Can Melatonin Alleviate Symptoms of Cognitive Impairment in Patients With Breast Cancer?

Cognitive impairment is a well-documented adverse effect (AE) of treatment from breast cancer, and it can appear soon after treatment begins or far down the road. The rate of occurrence, however, during chemotherapy is more than twice that from before treatment: 52% versus 23%, respectively. Oral melatonin may be of benefit to these patients.

This is according to results from Brazil published last week in PLoS One from the Melatonin as a Circadian Clock Regulator, Neuromodulator and Myelo-protector in Adjuvant Breast Cancer Chemotherapy trial. The randomized, double-blind, placebo-controlled trial investigated if a 20-mg oral dose of melatonin taken before and during the first cycle of adjuvant chemotherapy could improve cognition, depressive symptoms, and sleep quality among patients with breast cancer.

In addition, the authors looked at the accompanying levels of brain derived neurotrophic factor (BDNF) and tropomyosin kinase B (TrkB). “The BDNF/TrkB signaling pathway may act as a regulator of carcinogenesis and metastasis, and its overexpression may predict a poor clinical outcome and a worse prognosis in patients with breast cancer,” they noted.

Their study population was small. Thirty-six women from the Mastology and Oncology Service at Hospital de Clinicas of Porto Alegre in Brazil were randomized 1:1 to the treatment and placebo groups and were on treatment for 10 days, starting with the 3 days before chemotherapy initiation. The mean (SD) ages of both groups were 54.24 (10.59) and 54.11 (9.15) years, respectively, and the mean (SD) BDNF and TrkB levels were 42.92 (17.54) ng/mL and 0.48 (0.25) ng/mL and 42.24 (23.95) ng/mL and 0.47 (0.50) ng/mL.

Both treatment groups also received their oral dose of melatonin or placebo 1 hour before bedtime, and several tests were administered to measure cognitive performance, including the Trail-Making-Test (TMT) Parts A and B (A-B) and the Controlled Oral Word Association Test (COWAT). Quality of life (QOL) was assessed using the European Organization for Cancer Research and Treatment (EORTC QLQ-C30) questionnaire.

Overall, results show a “neuroprotective effect” from melatonin by way of reduced serum levels of both BDNF and TrkB. In addition, compared with the placebo group, the melatonin group post treatment had shorter performance times on the TMT A-B, could recite more words during the COWAT, and had higher scores for immediate and delayed recall evaluations.

EORTC QLQ-C30 results also overwhelmingly favored the melatonin group, which saw a marked improvement in AEs from before to after treatment:

• Melatonin group: Pretreatment median score, 30 (interquartile range [IQR], 8) Posttreatment median score, 23 (IQR, 17)
• Placebo group: Pretreatment median score, 26.5 (IQR, 12) Posttreatment median score, 26.5 (IQR, 5)

“The novelty of this study reveals the benefits of melatonin prior to adjuvant chemotherapy for breast cancer on different dimensions of cognition depressive symptoms and sleep quality allied to the baseline neuroplasticity state and changes in serum BDNF and TrkB induced by melatonin,” the study authors noted. “Indeed, these results showed a statistical difference in these outcome measures, and they have potential clinical relevance to highlight evidence of the neuroprotective effect of melatonin.”

One possible study limitation the authors cautioned about was not to associate the use of melatonin as an antidepressant. Their study was not designed for that, having been performed among a single population enduring great stress with starting chemotherapy.

Reference

Palmer ACS, Zortea M, Souza A, et al. Clinical impact of melatonin on breast cancer patients undergoing chemotherapy; effects on cognition, sleep and depressive symptoms: a randomized, double-blind, placebo-controlled trial. PLoS One. 2020;15(4):e0231379. doi: 10.1371/journal.pone.0231379.