Cognitive Functions under Anti-HER2 Targeted Therapy in Cancer Patients: A Scoping Review

Background and Objective: Pharmacological therapy targeting the HER2 protein is one of the major breakthroughs in the treatment of cancer patients overexpressing HER2 who have increased survival rates. Despite improved survival, it is important to determine the less frequent adverse effects in order to tailor treatments more personalized to the patients’ features. The possible impact of cancer treatments on cognitive functions is huge, and the effects of anti-HER 2 therapies on this issue have not been reviewed and are the objective of this study. Results: Analysis of PubMed, Scopus, Cochrane library and Web of Science databases revealed six studies performed in breast and serous uterine cancer patients analyzing cognitive function under chemotherapy regimens including anti-HER2 drugs. Four of these studies reported small to significant worsening of cognitive function following chemotherapy regimens containing trastuzumab (the most widely used anti-HER2 drug). In neoadyuvant settings, and in breast cancer patients, treatment with the new anti-HER-2 drug trastuzumab emtansine seems to induce less cognitive impairment than therapeutic regimens containing chemotherapy and trastuzumab. Acute administration of trastuzumab induced cognitive impairment in gastric cancer mice models, confirming its ability to alter cognitive function in patients,. Conclusions: More studies analyzing the impact of anti-HER2 therapy on cognitive function are necessary at preclinical and clinical levels in order to personalize pharmacological treatment and offers cancer patients a better quality of life.

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Training Cognitive Functions Using Mobile Apps in Breast Cancer Patients: Systematic Review (Preprint)

10.2196/preprints.10855 ◽

2018 ◽

Author(s):

Laura Vergani ◽

Giulia Marton ◽

Silvia Francesca Maria Pizzoli ◽

Dario Monzani ◽

Ketti Mazzocco ◽

...

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Cognitive Impairment ◽

Cognitive Function ◽

Cancer Patients ◽

Cognitive Training ◽

Cognitive Functions ◽

Mobile Apps ◽

Breast Cancer Patients ◽

Cognitive Domains

BACKGROUND Breast cancer is an invalidating disease and its treatment can bring serious side effects that have a physical and psychological impact. Specifically, cancer treatment generally has a strong impact on cognitive function. In recent years, new technologies and eHealth have had a growing influence on health care and innovative mobile apps can be useful tools to deliver cognitive exercise in the patient’s home. OBJECTIVE This systematic review gives an overview of the state-of-the-art mobile apps aimed at training cognitive functions to better understand whether these apps could be useful tools to counteract cognitive impairment in breast cancer patients. METHODS We searched in a systematic way all the full-text articles from the PubMed and Embase databases. RESULTS We found eleven studies using mobile apps to deliver cognitive training. They included a total of 819 participants. App and study characteristics are presented and discussed, including cognitive domains trained (attention, problem solving, memory, cognitive control, executive function, visuospatial function, and language). None of the apps were specifically developed for breast cancer patients. They were generally developed for a specific clinical population. Only 2 apps deal with more than 1 cognitive domain, and only 3 studies focus on the efficacy of the app training intervention. CONCLUSIONS These results highlight the lack of empirical evidence on the efficacy of currently available apps to train cognitive function. Cognitive domains are not well defined across studies. It is noteworthy that no apps are specifically developed for cancer patients, and their applicability to breast cancer should not be taken for granted. Future studies should test the feasibility, usability, and effectiveness of available cognitive training apps in women with breast cancer. Due to the complexity and multidimensionality of cognitive difficulties in this cancer population, it may be useful to design, develop, and implement an ad hoc app targeting cognitive impairment in breast cancer patients.

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An Evaluation of DNA Methyltransferase 1 (DNMT1) Single Nucleotide Polymorphisms and Chemotherapy-Associated Cognitive Impairment: A Prospective, Longitudinal Study

Scientific Reports ◽

10.1038/s41598-019-51203-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Alexandre Chan ◽

Angie Yeo ◽

Maung Shwe ◽

Chia Jie Tan ◽

Koon Mian Foo ◽

...

Keyword(s):

Breast Cancer ◽

Cognitive Impairment ◽

Cognitive Function ◽

Cancer Patients ◽

Dna Methyltransferase ◽

Dna Methyltransferases ◽

Breast Cancer Patients ◽

Prospective Longitudinal Study ◽

Cognitive Domains ◽

Prospective Longitudinal

Abstract Strong evidence suggests that genetic variations in DNA methyltransferases (DNMTs) may alter the downstream expression and DNA methylation patterns of neuronal genes and influence cognition. This study investigates the association between a DNMT1 polymorphism, rs2162560, and chemotherapy-associated cognitive impairment (CACI) in a cohort of breast cancer patients. This is a prospective, longitudinal cohort study. From 2011 to 2017, 351 early-stage breast cancer patients receiving chemotherapy were assessed at baseline, the midpoint, and the end of chemotherapy. DNA was extracted from whole blood, and genotyping was performed using Sanger sequencing. Patients’ self-perceived cognitive function and cognitive performance were assessed at three different time points using FACT-Cog (v.3) and a neuropsychological battery, respectively. The association between DNMT1 rs2162560 and cognitive function was evaluated using logistic regression analyses. Overall, 33.3% of the patients reported impairment relative to baseline in one or more cognitive domains. Cognitive impairment was observed in various objective cognitive domains, with incidences ranging from 7.2% to 36.9%. The DNMT1 rs2162560 A allele was observed in 21.8% of patients and this was associated with lower odds of self-reported cognitive decline in the concentration (OR = 0.45, 95% CI: 0.25–0.82, P = 0.01) and functional interference (OR = 0.48, 95% CI: 0.24–0.95, P = 0.03) domains. No significant association was observed between DNMT1 rs2162560 and objective cognitive impairment. This is the first study to show a significant association between the DNMT1 rs2162560 polymorphism and CACI. Our data suggest that epigenetic processes could contribute to CACI, and further studies are needed to validate these findings.

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Elucidating Pretreatment Cognitive Impairment in Breast Cancer Patients: The Impact of Cancer-related Post-traumatic Stress

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djv099 ◽

2015 ◽

Vol 107 (7) ◽

pp. djv099-djv099 ◽

Cited By ~ 38

Author(s):

K. Hermelink ◽

V. Voigt ◽

J. Kaste ◽

F. Neufeld ◽

R. Wuerstlein ◽

...

Keyword(s):

Breast Cancer ◽

Cognitive Impairment ◽

Cancer Patients ◽

Traumatic Stress ◽

Breast Cancer Patients ◽

Post Traumatic Stress ◽

Post Traumatic ◽

The Impact

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Managing Cancer and Living Meaningfully (CALM) Intervention on Chemotherapy-Related Cognitive Impairment in Breast Cancer Survivors

Integrative Cancer Therapies ◽

10.1177/1534735420938450 ◽

2020 ◽

Vol 19 ◽

pp. 153473542093845

Author(s):

Ke Ding ◽

Xiuqing Zhang ◽

Jingjing Zhao ◽

He Zuo ◽

Ziran Bi ◽

...

Keyword(s):

Breast Cancer ◽

Cognitive Impairment ◽

Psychological Distress ◽

Cognitive Function ◽

Cancer Therapy ◽

Cancer Patients ◽

Functional Assessment ◽

Breast Cancer Survivors ◽

Breast Cancer Patients ◽

Before And After

Objective: To evaluate the effectiveness and feasibility of Managing Cancer and Living Meaningfully (CALM), which is used to reduce chemotherapy-related cognitive impairment (CRCI), relieve psychological distress, and improve quality of life (QOL) in Chinese breast cancer survivors (BCs). Methods: Seventy-four BCs were enrolled in this study. All patients were randomly assigned to either the CALM group or the care as usual (CAU) group. All patients were evaluated by the Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog), Distress Thermometer (DT), and the Functional Assessment of Cancer Therapy–Breast (FACT-B) before and after CALM or CAU application to BCs with CRCI. We compared the differences in all these scores between the CALM group and the control group and analyzed the correlation between cognitive function and QOL. Results: Compared with the CAU group, the performance of the CALM group on the FACT-Cog, DT, and FACT-B showed significant differences before and after CALM ( t = −18.909, −5.180, −32.421, P = .000, .000, .000, respectively). Finally, there was a positive correlation between cognitive function and QOL in breast cancer patients before ( r = 0.579, P = .000) and after ( r = 0.797, P = .000) treatment. Conclusions: The present results indicated that CALM has salutary effects on the improvement of cognitive impairment and QOL and relieves psychological distress in breast cancer patients, which may be due to a positive correlation between psychological distress and cognitive function or QOL.

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Cognitive impairment after cytotoxic chemotherapy

Neuro-Oncology Practice ◽

10.1093/nop/npz052 ◽

2019 ◽

Vol 7 (1) ◽

pp. 11-21 ◽

Cited By ~ 2

Author(s):

Petra Huehnchen ◽

Antonia van Kampen ◽

Wolfgang Boehmerle ◽

Matthias Endres

Keyword(s):

Breast Cancer ◽

Colon Cancer ◽

Cognitive Impairment ◽

Cancer Patients ◽

Cytotoxic Chemotherapy ◽

Cytotoxic Drugs ◽

Cytotoxic Agents ◽

Cancer Type ◽

Breast Cancer Patients ◽

The Impact

Abstract Background Neurotoxicity is a frequent side effect of cytotoxic chemotherapy and affects a large number of patients. Despite the high medical need, few research efforts have addressed the impact of cytotoxic agents on cognition (ie, postchemotherapy cognitive impairment; PCCI). One unsolved question is whether individual cytotoxic drugs have differential effects on cognition. We thus examine the current state of research regarding PCCI. Neurological symptoms after targeted therapies and immunotherapies are not part of this review. Methods A literature search was conducted in the PubMed database, and 1215 articles were reviewed for predefined inclusion and exclusion criteria. Thirty articles were included in the systematic review. Results Twenty-five of the included studies report significant cognitive impairment. Of these, 21 studies investigated patients with breast cancer. Patients mainly received combinations of 5-fluorouracil, epirubicin, cyclophosphamide, doxorubicin, and taxanes (FEC/FEC-T). Five studies found no significant cognitive impairment in chemotherapy patients. Of these, 2 studies investigated patients with colon cancer receiving 5-fluorouracil and oxaliplatin (FOLFOX). Independent risk factors for PCCI were patient age, mood alterations, cognitive reserve, and the presence of apolipoprotein E e4 alleles. Conclusions There is evidence that certain chemotherapy regimens cause PCCI more frequently than others as evidenced by 21 out of 23 studies in breast cancer patients (mainly FEC-T), whereas 2 out of 3 studies with colon cancer patients (FOLFOX) did not observe significant changes. Further studies are needed defining patient cohorts by treatment protocol in addition to cancer type to elucidate the effects of individual cytotoxic drugs on cognitive functions.

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Prospective monitoring of circulating tumor cells in breast cancer patients treated with primary systemic therapy—A translational project of the German Breast Group study GeparQuattro

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21085 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21085-21085 ◽

Cited By ~ 6

Author(s):

V. Mueller ◽

S. Riethdorf ◽

S. Loibl ◽

M. Komor ◽

J. Houber ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Breast ◽

Primary Diagnosis ◽

Breast Cancer Patients ◽

Primary Systemic Therapy ◽

Her 2 ◽

The Impact

21085 Background: The impact of circulating tumor cells (CTC) in patients with primary breast cancer is still unclear. Primary systemic treatment (PST) allows the assessment of therapeutic efficacy in breast cancer patients without long follow-up periods. Here we present first results on the presence of CTC in peripheral blood of patients enrolled in the “GeparQuattro” study. Methods: This study incorporates three different chemotherapy approaches and additional Trastuzumab (Herceptin®) treatment for patients with HER-2/neu-positive tumors. Recruitment finished in November 2006 and not all patients have completed therapy yet. We used the CellSearch™ system to evaluate CTC before PST from 245 patients and after PST from 67 patients. CTC from 45 samples were also examined for HER-2/neu expression by immunocytochemistry in the CellSearch™ system. Results: Before PST we detected CTC in 54/245 patients (22%). CTC numbers in 7.5 mL blood ranged between 1 and 200 (mean 6.5). In 8 CTC-positive samples (3.3%) = 5 CTC were found. Her-2/neu-positive CTC were observed in 25/45 cases (55.6%). CTC could be detected in 7/67 patients (10.4%) after PST (1 or 2 CTC). Before and after PST blood was analyzed from 43 patients, 27 of them were CTC-negative at both time points. Ten initially CTC-positive cases were CTC-negative after PST whereas 6 cases were detected CTC-positive after PST although no CTC could be found before PST. Conclusions: With the CellSearch™ system CTC can be detected in non-metastatic breast cancer patients at primary diagnosis and also after PST. To our knowledge, this is the largest study evaluating the presence of CTC in this context. With the availability of response information from more patients, it will be possible to examine the correlation between the incidence of CTC and response as well as kinetics of HER-2/neu expression during Trastuzumab treatment. [Table: see text]

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