Types of participants
This review will consider studies that include adult women aged 18 years or older who have been managed with conventional treatment (surgery, radiotherapy and/or chemotherapy including hormonal therapy- either alone or in any combination) regardless of type, stage or grade of breast cancer.
Types of intervention(s) and comparators
The intervention of interest is coenzyme Q10 therapy following or in addition to conventional treatment (surgery, radiotherapy and/or chemotherapy, including hormonal therapy), either alone or in addition to other nutrients or antioxidants. This study will consider supplementation with coenzyme Q10 regardless of the route or dosage and for a minimum of one week administration.
The comparison group is adult women with breast cancer who have had conventional treatment (surgery, radiotherapy and/or chemotherapy, including hormonal therapy). In some study designs there may not be a comparator group and coenzyme Q10 will be considered as an exposure.
Types of outcomes
This review will consider the following parameters that indicate increased survival, reduced recurrence and tumor burden, and cancer cure.
- Death/survival rate;
- Blood concentrations of biochemical markers - standard tests (FBC, EUC, LFT); inflammatory markers erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)14; tumor markers (CA 15.3, CA 125, CEA)15; and tumor-related markers (such as but not limited to TNF-alpha, IL2, IL6 and IL8);
- Size of primary tumor assessed by ultrasound (US), mammography, computerized axial tomography (CAT scan), magnetic resonance imaging (MRI), positron emission tomography (PET);
- Number and size of secondary tumors assessed by ultrasound, chest X-ray, mammography, computerized axial tomography (CAT scan), magnetic resonance imaging (MRI) or positron emission tomography (PET scan);
- Adverse events resulting from coenzyme Q10;
- Adherence to conventional therapy;
- Impact of coenzyme Q10 on conventional treatment. This may be either to inhibit, augment or ameliorate actions or adverse events resulting from conventional treatment; and
- Effect of coenzyme Q10 on measures of patient quality of life (such as sleep, nausea, vomiting, hair loss, appetite, mobility, lymphedema, pain and patient satisfaction) related to the cancer as well as the cancer treatment-related symptoms.
Types of studies
This review will consider both experimental and epidemiological quantitative studies including randomized control trials, non-randomized control trials, quasi-experimental, case control, cohort case series and case reports which examine the effects of coenzyme Q10 on women with breast cancer.
A three-step search strategy will be used in this systematic review to find both published and unpublished studies between 1961 to the present date (April 2014). This deliberately broad time-frame is designed to capture any early clinical studies on coenzyme Q10. First, a limited search of MEDLINE and CINAHL, followed by analysis of the text words contained in the title and abstract, then the index terms used to describe the articles. Then, a second search will be conducted across all appropriate databases using all identified keywords and index terms. Then, a third search of the reference lists of all identified reports and articles will be done.
Studies published in any language will be considered for inclusion in this review.
Databases and repositories to be searched include PubMed, CINAHL, Scopus, BIOSIS, EMBASE, CancerLit, Science Direct, Web of Science, International Congress on Complementary Medicine Research, American Society of Clinical Oncology, MedNar, Cochrane Central Register of Controlled Trials, WHO register of trials, www.clinicaltrials.gov and www.controlled-trials.com. Australian National University Digital Theses, Open Access Theses and Dissertations and ProQuest Dissertations and Theses.
The following keywords/terms will be used for the initial search:
cancer/tumour/tumor/neoplasm/carcinoma/malignan*/breast/mammary/breast cancer/breast tumour/breast tumor, AND
coenzyme Q10/co-enzyme Q10/coQ10/CoQ 10/vitamin 10/ubiquinol/ubiquinone/ubiquinone Q10/ubiquinone 50/ubidecarenone/2,3-dimethoxy-5-methyl-6-decaprenylbenzoquinone/Q-ter/ubisemiquinone/ ubisemiquinone radical/Bio-Quinone Q10/coenzyme Q10, isomer/coenzyme Q10, ion (1-), (all E)-isomer
Studies identified by the search will be considered against the inclusion criteria. Those that match the criteria will undergo methodological quality assessment. Those that do not match the inclusion criteria will be excluded.
Assessment of methodological quality
Titles and abstracts of studies identified during the search process will be screened by the primary reviewer. Articles selected for retrieval based on title and abstract will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standard critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer.
Quantitative data will be extracted from papers included in this review using the standardized data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives. The information collected will include the following:
- Methods: study design, methods of allocation, allocation concealment, blinding, dropout rates from studies and reasons for dropping out.
- Participants: country of origin, setting, sample size, diagnosis, age, ethnicity.
- Intervention: type, program length, frequency, duration (for experimental and comparator interventions).
- Outcomes: type of outcomes, assessment instruments, assessment time point and follow-up time point.
Data will, where possible, be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratios (for categorical or dichotomous data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard Chi-square and also explored using subgroup analyses based on the different study designs included in this review. Where statistical pooling is not possible, the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate.
Conflicts of interest
As this systematic review forms partial submission for the degree award of Masters of Clinical Science through the University of Adelaide, a secondary reviewer (Ms Dagmara Riitano) will be used for critical appraisal of literature considered for inclusion in the review.
The primary reviewer wishes to thank the University of Adelaide and the Joanna Briggs Institute for this opportunity to extend her skill-base and do such interesting research. She also wishes to thank Associate Professor Edoardo Aromataris for previous supervision.
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Appendix I - Critical Appraisal instruments
MAStARI appraisal instruments
Appendix II: Data extraction instruments