Medicine (Baltimore). 2017 Mar;96(13):e6514. doi: 10.1097/MD.0000000000006514.

Chemotherapy-induced cognitive impairment in triple negative breast cancer patients

Wen Li, Chen Gan, Yue Lv, Haijun Chen, Huaidong Cheng*

Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China, 230601

This research was supported by the National Natural Science Foundation of China (No. 81372487)

*Correspondence:

Huaidong Cheng, Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, No. 678, Furong Road,Hefei,China, 230601. Tel: +8655163869542, Fax: +8655163869400, E-mail: chd1975ay@126.com


Abstract

Background: Our previous study had found that breast cancer patients with ER/PRstatus have significant impairment in event-based prospective memory (EBPM), but the related features about chemotherapy-induced cognitive impairment in triple negative breast cancer (TNBC) is still unclear. Objective: This study aimed to investigate the characteristics of chemotherapy-induced cognitive impairment in TNBC patients. Methods: A total of 244 patients with breast cancer who underwent chemotherapy following surgery were divided into two groups. Eighty TNBC survivors and 164 non-triple negative breast cancer (NTNBC) survivors matched for age and education were administered. After six cycles of postoperative adjuvant chemotherapy, all patients were administered neuropsychological and prospective memory tests, such as the Mini-Mental State Examination (MMSE), verbal fluency test (VFT), and digit span test (DST), as well as examination of EBPM and TBPM(time-based prospective memory). Results: As the neuropsychological background test results showed, the MMSE, VFT and DST scores were significantly greater in patients with NTNBC patients than in those TNBC patients (**: p<0.01). Compared with NTNBC patients after chemotherapy, the EBPM score of TNBC patients was 0.89±0.86, obviously lower than NTNBC group, exhibited statistical significance difference (z=-10.61, p<0.01), but the TBPM score of TNBC and NTNBC patients after chemotherapy were 4.65±0.83 and 4.80±0.92 (z=-1.48, P>0.05), indicating that TNBC patients have significant impairment in EBPM, although not in TBPM. Conclusion: TNBC and NTNBC patients all exhibited EBPM impairment, and the prospective memory of TNBC patients were worsen, show in EBPM, not in TBPM. The results of the present study indicate that different molecular type in patients with breast cancer may be associated with heterogeneity of chemotherapy-induced cognitive impairment.

Key words: Breast cancer; Triple negative breast cancer (TNBC); Neuropsychological tests; Cognitive.

PMID: 28353608

 

Supplement:

As shown in the figure1, MMSE score after chemotherapy in the TNBC group (25.58±1.93) was significantly lower than that in the NTNBC group (27.03±1.53, *: p< 0.01), and similarly, the DST and VFT values after chemotherapy (5.29±1.01 and 8.40±1.65, respectively) in the TNBC group were also significantly lower than in the NTNBC group(6.02±0.86, *: p< 0.01, and 10.77±1.87, *: p< 0.01, respectively).The average EBPM score after chemotherapy in the TNBC group (0.89±0.86) was significantly lower than that in the NTNBC group (2.59±0.90, *: p < 0.01), but the average TBPM score after chemotherapy in the TNBC group (4.65±0.83) wasn’t significantly difference than that in the NTNBC group (4.80±0.92, #: p > 0.05).

 

 

Figure1. Cognitive neuropsychological tests in patients with breast cancer

Note:Mini-Mental State Examination, MMSE; digit span test, DST; verbal fluency test,VFT; triple negative breast cancer ,TNBC; non-triple negative breast cancer ,NTNBC; event-based prospective memory,EBPM; time-based prospective memory,TBPM.

 

Our previous study had found that breast cancer patients after chemotherapy show impairment in EBPM but not in TBPM as compared with healthy control group [1]. Further research had been found that prospective memory impairment in patients with breast cancer after chemotherapy was associated with different expression of hormone receptors, manifested as significant EBPM impairment in patients with breast cancer patients in ER/PRgroup[2]. Recent studies had shown that that the intrinsic hippocampal functional connectivity network would be impaired in the patient group as compared with the cognitively normal control group in breast cancer patients[3].However, this study was limited to changes in the brain area between patients with breast cancer after chemotherapy and healthy control group, the characteristics of functional magnetic resonance imaging (fMRI) of chemotherapy-induced cognitive impairment (CICI)in patients with different molecular types of breast cancer need further study.

In order to further study the specific molecular genetical mechanism of occurrence in the different molecular subtypes of breast cancer patients with CICI. We had found that the distribution of alleles and genotypes of COMT (rs165599) between the TNBC and NTNBC groups was significantly different, and had an obvious linearity (β=-1.441, CI (95%) =-2.781 ~ -0.101) with the retrospective memory questionnaires[4]. This is the first time that we had found the evidence of molecular genetics of CICI in breast cancer patients with different molecular types.

In summary, the current research evidence suggested that the CICI is widespread and heterogeneity in breast cancer survivors, molecular biology research indicated that breast cancer had different molecular subtypes. However, the mechanism of CICI in different subtypes of breast cancer is not clear, the following two aspects of the problem remains our research team to be further clarified:

1, What is the specific characteristics of CICI based on different molecular subtypes of breast cancer?

2, Whether it has its specific mechanism on CICI of different molecular subtypes of breast cancer, if so, what is the exact mechanism of occurrence?

 

Reference

1 Cheng H, Yang Z, Dong B, et al. Chemotherapy-induced prospective memory impairment in patients with breast cancer.[J]. Psycho-Oncology, 2013, 22(10):2391–2395.

2 Li W, Gan C, Lv Y, et al. Chemotherapy-induced prospective memory impairment in breast cancer patients with different hormone receptor expression.[J]. Medicine, 2017, 96(13):e6514.

3 Cheng H, Wen L, Liang G, et al. Altered resting-state hippocampal functional networks associated with chemotherapy-induced prospective memory impairment in breast cancer survivors:[J]. Scientific Reports, 2017, 7:45135.

4 Cheng H, Li W, Gan C, et al. The COMT (rs165599) gene polymorphism contributes to chemotherapy-induced cognitive impairment in breast cancer patients[J]. American Journal of Translational Research, 2016, 8(11):5087.

 

 

Figure2. The members of Psycho-oncology Working Group. From left: Wen Li, Yue Lv, Huaidong Cheng, Chen Gan, Yingying Liu, Haijun Chen.