Health-Related Quality of Life Questionnaires in Breast Cancer Patients. A Comparative Study Plus Systematic Literature Review

Background: Breast cancer is the most common cancer in women globally as well as the principle cause of death. Despite the high incidence rates of this malignant disease, 89% of women diagnosed with breast cancer are still alive more than 5 years after their diagnosis. This outcome is due mainly to early diagnosis and treatment design with or without reconstructive aesthetic procedure. Satisfaction and seriously quality of life is the most important point of view in our systematic and extensive research study of international literature. Materials and Methods: We reviewed totally 31 studies containing a large number of different instruments measuring health related quality of life in breast cancer treatment, with or without reconstruction. Results: Overall, 24 different survey instruments were identified within the 31 included studies. The most frequently used questionnaires are SF-36 and then FACT-B and most studies used more than 1 questionnaire. Conclusions: The SF-36, FACT-B, EORTC-C30 and EORTC BR23 are most common questionnaires used in assessing health related quality of life in breast cancer. Suitable and correct approach to the patient is one of the best and important factors of the research. The patients feel comfortable of this reality from researcher’s interest so by this correct contact express their experience and opinions about disease treatment design.


Introduction What is (Health-related) quality of life?
The term Quality of Life (QOL) is used to refer to an individual's total wellbeing and it includes all emotional, social, and physical aspects of the person's life. In medicine we use to say Health Related Quality of Life (HRQOL), in an effort to describe how the person's wellbeing may be influenced by a disease, a disability, or a disorder.
The World Health Organization has defined quality of life as "an individual's perception of their position in life in the context of the culture and value system in which they live and in relation to their goals, expectations, standards, and concerns. It is a broad ranging concept affected in a complex way by the person's physical health, psychological state, level of independence, social relationships and their relationships to salient features of the environment." Donovan et al. citing Campbell suggested as an general definition of quality of life "a person's subjective sense of well-being, derived from current experience of life as a whole" [1,2]. Goodinson and Singleton described quality of life as "the degree of satisfaction with perceived present life circumstances" [3]. According to Bergner quality of life rises as the distance between achieved and desired ambitions diminish [4].
Quality of life includes both objective and subjective factors that affect person's well being. Money income, education and health status are the primary objective factors, while subjective factors include individual's satisfaction with education, income and conditions of living. Quality of life refers to a subjective estimation of the fulfillment of a person's wishes, needs and goals. Quality of life is a complex approach consisting of three main components: physical, emotional and social functioning. The first two elements are clearly linked to health-related quality of life. Many researchers consider that social functioning is out of the scope of the health domain. However according to the World Health Organization quality of life is an all-inclusive concept including all factors that influence an individual's life, even if those factors are external to health domain, such as political, cultural, aesthetic, economic and environmental aspects of a person's existence. Healthrelated quality of life contains those factor linked to an individual's health.
The project of Quality of Life measuring in health has been provoked by the need to assess the impact and consequences of clinical therapies and to control the relative benefits of rival health programs. Nowadays it is necessary to go beyond the classical old measures like number of successfully treated patients.
Bergner was one of the first researchers noted that patient's life was affected by side-effects of a treatment and hence it is crucial to assess all treatments consequences [4]. In the same context, Revicki compared three anti-hypertensive medicines, based also on their effect on patient's quality of life, considering their sideeffects on general well-being, sleep, sexual ability, social activity and psychological status. The drugs had almost equal efficacy in blood pressure, but their side-effects on physical well-being of the patients varied [5].
Health-related quality of life is best measured via instruments that asses the dimensions found to affect HQOL and combine them into a single index. The instruments to measure such a multidimensional and partial subjective term are the Quality of Life Questionnaires. The concept is based on self-reported measures that combined can help the scientist to assess the person's Quality of Life.

Breast Cancer and treatment strategy
Breast cancer is the most common cancer in women worldwide. It is also the principle cause of death from cancer among women globally. Despite the high incidence rates, in Western countries, 89% of women diagnosed with breast cancer are still alive 5 years after their diagnosis, which is due to detection and treatment [6].
The UK and USA have one of the highest incidence rates worldwide (together with the rest of North America and Australia/New Zealand), making these countries a priority for breast cancer awareness [6].
In the modified radical mastectomy the entire breast is removed, (skin, areola, nipple, and most axillary lymph nodes), sparing the pectoral is major muscle.
Complications originating from modified radical mastectomy include wound healing issues, such as skin necrosis, infection, chronic seroma, dehiscence and hematoma.
There is a risk of anaphylaxis for patients who prior to axillary dissection undergo sentinel lymph node biopsy and it is related to the isosulfan blue contrast agent. This rare complication often resolves intraoperatively [7].
The risk of developing lymphedema is high in patients who have undergone a complete axillary dissection. Chronic pain in that area, numbness under the axilla and hypersensitization are also complications of axillary dissection.
The post-mastectomy cosmetic result may cause concern to the patients, considering the change in the appearance of their breast(s). Breast reconstruction is possible for the majority of patients after mastectomy. Often, patients who are going to undertake a modified radical mastectomy may be candidates to undergo breast reconstruction surgery during the same procedure.
There has been conducted no large-scale prospective randomized trial to compare the benefits and safety of immediate vs. delayed reconstruction. In 1984 Webster et al reviewed the results of their first 85 immediate reconstructive procedures following mastectomy for breast cancer, obtaining acceptable cosmetic results in most patients with no mortality or life-threatening morbidity. A number of problems concerning the trauma and the prostheses were observed which decreased with increasing experience. The blood transfusion requirements and operating time were increased. There was no prejudicial effect on tumor behavior was observed when assessed as part of a case-control study [8]. Overall survival, local relapse and distant recurrence were equal, in the different the reconstructed cases and unreconstructed controls, suggesting that immediate reconstruction was safe [8].
In a small randomized trial conducted in Edinburgh (1983), immediate and delayed reconstruction was compared with psychosocial morbidity being measured in both groups [3]. For those who had immediate reconstruction, there were significant advantages in terms of return to work, freedom with dress and selfimage. Al-Ghazal et al. [4] Interviewed 121 patients after a mean of 5 years after either immediate or delayed reconstruction. Of those who had immediate reconstruction, 95% said that they preferred this approach, whereas 76% of those who had delayed reconstruction wished that an immediate operation had been possible. In terms of anxiety and depression, this was less in those who had immediate reconstruction, and body image and self-esteem were better in this group.
Wellis ch et al. evaluated two groups of patients from different plastic surgeon populations to compare the psychosocial conditions between those who underwent immediate versus delayed breast reconstruction. The cosmetic outcome was the same in the two groups, but the experience of living with the post mastectomy deformity in the group of delayed reconstruction diminished the level of satisfaction resulting in better psychological scale results [9].
The increasing number of treatment alternatives and the declining differences in cost of surgeries and clinical effectiveness make the importance of consistent and comparable health-related quality of life (HRQOL) parameters grows -both for medical and health financial evaluation.
The main survey instrument used in all the researches measuring the health related qualities of life are the Questionnaires. In this paper we are analyzing the questionnaires that are most frequently used in the medical projects evaluating and comparing the quality of life of patients who underwent modified radical mastectomy, followed or not by immediate or delayed breast reconstruction.
The questionnaire based survey for measuring healthrelated quality of life has become typical.

Material and Methods
We searched the PubMed database for manuscripts researching health-related quality of life in breast cancer patients, followed or not by mastectomy and breast reconstruction. We reviewed their survey instruments and their results.
A total of 31 studies were reviewed as it is presented in ( Table 1). The several questionnaires are briefly analyzed in this text of our review study. These series of questionnaires are recorded in (Table 2) in abbreviation terms.

Questionnaires of European Organization for Research and Treatment of Cancer (EORTC) EORTC QLQ C-30:
The EORTC QLQ-C30 is a 30-item selfreporting questionnaire developed to measure the quality of life of cancer patients. The QLQ-C30 Version 3.0 is the most recent version. It is composed by five subcategories of questions (role, physical, cognitive, emotional and social functioning). Fatigue, pain, and nausea and vomiting are also three assessed in three multi-item symptoms scales and there also questions about common symptoms of cancer patients. This questionnaire is copyrighted and has been translated and validated into 81 languages.

EORTC QLQ BR-23:
The BR-23 is the questionnaire produced by EORTC targeting Breast Cancer Patients. It is a 23-item breast cancer-specific questionnaire consisting of three symptom scales (arm issues, breast symptoms, and systematic therapy side effects) and two functional scales (body image satisfaction and sexual functioning) and. Sexual satisfaction and hair loss consequences are also measured through the rest of the questions.

Body Image Scale (BIS)
A 10-item scale was constructed by P. Hopwood et al in collaboration with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Study Group [10]. The scale was designed to be used to patients with any cancer site and any form of cancer therapy.
Body Image Scale interferes with the psychological effects of body alterations created by cancer disease, chemotherapy, radiotherapy and surgery. The patients report his feelings about the cosmetic results of his therapy.

The Hospital Anxiety and Depression Scale (HADS)
A.S. Zigmond and R. P. Snaith created the scale to asses the emonotional disorder of patients [11]. The HADS is a fourteen item scale that generates ordinal data. Half items are measuring anxiety and the other half depression. Each item on the questionnaire is scored from 0-3 thus the total score of a person can vary between 0 and 21 for either anxiety or depression [12].

Functional Assessment of Cancer Therapy-Breast Quality-of-Life Instrument (FACT-B)
This is a self report questionnaire created to measure multidimensional quality of life in breast cancer patients and it is consisted of FACT-General (FACT-G) and the Breast Cancer Subscale (BCS), which is focused on breast cancer complications and side effects (13). The Functional Assessment of Cancer Therapy-General (FACT-G) scale, was designed and validated by Cellaet al. [14] in the USA, is widely used to measure HRQOL in cancer patients. The latest version 4 of FACT consists of a total of 27 items separated into separate subscales: physical (seven items), emotional (six items), social/family (seven items) and functional (seven items) well-being .Patients respond to each question with a score of 0-4, where 0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit and 4 = very much.
The BCS is composed of ten items targeting in Quality of Life in breast cancer but not already mentioned in the FACT-G. When the BCS is accompanying to the FACT-G, a new the 37-item is created known as the FACT-Breast (FACT-B).

Brief Symptom Inventory (BSI)
The BSI measures current psychological distress. This survey instrument consists of 53 items, expressing a feeling or thought, and is scored on a 5-point scale: 0 (no such problem) to 4 (severe problem). The score reflects 9 dimensions including somatization, obsessivecompulsive, interpersonal sensitivity, depression, anxiety, hostility, psychoticism, phobic anxiety, and paranoid ideation. Scores are represented by a distribution of 0-100, with high scores denoting greater psychological distress.

Sexual Activity Questionnaire (SAQ)
The SAQ asses sexual behavior, quantifies the effects of cancer treatments on sexuality in the individual and it is consisted of three subcategories; pleasure (desire, enjoyment, and satisfaction), discomfort (dryness and pain), and habit (how usual the reported behavior is). Pleasure scores range from 0 to 18. Discomfort scores range from 0 to 6. Higher score shows lower discomfort and higher pleasure respectively [15].

Impact of Event Scale (IES)
A brief, easily answered self-report questionnaire consisting of 22 questions, not diagnostic for Post Traumatic Stress Disorder, is an instrument to assess the subjective response to a specific stressful event. It measures the frequency of disturbing and avoidant issues. The scale consists of 15 items (7 intrusion items and 8 avoidance items) [16,17].

Mishel Uncertainty in illness (MUIS)
The MUIS assesses complexity in accepting the meaning of illness-related events, consisting by four subscales that measure the patients' perceptions of the inconsistency, indistinctness and complexity of information given them. It has high internal reliability and Stavrakis

Profile of Mood States (POMS)
POMS is a standard validated psychological test formulated by McNair et al. [19]. The questionnaire contains 65 words/statements that describe feelings of patients. The test requires patients to indicate for each expression or statement how they have been feeling in the past week.

Michigan Breast Reconstruction Outcome Study satisfaction (MBROS-S)
This questionnaire comprises 7 items divided into two scales. Five items assess the patient's generic satisfaction and 2 items measure satisfaction with the cosmetic result [20].

MBROS-Body Image questionnaire (MBROS-BI)
This was the second questionnaire developed by the MBROS team [21]. It consists 9 items on one scale. It was designed to measure the patient's perception of her physical image after breast surgery. It manages to calculate a body image score (BI score).

Short Form Health Survey (SF-36)
The SF-36 is a generic, short-form health survey with 36 self reported items. It consists of an 8-scale profile including functional health, well-being scores, psychogological, physical and mental health summary measures and a health utility index. Accordingly, the SF-36 is useful in researches of general and specific populations, comparing the relative saddle of diseases and in discovering the health benefits produced by the variety of different treatments [22][23][24][25].

Body Image after Breast Cancer Questionnaire (BIBQ)
The BIBCQ is a survey instrument with 45 common items, 6 items for women with two breasts, and 2 items specific to women without one or both breasts. There are six scales, reflecting six domains of body image: vulnerability, body stigma, limitations, body concerns, transparency and arm concerns. The BIBCQ was created to measure body image in a wide-ranging and significant fashion, empowering useful measurements and comparisons. The subscales enable the flexible use of this questionnaire according to the needs of the research [25].

Breast impact of treatment scale (BITS)
This instrument assesses the body image in clinical oncology, conceptualizing the surgical therapy for breast cancer as a potential traumatic stress generator on a female's body image. BITS assess the body image distress as disturbing thoughts and avoidant behaviors are appearing. Intrusive items estimate insidious thoughts as ''things I see or hear remind me that my body is different''. Avoidant items measure limited cognitive experience, subjective knowledge of feelings, as ''I feel self conscious about letting my partner see my scar'' [26].

Body satisfaction scale (BSS)
BSS measures the subjective aspect of postoperative external body satisfaction with appearance and the weight [27]. BSS items are processed in a 5 point satisfaction/dissatisfaction scale with a lower score reflecting greater body satisfaction and a higher score reflecting greater body dissatisfaction.

Cancer Rehabilitation Evaluation System (CARES)
The CARES is a very detailed survey instrument assessing cancer patient's issues and needs. Its validity and reliability have been extensively proven [28,29]. The CARES scores are global and it includes five higher order factors referred to as summary scales and 31 more specific subscales. The domains assessed by five higher order summary scales are the following: physical, psychosocial, medical and sexual [30]

Rosenberg-EPM Self-Esteem Scale
The scale comprises 10 questions, with four answers possible: strongly agree, agree, disagree, or strongly disagree. The score of the scale ranges from 0 (best possible self-esteem) to 30 (worst possible self-esteem) [31].

State-Trait Anxiety Inventory (STAI)
The State-Trait Anxiety Inventory (STAI) 34 is a selfreport measure that estimates a patients current level of anxiety. The internal consistency reliability is very good and it has been widely used in clinical and medical populations [32,33].

Center for Epidemiologic Studies-Depression tool (CES-D)
This is a reliable 20-item self-report instrument measuring depression. Its focus on the affective elements Stavrakis   of depression rather than the physic symptoms makes it useful in medical populations. It has shown high consistency in both general and patient populations [34,35].

Body-Self-Relations Questionnaire-Appearance Evaluation (MBSRQ)
It assesses the degree of generic satisfaction with its body and physical appearance. It consists of seven 5-point items (disagree-agree) and high scores on the MBSRQ reflect favorable evaluations of overall appearance [36].

Body Image Visual Analogue Scale
It is a three item based scale that assesses total body satisfaction, fulfillment with chest area, and satisfaction with abdominal area. Participants rate items on a 1-to-10 scale, reflecting complete dissatisfaction to complete satisfaction [37].

Psychiatric Symptom Index (PSI)
The PSI is a quantitative measure of the severity of emotional distress during the 7 days prior to the interview. It is based on a 4-point scale grading from "never" to "very often." It's ranges from 0 (no symptoms) to 100 (all symptoms at maximum intensity) [38].

The Locke-Wallace Marital Adjustment Test (LWMAT)
This instrument is used to measure marital satisfaction. LWMAT scores ranging from 2 to 158, with higher scores reflecting higher satisfaction [39,40].

Breast-Q
Andrea Pusic, MD, of Memorial Sloan-Kettering Institute for Cancer Research, create a new patientreported outcome measure collecting and processing data about the impact and effectiveness of breast surgery. The BREAST-Q has with scales that evaluate both satisfaction and quality of life. It is evaluated and the results show high reliability, validity and approval to surgical intervention across all scales [41][42][43].

Results
Overall, 24 different survey instruments were identified within the 31 included studies (Diagram 1).
The most frequently used questionnaire is SF-36 and then FACT-B.
Most studies used more than 1 questionnaire (Diagram 2).
All those questionnaires could be separated in general about cancer and specific about breast cancer and outcome after mastectomy with or without reconstruction. Stavrakis   In those 31 studies a total of 66 questionnaires were used. 41 of those survey instruments were generic and the other 25 focused on specific breast issues (Diagram 3).

Number of instruments that studies used
Numbers of studies

Discussion
Items measured in quality of life questionnaires vary to their focus degree on particular aspects of patients' activities and functions and conditions. There are measures focusing on particular activities of daily living, while others assess physical conditions, other health related factors such as symptoms, emotional conditions, cognition, discernment of health etc (4).
The advantages offered in research by measuring specific items are the greater knowledge for physicians, more acute focus on areas of particular concern, and may promote better responsiveness to disease-targeting interventions. Howbeit general measured items promote comparisons across interference and diagnostic cases, which is particularly important for creating guidelines. They also allow inspect multiple disease conditions achieving dysfunctions to be identified (74,75). Quality of life all is affected by all the diseases and disabilities and all the effort of the Quality of Life measurement is not only to collect clinical data significant to the disease, but to reveal the effects of the disease on general function. Thus, general items seem to be more suitable as they can examine a wider range of dysfunctions, that may concern different systems (76) e.g. sexual and psychological disorders of women who underwent mastectomy.
According to our experience and in the handle of assessing Quality of Life of women who underwent mastectomy with or without following reconstruction, considering the wide effects of this surgical procedure and multidimensional appeal of the woman patient it is more ideal to use more than one instrument in the research. The main disadvantage of using all this amount of survey instruments is that patient may be bored and not so energetic to participate to the research. The combination of both generic and specific questionnaires in measuring health related quality of life of breast cancer patients is the best method. The combination of the results of those questionnaires can guarantee reliability and validity of the research.
One of the biggest issues in HQL evaluation is the quality assurance. The lack of quality in a medical research can dissipate all the efforts of achieving sufficient population orientation, statistical analysis and results. Quality-control projects are successful if they approximate existing quality-control mechanisms in the trial group. Nevertheless, it is wise to use more qualitycontrol mechanisms. The management of a HQL research is better to be organized by one person, who has the primary role and responsibility of checking periodically the quality guidelines and handling the collected data.

Conclusions
The use of both generic, like SF-36, EORTC QLQ Q30, and breast cancer specific questionnaires, like EORTC QLQ BR23and Brest-Q is best approach to the study of health related quality of life of breast cancer patients. The researchers should keep in mind that a large number of questionnaires is not easily answered by patients.
When the researchers use more than one questionnaire some of the questions are repeated. With great precaution the researcher could avoid the repeat of same questions in order to help the patient to quicker answer all the scaled requested.
In order to search the truth about the consequences in patient's life after the dramatic effect of breast cancer and mastectomy, researchers should approach the women with care. The most correct communication will emerge the best contact result and by this way the patients trust the researchers and speak honestly about their real feelings and thoughts in relation to their new life reality and activities.