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Abstract
Objectives The aims of this systematic review were to assess the impact of neoadjuvant chemotherapy (NAC) on breast cancer (BC) patients’ quality of life (QOL), to compare the different regimens of NAC on BC patients’ QOL, to compare NAC versus adjuvant chemotherapy on BC patients’ QOL and to identify predictors of QOL on patients with BC receiving NAC.
Design The design used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
Data sources Cinahl, Embase, Pubmed, Scopus, Web of Science, Cochrane library and PsycINFO were searched through 27 December 2021.
Eligibility criteria for selecting studies The inclusion criteria were included: patients with BC receiving NAC, outcome measures related to QOL and published in English. The exclusion criteria were included: duplicates or overlapping participants, not original research, data or full text not available and qualitative study.
Data extraction and synthesis Two independent reviewers used standardised methods to search, screen and code included studies. The risk of bias in individual studies was evaluated with Cochrane collaboration’s tool for assessing risk bias, Newcastle Ottawa Score or Joanna Briggs Institute Critical Appraisal tool. This systematic review performs narrative synthesis based on several different themes.
Results The initial search resulted in 2994 studies; 12 of these studies fulfilled inclusion criteria. There was no significant difference in the QOL of BC before and after NAC, but patients experienced adverse reactions and depression during chemotherapy. Different regimens of NAC have different effects on patients’ QOL. Patients with NAC had more severe physical discomfort than those with adjuvant chemotherapy. However, BC patients’ QOL can be improved by intervening on social or family support, and these predictors, including chronotype, QOL before NAC and depression.
Conclusions More original research is needed in future to understand the profile and predictors of QOL in patients with BC on NAC, which will help clinicians and patients make decisions and deal with NAC-related issues.
- chemotherapy
- breast tumours
- mental health
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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Strengths and limitations of this study
This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
Our information sources were 7 research databases from inception through 27 December 2021.
This review included studies published in the English language only.
Introduction
Breast cancer (BC) is the most common disease in women worldwide, with the prevalence now surpassing lung cancer as the leading global cancer incidence in women in 2020, with 11.7% of all new cases (2.3 million); and it is the fifth leading cause of cancer deaths worldwide, accounting for 6.9%.1 Treatment of BC usually consists of two parts: local surgical treatment and systemic treatment; systemic treatment can precede surgical treatment (neoadjuvant) or follow it (adjuvant).2 Neoadjuvant chemotherapy (NAC) is used in patients with locally advanced BC or inoperable BC to improve the likelihood of breast-conserving surgery by reducing the size of the tumour in the past. Current studies have shown that NAC can also be used in the treatment of patients with early-stage operable BC to improve cosmetic outcomes and reduce postoperative complications, such as lymphoedema and prolong survival.3–5 NAC is associated with improved survival compared with adjuvant chemotherapy in patients with triple-negative BC only after complete pathologic response,6 and the same effect has been observed in other cancers like bladder cancer and colon cancer.7 8 NAC is widely used, while more and more scholars are studying the survival outcomes of patients after NAC, such as pathologic complete response, disease-free survival and overall survival.4 9
However, the goals of cancer treatment should include not only survival outcomes but also quality of life (QOL), which is an important outcome measure in clinical investigations and survival studies in BC.10–12 Now, the treatment regimens of BC are numerous and effective, but the side effects associated with different treatment modalities and the impact on QOL are different. So, optimal stratification and ranking of treatment strategies should focus on individual risk profiles as well as QOL.13 Meanwhile, QOL is a major factor in treatment decisions for advanced or metastatic disease.14 It is worthwhile to consider the choice of an effective, least toxic anticancer treatment before implementing definitive therapy. Therefore, studying the QOL of NAC patients and comparing it to other treatments can help patients and clinicians make decisions.
The aims of this systematic review were (1) to assess the impact of NAC on BC patients’ QOL, (2) to compare the different regimens of NAC on BC patients’ QOL, (3) to compare NAC vs adjuvant chemotherapy on BC patients’ QOL and (4) to identify predictors of QOL on patients with BC receiving NAC.
Methods
We primarily followed the Joanna Briggs Institute guidelines15 on systematic reviews and we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement16 (figure 1).
Flow chart for systematic review methodology as per PRISMA guidelines. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Search strategy
A systematic search of the following databases was performed: CINAHL, Embase, Pubmed, Scopus, Web of Science, Cochrane library and PsycINFO. The final search was in December 2021. Three categories of terms were searched: (1) BC, (2) NAC and (3) QOL. In PubMed and Cochrane library, medical subject headings were used (breast neoplasms, neoadjuvant therapy, QOL, sexuality, anxiety, depression and social support). In Embase, Emtree terms were exploded (breast tumour, NAC, QOL, sexuality, anxiety, depression and social support). In Scopus, Web of Science, CINAHL and PsycINFO, only keywords were used (online supplemental material 1).
Supplemental material
Data analysis
The inclusion criteria were as follows: (1) adult patients (18 years older); (2) patients with BC receiving NAC; (3) outcome measures related to QOL, including QOL, psychological impact, support from various sources and so on and (4) published in the English language. The exclusion criteria were as follows: (1) data could not be extracted; (2) duplicates or overlapping participants; (3) not original research, such as commentaries, editorials or reviews; (4) full text not available and (5) qualitative study. Two independent researchers (YZ and XZ) screened for potentially relevant studies by reviewing abstracts. The full texts were then screened further according to the inclusion and exclusion criteria. Any uncertainty was solved by a third researcher (YS). Two researchers (YZ and XZ) independently extracted and recorded the following information from the enrolled studies: author, published year, country, study design, sample size, age, regimens of NAC, timing of assessment, instrument and outcomes. The risk of bias in individual studies was evaluated by two independent researchers (YZ and LC) in accordance with Cochrane collaboration’s tool for assessing risk bias,17 or Newcastle Ottawa Score (NOS)18 or Joanna Briggs Institute Critical Appraisal tool.19 Any disagreement was resolved by a third researcher (YS).
Patient and public involvement
Patients or the public were not involved in the conceptualisation or carrying out of this research.
Results
Flow of included studies
An initial search identified a total of 2994 studies (PubMed: 98, Scopus: 1191, Embase: 281, Web of Science: 1011, CINAHL:1 89, Cochrane library: 35 and PsycINFO: 189). After removing the duplicates, the total number of studies left was 2327 and all of these were screened. On screening, 2223 studies failed to meet our inclusion criteria and were removed from the analysis. The full text was obtained for 104 studies. Out of these 104 studies, an additional 92 were excluded and 12 met our inclusion criteria as defined above (figure 1).
Risk of bias in the included studies
The quality of cohort studies was assessed by NOS, randomised controlled trials (RCTs) by Cochrane collaboration’s tool and cross-sectional study by Joanna Briggs Institute Critical Appraisal tool (online supplemental tables S1–S3).
Characteristics of included studies
Characteristics of included studies
Seven studies were designed as prospective cohort studies,20–25 three were RCTs,26–28 one was a retrospective cohort study29 and one was a cross-sectional study.30 Two studies were each from Brazil25 27 and Korea,21 31 and one each from China,20 Japan,29 India,22 UK,26 Germany,23 Indonesia,30 Iran24 and the USA.28 One study compared QOL in BC patients with NAC and adjuvant therapy,25 and three studies compared QOL in patients with different regimens of NAC.22 24 26 Two studies were in the same clinical trial registration with different included subjects.21 31 The QOL-related instruments used were: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, the Quality of Life Questionnaire-Breast Cancer Module, the Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, Multinational Association of Supportive Care in Cancer Antiemesis Tool, Quality of Life Questionnaire for Cancer Patients Treated with Anti-Cancer Drugs-Breast, Functional Assessment of Cancer Therapy of Breast, Functional Assessment of Cancer Therapy-Taxane, 36-Item Short Form Health Survey Questionnaire, Body Image Scale, Rotterdam Symptom Checklist, Mood Rating Scale, Global Distress Scale, Treatment Side-Effects Questionnaire, Fragebogen erlebter Defizite der Aufmerksamkeit, Rosenberg Self Esteem Scale, Brief Fatigue Inventory and Centre for Epidemiologic Studies–Depression Scale (table 1).
Quality of life
Physical symptoms
Ten studies evaluated patients’ physical aspects with NAC. NAC affects all aspects of a patient’s body and 80% of the patients had adverse physical symptoms (table 2; figure 2). Three studies evaluated dyspnoea20 24 25 and pain,26 27 29 respectively, two evaluated nausea/vomit,21 27 fatigue20 24 and cognitive function,23 24 respectively, one evaluated body image28 and five evaluated other symptoms.22 24 25 27 29 Lee et al21 found that 48.5% of patients undergoing NAC experienced chemotherapy-induced nausea and vomiting (CINV), with delayed CINV (prevalence 42.5%) being more common than acute CINV (prevalence 39.6%). Ding et al20 reported patients experienced increased dyspnoea and fatigue after chemotherapy. Takada et al29 found that before NAC, the low QOL group had significantly lower scores on the subscale of Physical symptoms and pain, and the subscale of Dress, sexual aspect, other categories than the high QOL groups (both p<0.001). However, there was no significant difference between the two groups of these subscales after NAC. Hermelink et al23 reported during NAC that cognitive function remained stable in most patients with BC, but cognitive decline predominated in 27% of patients. It is caused by anxiety and depression from chemotherapy.
Summary results of the proportion of each negative impact on QOL. QOL, quality of life.
QOL of patients with BC
Different regimens of NAC
Three studies investigated the changes in physical symptoms with different treatment regimens of NAC. Chellappan22 showed that there was no difference in physical problems between the weekly regimen of paclitaxel and the 3-weekly regimen of paclitaxel. Rezapour et al24 reported that QOL declined in both doxorubicin and cyclophosphamide (AC) and paclitaxel and gemcitabine (PG) groups, but the two were reflected in different symptoms. The AC group had a significantly better situation in fatigue, pain, cognitive functioning and constipation compared with the PG group. Nausea and vomiting, dyspnoea, insomnia and diarrhoea were better in the PG group. There was no statistically significant difference in physical performance and physical capability between the two groups. Walker et al26 reported patients had severe pain in the 3-weekly group compared with the weekly docetaxel group (p=0.034).
Neoadjuvant versus adjuvant chemotherapy
Only one study compared the effects of neoadjuvant and adjuvant chemotherapy on physical symptoms. Coelho et al25 observed that QOL was altered with the greater loss for getting NAC compared with adjuvant. Physical function and dyspnoea symptoms had a greater impact in the neoadjuvant group compared with the adjuvant group. It is attributed to late diagnoses that provide aggressive treatments.
Intervention in NAC
Two of these studies intervened in BC patients on NAC. Souza et al27 showed that nutritional interventions improved patients' grip strength, positively affected the occurrence of nausea/vomiting and loss of appetite, and reduced the frequency of leucopenia and abdominal pain during NAC. Basen-Engquist et al28 reported that weight gain prevention intervention reduced more in waist circumference (p=0.03) and greater improvements in self-reported vitality scores (p=0.03) compared with the control group. The majority of participants reported being satisfied with the intervention during chemotherapy (88%).
Psychological effects
Eight studies evaluated psychological effects during NAC and 52% of patients get negative effects on psychological aspects (table 2; figure 2). Four studies evaluated emotional function,22 24 25 28 three studies evaluated anxiety/depression21 26 31 and two evaluated role function.24 27 Lee et al31 reported that the depression in BC patients was most severe during NAC compared with before and after NAC. Anxiety was most severe before NAC but gradually improved throughout the treatment session. Lee et al21 reported that overall CINV was significantly associated with anxiety.
Different regimens of NAC
Three studies investigated the changes in psychological effects with different regimens of NAC. Chellappan et al22 studied NAC with different regimens and showed that patients who were treated once a week had a high level of emotional well-being than those who were treated three times a week. But depression among the two groups was not statistically significant. Meanwhile, Walker et al26 found anxiety and depression were not statistically significant between the weekly group and the 3-weekly group. Rezapour et al24 reported that the AC group had a high level of role functioning than the PG group. The emotional functioning was better in the PG group compared with the AC group.
Neoadjuvant vs adjuvant chemotherapy
One study investigated the psychological effects between NAC and adjuvant chemotherapy. Coelho et al25 reported that emotional function was significantly affected in adjuvant chemotherapy and NAC, but there was no difference in the effects of the two treatments.
Support
Five studies evaluated support from society or family and 55% of patients did not receive adequate support (table 2; figure 2). Aprilianto et al30 reported that 64.3% of the respondents reported that social support for the patient’s family was mostly in the good category, and 48.2% of the patients with BC had a moderate level of self-esteem. There was a strong positive correlation between family social support and patient self-esteem.
Different regimens of NAC
Three studies evaluated support between different regimens of NAC. Chellappan et al22 reported that weekly group had a high level of social well-being than 3-weekly group (p=0.007). Rezapour et al24 reported that the AC group had significantly better social function compared with the PG group. Walker et al26 showed that the weekly group and the 3-weekly group had no significant difference in the social dimension.
Intervention in NAC
Basen-Engquist et al28 reported that weight gain prevention intervention couldn't change social function of patients.
QOL-related predictors
Three studies have extrapolated QOL-related predictors of BC patients during NAC: chronotype, QOL before NAC, and depression.21 29 31 Lee KM et al21 suggest late chronotype may be a predictor of CINV. Patients with BC with late chronotype have an increased risk of CINV during NAC. In another study, Lee et al31 indicated that depression during NAC was a mediator in the relationship between resilience and health-related QOL in patients with BC, and QOL after NAC can be improved by screening and intervening for depression during NAC in patients with BC. Meanwhile, Takada et al29 reported that high QOL before chemotherapy was an independent factor in overall survival (table 3).
QOL-related predictors
Discussion
In recent years, NAC has been widely used in the treatment of BC, and its efficiency in early-stage BC is as high as 70%~90% and has improved the success rate of breast-conserving surgery and the long-term prognosis of patients in complete pathological remission.32 33 However, it also has significant side effects on various organs of patients. Patients with BC after NAC require further surgical treatment. Chemotherapy-related symptoms and poor QOL inevitably affect the patient’s surgical tolerance and it may delay the patient’s surgical treatment in severe cases. The initial stages of treatment and the months following the end of treatment can be difficult times for patients, both physically and emotionally, and patients with BC are vulnerable to maladjustment and decreased QOL during these periods.34 Therefore, information about expected QOL will play an important role in the decision-making process of patients and clinicians considering NAC, so this study was conducted to systematically evaluate the QOL of NAC patients.
The results of this systematic review showed no significant change in overall QOL before and after NAC in patients with BC. However, during chemotherapy, patients’ QOL decreased, patients experienced increased pain, nausea and vomiting, dyspnoea and fatigue,20 21 24 25 29 and nausea remained unimproved despite the use of an antiemetic regimen that relieved vomiting.21 Patients’ QOL decreases during chemotherapy due to the toxic effects of chemotherapy drugs, and after chemotherapy, some of the toxic effects diminish and patients’ QOL improves. Emotional problems, such as anxiety and depression, are also aggravated during chemotherapy, but they all resolve at the end of chemotherapy.25 31 Emotional problems during NAC showed a significant association with resilience before NAC. These findings are largely consistent with previous studies on QOL during NAC for other cancers, such as oesophageal cancer,35 rectal cancer,36 pancreatic cancer37 and muscle-invasive bladder cancer.38 A transient increase in physical symptoms and a decrease in QOL were seen after neoadjuvant therapy, and in those patients who underwent surgery, most domains returned back by several months.35–38 Different regimens of NAC have different aspects of impact on patients’ QOL. The regimen of doxorubicin, cyclophosphamide and docetaxel weekly had less distressing side effects compared with the 3-weekly group,26 and another regimen of paclitaxel and doxorubicin had fewer social well-being compared with weekly group.22 Comparisons of AC and PG regimens showed that PG had fewer physical adverse effects and AC had better psychological effects.24 Only one study of included studies compared the impact of NAC to adjuvant chemotherapy on BC patients’ QOL,25 both regimens could affect patients’ emotions. However, NAC was more damaging in the terms of physical, cognitive and personal performance due to more toxicity of the drugs in NAC. QOL can be improved in various ways, including appropriate interventions and enhanced social or family support. Past studies reported that women who are malnourished have a serious negative impact on QOL,34 and nutritional intervention can improve the symptoms of nausea, vomiting, and loss of appetite in patients with BC, and exercise can reduce fatigue and improve the physical quality of patients with BC.27 39 40 Good nutritional status enables patients to better cope with intensive cancer treatment regimens.41 Patients with BC with high levels of social support have lower severity of chemotherapy-related symptoms.42 In addition, interventions can be based on QOL predictors of BC, such as chronotype, the level of QOL before chemotherapy and depression.
The limitations of this study are mainly in the low inclusion of literature on some subtopics and insufficient evidence, especially the contrast between NAC and adjuvant chemotherapy. This study suffered from publication bias and language bias and did not included some grey literature or unpublished, non-English language literature.
More original studies of high quality are needed. A potential area for further investigations provided by this systematic review is QOL in the perioperative and long-term postoperative periods after NAC. It is important to improve the long-term survival prognosis of NAC but also to focus on and improve QOL during and after NAC.
Conclusion
The results of this systematic review showed that BC patients’ QOL was significantly lower during NAC. There was no significant change in overall QOL before and after NAC. And this review found that the influences are mainly reflected in physical symptoms (80%), psychological effects (52%) and support from society or family (55%). QOL could be improved with appropriate interventions. Factors that affect QOL include chronotype, QOL before NAC and depression can affect the QOL. More original research is needed in the future to understand the profile and predictors of QOL in patients on neoadjuvant therapy, which will help clinicians and patients make better decisions and deal with NAC-related issues.
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.
Ethics statements
Patient consent for publication
Ethics approval
Not applicable.
Acknowledgments
The authors sincerely thank all colleagues of Nursing Division of Breast for their generous support for the study.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors YS is responsible for the overall content as guarantor, including study conducted, data accessed, and the publishing decision. YZ and XZ screened abstracts and full-text articles for inclusion. YZ and LC appraised study quality. Any disagreements or uncertainties during the screening and quality appraisal process were resolved to YS. YZ drafted the manuscript, which was reviewed, edited, and approved by YS.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.