Sexual Function in Women with Breast Cancer: An Evidence Map of Observational Studies

Breast cancer (BC) is the leading cause of cancer in women, and has implications for sexual function (SF). In this study, we used an evidence map to identify, describe, and organise the current available evidence regarding SF in women with BC. We searched the MEDLINE, PsycINFO, and CINAHL databases for observational studies assessing SF in women with BC published in English, Spanish, Portuguese, and French between 2000 and 2021 (sample ≥ 50 women). Of the 64 included studies (13,257 women with BC), 58 were published since 2010. Women who were married, partnered, or in relationships represented 74.1% of the entire sample. Only a single study was conducted on women representing a sexual minority. We identified 22 assessment instruments and 40 sexual dysfunction (SdF) domains. The number of publications on SF in women with BC has increased in the last 10 years, but still remains low. Some groups of women are underrepresented, and some SdF domains are underdiagnosed, with the assessment instrument used affecting which domains are studied. Women with BC need to be better screened, as their quality of life (QoL) is affected by SdF.


Introduction
Female breast cancer (BC) is the fifth leading cause of cancer mortality worldwide; it accounts for one in four cancer cases and one in six cancer deaths. In 2020, BC represented 11.7% of all new cancer cases (an estimated 2.3 million new cases). The incidence rates are 88% higher in emerging countries than in transitioned countries, and countries with lower human-development-index (HDI) scores have a 17% higher mortality rate than countries with higher HDI scores [1].
In recent years, BC survival has improved due to early detection strategies and access to timely, effective, and affordable care [2]. However, health providers and health systems need to address BC survivor issues and concerns regarding the treatment and disease course.
In a recent systematic review on adverse mental health outcomes, the researchers revealed that BC survivors have an increased risk of anxiety, depression, neurocognitive dysfunction, sexual dysfunction (SdF), and suicide compared with noncancer groups. The prevalence of SdF, in particular, is reported to range between 20% and 60% [3]. In another Int. J. Environ. Res. Public Health 2022, 19, 13976 2 of 21 study, the researchers reported that women with BC have a high prevalence of SdF (73.4%) and lower average sexual function (SF) scores [4]; the main problems include penetration pain, desire, lubrication, dysfunctional excitement, and reproductive concerns [5,6]. In a study conducted in our hospital to evaluate the social, economic, and professional impacts of BC on women, the researchers found that SF was the most affected qualityof-life (QoL) dimension, and especially during treatment, with a score of 20.7% in the European Organisation for Research and Treatment of Cancer Quality of Life 23-item breast cancer questionnaire [7].
According to the fifth edition of the Diagnostic and Statistical Manual of Mental Health Disorders (DSM-5) [8], SdF covers a heterogeneous group of disorders that are typically characterised by a clinically substantial impairment in a person's ability to sexually respond or experience sexual pleasure. Female SF, for which researchers have characterised several models in the literature, comprises more than just arousal and orgasm [9].
We need to organise the substantial evidence reported in the scientific literature assessing SF in women who have had BC through a standardised methodology.
The Global Evidence Mapping (GEM) initiative was established in 2007 to provide a general overview of the existing research on traumatic brain and spinal cord injuries [10]. Such evidence maps, which are based on systematic and wide-ranging searches to identify knowledge gaps and future research needs, present results in a user-friendly format (often a visual, graph, or searchable database) [11]. They are both a useful first step in the systematic review process and support for the decision-making process for policy and practice [12,13].
The purpose of our evidence map was to identify, describe, and organise the available evidence regarding SF in women who have BC in order to aid a better understanding of the existing studies, identify the evidence gaps in the literature, and make recommendations for future research.

Study Design
We based this mapping review, which we carried out in accordance with the GEM initiative, on a methodology that involved three core tasks: setting the map boundaries and context; searching for and selecting relevant studies; reporting on the yield and study characteristics [10]. We also followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) recommendations [14]. We designed a protocol and published it in the Open Science Framework (https://osf.io/ 4qbgu/).

Eligibility Criteria
We considered observational studies with samples of ≥50 women with BC, published between January 2000 and March 2021 in English, Spanish, Portuguese, or French, and evaluating SF using a specific structured measure, as eligible studies. We did not include older published studies, as sexuality is a controversial subject that is influenced by multiple factors and is variable over the years.

Search Strategy
We performed the systematic literature searches for original articles in the following databases: MEDLINE (via PubMed), PsycINFO, and CINAHL. We conducted the last search on 7 March 2021. We used comprehensive controlled vocabulary and free-text terms. The full electronic search strategy for MEDLINE (via PubMed) was as follows: (("breast neoplasms" [mesh] OR "breast cancer" [ti]) AND ("sexuality" [majr] OR "sexual dysfunction, physiological" [mesh] OR "sexual activit*" [tiab] OR "sexual dysfunction" [tiab] OR "sexual function*" [tiab] OR "sexual interest*" [tiab] OR "sexual desire*" [tiab] OR "sexuality" [tiab] OR "sexual*" [ti])). We adapted the search strategy to the requirements of each database.

Study Selection
We imported the retrieved studies into COVIDENCE reference manager software. We first eliminated duplicate articles, after which two independent researchers screened the titles and abstracts and applied the predefined eligibility criteria to remove ineligible studies. We next eliminated the full texts of the eligible studies to make a final decision regarding the eligibility. We resolved the disagreements in a final online meeting. We clearly justified the reasons for the study exclusions.

Data Extraction
To manage the data and records, we designed a template form in Microsoft Word to individually record the data for each included study. We recorded data on the authors, publication years, journals, study designs, countries, objectives, participants (marital status, sexual orientation, and age recorded as mean/median or range), instruments used to assess sexual function, and domains.

Selected Studies
After we removed the duplicates, we screened a total of 1516 titles and abstracts for eligibility. Of the 254 articles selected for full-text screening, we included 64 that met the eligibility criteria in this review. We present the details on the study inclusion and reasons for exclusion in the flowchart in Figure 1.

Study Selection
We imported the retrieved studies into COVIDENCE reference manager softw We first eliminated duplicate articles, after which two independent researchers scre the titles and abstracts and applied the predefined eligibility criteria to remove ineli studies. We next eliminated the full texts of the eligible studies to make a final dec regarding the eligibility. We resolved the disagreements in a final online meeting clearly justified the reasons for the study exclusions.

Data Extraction
To manage the data and records, we designed a template form in Microsoft Wo individually record the data for each included study. We recorded data on the auth publication years, journals, study designs, countries, objectives, participants (marita tus, sexual orientation, and age recorded as mean/median or range), instruments use assess sexual function, and domains.

Selected Studies
After we removed the duplicates, we screened a total of 1516 titles and abstract eligibility. Of the 254 articles selected for full-text screening, we included 64 that me eligibility criteria in this review. We present the details on the study inclusion and rea for exclusion in the flowchart in Figure 1.

Study Characteristics
We present the details of the authors, years of publication, designs, countries, objectives, and participants for the 64 studies in Table 1. The 64 studies, with minimum and maximum sample sizes of 55 and 1957, respectively, included 13,257 women with BC. One study was conducted with 85 lesbian or bisexual women with a female partner, and 51 studies provided data on the mean age, which ranged from 31.4 to 63.4 years. Of the 59 studies (9825 women, 74.1%) that included women who were married, partnered, or in a relationship, in 19 of them, the researchers exclusively focused on women with this profile.

Annals of Surgical Oncology
Prospective Canada To report on the changes in the psychosocial functioning over 1 year following breast cancer surgery in three groups of women, including those with mastectomy alone, those with mastectomy and immediate reconstruction, and those with delayed reconstruction.

SF Assessment
In most of the studies, the researchers used a single instrument to assess the SF, although six studies used two instruments. We present the summaries of the 22 different instruments that we identified in Table S1. The most frequently used instrument was the Female Sexual Function Index (n = 35), followed by the Sexual Activity Questionnaire (n = 8), PROMIS Sexual Function and Satisfaction Measures Brief Profile (SexFS) (n = 4), and Watts Sexual Function Questionnaire and Cancer Rehabilitation Evaluation System Short Form (CARES-SF) sexual subscale (n = 3 each). The instruments used in just a single study were as follows: the Short Sexual Function Scale; Specific Sexual Problems Questionnaire;

SF Assessment
In most of the studies, the researchers used a single instrument to assess the SF, although six studies used two instruments. We present the summaries of the 22 different instruments that we identified in Table S1. The most frequently used instrument was the Female Sexual Function Index (n = 35), followed by the Sexual Activity Questionnaire We identified a total of 40 independently assessed domains, as follows: desire and satisfaction (n = 41 each); orgasm (n = 40); lubrication (n = 39); arousal (n = 37); pain (n = 36); pleasure (n = 8); discomfort and interest (n = 6 each); frequency (n = 5); vaginal discomfort (n = 4); relationship (n = 3); vaginismus, excitation, habit, vulvar discomfort-labial, and vulvar discomfort-clitoral (n = 2 each). Other domains were evaluated only in a single study (swelling of the labia; reduced length of the vagina; reduced elasticity of the vagina; communication; avoidance; touch; anticipatory anxiety; sexual initiative; masturbation problems; activity; sexual drive; sexual aversion; importance; tiredness; sexual attractiveness; feeling; responsibility; libido; partner problems; responsiveness; sexual enjoyment; distress).
In 32 studies, researchers report data on the relationship between SdF and age, which is associated with older age groups (n = 14), younger age groups (n = 3), and non-associated with age (n = 15). The type of treatment was negatively related to SdF, whether it was mastectomy (n = 15/29), chemotherapy (n = 11/28), or hormone therapy (n = 11/30).

Discussion
On this evidence map, we included 64 studies published in the last 20 years, comprising a total of 13,257 women with BC for whom SdF was assessed. We observed an evident increase in the number of publications over time (58 of the 64 included studies were pub-lished in the last 10 years), which suggests a growing interest in understanding how BC impacts women's SF.
However, given the importance of the issue, we consider the number of publications to be too low. SdF is a common side effect of cancer treatments, and so it is imperative for health providers to routinely include a comprehensive evaluation of sexual health in the workups for such patients from the outset [77]. Female sexuality is a complex issue, as physiological, psychological, and sociocultural factors and interpersonal relationships all play a part, not to mention the fact that the delayed study of this issue may be due to the historical stigmatisation of women and their sexuality [78].
Interestingly, most of the included women were married, partnered, or in relationships, with a substantial number of researchers selecting this status as an inclusion criterion, which suggests that women without partners, who may experience their sexuality in a different way (e.g., masturbation), are underrepresented.
Only one study was conducted with lesbian or bisexual women having a female partner [21]. Researchers have found that SF is independent of sexual orientation, and the fact that sexual minorities appear to have different social attitudes and sexual practices may imply specific consequences of the physical effects of cancer and its treatment for lesbian, gay, and bisexual populations [79][80][81]. The limited literature on SF in women with BC from sexual minorities remains a key aspect of survivor health outcomes that requires further study [82,83].
On our evidence map, we identified 22 validated instruments used by the authors to assess SF in women with BC. Authors used the Female Sexual Function Index in over 50% of the studies (n = 35). This brief 19-item multidimensional self-report instrument for assessing the key dimensions of SF in women, which incorporates the criteria of SdF as defined and recognised by international diagnostic systems [8], was designed and validated for use in clinical trials and epidemiological studies [84]. Women with BC found it to be the right length, easy to complete, and relevant to their experience, and it also demonstrates excellent psychometric properties (high internal consistency, test-retest reliability, and evidence of construct validity) [85]. The second most-used instrument was the Sexual Activity Questionnaire, which is rapidly and easily administered and an acceptably reliable measure. The questionnaire describes SF in terms of the levels of sexual activity, pleasure, and discomfort [86], has been demonstrated to be a useful instrument for measuring sexual activity in women with cancer [87], has been validated in different countries, and has good psychometric properties [88][89][90]. The PROMIS Sexual Function and Satisfaction Measures Brief Profile (SexFS) is also widely used, which is another reliable and valid tool for measuring self-reported SF and satisfaction among men and women with cancer. The instrument is comprehensive in scope, covering both physical and psychological constructs, and provides a comprehensive assessment of satisfaction and key SF domains [91]. Although researchers have previously validated all the instruments and they have good psychometric properties, their scopes differ, and they do not evaluate the same domains. Furthermore, some authors present results as a total SF score, overlooking the fact that an individual may have several simultaneous SdF disorders and that diagnosis should be individual [8].
The researchers assessed a total of 40 domains with the 22 assessment instruments. The most studied domains were desire, satisfaction, orgasm, lubrication, arousal, and pain. Some of the domains reflect internationally accepted classifications as reviewed by the Fourth International Consultation on Sexual Medicine [92], with the following considered to reflect SdF: hypoactive sexual desire dysfunction; female sexual arousal dysfunction; female orgasmic dysfunction; female genital-pelvic pain dysfunction; persistent genital arousal disorder; postcoital syndrome; hypohedonic orgasm; painful orgasm. However, several of the domains reflected in our review are not included in international classifications, which indicates a lack of agreement and the need for further work regarding the definitions and diagnostic criteria, given the need to avoid underestimating SdF [93]. No single assessment instrument measured all the reported domains, which is a fact that adds further complexity to the concept of SdF and leads to the underestimation and underdiagnosis of potential SdF in women with BC.
Finally, in some studies, researchers report measures of the relationships between SdF and age, mastectomy, chemotherapy, and hormone therapy. While Park et al. found that older women were more likely to have a poorer QoL than younger women, especially in terms of the items directly related to sexuality [94], other researchers found that younger women experienced more SF problems [95,96]. Some of the heterogeneity in the data may be explained by the age cut-off for younger versus older women, as well as certain sociocultural factors. In relation to the type of treatment, in a systematic review, the authors report that surgical options other than mastectomy have a better impact on the SF of women with BC [97]. In another study, the authors report that hormone therapy has significant side effects for the QoL of women, including SdF, specifically in terms of the loss of sexual interest, vaginal dryness, and pain during sex [98]. The loss of ovarian function and subsequent early menopause, as side effects due to chemotherapy, often cause SdF symptoms [99]. Nonetheless, certain individual features (e.g., culture, religion, and psychological and physical status) may also influence the way women experience BC.

Study Limitations
This evidence map has some limitations. The search was last updated in March 2021, which means that we may have missed studies published after that date. Furthermore, we only searched three databases; however, these databases are comprehensive, and so we consider that this limitation did not substantially affect our main findings. Another limitation was that we only selected specific SF assessment instruments and excluded studies based on general instruments (e.g., QoL instruments) that only partially evaluate certain aspects of SF. Although we recognise the importance of general instruments, we consider that specific measures may be more sensitive for the detection of small changes in this specific concept.
As for the strengths, as far as we are aware, ours may be the first evidence map that provides a comprehensive synthesis of the available evidence on SF in women with BC reported in the last 20 years. Furthermore, we based our evidence map on a standardised methodology that requires a systematic search and enables the results to be presented for easy and user-friendly interpretation.

Clinical Implications
The evidence map methodology used in this study highlights the important knowledge gaps and identifies future research needs. Our review suggests that SF in women with BC is a broad and complex concept. We suggest that health providers, researchers, and policymakers may need to rethink the concept of SF in a more inclusive way, and they should furthermore consider improving the assessment instruments used to date by including every domain, thereby avoiding underdiagnosis. A valid, reliable, interesting, and easy-to-use measurement instrument allows us to more precisely evaluate SF. Although every health system depends on its own principles, culture, and resources, we strongly recommend that clinicians use/introduce the most suitable instrument in their clinical practice to support decision-making and improve the QoL of woman with BC.

Conclusions
This evidence map provides a broad vision on how the research on SF in women with BC has been conducted so far.
While studies of SF in women with BC have substantially increased in number over the last 10 years, the importance and frequency of this health problem indicate that the number is still too low. Most of the studies include only women who are married, partnered, or in relationships, which leaves single, lesbian, and bisexual women underrepresented, which can be solved with new studies conducted on these specific groups of women.
Although the studies include a significant number of SF-related domains, this very much depended on the specific assessment instrument used, leading to the underestimation and underdiagnosis of some dysfunctions. Therefore, SdF should not be undervalued, as it can cause suffering in these women and might delay recovery. Future research should focus on ways to better screen for SdF in women with BC and improve their QoL.
Supplementary Materials: The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/ijerph192113976/s1, Table S1: Assessment instruments used.  Data Availability Statement: All the data generated or analysed during this study are included in the published review article.

Conflicts of Interest:
The authors declare no conflict of interest.