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

Background Quality of life in patients with breast cancer is an important outcome. This paper presents an extensive overview on the topic ranging from descriptive findings to clinical trials. Methods This was a bibliographic review of the literature covering all full publications that appeared in English language biomedical journals between 1974 and 2007. The search strategy included a combination of key words 'quality of life' and 'breast cancer' or 'breast carcinoma' in titles. A 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. The major findings are summarized and presented under several headings: instruments used, validation studies, measurement issues, surgical treatment, systemic therapies, quality of life as predictor of survival, psychological distress, supportive care, symptoms and sexual functioning. Results Instruments-Several valid instruments were used to measure quality of life in breast cancer patients. The European Organization for Research and Treatment of Cancer Core Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and its breast cancer specific complementary measure (EORTC QLQ-BR23) and the Functional Assessment Chronic Illness Therapy General questionnaire (FACIT-G) and its breast cancer module (FACIT-B) were found to be the most common and well developed instruments to measure quality of life in breast cancer patients. Surgery-different surgical procedures led to relatively similar results in terms of quality of life assessments, although mastectomy patients compared to conserving surgery patients usually reported a lower body image and sexual functioning. Systemic therapies-almost all studies indicated that breast cancer patients receiving chemotherapy might experience several side-effects and symptoms that negatively affect their quality of life. Adjuvant hormonal therapies also were found to have similar negative impact on quality of life, although in general they were associated with improved survival. Quality of life as predictor of survival-similar to known medical factors, quality of life data in metastatic breast cancer patients was found to be prognostic and predictive of survival time. Psychological distress-anxiety and depression were found to be common among breast cancer patients even years after the disease diagnosis and treatment. Psychological factors also were found to predict subsequent quality of life or even overall survival in breast cancer patients. Supportive care-clinical treatments to control emesis, or interventions such as counseling, providing social support and exercise could improve quality of life. Symptoms-Pain, fatigue, arm morbidity and postmenopausal symptoms were among the most common symptoms reported by breast cancer patients. As recommended, recognition and management of these symptoms is an important issue since such symptoms impair health-related quality of life. Sexual functioning-breast cancer patients especially younger patients suffer from poor sexual functioning that negatively affect quality of life. Conclusion There 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.

patients. As recommended, recognition and management of these symptoms is an important issue since such symptoms impair health-related quality of life. Sexual functioning-breast cancer patients especially younger patients suffer from poor sexual functioning that negatively affect quality of life.

Conclusion:
There 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.

Background
Health-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 [1][2][3][4]. 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 [5]. 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 healthrelated quality of life (54%), followed by economic analyses (38%), and patient satisfaction (14%). Only 9% measured patient preferences [6].
Over 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.

Methods
As 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  1974  246  13  1  1  1975  312  23  0  0  1976  358  34  1  1  1977  522  27  0  0  1978  527  33  0  0  1979  489  34  0  0  1980  662  36  1  1  1981  634  45  1  0  1982  647  71  1  1  1983  661  89  2  2  1984  830  73  0  0  1985  844  97  2  2  1986  920  134  1  1  1987  961  211  2  2  1988  1125  223  2  2  1989  1333  294  2  2  1990  1470  422  7  6  1991  1423  394  8  7  1992  1805  603  8  8  1993  2088  641  18  17  1994  2342  747  16  15  1995  2444  948  11  10  1996  2926  1422  16  15  1997  3249  1756  19  16  1998  3597  2049  29  25  1999  3872  2457  39  30  2000  5026  2639  37  30  2001  5206  2985  34  27  2002  5720  3233  42  26  2003  6441  3900  38  31  2004  7422  4811  74  47  2005  7862  5276  73  53  2006  7021  4592  63  48  2007  4641  2207  58  51   Total  85626  42519  606  477 * Excluding duplicates and papers that appeared online and indexed ahead of publication. ** Excluding all meetings abstracts, editorials, brief commentaries, letters, replies, erratum, and dissertation abstracts. For all citations see Additional file 1.   Mols 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 [34]. Grimison and Stockler reviewed quality of life in earlystage 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 [35].

Two historical papers
The 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 [36]. 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 [37]. 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.  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.

Validation studies
Development 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 [35]. 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 [48,54,56]).

Measurement issues
Papers 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 .

Surgical treatment
Breast 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[  The 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 mastec-

Author(s) [Ref.] Year Main focus Conclusion(s)/Recommendation
Baum et al. [60] 1990 The issue of measuring QOL in advanced breast cancer Efforts are being made to find out ways to measure QOL in advanced breast cancer patients.
Sutherland et al. [61] 1990 Ratings of the importance of QOL variables Breast cancer patients give different weights to different QOL variables.
Gelber et al. [62] 1992 Explaining about the QOL adjusted Time Without Symptom and Toxicity Integration of two methods (QOL and symptom free duration) could provide a new tool.
Ganz et al. [63] 1992 The influence of multiple variables on the relationship of age to QOL The casement plot methodology should be employed for simultaneous evaluation of multiple variables.
Gelber et al. [64] 1993 Description of survival estimates with applications to QOL evaluation (Quality adjusted Time Without Symptoms of disease and Toxicity of treatment) Estimation showed that patients continued to benefit greatly from long-term-duration chemotherapy between 5 and 10 years following treatment.
Hyden et al. [65] 1993 Pitfalls in collecting QOL data Several recommendations were made: (a) build support for QOL assessment among the group's leadership, (b) involve physicians and oncology nurses in the study design, (c) identify a QOL liaison at each participating institution, and (d) aggressively monitor the quality and timeliness of data submission.
Fallowfield [66] 1993 Measurement issues Some recommendations for selecting well validated measures.
Gerard et al. [67] 1993 Framing and labeling effects in measuring quality adjusted life years A significant difference was found in the particular values of descriptions that were written in the third person that differed in terms of whether the word "cancer" was used.
Hurny et al. [68] 1994 Timing of baseline QOL assessment Timing is an important consideration in QOL assessment.
Fallowfield [69] 1995 Discussion on some instruments used to measure QOL Monitoring QOL in breast cancer should be a mandatory part of follow-up in clinical trials.
Hietanen [70] 1996 Measurement and practical aspects of QOL assessment Main factors affecting QOL in the treatment of breast cancer.
Bernhard et al. [71] 1997 The International Breast Cancer Study Group (IBCSG) approach Confirmation of the feasibility, validity and clinical relevance of quality of life assessment.
Bernhard et al. [72] 1998 Factors affecting baseline QOL assessment Cultural and biomedical factors are influencing baseline QOL data and should be considered when evaluating the impact of treatment.
Bernhard et al. [73] 1998 Practical issues and factors associated with missing data The factors most highly associated with missing data were institution and chemotherapy compliance.
Ganz et al. [74] 1998 Compliance with QOL data collection Educational level of a trial participants might contribute to it compliance.
Coates and Gebski [75] 1998 Approaches to missing data Missing data cannot be assumed to be similar to those available. Optimal assessment requires careful prospective attention to complete data collection.
Curran et al. [77] 2000 Summary measures and statistics Different techniques in analysis might result in different conclusions.
Perez et al. [78] 2001 The application of a time trade-off utility measure The utility measure and a QOL measure showed fair to moderate concordance. tomy may depend on patient's age at diagnosis [93]. 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 [100].
In 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 [101]. 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 [105]. 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 [111]. 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 longterm 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 [113].

Systemic therapies
In 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 [36,37,.
Chemotherapy 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' [114] 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 [116]. Perry et al. [84] 2007 Benefits, acceptability and utilization of QOL assessment in women with breast cancer Summarized the benefits, challenges, and barriers of QOL measurement for female breast cancer patients.  In summary, as noted by Grimison and Stockler, for the majority of breast cancer patients most aspects of healthrelated 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 [35].

Quality of life as predictor of survival
Until recently, only a few studies had reported a relationship between quality of life and survival in breast cancer patients [115]. 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 [170]. 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 [171].
Engel et al [105] 2004 MAS or BCS (5 years follow-up) MAS patients had lower body image, role and sexual functioning; BCS should be encouraged in all ages.
Ganz et al. [106] 2004 Lumpectomy + chemotherapy or MAS + chemotherapy or Lumpectomy alone or MAS alone in non-metastatic breast cancer patients At the end of primary treatment all treatment groups reported good emotional functioning but decreased physical health especially among women who had MAS or received chemotherapy.
Elder et al. [108] 2005 MAS + immediate breast reconstruction (before and 12 months after) After 12 months good QOL comparable with aged-matched women from the general population.
Fleissig [110] 2006 SLNB vs. ALND Regarding arm functioning and QOL the use of SNB was recommended in patients with node negative breast cancer.
Pandey et al. [111] 2006 MAS or BCS No significant change in overall QOL after surgery; poorer QOL in MAS patients.
Rietman et al. [112] 2006 SLNB or ALND (before and after 2 years) Less treatment related upper limb morbidity, perceived disability in activities of daily life and worsening of QOL after SNLB compared with ALND.
Parker et al. [113] 2007 MAS or MAS+ reconstruction or BCS (short-and longterm effects on aspects of psychosocial adjustment and QOL Overall, the general patterns of psychosocial adjustment and QOL were similar among the three surgery groups.

Author(s) [Ref.] Year Treatment/patients Conclusion(s)
Moore et al. [36] 1974 Adrenalectomy + chemotherapy in advanced breast cancer In most patients the subjective palliation involved a return to normal living.
Priestman and Baum [37] 1976 Chemotherapy in advanced breast cancer Toxicity is not related to the patients' age and diminished with successive courses of drugs.
Palmer et al. [114] 1980 A single agent vs. five drug combination in node positive primary breast cancer Better QOL in single agent group.
Coates et al. [115] 1987 Intermittent vs. continuous chemotherapy in metastatic breast cancer Continuous chemotherapy was better; changes in the QOL were independent prognostic factor of survival.
Kiebert et al. [116] 1990 Peri-operative chemotherapy vs. no chemotherapy in early stage breast cancer No differences 1 year after; patients considered chemotherapy most burdensome aspect of treatment.
Gelber et al. [117] 1991 Single cycle of combination chemotherapy vs. longer duration chemotherapy for pre-menopausal or chemo-endocrine therapy for postmenopausal women Better QOL in longer duration chemotherapy or chemoendocrine therapy.
Berglund et al. [118] 1991 Late effects of adjuvant chemotherapy vs. postoperative radiotherapy in pre-and postmenopausal breast cancer Chemotherapy patients had higher overall QOL.
Richards et al. [119] 1992 A (weekly for 12 courses vs. every three weeks for 4 courses) in advanced breast cancer Similar survival but higher psychological distress in the three weeks group.
Hurny et al. [120] 1992 CMF (6 cycles vs. 3 cycles) in operable breast cancer QOL improved with increasing time from the study entry.
Campora et al. [121] 1992 Adjuvant chemotherapy vs. palliative chemotherapy in metastatic breast cancer No significant difference between groups.
Fraser et al. [122] 1993 CMF vs. E in advanced breast cancer Similar survival and no significant difference in overall global QOL.
Twelves et al. [123] 1994 Iododoxorubicin in advanced breast cancer Little evidence of benefit in terms of physical symptom relief, level of activity, psychological symptoms or global QOL.
Bertsch and Donaldson. [124] 1995 Vinorelbine vs. melphalan Vinorelbine was better in some aspects of QOL.
Swain et al. [125] 1996 AC + G-CSF in node positive breast cancer Tolerable physical symptoms and emotional distress.  Hopwood et al. [169] 2007 Adjuvant radiotherapy QOL and mental health were favorable for most patients about to start radiotherapy but younger age and receiving chemotherapy were significant risk factors for poorer QOL.

list of studies on systemic therapies and quality of life in breast cancer patients (1974-2007) (Continued)
Studies have shown that baseline quality of life predicts survival in advanced breast cancer but not in early stage of disease [172]. 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 [173]. The other study with a sample of 448 locally advanced breast cancer patients, reported that baseline healthrelated quality of life parameters had no prognostic value in a non-metastatic breast cancer population [174]. However, other studies have demonstrated that some aspects of quality of life data including physical health [175], pain [139,176], and loss of appetite [177] 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 [178].

Psychological distress
Women 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 .
Psychological 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 [211][212][213].
Studies have shown that psychological factors predict subsequent quality of life [200] or even overall survival in breast cancer patients [214]. 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 [215]. 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 [216].

Supportive care
A 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.

Symptoms
There 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 .
Fatigue 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 recurrencefree survival [214].

Sexual functioning
Breast 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 [281][282][283][284][285][286]. 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.

Discussion
This 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

Author (s) [Ref.] Years Main focus Results/conclusion(s)
Ferrero et al. [179] 1994 Mental adjustment to cancer in newly-diagnosed non-mtastatic breast cancer(an xploratory study) Strong association between mental adjustment to cancer and reported vague physical symptoms; fighting spirit and denial was associated with better QOL and helpless/hopeless and anxious preoccupation and fatalism were negatively correlated with wellbeing.
Ganz et al. [180] 1996 Psychosocial concerns 2 and 3 years after primary treatment Problems associated with physical and recreational activities, body image, and sexual functions were observed, although many positive aspects from cancer experience were reported.
Maunsell et al. [181] 1996 Brief psychological intervention vs. Brief psychological intervention + psychological distress screening Distress screening did not improve QOL. Minimal psychological intervention at initial treatment alone was recommended.
Andrykowski et al. [182] 1996 Psychological adjustment in women with breast cancer or benign breast problems Breast cancer patients reported poorer physical health but greater positive psychosocial adaptation and improved life outlook, no difference in psychological distress between two groups.
Marchioro et al. [183] 1996 Evaluation of the impact of a psychological intervention vs. standard care in non-metastatic breast cancer patients Cognitive psychotherapy and family counseling improved both depression and QOL indexes.
Weitzner et al. [184] 1997 QOL and mood in long-term breast cancer survivors Psychological measures were found to be more robust predictors of QOL than the demographic variables; long-term survivors continue to experience significant depression and lower QOL.
Bloom et al. [186] 1998 Intrusiveness of illness in young women with newly-diagnosed breast cancer Intrusiveness of illness mediated the effect of disease and treatment factors on QOL; neither time post-diagnosis nor type of treatment affected the psychological component of QOL.
Longman et al. [187] 1999 Psychological adjustment over time Over time depression burden and anxiety burden persist and each was negatively associated with overall and present QOL.
Cotton et al. [188] 1999 Relationship among spiritual well-being, QOL, and psychological adjustment Spiritual well-being was correlated with both QOL and psychological adjustment, but relationship was found to be more complex and indirect than previously considered.
Ashing-Giwa [189] 1999 Psychological outcome in long-term survivors of breast cancer (focus on African-American) Patients relied on spiritual faith and family support to cope; sociocultural contexts of the women's lives need to be considered when studying QOL.
Lewis et al. [190] 2001 Cancer-related intrusive thoughts and social support In women with social support cancer-related intrusive thoughts had no significant negative impact on QOL, but in women with low social support there was negative effect on QOL.
Amir and Ramati [191] 2002 Post-traumatic distress disorder (PTSD), QOL, and emotional distress in long term survivors of breast cancer and a control group Higher PSTD, emotional distress and lower QOL in breast cancer mainly due to chemotherapy and disease stage.
Ganz et al. [192] 2003 Psychosocial adjustment 15 months after diagnosis in older women with breast cancer Psychosocial adjustment at 15 months was predicted by better mental health, emotional social support and better self-rated interaction with health care providers.
Bordeleau et al. [193] 2003 Randomized trial of group psychological support vs. control in metastatic breast cancer Supportive-expressive group therapy did not appear to influence QOL.
Badger et al. [194] 2004 Depression burden and psychological adjustment Depression burden had negative effect on psychological adjustment and QOL.
Schreier and Williams [195] 2004 Anxiety in women receiving either radiation or chemotherapy for breast cancer No significant differences for total QOL or any subscales by treatment; trait anxiety was higher for chemotherapy patients; state anxiety was high and did not decrease over the course of the treatment for either group.
Kershaw et al. [196] 2004 Coping strategies in advanced breast cancer patients and their family caregivers Patients use more emotional support, religion and positive reframing strategies while family use more alcohol or drug. In both active coping was associated with higher QOL.
Lehto et al. [197] 2005 Psychological stress factors as predictors of QOL in patients receiving surgery alone vs. adjuvant treatment Psychosocial factors were strongest predictors of QOL but not cancer type or treatment; non-cancer related stresses showed strongest QOL decreasing influence.
Roth et al. [198] 2005 Affective distress in women seeking immediate vs. delayed breast reconstruction after mastectomy Women seeking immediate breast reconstruction showed relatively higher psychological impairment and physical disability.
Okamura et al. [199] 2005 Psychiatric disorders and associated factors after first breast cancer recurrence Patients' psychiatric disorders were associated with lower QOL.
Golden-Kreutz et al. [200] 2005 Traumatic stress, perceived global stress, and life events Initial stress at diagnosis predicted both psychological and physical health at follow-up.
Deshields et al. [201] 2005 Emotional adjustment (at 4 points in time) Primary psychological changes occur quickly after treatment conclusion and then it appeared to become stabled.
Laid law et al. [202] 2005 Self-hypnosis or Japanese healing or. control Positive change in anxiety level, a general increase in mood and a better QOL were observed.
Schou et al. [203] 2005 Dispositional optimism and QOL. Optimism was predictive for better emotional and social functioning one year after surgery; at time of diagnosis and throughout post-diagnosis dispositional optimism was associated with better QOL and fewer symptoms.
Antoni et al. [205] 2006 Stress management after treatment for breast cancer Stress management skill taught had beneficial effects on reduced social disruption, and increased emotional well-being, positive states of mind, benefit finding, positive lifestyle change, and positive affect.
Wonghongkul et al. [206] 2006 Uncertainty appraisal coping Social support was used most to cope and confront-coping used the least; year of survival, uncertainty in illness and harm appraisal influenced QOL.
Yen et al. [207] 2006 Depression and stress in breast cancer versus benign tumor Stress from health problem was the most significant predictor for QOL among malignant group.
Costanzo et al. [208] 2007 Adjustment to life after treatment While breast cancer survivors demonstrated good adjustment on general distress following treatment, some women were at risk for sustained distress.
Wong and Fielding [209] 2007 Change in psychological distress and change in QOL The magnitude of change in psychological distress significantly impacted physical and functional, but not social QOL in breast cancer patients.
Meneses et al. [210] 2007 Psycho-educational intervention and QOL Breast cancer education intervention is an effective intervention in improving QOL during the first year of breast cancer survivorship.

Author (s) [Ref.] Year Intervention Results/conclusion(s)
van Holten-Verzantvoort et al. [217] 1991 Pamidronate vs. control to reduce skeletal morbidity Less short-term mobility impairment and bone pain in treatment group but not at long term.
Young-McCaughan and Sexton [218] 1991 Aerobic exercise Higher QOL in women who exercised.
Kornblith et al. [220] 1993 Megestrol acetate in dose-response trial to prevent appetite loss Lower dose was optimal achieving fewest side effects and a better QOL.
Clavel et al. [221] 1993 Ondansetron to control emesis (review of five randomized trials) Ondansetron provided significant QOL benefits compared with metoclopramide and alizapride) Ashbury et al. [222] 1998 One-on-one peer support (Reach to Recovery programme) Patients were satisfied and the programme had incremental benefits to QOL of patients.
Lee [223] 1997 Social support (Reach to Recovery programme) Social support plays a vital role in promoting overall QOL.
Wengstrom et al. [224] 1999 Nursing intervention vs. control No measurable effect on side effects or QOL but proved to have a positive effect in minimizing stress.
Lachaine et al. [225] 1999 Ondansetron or metoclopramide to control emesis Emesis control was significantly better in ondansetron; global QOL decreased more with metoclopramide.
Ritz et al. [226] 2000 Advanced nursing care (APN)+ standard care vs. standard care APN improved some QOL indicators.
Molenaar et al. [227] 2001 Decision support to help patients to choose mastectomy or breast conservation Decision-making improved as evaluated in terms of satisfaction and QOL.
Sammarco [228] 2001 Perceived social support and uncertainty in younger breast cancer survivors Significant positive correlation between perceived social support and QOL, and significant negative correlation between uncertainty, and QOL.
Michael et al. [229] 2002 Social networks Pre-diagnosis level of social integration was important factor in future QOL, and explains more of the variance than treatment or tumour characteristics.
Olsson et al. [230] 2002 Erythropoietin (randomized to two different doses epoetin-beta) for treatment of anemia Global QOL was significantly improved and there was no difference between two study arms.
O'Shaughnessy [231] 2002 Effects of epoetin-alfa to prevent neuronal apoptosis vs. placebo Improved cognitive function, mood and QOL in treatment group.
Graves et al. [232] 2003 8-week intervention based on social cognitive theory vs. standard care Women in intervention group improved more on QOL, mood, self-efficacy, and outcome expectations.
Headley et al. [235] 2004 Effect of seated exercise vs. control Women with advanced breast cancer randomized to the seated exercise had a slower decline in total physical well-being and less increase in fatigue.
Weinfurt et al. [236] 2004 Zoledronic asid or pamidornate disodium for metastatic bone lesion Overall increase in QOL was observed.
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 Diel et al. [237] 2004 Ibandronate vs. placebo in breast cancer with metastatic bone pain A significant improvement in QOL was observed in intervention group; fatigue and pain were also reduced.
Body et al. [238] 2004 Ibandronate vs. placebo in breast cancer with metastatic bone pain Oral ibandronate had beneficial effects on bone pain and QOL and was well tolerated.
Wardley et al. [239] 2005 Zoledronic acid in community setting vs. hospital setting in breast cancer patients with bone metastases No difference between settings; safety and QOL benefits were observed.
Yoo et al. [240] 2005 Muscle relaxation training and guided imagery vs. control Less anticipatory and post-chemotherapy nausea and vomiting and higher QOL in intervention group.
Manning-Walsh [241] 2005 Relationships between persona land religious support and symptom distress and QOL Personal support was positively related to QOL and had partial mediated effects on symptom distress but religious support was not.
Gordon et al. [242] 2005 Home-based physiotherapy or group-based exercise or no intervention Physiotherapy was found beneficial for functioning, physical and overall QOL.
Kendall et al. [243] 2005 Influence of exercise (13.2 years following diagnosis) High level of functioning was observed; those whose exercise increased, maintained a better QOL.
Chang et al. [244] 2005 Effect of weekly epoetin alfa on maintaining hemoglobin levels, and reduction of transfusion vs. standard care Epoetin alfa improved QOL, maintained hemoglobin levels and reduced of transfusion.
Hudis et al [245] 2005 Effect of weekly epoetin alfa on hemoglobin levels Epoetin alfa improved hemoglobin levels, and QOL in mildly anemic patients.
Badger et al. [246] 2005 Telephone interpersonal counseling (TPC) vs. usual care TIP-C was partially effective in symptom management and improved QOL.
Cheema and Gual [247] 2006 Full-body exercise training (before and after evaluation study) Significant improvements were observed in upperand lower-body strength, endurance, and QOL.
Sutton and Erlen [248] 2006 Mutual dyadic support intervention Most dyadic relationships were supportive, some reciprocal and some experienced conflicts.
Round et al. [249] 2006 Recovery advice to prevent treatment problems Recovery advice given to women neither was supported nor refuted to be able improve QOL.
Giese-Davis et al. [250] 2006 Peer counseling intervention (newly diagnosed and peer counselors) Significant improvement in newly diagnosed was observed in trauma symptoms, emotional well-being, and self-efficacy but increased emotional suppression and declined QOL in peer counselors.
Moadel et al. [251] 2007 Effects of yoga on QOL Yoga was associated with beneficial effects on social functioning among breast cancer survivors.
Hartmann et al. [252] 2007 Effects of a step-by-step inpatient rehabilitation programme and QOL Although not generally superior to conventional inpatient rehabilitation programmes, the step-by-step rehabilitation provided marked benefits for patients with cognitive impairments.
Kim et al. [253] 2007 Effect of complex decongestive therapy (CDT) on edema and QOL in breast cancer patients with unilateral leymphedema CDT for upper limb lymphedema resulted in significant improved edema and QOL.

Author (s) [Ref.] Year Main focus Results/conclusion(s)
Hann et al. [254] 1998 Fatigue following radiotherapy Women experienced fatigue but not worse than expected.
Carpenter et al. [255] 1998 Hot flushes 65% (n = 114) reported ht flushes, with 59% of women with hot flushes rating the symptom as severe; hot flushes were most severe in women with a higher body mass index, those who were younger at diagnosis, and those receiving tamoxifen.
Hann et al. [256] 1999 Fatigue after high-dose therapy and autolougous stem cell rescue Fatigue was related to medical and psychosocial factors.

Velanovich and
Szymanski [257] 1999 Lymphedema Lymphedema occurred in a minority of patients and negatively affected QOL.
Bower et al. [258] 2000 Fatigue, occurrence, and correlates About one-third (n = 1957) reported more severe fatigue which was associate with higher level of depression, pain, and sleep difficulties.
Kuehn [259] 2000 Surgery related symptoms following ALND Shoulder-arm morbidity following ALND was found to be the most important long-term sources of distress.
Stein et al. [260] 2000 Hot flushes Hot flushes have a negative impact on QOL that may be due to fatigue and interference with sleep.
Beaulac et al. [261] 2002 Lymphedema in survivors of early-stage breast cancer MAS or BCS patients had similar lymphedema rates (28%-42/151) and had negative impact on long-term QOL in survivors.
Kwan et al. [262] 2002 Arm morbidity after curative breast cancer treatment Symptomatic patients and patients with lymphedema had impaired QOL compared to patients with no symptoms.
Fortner et al. [263] 2002 Sleep difficulties Most patients had significant sleep problems that frequently being disturbed by pain, nocturia, feeling too hot, and coughing or snoring loudly; patients having significant sleep problems had greater deficits in QOL.
Engel et al. [264] 2003 Arm morbidity Up to 5 years after diagnosis 38% (n = 990) were still experienced arm problems and for these patients QOL was significantly lower than patients without arm morbidity; extent of axilla, younger age, and operating clinic significantly contributed to arm morbidity.  [287]; 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 [288]; and the Fallowfield's Sexual Activity Questionnaire (FSAQ), which is a useful tool for measuring sexual activity in women with cancer [289].
There 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 [84]. 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 ALND: axillary lymph node dissection, ASCT: autologous stem cell transplantation, SLNB: sentinel lymph node biopsy. 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?
The present review covered several topics and provided tables to indicate areas that need more attention. It appears that the most common and important diseaseand 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 [290]. 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 [35]. 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 [291].
There 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 [180]. 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 [292].

Conclusion
There 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 evidencebased 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.