Our results indicate that research into the HRQL of breast cancer patients is a little developed field in Spain. Despite being one of the most populated countries in Western Europe, Spain ranks among those with the lowest number of studies addressing this issue. There appear to be two different publishing patterns among European researchers active in this field. In the majority of cases, papers are published in medical journals, and so PubMed is the bibliographic database with most information. In the case of Germany and The Netherlands, however, there are similar numbers of papers in PsycINFO and PubMed, probably reflecting a more multidisciplinary approach. This would also seem to apply to Spain. Almost half the studies included in this review were indexed in PsycINFO. Fewer papers were published from the medical side. Indeed, the leading medical bibliographic database, PubMed, contained only four of the studies included in this systematic review, all of which had been published in international journals [19, 28, 31, 35].
In this systematic review, we found only 25 papers that met all inclusion criteria. Five of these, published between 1993 and 2001, reported validations or cultural adaptations of questionnaires. Most of the others examined HRQL by type of treatment, or analysed the influence of treatments and specific symptoms on HRQL. A different approach was shown by the three studies that assessed differences in HRQL by psychological traits. Lastly, one report compared the HRQL of patients with healthy women.
The total number of papers identified was low, despite the general recommendation to include HRQL as an outcome in clinical studies involving breast cancer patients , and the fact that HRQL questionnaires are routinely used in clinical research. This reflects the scant attention paid to the information afforded by these instruments. Excluding validation studies, the instruments most commonly used to measure quality of life were the EORTC questionnaires (EORTC QLQ-C30 and QLQ-B23) or modified versions of these (13 studies), with the FACT-B ranking second (3 studies). Aside from being instruments with adequate psychometric characteristics for measuring HRQL in cancer patients [19, 42, 45], they are also the most widely used in international breast cancer studies . However, only the EORTC QLQ-C30 and QLQ-B23 have versions validated in Spanish [20, 21, 43].
Breast cancer is one of the neoplasms in which the treatment of choice, surgery, tends to be combined with other therapeutic strategies, such as chemo-, radio- or hormonal therapy. Yet, our results show that studies in Spain aimed at evaluating the effect of treatments on HRQL are clearly insufficient, and in the case of some therapies, non-existent. Surgical repercussions on HRQL are a relatively common issue in international studies . This is because surgery is the initial treatment, at least in stages I, II and III, for most breast cancer patients . Nevertheless, there is a notable lack of papers in Spain focused on the effect of surgery on HRQL. Indeed, this review was able to locate only four papers which made reference to this topic [31, 32, 34, 41], and only one of these included the questionnaire scores . This last-mentioned study compared conservative with radical surgery. It reported better results for the former treatment in all components of HRQL in the short term. In this particular instance, differences were not studied by age group, though these were reported in a paper from Canada . Studies undertaken in other countries (Canada, Germany, and Japan) report contradictory results for these two surgical approaches in terms of differences in HRQL in the long term [51–53]. Only one of the Spanish studies considered axillary surgery . While the authors reported that HRQL was better among sentinel lymph node biopsy patients than axillary emptying, they failed to furnish the specific results.
Insofar as radiotherapy was concerned, we found a single follow-up study , which observed no significant differences at 6 months of treatment, whether overall or by age group. This reinforces the idea that age should not be the only factor considered when deciding about oncology treatments, as reported in a study from the United Kingdom .
The most common objective (seven studies) was to assess the possible beneficial effect of psychotherapy [22–28]. The improvements in HRQL associated with psychological therapies observed in Spanish studies are consistent with the results reported in two papers from the USA and Australia, respectively [55, 56]. Two studies about the relationship between mental adaptation to cancer and HRQL observed differences according to patients' age and coping strategies [38, 39]. These results partially agree with those yielded by a study that targeted older women from the USA . Nevertheless, it is difficult for our results to be compared with those of other studies, due to differences in study goals and in HRQL assessments involving psychological factors [58, 59].
Only two studies addressed the negative impact of lymphedema on the HRQL of Spanish women with breast cancer [36, 37], with findings consistent with two USA case-control studies [60, 61]. In addition, our review revealed a lack of studies addressing the impact of other common symptoms, such as pain, fatigue or menopausal symptoms. This is in contrast with the attention paid to these items in international literature .
Just one study compared the HRQL of breast cancer patients with that of healthy women . This is an area of great interest for quantifying the impact of breast cancer on our society in terms of HRQL. However, no longitudinal study was identified that was capable of evaluating trends in HRQL over time. In view of the low fatality rate of breast cancer patients at the present time, it would be of great value to have access to studies designed to assess the long-term repercussions of the disease on the lives of the women affected.
Some studies (e.g., such as those undertaken by the Breast Cancer Study Group (http://www.ibcsg.org/), in which a Spanish team participated , and the papers by Martín et al [63, 64]), were excluded in spite of Spanish patients being included in the sample. This was due to failure to report the results with a breakdown by country. Similarly, no consideration was given to studies that pooled patients with different types of cancer but furnished no specific information about women with breast cancer [65–69]. Finally, we also excluded studies that failed to use HRQL-specific instruments  or reported no specific results for this construct .
The bibliographic search-and-screening phase showed us that the term HRQL has not been interpreted by some Spanish authors in line with the concept of the multidimensional construct to which it refers. According to the WHO, quality of life is, "an individual's perception of his/her position in life in the context of the culture and value systems in which he/she lives, and in relation to his/her goals, expectations, standards and concerns" (1994). This definition stresses the importance of self-evaluation of cultural factors . It was for this reason that studies using one-dimensional questionnaires on anxiety, depression or other mental states or physical symptoms, without considering the multidimensionality of the HRQL construct, were excluded from the analysis.
This study, aimed at reviewing research on HRQL among breast cancer patients in Spain, is purely descriptive in nature. The small sample size of existing studies conducted directly in Spain, with almost half the studies identified including fewer than 100 women [23, 25, 26, 29–31, 35, 36, 38–40], renders it difficult to draw conclusions about the HRQL of Spanish breast cancer patients. In such a context, publication bias cannot be regarded as a major problem when compared with the lack of studies providing data on the subject. A further problem was the use of HRQL questionnaires that were in-house and/or not validated for the Spanish population. Lack of information on adaptation and translation of questionnaires is an additional limitation when it comes to comparing, generalizing and, above all, replicating results. The use of questionnaires adapted to and validated for the Spanish population is indispensable for lending credibility to and standardizing the results obtained.
Although there is abundant international research in this field [2, 3], the results might not be wholly applicable to our patients, since perception of HRQL is linked to an immediate reality that is specific to the woman who has the disease. Accordingly, our study complements an important review by Montazeri , which excluded papers not written in English. The concept of HRQL depends on cultural norms, behaviour patterns, and personal expectations . It presupposes the ability to make a cultural synthesis of all the elements regarded by a given society as making up its pattern of comfort and wellbeing . Moreover, it is reasonable to assume that if there are socio-cultural and health care differences there will also be differences in assessment of HRQL among breast cancer patients in different countries, as has been shown in the case of other tumours . In this respect, attention should be drawn to the fact that international studies do not routinely furnish comparative information on HRQL stratified by country.
This paper is the first one to include articles in Spanish about studies on the quality of life of women with breast cancer, not included in previous reviews. The comprehensive search performed, which included international as well as national bibliographic databases, as well as the review process have been performed following PRISMA statement criteria. However, we could not perform a meta-analysis due to the small number of studies found and to the heterogeneity of goals and results. Additionally, the exclusion of some international studies[62–64] due to the inclusion criteria adopted could be seen as a limitation of the review in its goal to reflect the research made in Spain on HRQL in Breast Cancer patients.
In brief, there is clearly insufficient information available on the HRQL of Spanish women with breast cancer. Since HRQL is one of the principal result indicators for improving the care of and evaluating new treatments for such patients, encouragement should be given to promoting research and publication in this field.