Health-related quality of life in breast cancer patients: A bibliographic review of the literature from 1974 to 2007

1Health-related quality of life is now considered an important endpoint in cancer clinical trials. It has been shown that assessing quality of life in cancer patients could contribute to improved treatment and could even be as prognostic as medical factors could be prognostic. Above all, studies of quality of life can further indicate the directions needed for more efficient treatment of cancer patients. Among the quality of life studies in cancer patients, breast cancer has received most attention for several reasons. First, the number of women with breast cancer is increasing. It has been reported that each year over 1.1 million women worldwide are diagnosed with breast cancer and 410,000 die from the disease. Secondly, early detection and treatment of breast cancer have improved and survivors now live longer, so studying quality of life in this context is important. Thirdly, breast cancer affects women's identities and therefore studying quality of life for those who lose their breasts is vital. In addition, it is believed that females play important roles as partners, wives, and mothers within any family. Thus, when a woman develops breast cancer, all members of family might develop some sort of illnesses. In fact, breast cancer is a family disease. Other reasons could be added, but overall it is crucial to recognize that with increasing improvements in medicine and medical practice during recent years studying quality of life for any cancer, for any anatomical site and for either gender is considered highly relevant. A descriptive study of the published papers (230 articles) on non-biomedical outcomes (quality of life, preferences, satisfaction and economics) in breast cancer patients, covering the literature from 1990 to 2000, found that the most frequently reported outcomes were health-related quality of life (54%), followed by economic analyses (38%), and patient satisfaction (14%). Only 9% measured patient preferences.

2Over the past 10 years, much clinical effort has been expended in the treatment of breast cancer in order to improve survival. Now the question is: to what extent have studies of quality of life in breast cancer patients added to our information or contributed to improved outcomes in breast cancer care? This is very difficult to answer, but it is possible to try to investigate the contribution of quality of life studies to breast cancer care as a whole. There are several useful review papers on quality of life in breast cancer patients. However, most published papers have either been overviews or systematic literature searches with very focused objectives. The aim of this review is to collect and examine all literature published since the topic first appeared in English language biomedical journals. It is hoped that this extensive review may contribute to existing knowledge, help both researchers and clinicians to have a better profile on the topic, and consequently aid in improving quality of life in breast cancer patients.

3As part of a study on quality of life in breast cancer patients, an extensive literature search was carried out using MEDLINE, EMBASE, the Science Citation Index (ISI), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the PsycINFO, the Allied and Complementary Medicine (AMED), and Global Health databases. The intention was to review all full publications that have been appeared in English language biomedical journals between 1974 and 2007. The year 1974 was chosen because the first study on quality of life in breast cancer patients was published then. The search strategy included the combination of key words 'quality of life' and 'breast cancer' or 'breast carcinoma' in titles of publications. It was though that this might help to focus the investigation. It provided the initial database for the review. The initial search was carried out in early 2006 and updated twice in 2006, twice at the end of January and December 2007, and once for a final check in April 2008.

4A total of 971 citations were identified and after exclusion of duplicates, the abstracts of 606 citations were reviewed. Of these, meetings abstracts, editorials, brief commentaries, letters, errata and dissertation abstracts and papers that appeared online and were indexed ahead of publication were also excluded. The remaining 477 papers were examined in this bibliographic review. The statistics are shown in Table 1 and a chronological list of all papers is available [Additional file 1]. Here, the major findings are summarized and presented under the following headings.

5There were several review papers. These were divided into two categories: overviews, and systematic reviews. Whilst there were quite significant numbers of commentaries, some brief, a few systematic reviews with focused objectives were also identified. These are summarized in Tables 2 and 3. Both overviews and systematic reviews touched interesting topics pointed to helpful comments and findings among published papers. For instance, a paper by Rozenberg et al. highlighted that most women affected by breast cancer will not die from it but from other diseases, owing to recent improvements in treatment. They also pointed out that women with breast cancer and three or more co-morbid conditions have a 20-fold higher rate of mortality from causes other than breast cancer and a 4-fold higher rate of all-cause mortality when compared with patients who have none.

6Health-related quality of life in patients undergoing systemic therapy for advanced breast cancer was reviewed by Bottomley and Therasse, covering the literature from 1995 to 2001. They indicated that there were 19 studies. Among these, there were 12 studies on chemotherapy, 6 hormonal trials and 1 on biological therapy (Trastuzumab). They concluded that quality of life data provided invaluable insights into the treatment and care of patients.

7To help the selection of optimal treatment, Goodwin et al. conducted a review of measurements of health-related quality of life in randomized clinical trials in breast cancer patients, covering the literature from 1980 to 2000. They identified a total of 256 randomized trials in breast cancer that included health-related quality of life or psychosocial outcomes. Of these, 66 trials involved randomized of different treatment options, 46 evaluated biomedical interventions and 20 evaluated psychosocial interventions. They concluded that until the results of ongoing trials are available, caution is recommended in initiating new quality of life studies unless treatment equivalence is expected or unless unique or specific issues can be addressed. Similarly, Fossati's critical review of published literature on randomized clinical trials of cytotoxic or hormonal treatments of advanced breast cancer indicated that quality of life assessments added relatively little value to classical clinical endpoints.

8Mols et al. reviewed the literature on quality of life among long-term survivors of breast cancer and found that although these patients experienced some specific problems such as a thick and painful arm and problems with sexual functioning, most reported good overall quality of life. The review also indicated that the current medical condition, amount of social support and current income level were strong positive predictors of quality of life, and the use of adjuvant chemotherapy emerged as a negative predictor. The authors concluded that focusing on the long-term effects of breast cancer is important when evaluating the full extent of treatment.

9Grimison and Stockler reviewed quality of life in early-stage breast cancer patients receiving adjuvant systemic therapy, review of clinical randomized trials covering the literature from 1996 to 2007, and concluded that the long-term effects of chemotherapy-induced menopause and hormonal therapy on quality of life were poorly recognized. They found that vasomotor symptoms and altered sexual function were common, distressing and inadequately treated.

10The first paper on quality of life in breast cancer patients was published in 1974. In this historical paper advanced breast cancer patients receiving adrenalectomy with chemotherapy were assessed for objective and subjective response rates, survival and quality of life. The results showed that in 64% of the patients the subjective palliation involved a return to essentially normal living during the period of improvement. The second historical paper on the topic was appeared two years later, in 1976; Priestman and Baum used a linear analogue self-assessment (LASA) to measure the subjective effects of treatment in women with advanced breast cancer. The results showed that this technique might be used to monitor the subjective benefit of treatment and to compare the subjective toxicities of different therapeutic regimens. The results also suggested that the subjective toxicity of cytotoxic therapy was not related to the patient's age and diminished with successive courses of drugs. However, not until the late 1980s and early 1990s was the literature gradually supplemented with papers using relatively standard and established instruments to measure quality of life in breast cancer patients.

11Broadly, quality of life measures can be classified as: general, disease specific, and site-specific. Although the early studies did not use standard measures, several valid instruments for measuring quality of life in breast cancer patients have been developed in recent years. The most commonly-used instruments were: the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire and its Breast Cancer supplement (EORTC QLQ-C30 and QLQ-BR23); the Functional Assessment of Chronic Illness Therapy General Questionnaire and its Breast Cancer Supplement (FACIT-G and FACIT-B formerly FACT questionnaires); the Breast Cancer Chemotherapy Questionnaire (BCQ); the Hospital Anxiety and Depression Scale (HADS); and the Medical Outcomes Study Short Form Survey (SF-36). Table 4 lists a number of most important instruments used in studies of quality of life in breast cancer patients. Almost all these instruments proved to be valid and were found to be very popular among researchers and clinicians.

12Development of instruments for measuring quality of life in breast cancer patients, or cultural adaptation and validation studies of the existing instruments, was the major theme in a number of papers. These are presented in Table 5. A paper by Levine et al. in 1988 was the first validation study in this field. It reported a quality of life measure in breast cancer patients called the Breast Cancer Chemotherapy Questionnaire (BCQ). This is a 30-item questionnaire that focuses on loss of attractiveness, fatigue, physical symptoms, inconvenience, emotional distress and feelings of hope and support from others. A few studies reported translation and validation findings for the instruments used to assess quality of life among breast cancer patients in different cultures (for example see).

13Papers that dealt with issues of quality of life measurement in breast cancer patients encompassed a variety of topics, mainly focusing on methodological and practical concerns in such assessment, especially in clinical settings. Most authors have tried first to convince clinicians to assess quality of life, and secondly to show how quality of life data could contribute to care and management of breast cancer patients. Table 6 presents a summary of the results.

14Breast cancer surgery including conservative surgery followed by irradiation, and modified radical mastectomy or radical mastectomy followed by immediate reconstruction is associated with different side-effects including pain, and fatigue and thus affecting quality of life in breast cancer patients. A list of studies on surgery and quality of life in breast cancer patients is given in Table 7

15The most important topic in studies of breast cancer surgery and quality of life relates to the type of surgery. Recent findings suggest that partial and total mastectomy appear to be equivalent treatments in terms of patients' long-term quality of life. However, both short-term and long-term distress levels after partial and total mastectomy may depend on patient's age at diagnosis. A study of early breast cancer patients one year after mastectomy or conservative surgery and radiation therapy found that the differences between treatment groups were mainly accounted for by adjuvant therapies. Those treated by breast conservation reported better body image but worse physical functions. The negative impact of breast cancer and its treatment was greater for younger women across a number of dimensions of quality of life measures regardless of treatment type.

16In addition, one study found that aspects of quality of life other than body image were no better in women who underwent breast-conserving surgery or mastectomy with reconstruction than in women who had mastectomy alone. Furthermore, mastectomy with reconstruction was associated with greater mood disturbance and poorer health. However, the results of a 5-year prospective study on quality of life following breast-conserving surgery or mastectomy indicated that mastectomy patients had a significantly worse body image; role and sexual functioning, and their lives were more disrupted. A recent Japanese study on the early effects of surgery in patients with breast cancer performing multivariate analysis reported that there were no significant differences in quality of life before and after surgery, but quality of life was significantly better among women undergoing breast conservation than those undergoing mastectomy. A study comparing the short- and long-term effects of mastectomy with reconstruction, mastectomy without reconstruction, and breast conservation therapy on aspects of psychosocial adjustment and quality of life in a sample of 258 women with breast cancer concluded that overall, the general patterns of psychosocial adjustment and quality of life were similar among the three surgery groups. In addition the study results showed that during the long-term follow-up period (6 months to 2 years after surgery), women in all three groups experienced marked improvements in psychosocial adjustment (depressive symptoms, satisfaction with chest appearance, sexual functioning) and quality of life in physical and mental health domains.

17In order to reduce the risk of recurrence and death, breast cancer patients usually receive systemic therapies (chemotherapy, hormonal therapy and biological treatments) after surgery. Several studies evaluated quality of life in breast cancer patients receiving systemic therapies. A list of studies reporting on the topic is given in Table 8.

18Chemotherapy has considerable effect on quality of life of breast cancer patients. In a study of postoperative adjuvant chemotherapy in primary node positive breast cancer patients (one or more axillary node), women receiving a single agent or a multi-drug regimen indicated that the treatment was 'unbearable' or in a study of patients with early breast cancer receiving preoperative chemotherapy almost all patients considered chemotherapy the most 'burdensome' aspect of the treatment.

19The side-effects of chemotherapy on quality of life in breast cancer patients were the topic of many investigations. In these studies, investigators looked at the issue from different perspectives. For instance, using a decision-analytic approach to evaluate tradeoffs between efficacy and quality of life in the choice of three adjuvant treatments (chemotherapy, surgical ovarian suppression, and medical ovarian suppression) in pre-menopausal women with newly-diagnosed, hormone-responsive early breast cancer, Elkin et al. concluded that when different treatments have similar efficacy, there may be a subgroup of women for whom quality of life considerations dominate the choice. However, they stated that small differences in the relative efficacy of these therapies have a substantial impact on treatment choice.

20To improve clinical outcomes an international randomized controlled trial compared dose-intensive chemotherapy with standard systemic chemotherapy in patients with locally advanced breast cancer and showed that a dose-intensive regimen only has a temporary effect on health-related quality of life, thus enabling more research on intensive treatment for patients with locally advanced breast cancer, as it might also offer a survival benefit.

21However, recent studies focusing on adjuvant hormonal therapies (tamoxifen or aromatase inhibitors such as anastrozole, letrozole, exemestane) and quality of life in postmenopausal early-stage breast cancer patients reported more encouraging results. Most studies found that overall quality of life was improved in patients receiving either anstrozole or tamoxifen but patients reported different side effects. A trial comparing tamoxifen with exemestane showed that quality of life did not change significantly in either groups, but there were improvements in endocrine-related symptoms.

22In summary, as noted by Grimison and Stockler, for the majority of breast cancer patients most aspects of health-related quality of life recover after adjuvant chemotherapy ends without long-term effects except vasomotor symptoms and sexual dysfunction. However, tamoxifen and aromatase inhibitors cause long-term effects due to vasomotor, gynecological and sexual problems.

23Until recently, only a few studies had reported a relationship between quality of life and survival in breast cancer patients. A study using the Daily Diary Card to measure quality of life in advanced breast cancer showed that the instrument offered accurate prognostic data regarding subsequent response to treatment and survival duration. Similarly, Seidman et al. evaluated quality of life in two phase II clinical trials of metastatic breast cancer and found that baseline scores of two validated quality of life instruments independently predicted the overall likelihood of tumour responses.

24Studies have shown that baseline quality of life predicts survival in advanced breast cancer but not in early stage of disease. Two recently published papers also confirmed that baseline quality of life is not a prognostic factor in non-metastatic breast cancer patients. One of these two studies, using Cox survival analysis, indicated that neither health-related quality of life nor psychological status at diagnosis or 1 year later was associated with medical outcome in women with early-stage breast cancer. The other study with a sample of 448 locally advanced breast cancer patients, reported that baseline health-related quality of life parameters had no prognostic value in a non-metastatic breast cancer population. However, other studies have demonstrated that some aspects of quality of life data including physical health, pain, and loss of appetite were significant prognostic factors for survival in women with advanced breast cancer. In addition, one study demonstrated that baseline physical aspects of quality of life and its changes were related to survival, but psychological and social aspects were not.

25Women with breast cancer might develop psychological distress including anxiety and depression during diagnosis and treatment and after treatment. The psychological impact of breast cancer has received considerable attention. Since this is a separate topic, the focus here is on psychological distress as it relates to quality of life studies in breast cancer patients. Table 9 summarizes the papers on the topic.

26Psychological distress in breast cancer patients is mostly related to depression, anxiety, and low emotional functioning and almost all studies have shown that psychological distress contributed to impaired quality of life especially emotional functioning, social functioning, mental health and overall quality of life. The diagnosis of the disease, importance of fears and concerns regarding death and disease recurrence, impairment of body image, and alteration of femininity, sexuality and attractiveness are factors that can cause unexpected psychological distress even years after diagnosis and treatment.

27Studies have shown that psychological factors predict subsequent quality of life or even overall survival in breast cancer patients. A study showed that patients with lower coping capacity reported higher prevalence of symptoms, experienced higher levels of distress, and experienced worse perceived health, which in turn decreased their quality of life. Furthermore, it has been shown that psychological adjustment such as the ability to cope with the disease, treatment and effects of treatment could improve outcome. The relationship between positive thinking and longer survival and a better quality of life is well documented.

28A variety of topics were covered to address supportive care issues in breast cancer patients. These ranged from papers on controlling emesis to papers that reported issues related to counseling, social support and exercise to improve quality of life. The results are summarized in Table 10.

29There were studies on breast cancer symptoms and their relationship to quality of life. Most of these studies were related to fatigue, lymphedema, pain, and menopausal symptoms. The results are summarized in Table 11.

30Fatigue is the least definable symptom experienced by patients with breast cancer and its effect on impaired quality of life cannot be explained precisely. A recent publication studying 1,588 breast cancer patients showed that fatigue (as measured by the EORTC QLQ-C30 fatigue subscale) independently predicted longer recurrence-free survival when biological factors were controlled in the analysis. When combined with the biological model, fatigue still remained a significant predictor of recurrence-free survival.

31Breast cancer could be regarded as a disease that relates to women's identities. In this respect, sexual functioning is an important issue, especially in younger breast cancer patients. Among quality of life studies in breast cancer patients only six papers focused especially on sexual functioning. The findings indicated that disrupted sexual functioning or unsatisfactory sexual life was related to poorer quality of life at younger age, treatment with chemotherapy, total mastectomy, emotional distress consequent on an unsatisfactory sexual life, and difficulties with partners because of sexual relationships.

32This bibliographic review has provided an extensive list of studies that focused on quality of life in breast cancer patients. The article might be criticized on the grounds that it included every paper on the topic and that it provides more enumeration than insight. However, this was not an in-depth review but rather, as indicated in the title, a bibliographic investigation and descriptive in nature. The benefit of such an approach is that it reveals how much effort has been made in this area and shows the achievements of a journey that was started more than 30 years ago. If quality of life has now become an important part of breast cancer patients' care, it is due to all these efforts. Furthermore, this approach might help potential investigators to formulate new questions or conduct more focused studies on the topic in the future. It should be admitted that investigations of this type have limitations and are inconclusive. Since in this review the search strategy was limited to the key words 'quality of life' and 'breast cancer' in titles, perhaps many other papers also were missed even from enumeration. However, an up coming complementary review by the author will focus on these missing papers.

33A number of studies that covered measurement issues and introduced instruments used to measure quality of life in breast cancer patients. Hopefully there is now sufficient evidence to use these valid instruments and to adopt the practices that are needed to assess quality of life in research or clinical settings. Since 1974, when the first study on quality of life in breast cancer patients was published, there has been quite impressive progress and improvement, indicating that measuring quality of life in breast cancer patients is both crucial and scientific. Now several valid instruments that capture quality of life dimensions in cancer patients in general and in breast cancer patients in particular are available. The EORTC QLQ-C30, EORTC QLQ-BR23, FACIT-G and FACIT-B are among the most acceptable instruments to patients and health professionals. They have been used in many studies, so it is possible to compare results between studies with similar objectives. It seems that it is time to stop developing new instruments, since there are enough valid and comprehensive measures to assess quality of life in breast cancer patients. New instruments might cause confusion and may be regarded as a waste of resources, so any such developments would need robust justification. Depending on the objectives of any single study, one might use other existing valid measures such as the Satisfaction with Life Domains Scale for Breast Cancer (SLDS-BC), which can briefly and rapidly assess quality of life across the breast cancer continuum of care; the Body Image After Breast Cancer Questionnaire (BIBCQ); which is a valid measure for assessing the long-term impact of breast cancer on body image; and the Fallowfield's Sexual Activity Questionnaire (FSAQ), which is a useful tool for measuring sexual activity in women with cancer.

34There were some important technical issues that should be addressed. Some believe that if we perform complex analyses of quality of life data or if we use several instruments in a single study then we might achieve more scientific results. There is evidence that this could merely lead to misleading findings and might be a source of suffering for the patients. The recommendation is to analyze data in a simple way and avoid complexity. The presentation of data should be straightforward and easy to follow; otherwise those who are critical of such findings might conclude that these are manipulations of data, or they might ask whether these numbers and statistics reflect what really happens to breast cancer patients or the clinical teams that care for them. Do these figures convey difficulties that exist in treating breast cancer patients or help to manage their symptoms?

35The present review covered several topics and provided tables to indicate areas that need more attention. It appears that the most common and important disease- and treatment-related side-effects and symptoms in breast cancer patients including arm morbidity, pain, fatigue and postmenopausal symptoms, are among neglected topics. As noted by Cella and Fallowfield, recognition and management of treatment-related side-effects for breast cancer patients receiving adjuvant endocrine therapy is an important issue since such side-effects negatively affect health-related quality of life and adherences to therapy. These authors argue that adverse events constitute the main reason for non-adherence to endocrine treatment, and across all adjuvant endocrine trials regardless of the treatment, vasomotor symptoms such as hot flushes are the most common side effects. Other frequently reported side-effects such as vaginal discharge, vaginal dryness, dyspareunia, and arthralgia vary in prevalence between tamoxifen and aromatase inhibitors. It has been recommended that currently in assessing quality of life in breast cancer patients priorities should be given to cognitive functioning, menopausal symptoms, body image and long-term effects of new therapies that might cause musculoskeletal and neurological side-effects. In addition, sexual functioning seems important area that needs more attention, especially for younger breast cancer survivors. It is argued that younger survivors may need interventions that specifically target their needs related to menopausal symptoms and problems with relationships, sexual functioning and body image.

36There were few qualitative studies. Since these could provide more insight into quality of life in breast cancer patients, we need more such studies to collect data and indicate how breast cancer patients interpret life after diagnosis and during and after treatment. Breast cancer survivors even might rate their quality of life more favorably than outpatients with other common medical conditions and identify many positive aspects from the cancer experience. However, it is not only the study of quality of life in newly diagnosed breast cancer patients that is necessary; studying quality of life in long-term survivors is equally important. As suggested, when assessing quality of life in breast cancer patients, the stage of disease should also be considered. There are differences in quality of life between patients with non-invasive breast cancer, newly diagnosed breast cancer and advanced local breast cancer, and disease-free breast cancer survivors, women with recurrence breast cancer, and women with advanced metastatic breast cancer.

37There was quite an extensive body of the literature on quality of life in breast cancer patients. These papers have made a considerable contribution to improving breast cancer care, although their exact benefit was hard to define. However, quality of life data provided scientific evidence for clinical decision-making and conveyed helpful information concerning breast cancer patients' experiences during the course of the disease diagnosis, treatment, disease-free survival time, and recurrences; otherwise finding patient-centered solutions for evidence-based selection of optimal treatments, psychosocial interventions, patient-physician communications, allocation of resources, and indicating research priorities were impossible. It seems that more qualitative research is needed for a better understanding of the topic. In addition, issues related to the disease, its treatment side effects and symptoms, and sexual functioning should receive more attention when studying quality of life in breast cancer patients.

38The author declares that they have no competing interests.

39The author carried out this review and wrote the manuscript, and prepared all the tables and the additional file.