to confirm if the findings can be extrapolated to other cancer types.