Abstract
Purpose
To culturally adapt and initially evaluate the psychometric properties of the Latvian versions of the EORTC QLQ-C30 and breast cancer-specific EORTC QLQ-BR45 in women with breast cancer.
Methods
The study was conducted within a pilot project implementing the ICHOM Breast Cancer Standard Set in a specialised university hospital in Latvia. Translation and cultural adaptation followed the EORTC procedure and included expert review and cognitive debriefing. Psychometric evaluation used baseline data from 142 women and six-month follow-up data from 47. Analyses included item-level indicators, internal consistency, multitrait scaling, inter-scale correlations, correlations with the Stress Symptom Scale, and paired change analyses. Conditional QLQ-BR45 items were treated as structurally missing when not applicable.
Results
Expert review and cognitive debriefing supported linguistic, conceptual, and cultural appropriateness. Reliability and item-scale correspondence were acceptable for several domains, with particularly strong multitrait scaling results for QLQ-BR45 Body Image, Sexual Functioning, and Breast Symptoms. Correlations between EORTC functioning and symptom domains and the Stress Symptom Scale were generally in the hypothesised directions. Six-month findings showed clinically plausible changes in functioning and treatment-related symptoms, but estimates were based on a smaller follow-up sample and reduced valid samples for some conditional scales.
Conclusion
The Latvian EORTC QLQ-C30 and QLQ-BR45 showed acceptable preliminary psychometric performance. The findings provide initial support for their use to assess HRQoL and breast cancer-specific symptoms in Latvia, while larger multicentre and longitudinal studies are needed to evaluate additional measurement properties and responsiveness.
Keywords: Patient-reported outcome measures, Breast cancer, Health-related quality of life, EORTC QLQ-C30, EORTC QLQ-BR45, Validation
Plain language summary
This study evaluated Latvian versions of two questionnaires used internationally to understand quality of life and symptoms in women with breast cancer: the EORTC QLQ-C30 and QLQ-BR45. Latvia lacked a comprehensive evaluation of these versions in women receiving breast cancer care. The translations were reviewed by specialists and tested with patients to ensure that the wording was understandable and culturally appropriate.
We then analysed questionnaire data from 142 women before treatment and from 47 women six months later. Several questionnaire scales showed acceptable reliability and the expected relationships with related symptoms. The follow-up results also showed plausible changes during treatment, although the smaller follow-up group means these findings are preliminary. Overall, the Latvian questionnaires appear suitable for cautious use in research and clinical practice, but larger studies are needed to confirm how well they perform across different patient and treatment groups.
Introduction
Breast cancer is the most frequently diagnosed malignancy among women worldwide and remains a major public health concern. In Latvia, 1,335 new breast cancer cases were diagnosed in women in 2024 [1]. Health-related quality of life (HRQoL) complements clinical outcomes by capturing the physical, psychological, and social effects of cancer and its treatment, including fatigue, body-image concerns, and treatment-related symptoms [2, 3].
The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 is a widely used core cancer HRQoL questionnaire, supplemented by disease-specific modules [4]. The QLQ-BR45 extended the earlier breast cancer module to reflect contemporary treatments and associated patient-reported outcomes [5]. Three items were subsequently removed during final validation, resulting in the QLQ-BR42; however, the QLQ-BR42 was published after the present project had begun, so the QLQ-BR45 was used in this study [5, 6].
Cross-cultural use of patient-reported outcome measures requires careful translation and evaluation to preserve conceptual equivalence and measurement properties, particularly for culturally sensitive domains such as sexuality and body image. Although Latvian translations of EORTC instruments are needed for clinical and research use, comprehensive psychometric evaluation of the Latvian QLQ-C30 and QLQ-BR45 in women with breast cancer has been lacking.
This study therefore aimed to culturally adapt and initially evaluate the psychometric properties of the Latvian versions of the EORTC QLQ-C30 and QLQ-BR45 in women with breast cancer.
Method
The study was conducted within a pilot project implementing the ICHOM Breast Cancer Standard Set at Pauls Stradiņš Clinical University Hospital, Latvia. Patient-reported outcomes were collected electronically before treatment (T1) and at six (T2) and 12 months (T3); the present analysis used T1 and T2 data. Adaptation of the QLQ-BR45 followed the EORTC Quality of Life Group (QLG) Translation Procedure [7, 8].
Translation sought conceptual and linguistic equivalence while preserving the original item content, order, response options, and scoring structure [7, 9].
Translation and cultural adaptation
After permission from the EORTC QLG, two independent forward translations into Latvian were reconciled by the translators with input from six clinicians and a psychometrics specialist. The expert review assessed linguistic accuracy, conceptual equivalence, cultural appropriateness, and comprehensibility; it was not intended to re-evaluate the content validity of the original EORTC instruments. Expert comments were used only for translation-level refinement.
Two independent back-translations were then prepared by native English speakers fluent in Latvian and blinded to the original questionnaire. Discrepancies were reviewed against the source version, and translation decisions and revised materials were submitted to the EORTC QLG for approval.
Cognitive debriefing
Ten Latvian-speaking breast cancer survivors with experience of different treatments completed the Latvian QLQ-C30 and QLQ-BR45 and participated in structured interviews on item clarity, acceptability, cultural appropriateness, and response options [7]. Minor linguistic refinements were documented and submitted to the EORTC QLG; underlying concepts and scoring were unchanged.
Psychometric evaluation
The psychometric evaluation followed EORTC guidance and scoring procedures [8, 10, 11]. Analyses were selected to match the available sample and included item-level performance, internal consistency, multitrait scaling, correlation-based construct validity, and preliminary change over time. Confirmatory factor analysis and measurement invariance testing were not conducted because the sample was insufficient for stable model-based analyses.
Participants
Phase 1 included six clinical experts: two surgical oncologists, two general practitioners, one nurse, and one occupational therapist.
Phase 2 included ten Latvian-speaking breast cancer survivors in remission who had experienced a range of treatments, including surgery, systemic therapy, radiotherapy, endocrine therapy, reconstruction, and prophylactic procedures.
Phase 3 included women aged 18 years or older with a first-time breast cancer diagnosis, sufficient Latvian proficiency, and treatment at the Breast Cancer Centre of Pauls Stradiņš Clinical University Hospital. Participants provided informed consent before accessing the electronic platform. Recruitment occurred from November 2024 to February 2026; 142 women completed baseline assessment and 47 completed the six-month follow-up.
Data collection and instruments
Baseline data included demographic characteristics, information received about treatment options, self-reported health characteristics and comorbidities, and clinical disease and treatment information extracted from electronic health records.
The EORTC QLQ-C30 is a 30-item cancer-specific HRQoL questionnaire comprising global health/QoL, five functioning scales (Tables 1 and 2), three multi-item symptom scales, and six single-item symptoms/problems [12, 13].
Table 1.
Structure of the EORTC QLQ-C30 [13]
| Scale | Number of items (n) | Item range* | Item numbers | |
|---|---|---|---|---|
| Global health status/QoL | ||||
| Global health status/QoL | QL2 | 2 | 6 | 29, 30 |
| Functional scales | ||||
| Physical functioning | PF2 | 5 | 3 | 1–5 |
| Role functioning | RF2 | 2 | 3 | 6–7 |
| Emotional functioning | EF | 4 | 3 | 21–24 |
| Cognitive functioning | CF | 2 | 3 | 20, 25 |
| Social functioning | SF | 2 | 3 | 26–27 |
| Symptom scales/items | ||||
| Fatigue | FA | 3 | 3 | 10, 12, 18 |
| Nausea and vomiting | NV | 2 | 3 | 14–15 |
| Pain | PA | 2 | 3 | 9, 19 |
| Dyspnoea | DY | 1 | 3 | 8 |
| Insomnia | SL | 1 | 3 | 11 |
| Appetite loss | AP | 1 | 3 | 13 |
| Constipation | CO | 1 | 3 | 16 |
| Diarrhoea | DI | 1 | 3 | 17 |
| Financial difficulties | FI | 1 | 3 | 28 |
*Item range = maximum minus minimum response. Items 1–28 use 1–4 responses (range = 3); items 29–30 use 1–7 responses (range = 6)
Table 2.
Structure of the EORTC QLQ-BR45 [9]
| Scale | Number of items (n) | Item range* | Item numbers | |
|---|---|---|---|---|
| Functional scales | ||||
| Body Image | BI | 4 | 3 | 39–42 |
| Future Perspective | FU | 1 | 3 | 43 |
| Sexual Functioning | SX | 2 | 3 | 44–45 |
| Sexual Enjoyment | SE | 1 | 3 | 46 |
| Symptom scales | ||||
| Systemic Therapy Side Effects | SYS | 7 | 3 | 31–34, 36–38 |
| Upset by Hair Loss | HU | 1 | 3 | 35 |
| Arm Symptoms | ARM | 3 | 3 | 47–49 |
| Breast Symptoms | BR | 4 | 3 | 50–53 |
| Endocrine Therapy Symptoms | ET | 10 | 3 | 54–56, 63–69 |
| Skin Mucosis Symptoms | SM | 6 | 3 | 57–62 |
| Endocrine Sexual Symptoms | ES | 4 | 3 | 70–73 |
*“Item range” is the difference between the possible maximum and the minimum response to individual items. All items are scored 1 to 4, giving range = 3
QLQ-C30 scores were transformed to 0–100 scales according to the EORTC scoring manual; higher functioning/global health scores indicate better status, whereas higher symptom scores indicate greater symptom burden [11, 13].
The EORTC QLQ-BR45 is a 45-item breast cancer-specific module used with the QLQ-C30. It assesses body image, future perspective, sexuality, and breast cancer- and treatment-related symptoms [5, 9]. Scores were transformed to 0–100 using EORTC procedures.
Most QLQ-BR45 items use four response categories. Sexual and endocrine-sexual items refer to the previous four weeks. Sexual Enjoyment and Endocrine Sexual Symptoms are conditional on sexual activity, and Upset by Hair Loss is conditional on reported hair loss; non-applicable responses were treated as structurally missing rather than as absence of symptoms.
The 56-item Stress Symptom Scale includes physical, cognitive, psychological, and emotional symptom domains rated from 0 (almost never/never) to 5 (almost all the time/continuously) [14]. It was used as a related external comparison measure, not as a criterion measure of cancer-specific HRQoL, because validated Latvian-language comparison measures are limited and several stress domains overlap conceptually with EORTC functioning and symptom domains.
Statistical analysis
Scale scores were calculated according to EORTC rules. Multi-item scale scores were computed when at least half of the constituent items had valid responses; otherwise the score was missing. Conditional QLQ-BR45 items/scales were structurally missing when not applicable. Reliability analyses used valid scale-level cases, and correlations used pairwise deletion; valid N therefore varied across conditional scales and coefficients.
Analyses were conducted in Microsoft Excel and IBM SPSS 29. Descriptive statistics and corrected item–total correlations were calculated. Internal consistency was assessed with Cronbach’s alpha for multi-item scales and McDonald’s omega where applicable [15–17]. Multitrait scaling used corrected item–own scale correlations for convergence and item–other scale correlations for distinctiveness; convergent success required item–own r ≥ .40, and scaling success required item–own r to exceed the highest absolute item–other scale correlation. Spearman correlations assessed relationships between EORTC scales and with the Stress Symptom Scale. Functioning scales were hypothesised to correlate negatively with stress scores and symptom scales positively. Paired T1–T2 changes were tested with Wilcoxon signed-rank tests using participants with valid scores at both time points and were interpreted as preliminary evidence of change rather than definitive responsiveness. Expert agreement indices used the CVI approach [18, 19].
Results
Phase 1: expert review of translation equivalence and cultural appropriateness
Expert agreement supported the translated versions. For the QLQ-C30, item-level agreement indices ranged from 0.83 to 1.00 and the scale-level average was 0.90. For the QLQ-BR45, item-level indices ranged from 0.67 to 1.00. Lower agreement identified translation-level issues requiring review rather than item deletion or conceptual modification.
Expert comments focused mainly on wording in sensitive or clinically specific items, including QLQ-BR45 items 41, 50, 51, 53, and 57 and QLQ-C30 item 23. These items were linguistically refined without changing their constructs, item content, or standard EORTC scoring structure.
Phase 2: cognitive debriefing
Cognitive debriefing indicated good overall acceptability. Nine of ten participants reported no difficulties; one commented on wording in three items. Minor translation-tone and orthographic issues were reviewed and corrected where consistent with the source concepts. No conceptual changes were introduced.
Phase 3: psychometric evaluation
At baseline, 142 women participated and 47 completed the six-month follow-up (Table 3). The baseline mean age was 56.1 years; 57.7% had higher education and 76.1% were married or in a relationship. Right- and left-sided tumours were similarly represented. Baseline clinical characteristics and the health status of the follow-up subsample are summarised in Tables 4 and 5.
Table 3.
Demographic characteristics of the study participants
| Patient characteristics | Baseline (T1) N = 142 | Follow-up (T2) N = 47 |
|---|---|---|
| Age (years), mean ± SD | 56.1 ± 12.8 | 53.7 ± 12.5 |
| Place of residence, n (%) | ||
| Capital region | 72 (50.7) | 22 (46.8) |
| Other regions | 70 (49.3) | 25 (53.2) |
| Nationality, n (%) | ||
| Latvian | 104 (73.2) | 36 (76.6) |
| Russian | 25 (17.6) | 7 (14.9) |
| Other | 9 (6.3) | 2 (4.3) |
| Prefer not to answer | 4 (2.8) | 2 (4.3) |
| Level of education, n (%) | ||
| Primary education | 4 (2.8) | 1 (2.1) |
| Secondary education | 19 (13.4) | 4 (8.5) |
| Vocational education | 37 (26.1) | 15 (31.9) |
| Higher education | 82 (57.7) | 27 (57.4) |
| Marital status, n (%) | ||
| Single | 8 (5.6) | 1 (2.1) |
| Married/in a relationship | 108 (76.1) | 39 (83.0) |
| Divorced | 13 (9.2) | 5 (10.6) |
| Widowed | 12 (8.3) | 2 (4.3) |
| Prefer not to answer | 1 (0.7) | 0 (0.0) |
| Laterality, n (%) | ||
| Right | 72 (50.7) | 24 (51.1) |
| Left | 64 (45.1) | 21 (44.7) |
| Both | 6 (4.2) | 2 (4.3) |
| BMI, mean ± SD | 27.7 ± 5.4 | 27.6 ± 4.9 |
Table 4.
Summary of health status, cancer characteristics, and treatment in the baseline sample at T1
| Domain | Characteristic | n/N (%) or M (SD) |
|---|---|---|
| Data availability | Health-status questionnaire records available | 142/142 (100.0%) |
| Dedicated treatment-strategy records available | 85/142 (59.9%) | |
| Clinical records available | 137/142 (96.5%) | |
| Health status | Tumor laterality: right/left/bilateral | 72 (50.7%)/64 (45.1%)/6 (4.2%) |
| BMI, kg/m², M (SD); median [range] | 27.66 (5.37); 27.5 [17.9–44.8] | |
| BMI category: underweight/normal/overweight/obesity | 1 (0.7%)/50 (35.5%)/47 (33.3%)/43 (30.5%) | |
| Any comorbid/medical condition | 112 (78.9%) | |
| Number of comorbid conditions: 0/1/2/3/>=4 | 30 (21.1%)/37 (26.1%)/33 (23.2%)/13 (9.2%)/29 (20.4%) | |
| Most frequent comorbidities | Back pain | 70 (49.3%) |
| High blood pressure | 47 (33.1%) | |
| Other medical problems | 32 (22.5%) | |
| Cardiovascular disease | 20 (14.1%) | |
| Osteoarthritis/degenerative arthritis | 19 (13.4%) | |
| Gastric ulcer/gastrointestinal disease | 17 (12.0%) | |
| Lung disease | 16 (11.3%) | |
| Clinical characteristics | Menopausal status: premenopausal/postmenopausal | 56 (40.9%) /81 (59.1%) |
| Tumour behaviour: invasive/in situ/other | 120 (87.6%)/16 (11.7%)/1 (0.7%) | |
| Morphology: ductal/lobular/other | 117 (85.4%)/11 (8.0%)/9 (6.6%) | |
| Grade: 1/2/3/not applicable | 24 (17.5%)/64 (46.7%)/32 (23.4%)/17 (12.4%) | |
| Receptor status: ER+/PR+/HER2+/triple negative | 100 (73.0%)/94 (68.6%)/15 (10.9%)/24 (17.5%) | |
| Oncotype test performed | 39 (28.5%) | |
| Clinical tumour size: Tis/T1/T2/T3–T4 | 15 (10.9%)/67 (48.9%)/38 (27.7%)/17 (12.4%) | |
| Clinical nodal status: N0/N1/N2-N3/Nx | 89 (65.0%)/33 (24.1%)/11 (8.0%)/4 (2.9%) | |
| Clinical metastasis status: M0/M1/Mx | 130 (94.9%)/4 (2.9%)/3 (2.2%) | |
| MDT assigned treatment strategy | Surgical treatment | 119 (86.9%) |
| Radiotherapy | 98 (71.5%) | |
| Hormonal therapy | 87 (63.5%) | |
| Neoadjuvant/adjuvant chemotherapy | 42 (30.7%)/ 18 (13.1%) | |
| Targeted therapy/immunotherapy | 25 (18.2%)/24 (17.5%) | |
| Supportive therapy/palliative care | 4 (2.9%) | |
| Surgery type | Breast-conserving surgery ± mammoplasty | 72/119 (60.5%) |
| Mastectomy ± immediate reconstruction | 47/119 (39.5%) | |
| Documented treatment | Received MDT-recommended therapy | 104/137 (75.9%) |
| Sentinel lymph node biopsy/axillary dissection | 113 (95.0%)/ 32 (26.9%) | |
| Radiotherapy | ||
| Hormone therapy received | 98 (71.5%) /89 (65.0%) | |
| Neoadjuvant/adjuvant chemotherapy received | 40 (29.2%)/ 18 (13.1%) | |
| Targeted therapy/immunotherapy received | 29 (21.2%)/ 23 (16.8%) |
Baseline health-status data were available for 142 participants. Clinical characteristics were based on available electronic health records; denominators therefore varied across variables. BMI categories use n = 141 because one implausible BMI value was excluded. Comorbidity rows list the most frequent conditions (≥ 10%). Multiple treatments could be recorded. BCS = breast-conserving surgery; MDT = multidisciplinary team
Table 5.
Summary of health status in the six-month follow-up subsample
| Domain | Characteristic | n/N (%) or M (SD) |
|---|---|---|
| Data availability | Second-measurement participants | 47/47 (100.0%) |
| Health-status questionnaire records available | 47/47 (100.0%) | |
| Treatment-strategy records available | 40/47 (85.1%) | |
| Clinical records available | 28/47 (59.6%) | |
| Health status | Tumor laterality: right/left/bilateral | 24 (51.1%)/21 (44.7%)/2 (4.3%) |
| BMI, kg/m², M (SD); median [range] | 27.57 (4.93); 27.0 [19.5–43.7] | |
| BMI category: normal/overweight/obesity | 14 (29.8%)/21 (44.7%)/12 (25.5%) | |
| Any comorbid/medical condition | 33 (70.2%) | |
| Number of comorbid conditions: 0/1/2/3/>=4 | 14 (29.8%)/11 (23.4%)/10 (21.3%)/4 (8.5%)/8 (17.0%) | |
| Most frequent comorbidities | Back pain | 23 (48.9%) |
| High blood pressure | 11 (23.4%) | |
| Other medical problems | 10 (21.3%) | |
| Lung disease | 6 (12.8%) | |
| Gastric ulcer/gastrointestinal disease | 5 (10.6%) | |
| Osteoarthritis/degenerative arthritis | 5 (10.6%) |
The follow-up subsample included 47 participants with second-measurement data. Baseline health-status data were available for all 47; percentages are based on the available denominator for each characteristic. Comorbidity rows list the most frequent conditions (≥ 10%)
Clinical records were available for most baseline participants, although completeness varied by variable. Most recorded tumours were invasive and hormone-receptor positive, and surgery was the most commonly documented treatment, followed by radiotherapy and endocrine therapy (Table 4). The 47-person follow-up subsample was broadly similar to the baseline cohort on the main recorded health characteristics (Table 5).
Item-level results and reliability estimates are shown in Table 6. Several QLQ-C30 scales had lower internal consistency at baseline, particularly Social Functioning, Fatigue, and Pain, whereas follow-up estimates were generally higher. In the QLQ-BR45, Body Image and Sexual Functioning showed strong internal consistency at both assessments. Estimates for conditional scales were based on smaller valid samples and should be interpreted cautiously.
Table 6.
Item-level psychometric indicators for the EORTC QLQ-C30 and EORTC QLQ-BR45
| Scale | Item | Baseline (T1) | Follow-up assessment (T2) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n | M | SD | r_it | α | ω | n | M | SD | r_it | α | ω | ||
| EORTC QLQ-C30 | |||||||||||||
| Global health status/QoL | |||||||||||||
| Global health status/QoL (QL2) | QL2_29 general health | 142 | 5.34 | 1.184 | 0.722 | 0.837 | – | 47 | 5.17 | 1.239 | 0.893 | 0.937 | – |
| QL2_30 general quality of life | 142 | 5.12 | 1.114 | 0.722 | 47 | 5.06 | 1.051 | 0.893 | |||||
| Functional scales | |||||||||||||
| Physical functioning (PF2) | PF2_1 carrying heavy objects | 142 | 1.98 | 0.879 | 0.448 | 0.756 | 0.752 | 47 | 2.38 | 0.848 | 0.515 | 0.789 | 0.830 |
| PF2_2 long walks | 142 | 1.95 | 0.688 | 0.561 | 47 | 1.96 | 0.833 | 0.758 | |||||
| PF2_3 short walks | 142 | 2.06 | 0.877 | 0.452 | 47 | 1.36 | 0.605 | 0.748 | |||||
| PF2_4 time spent lying down or sitting | 142 | 1.70 | 0.744 | 0.692 | 47 | 1.64 | 0.870 | 0.648 | |||||
| PF2_5 help with self-care | 142 | 1.45 | 0.710 | 0.507 | 47 | 1.11 | 0.429 | 0.221 | |||||
| Role functioning (RF2) | RF2_6 work on daily activities | 142 | 1.25 | 0.497 | 0.501 | 0.541 | – | 47 | 1.70 | 0.623 | 0.699 | 0.817 | – |
| RF2_7 hobbies | 142 | 1.04 | 0.220 | 0.501 | 47 | 1.68 | 0.726 | 0.699 | |||||
| Emotional functioning (EF) | EF_21 tension | 142 | 1.42 | 0.737 | 0.423 | 0.632 | 0.695 | 47 | 1.83 | 0.637 | 0.636 | 0.813 | 0.828 |
| EF_22 worry | 142 | 1.16 | 0.456 | 0.611 | 47 | 1.98 | 0.571 | 0.585 | |||||
| EF_23 irritability | 142 | 1.30 | 0.581 | 0.569 | 47 | 2.02 | 0.847 | 0.703 | |||||
| EF_24 depression | 142 | 1.04 | 0.185 | 0.151 | 47 | 1.94 | 0.734 | 0.649 | |||||
| Cognitive functioning (CF) | CF_20 concentration difficulties | 142 | 1.50 | 0.722 | 0.482 | 0.646 | – | 47 | 1.47 | 0.747 | 0.634 | 0.774 | – |
| CF_25 memory problems | 142 | 1.42 | 0.622 | 0.482 | 47 | 1.87 | 0.679 | 0.634 | |||||
| Social functioning (SF) | SF_26 family life | 142 | 1.39 | 0.641 | 0.174 | 0.291 | – | 47 | 1.81 | 0.798 | 0.720 | 0.831 | – |
| SF_27 social activities | 142 | 1.28 | 0.524 | 0.174 | 47 | 1.96 | 0.932 | 0.720 | |||||
| Symptom scales/items | |||||||||||||
| Fatigue (FA) | FA_10 need to rest | 142 | 1.96 | 0.683 | 0.479 | 0.530 | 0.596 | 47 | 2.26 | 0.675 | 0.732 | 0.872 | 0.878 |
| FA_12 weakness | 142 | 1.63 | 0.856 | 0.369 | 47 | 2.15 | 0.780 | 0.734 | |||||
| FA_18 fatigue | 142 | 1.73 | 0.640 | 0.213 | 47 | 2.34 | 0.788 | 0.810 | |||||
| Nausea and vomiting (NV) | NV_14 nausea | 142 | 1.92 | 0.719 | 0.620 | 0.764 | – | 47 | 1.40 | 0.614 | 0.566 | 0.627 | – |
| NV_15 vomiting | 142 | 2.38 | 0.788 | 0.620 | 47 | 1.11 | 0.312 | 0.566 | |||||
| Pain (PA) | PA_9 pain | 142 | 1.21 | 0.517 | 0.282 | 0.432 | – | 47 | 2.11 | 0.729 | 0.734 | 0.846 | – |
| PA_19 pain interferes with daily activities | 142 | 1.39 | 0.641 | 0.282 | 47 | 1.81 | 0.770 | 0.734 | |||||
| Dyspnoea (DY) | DY_8 dyspnoea | 142 | 1.30 | 0.556 | – | – | – | 47 | 1.47 | 0.718 | – | – | – |
| Insomnia (SL) | SL_11 insomnia | 142 | 1.46 | 0.670 | – | – | – | 47 | 2.17 | 0.816 | – | – | – |
| Appetite loss (AP) | AP_13 appetite loss | 142 | 1.21 | 0.544 | – | – | – | 47 | 1.51 | 0.688 | – | – | – |
| Constipation (CO) | CO_16 constipation | 142 | 1.83 | 0.714 | – | – | – | 47 | 1.66 | 0.788 | – | – | – |
| Diarrhoea (DI) | DI_17 diarrhoea | 142 | 1.82 | 0.708 | – | – | – | 47 | 1.30 | 0.587 | – | – | – |
| Financial difficulties (FI) | FI_28 financial difficulties | 142 | 1.88 | 0.709 | – | – | – | 47 | 1.68 | 0.837 | – | – | – |
| EORTC QLQ-BR45 | |||||||||||||
| Functional scales | |||||||||||||
| Body Image (BI) | BI_39 physical attractiveness | 140 | 1.43 | 0.701 | 0.726 | 0.865 | 0.859 | 46 | 1.98 | 1.000 | 0.841 | 0.924 | 0.924 |
| BI_40 femininity | 140 | 1.45 | 0.692 | 0.734 | 46 | 2.02 | 1.064 | 0.863 | |||||
| BI_41 naked appearance | 140 | 1.42 | 0.720 | 0.724 | 46 | 1.87 | 0.934 | 0.831 | |||||
| BI_42 body satisfaction | 140 | 1.56 | 0.681 | 0.673 | 46 | 2.11 | 0.900 | 0.768 | |||||
| Future Perspective (FU) | FU_43 future perspective | 140 | 2.99 | 0.818 | – | – | – | 46 | 2.65 | 0.948 | – | – | – |
| Sexual Functioning (SX) | SX_44 interest in sex | 140 | 3.31 | 0.658 | 0.687 | 0.814 | – | 46 | 3.37 | 0.679 | 0.806 | 0.893 | – |
| SX_45 sexual activity | 140 | 3.31 | 0.645 | 0.687 | 46 | 3.33 | 0.668 | 0.806 | |||||
| Sexual Enjoyment (SE) | SE_46 sexual enjoyment | 83 | 2.70 | 0.694 | – | – | – | 26 | 2.54 | 0.706 | – | – | – |
| Symptom scales | |||||||||||||
| Systemic Therapy Side Effects (SYS) | SYS_31 dry mouth | 140 | 1.66 | 0.716 | 0.437 | 0.690 | 0.687 | 46 | 1.91 | 0.890 | 0.208 | 0.701 | 0.726 |
| SYS_32 changes in taste | 140 | 1.10 | 0.324 | 0.446 | 46 | 1.50 | 0.810 | 0.666 | |||||
| SYS_33 eye discomfort | 140 | 1.48 | 0.605 | 0.452 | 46 | 1.74 | 0.801 | 0.483 | |||||
| SYS_34 hair loss | 140 | 1.42 | 0.720 | 0.478 | 46 | 2.09 | 1.226 | 0.311 | |||||
| SYS_36 feeling unwell | 140 | 1.53 | 0.662 | 0.415 | 46 | 1.91 | 0.865 | 0.663 | |||||
| SYS_37 hot flushes | 140 | 1.64 | 0.732 | 0.296 | 46 | 2.50 | 1.188 | 0.457 | |||||
| SYS_38 headache | 140 | 1.66 | 0.676 | 0.374 | 46 | 1.65 | 0.674 | 0.215 | |||||
| Upset by Hair Loss (HU) | HU_35 upset by hair loss | 44 | 2.25 | 0.967 | – | – | – | 25 | 2.56 | 1.083 | – | – | – |
| Arm Symptoms (ARM) | ARM_47 pain in the arm or shoulder | 140 | 1.64 | 0.798 | 0.537 | 0.573 | 0.768 | 46 | 1.98 | 0.802 | 0.554 | 0.744 | 0.747 |
| ARM_48 swelling in the arm or shoulder | 140 | 1.12 | 0.328 | 0.258 | 46 | 1.46 | 0.721 | 0.547 | |||||
| ARM_49 difficulty lifting or moving the arm | 140 | 1.34 | 0.609 | 0.472 | 46 | 1.85 | 0.788 | 0.611 | |||||
| Breast Symptoms (BR) | BR_50 breast pain | 140 | 1.71 | 0.662 | 0.527 | 0.693 | 0.728 | 46 | 1.91 | 0.661 | 0.668 | 0.777 | 0.779 |
| BR_51 skin swelling in the breast area | 140 | 1.40 | 0.655 | 0.541 | 46 | 1.54 | 0.690 | 0.497 | |||||
| BR_52 skin sensitivity in the breast area | 140 | 1.71 | 0.742 | 0.618 | 46 | 1.87 | 0.687 | 0.582 | |||||
| BR_53 skin problems in the breast area | 140 | 1.21 | 0.506 | 0.240 | 46 | 1.65 | 0.706 | 0.582 | |||||
| Endocrine Therapy Symptoms (ET) | ET_54 sweating | 12 | 2.92 | 0.996 | 0.352 | 0.857 | *** | 12 | 2.42 | 0.900 | 0.492 | 0.717 | *** |
| ET_55 mood swings | 12 | 2.17 | 0.718 | 0.629 | 12 | 2.25 | 0.965 | 0.351 | |||||
| ET_56 dizziness | 12 | 2.00 | 0.953 | 0.591 | 12 | 1.83 | 0.835 | 0.542 | |||||
| ET_63 joint problems | 12 | 2.50 | 0.522 | 0.610 | 12 | 2.17 | 0.389 | 0.111 | |||||
| ET_64 joint stiffness | 12 | 2.42 | 0.793 | 0.930 | 12 | 2.08 | 0.669 | 0.338 | |||||
| ET_65 joint pain | 12 | 2.42 | 0.793 | 0.903 | 12 | 2.25 | 0.452 | 0.306 | |||||
| ET_66 bone pain | 12 | 2.00 | 1.044 | 0.942 | 12 | 2.25 | 0.965 | 0.638 | |||||
| ET_67 muscle pain | 12 | 2.25 | 0.866 | 0.649 | 12 | 1.92 | 0.669 | 0.387 | |||||
| ET_68 weight gain | 12 | 2.33 | 0.651 | 0.276 | 12 | 2.50 | 0.674 | 0.268 | |||||
| ET_69 problems caused by weight gain | 12 | 1.92 | 0.996 | 0.050 | 12 | 2.50 | 1.168 | 0.334 | |||||
| Skin/Mucosis Symptoms (SM) | SM_57 mouth pain | 140 | 1.06 | 0.299 | 0.339 | 0.675 | *** | 46 | 1.13 | 0.400 | 0.186 | 0.621 | *** |
| SM_58 redness in the mouth | 140 | 1.07 | 0.332 | 0.292 | 46 | 1.07 | 0.250 | 0.286 | |||||
| SM_59 pain in the palms and soles | 140 | 1.29 | 0.566 | 0.556 | 46 | 1.61 | 0.682 | 0.294 | |||||
| SM_60 redness/rash | 140 | 1.02 | 0.188 | 0.049 | 46 | 1.09 | 0.285 | 0.128 | |||||
| SM_61 tingling in the fingers and toes | 140 | 1.56 | 0.779 | 0.623 | 46 | 2.00 | 0.989 | 0.734 | |||||
| SM_62 numbness in the fingers or toes | 140 | 1.24 | 0.583 | 0.585 | 46 | 1.57 | 0.779 | 0.580 | |||||
| Endocrine Sexual Symptoms (ES) | ES_70 vaginal dryness | 83 | 1.31 | 0.623 | 0.584 | 0.740 | 0.748 | 26 | 1.88 | 0.952 | 0.659 | 0.887 | 0.875 |
| ES_71 vaginal discomfort | 83 | 1.20 | 0.406 | 0.645 | 26 | 1.73 | 0.827 | 0.840 | |||||
| ES_72 vaginal pain during sexual activity | 83 | 1.17 | 0.377 | 0.378 | 26 | 1.77 | 0.765 | 0.815 | |||||
| ES_73 vaginal dryness during sex | 83 | 1.27 | 0.520 | 0.593 | 26 | 1.85 | 0.784 | 0.733 | |||||
M = mean; SD = standard deviation; r_it = corrected item–total correlation; α = Cronbach’s alpha; ω = McDonald’s omega. Valid n indicates participants with valid item/scale data at the respective assessment. QLQ-C30 global health/QoL items range from 1 to 7; other EORTC item responses range from 1 to 4. QLQ-BR45 items 44–46 are shown after reverse coding, consistent with scoring of Sexual Functioning and Sexual Enjoyment. Single-item scales are descriptive only. Conditional QLQ-BR45 scales were structurally missing when not applicable. *** Omega was not reported where assumptions for a stable estimate were not met
Multitrait scaling results are summarised in Table 7. The strongest scaling support was observed for QLQ-BR45 Body Image, Sexual Functioning, and Breast Symptoms, with all items showing scaling success. Endocrine Sexual Symptoms also performed relatively well, although based on a smaller valid sample. Scaling success was weaker for several QLQ-C30 domains and for QLQ-BR45 Systemic Therapy Side Effects, Arm Symptoms, Endocrine Therapy Symptoms, and Skin/Mucosis Symptoms, indicating overlap among clinically related functioning and symptom constructs.
Table 7.
Multitrait Scaling Summary for the EORTC QLQ-C30 and EORTC QLQ-BR45 at Baseline
| Instrument | Scale | k | N | Item–own r | Highest item–other |r| | Convergent success | Scaling success |
|---|---|---|---|---|---|---|---|
| C30 | Global health/QoL (QL2) | 2 | 142 | 0.72 | 0.60–0.62 | 2/2 | 2/2 (100%) |
| C30 | Physical functioning (PF2) | 5 | 142 | 0.45–0.69 | 0.41–0.68 | 5/5 | 3/5 (60%) |
| C30 | Role functioning (RF2) | 2 | 142 | 0.50 | 0.42–0.52 | 2/2 | 1/2 (50%) |
| C30 | Emotional functioning (EF) | 4 | 142 | 0.15–0.61 | 0.25–0.64 | 3/4 | 0/4 (0%) |
| C30 | Cognitive functioning (CF) | 2 | 142 | 0.48 | 0.65–0.70 | 2/2 | 0/2 (0%) |
| C30 | Social functioning (SF) | 2 | 142 | 0.17 | 0.41–0.69 | 0/2 | 0/2 (0%) |
| C30 | Fatigue (FA) | 3 | 142 | 0.21–0.48 | 0.36–0.70 | 1/3 | 0/3 (0%) |
| C30 | Nausea/vomiting (NV) | 2 | 142 | 0.62 | 0.24–0.36 | 2/2 | 2/2 (100%) |
| C30 | Pain (PA) | 2 | 142 | 0.28 | 0.50–0.70 | 0/2 | 0/2 (0%) |
| BR45 | Body image (BI) | 4 | 140 | 0.67–0.73 | 0.39–0.44 | 4/4 | 4/4 (100%) |
| BR45 | Sexual functioning (SX) | 2 | 140 | 0.69 | 0.33–0.44 | 2/2 | 2/2 (100%) |
| BR45 | Systemic side effects (SYS) | 7 | 140 | 0.30–0.48 | 0.39–0.78 | 5/7 | 2/7 (29%) |
| BR45 | Arm symptoms (ARM) | 3 | 140 | 0.26–0.54 | 0.31–0.71 | 2/3 | 1/3 (33%) |
| BR45 | Breast symptoms (BR) | 4 | 140 | 0.24–0.62 | 0.18–0.45 | 3/4 | 4/4 (100%) |
| BR45 | Endocrine therapy symptoms (ET) | 10 | 12 | 0.05–0.94 | 0.39–0.88 | 7/10 | 4/10 (40%) |
| BR45 | Skin/mucosis symptoms (SM) | 6 | 140 | 0.05–0.62 | 0.14–0.47 | 3/6 | 3/6 (50%) |
| BR45 | Endocrine sexual symptoms (ES) | 4 | 83 | 0.38–0.65 | 0.12–0.84 | 3/4 | 3/4 (75%) |
T1 = baseline; k = number of items. Single-item scales were excluded. Item–own correlations are corrected item–total correlations. Highest item–other |r| is the highest absolute correlation with another multi-item scale within the same questionnaire/module. Convergent success = item–own r ≥ .40; scaling success = item–own r exceeding the highest item–other |r|. Conditional QLQ-BR45 scales used available valid subsamples
Standardised scale scores are presented in Table 8. Descriptively, global health/QoL was relatively stable at follow-up and physical functioning changed little, whereas role, emotional, cognitive, and social functioning were lower. Several treatment-related symptom scores were higher at follow-up. Conditional QLQ-BR45 scales had reduced valid N.
Table 8.
Descriptive Statistics for the EORTC QLQ-C30, EORTC QLQ-BR45, and Stress Symptom Scale Scores at Baseline and Follow-Up
| Scale | N of items | Valid N | Baseline (T1) | Follow-up assessment (T2) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| M | SD | Min | Max | Valid N | M | SD | Min | Max | |||
| EORTC QLQ-C30 | |||||||||||
| Global health status/QoL | |||||||||||
| Global health status/QoL (QL2) | 2 | 142 | 70.48 | 17.77 | 16.67 | 100.00 | 47 | 68.62 | 18.57 | 33.33 | 100.00 |
| Functional scales | |||||||||||
| Physical functioning (PF2) | 5 | 142 | 72.39 | 18.58 | 0.00 | 100.00 | 47 | 77.02 | 18.11 | 20.00 | 100.00 |
| Role functioning (RF2) | 2 | 142 | 95.19 | 10.61 | 16.67 | 100.00 | 47 | 76.95 | 20.72 | 33.33 | 100.00 |
| Emotional functioning (EF) | 4 | 142 | 92.37 | 12.18 | 41.67 | 100.00 | 47 | 68.62 | 18.81 | 16.67 | 100.00 |
| Cognitive functioning (CF) | 2 | 142 | 84.74 | 19.30 | 0.00 | 100.00 | 47 | 77.66 | 21.50 | 16.67 | 100.00 |
| Social functioning (SF) | 2 | 142 | 88.73 | 14.93 | 33.33 | 100.00 | 47 | 70.57 | 26.74 | 0.00 | 100.00 |
| Symptom scales/items | |||||||||||
| Fatigue (FA) | 3 | 142 | 25.74 | 17.52 | 0.00 | 77.78 | 47 | 41.61 | 22.28 | 0.00 | 88.89 |
| Nausea and vomiting (NV) | 2 | 142 | 38.26 | 22.61 | 0.00 | 100.00 | 47 | 8.51 | 13.85 | 0.00 | 50.00 |
| Pain (PA) | 2 | 142 | 10.09 | 15.50 | 0.00 | 83.33 | 47 | 31.91 | 23.27 | 0.00 | 83.33 |
| Dyspnoea (DY) | 1 | 142 | 9.86 | 18.53 | 0.00 | 100.00 | 47 | 15.60 | 23.93 | 0.00 | 66.67 |
| Insomnia (SL) | 1 | 142 | 15.26 | 22.32 | 0.00 | 100.00 | 47 | 39.01 | 27.20 | 0.00 | 100.00 |
| Appetite loss (AP) | 1 | 142 | 7.04 | 18.12 | 0.00 | 100.00 | 47 | 17.02 | 22.92 | 0.00 | 66.67 |
| Constipation (CO) | 1 | 142 | 27.70 | 23.81 | 0.00 | 100.00 | 47 | 21.99 | 26.26 | 0.00 | 100.00 |
| Diarrhoea (DI) | 1 | 142 | 27.46 | 23.59 | 0.00 | 100.00 | 47 | 9.93 | 19.55 | 0.00 | 66.67 |
| Financial difficulties (FI) | 1 | 142 | 29.34 | 23.65 | 0.00 | 100.00 | 47 | 22.70 | 27.89 | 0.00 | 100.00 |
| EORTC QLQ-BR45 | |||||||||||
| Functional scales | |||||||||||
| Body Image (BI) | 4 | 140 | 84.52 | 19.65 | 0.00 | 100.00 | 46 | 66.85 | 29.37 | 0.00 | 100.00 |
| Future Perspective (FU) | 1 | 140 | 33.57 | 27.26 | 0.00 | 100.00 | 46 | 44.93 | 31.60 | 0.00 | 100.00 |
| Sexual Functioning (SX) | 2 | 140 | 22.98 | 19.94 | 0.00 | 66.67 | 46 | 21.74 | 21.33 | 0.00 | 66.67 |
| Sexual Enjoyment (SE) | 1 | 83 | 43.37 | 23.13 | 0.00 | 100.00 | 26 | 48.72 | 23.53 | 0.00 | 100.00 |
| Symptom scales | |||||||||||
| Systemic Therapy Side Effects (SYS) | 7 | 140 | 16.60 | 12.77 | 0.00 | 61.90 | 46 | 30.02 | 18.78 | 0.00 | 71.43 |
| Upset by Hair Loss (HU) | 1 | 44 | 41.67 | 32.25 | 0.00 | 100.00 | 25 | 52.00 | 36.11 | 0.00 | 100.00 |
| Arm Symptoms (ARM) | 3 | 140 | 12.22 | 14.92 | 0.00 | 66.67 | 46 | 25.36 | 20.91 | 0.00 | 100.00 |
| Breast Symptoms (BR) | 4 | 140 | 16.96 | 15.56 | 0.00 | 66.67 | 46 | 24.82 | 17.70 | 0.00 | 75.00 |
| Endocrine Therapy Symptoms (ET) | 10 | 12 | 43.06 | 18.72 | 20.00 | 83.33 | 12 | 40.56 | 14.20 | 16.67 | 63.33 |
| Skin/Mucosis Symptoms (SM) | 6 | 140 | 6.90 | 10.30 | 0.00 | 50.00 | 46 | 13.65 | 12.27 | 0.00 | 50.00 |
| Endocrine Sexual Symptoms (ES) | 4 | 83 | 7.93 | 12.27 | 0.00 | 50.00 | 26 | 26.92 | 24.07 | 0.00 | 100.00 |
| Stress Symptom Scale | |||||||||||
| Physical Stress Symptoms (F) | 21 | 141 | 1.01 | 0.70 | 0.00 | 4.57 | 43 | 1.23 | 0.71 | 0.24 | 2.86 |
| Impaired Cognitive Functioning (K) | 14 | 141 | 1.02 | 0.85 | 0.00 | 4.86 | 43 | 1.33 | 0.92 | 0.00 | 3.93 |
| Psychological Stress Symptoms (P) | 15 | 141 | 0.75 | 0.85 | 0.00 | 4.67 | 43 | 0.88 | 0.85 | 0.00 | 3.07 |
| Emotional Stress Symptoms (E) | 6 | 141 | 0.77 | 0.74 | 0.00 | 3.50 | 43 | 1.08 | 0.92 | 0.00 | 3.50 |
| Stress symptoms sum (SSS) | 56 | 141 | 3.55 | 2.74 | 0.00 | 17.60 | 43 | 4.51 | 2.96 | 0.59 | 12.89 |
EORTC scores range from 0 to 100. Higher functioning/global health scores indicate better functioning or quality of life; higher symptom scores indicate greater symptom burden. Stress Symptom Scale domains are means from 0 to 5; SSS is the sum of the four domain means. Valid N indicates available scale scores. Conditional QLQ-BR45 scales were structurally missing when not applicable; valid N therefore varies across scales
Paired analyses (Table 9) showed significant decreases in role, emotional, cognitive, and social functioning and increases in fatigue, pain, insomnia, and appetite loss. QLQ-BR45 Body Image decreased, Future Perspective increased, and several treatment-related symptom scales increased. Physical, cognitive, emotional, and total stress symptom scores also increased. These clinically plausible changes are preliminary because follow-up involved only 47 participants and some conditional scales had substantially smaller paired samples.
Table 9.
Paired baseline and six-month follow-up comparisons (Wilcoxon Signed-Rank Test)
| Scale | n | T1 M (SD) | T2 M (SD) | ΔM | W | p |
|---|---|---|---|---|---|---|
| EORTC QLQ-C30 | ||||||
| Global health status/QoL (QL2) | 47 | 71.45 (16.09) | 68.62 (18.57) | − 2.84 | 292.0 | 0.368 |
| Physical functioning (PF2) | 47 | 76.31 (14.70) | 77.02 (18.11) | 0.71 | 392.0 | 0.617 |
| Role functioning (RF) | 47 | 97.87 (5.62) | 76.95 (20.72) | − 20.92 | 4.0 | < 0.001*** |
| Emotional functioning (EF) | 47 | 93.79 (10.05) | 68.62 (18.81) | − 25.18 | 5.0 | < 0.001*** |
| Cognitive functioning (CF) | 47 | 87.59 (14.52) | 77.66 (21.50) | − 9.93 | 119.5 | 0.006** |
| Social functioning (SF) | 47 | 89.72 (12.31) | 70.57 (26.74) | − 19.15 | 37.5 | < 0.001*** |
| Fatigue (FA) | 47 | 23.40 (17.22) | 41.61 (22.28) | 18.2 | 48.5 | < 0.001*** |
| Nausea and vomiting (NV) | 47 | 37.94 (20.17) | 8.51 (13.85) | − 29.43 | 46.5 | < 0.001*** |
| Pain (PA) | 47 | 7.09 (11.39) | 31.91 (23.27) | 24.82 | 32.0 | < 0.001*** |
| Dyspnoea (DY) | 47 | 7.80 (18.67) | 15.60 (23.93) | 7.8 | 63.5 | 0.056 |
| Insomnia (SL) | 47 | 12.06 (17.62) | 39.01 (27.20) | 26.95 | 22.0 | < 0.001*** |
| Appetite loss (AP) | 47 | 7.09 (13.79) | 17.02 (22.92) | 9.93 | 57.0 | 0.016* |
| Constipation (CO) | 47 | 29.08 (22.65) | 21.99 (26.26) | − 7.09 | 155.5 | 0.150 |
| Diarrhoea (DI) | 47 | 30.50 (20.65) | 9.93 (19.55) | − 20.57 | 54.0 | < 0.001*** |
| Financial difficulties (FI) | 47 | 28.37 (19.63) | 22.70 (27.89) | − 5.67 | 200.5 | 0.311 |
| EORTC QLQ-BR45 | ||||||
| Body Image (BI) | 46 | 89.67 (14.93) | 66.85 (29.37) | − 22.83 | 28.5 | < 0.001*** |
| Future Perspective (FU) | 46 | 31.16 (25.73) | 44.93 (31.60) | 13.77 | 55.5 | 0.004** |
| Sexual Functioning (SX) | 46 | 27.17 (19.68) | 21.74 (21.33) | − 5.43 | 90.5 | 0.084 |
| Sexual Enjoyment (SE) | 23 | 46.38 (16.63) | 49.28 (24.35) | 2.9 | 19.0 | 0.662 |
| Systemic Therapy Side Effects (SYS) | 46 | 14.80 (9.90) | 30.02 (18.78) | 15.22 | 74.0 | < 0.001*** |
| Upset by Hair Loss (HU) | 12 | 50.00 (30.15) | 63.89 (26.43) | 13.89 | 0.0 | 0.062 |
| Arm Symptoms (ARM) | 46 | 7.97 (12.32) | 25.36 (20.91) | 17.39 | 13.5 | < 0.001*** |
| Breast Symptoms (BR) | 46 | 15.76 (16.12) | 24.82 (17.70) | 9.06 | 195.0 | 0.011* |
| Endocrine Therapy Symptoms (ET) | 3 | 42.22 (10.18) | 42.22 (16.44) | − 0.0 | 3.0 | 1.000 |
| Skin/Mucosis Symptoms (SM) | 46 | 4.23 (6.33) | 13.65 (12.27) | 9.42 | 51.0 | < 0.001*** |
| Endocrine Sexual Symptoms (ES) | 23 | 11.59 (12.75) | 28.62 (24.08) | 17.03 | 0.0 | < 0.001*** |
| Stress Symptom Scale | ||||||
| Physical Stress Symptoms (F) | 43 | 0.91 (0.49) | 1.23 (0.71) | 0.31 | 219.0 | 0.006** |
| Impaired Cognitive Functioning (K) | 43 | 0.92 (0.68) | 1.33 (0.92) | 0.41 | 250.5 | 0.020* |
| Psychological Stress Symptoms (P) | 43 | 0.61 (0.63) | 0.88 (0.85) | 0.27 | 277.5 | 0.075 |
| Emotional Stress Symptoms (E) | 43 | 0.74 (0.76) | 1.08 (0.92) | 0.34 | 185.5 | 0.034* |
| Stress symptoms sum (SSS) | 43 | 3.19 (2.16) | 4.51 (2.96) | 1.33 | 246.5 | 0.006** |
Analyses include participants with valid paired T1 and T2 scores for each scale. Positive ΔM indicates higher follow-up scores. Higher EORTC functioning scores indicate better functioning; higher symptom scores indicate greater burden. Wilcoxon signed-rank tests were used because of the small follow-up sample and reduced valid n for conditional scales. Endocrine Therapy Symptoms should be interpreted with particular caution because of the very small paired sample
*p < 0.05. **p < 0.01. ***p < 0.001
Baseline inter-scale correlations (Table 10) were broadly consistent with the expected scoring directions: functioning domains tended to correlate positively with other functioning domains and negatively with symptom domains, while symptom domains tended to correlate positively with one another. The pattern provides partial support for construct validity and scale distinctiveness.
Table 10.
Inter-scale correlations between the EORTC QLQ-C30 and EORTC QLQ-BR45 scales at baseline
| PF2 | RF2 | EF | CF | SF | FA | NV | PA | DY | SL | AP | CO | DI | FI | QL2 | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BI | 0.493*** | 0.285*** | 0.333*** | 0.428*** | 0.391*** | − 0.484*** | − 0.372*** | − 0.418*** | − 0.165 | − 0.354*** | − 0.234** | − 0.364*** | − 0.217** | − 0.371*** | 0.426*** |
| FU | 0.271** | 0.110 | 0.182* | 0.216* | 0.205* | − 0.277*** | − 0.509*** | − 0.237** | − 0.039 | − 0.193* | − 0.189* | − 0.429*** | − 0.419*** | − 0.306*** | 0.288*** |
| SX | 0.137 | 0.033 | 0.127 | 0.088 | 0.120 | − 0.207* | − 0.123 | − 0.061 | 0.010 | − 0.248** | − 0.072 | − 0.165 | − 0.116 | − 0.140 | 0.212* |
| SE | 0.163 | 0.153 | 0.112 | 0.080 | 0.015 | − 0.148 | − 0.141 | − 0.286** | − 0.141 | − 0.154 | − 0.138 | − 0.248* | − 0.244* | − 0.217* | 0.354** |
| SYS | − 0.501*** | − 0.319*** | − 0.292*** | − 0.286*** | − 0.333*** | 0.476*** | 0.238** | 0.371*** | 0.091 | 0.288*** | 0.243** | 0.228** | 0.179* | 0.570*** | − 0.495*** |
| HU | − 0.069 | 0.078 | − 0.151 | − 0.009 | − 0.230 | 0.159 | 0.182 | 0.202 | − 0.090 | 0.035 | 0.194 | − 0.053 | 0.023 | 0.036 | − 0.166 |
| ARM | − 0.395*** | − 0.284*** | − 0.448*** | − 0.349*** | − 0.364*** | 0.453*** | 0.121 | 0.367*** | 0.191* | 0.484*** | 0.153 | 0.122 | 0.065 | 0.370*** | − 0.406*** |
| BR | − 0.305*** | − 0.237** | − 0.259** | − 0.370*** | − 0.273** | 0.249** | 0.168* | 0.275*** | 0.211* | 0.362*** | 0.185* | 0.097 | 0.041 | 0.289*** | − 0.238** |
| ET | − 0.819** | − 0.333 | − 0.843*** | − 0.343 | − 0.197 | 0.684* | 0.199 | 0.347 | − 0.299 | − 0.062 | 0.122 | 0.178 | 0.479 | 0.829*** | − 0.510 |
| SM | − 0.367*** | − 0.228** | − 0.312*** | − 0.392*** | − 0.286*** | 0.422*** | 0.114 | 0.385*** | 0.127 | 0.302*** | 0.120 | 0.255** | 0.169* | 0.388*** | − 0.458*** |
| ES | 0.041 | 0.010 | 0.015 | − 0.065 | 0.005 | − 0.012 | 0.145 | 0.166 | 0.040 | − 0.054 | 0.062 | 0.074 | 0.084 | 0.042 | − 0.029 |
*p < 0.05, **p < 0.01, ***p < 0.001
Correlations used pairwise deletion, so valid N varied across coefficients. Scale-specific valid N values are presented in Table 8 and should be considered for conditional QLQ-BR45 scales
Correlations with the Stress Symptom Scale (Table 11) were also generally in the hypothesised directions. Most QLQ-C30 functioning scales correlated negatively with stress symptoms, whereas symptom scales generally correlated positively. QLQ-BR45 functioning scales showed mainly negative and several symptom scales positive associations. Weaker or non-significant associations were observed for some treatment-related and conditional domains, which were less clinically salient before treatment or had smaller valid samples.
Table 11.
Correlations between the EORTC QLQ-C30, EORTC QLQ-BR45, and stress symptom scale scores at baseline
| QLQ-C30 | F | K | P | E | SSS |
|---|---|---|---|---|---|
| PF2 | − 0.525*** | − 0.377*** | − 0.252** | − 0.174* | − 0.386*** |
| RF2 | − 0.339*** | − 0.234** | − 0.131 | − 0.071 | − 0.226** |
| EF | − 0.261** | − 0.240** | − 0.113 | − 0.098 | − 0.218** |
| CF | − 0.358*** | − 0.246** | − 0.167* | − 0.168* | − 0.262** |
| SF | − 0.298*** | − 0.170* | − 0.105 | − 0.061 | − 0.178* |
| FA | 0.429*** | 0.352*** | 0.242** | 0.117 | 0.333*** |
| NV | 0.406*** | 0.498*** | 0.483*** | 0.483*** | 0.545*** |
| PA | 0.386*** | 0.262** | 0.160 | 0.246** | 0.299*** |
| DY | 0.132 | 0.102 | 0.022 | 0.055 | 0.077 |
| SL | 0.298*** | 0.159 | 0.061 | 0.021 | 0.160 |
| AP | 0.302*** | 0.388*** | 0.279*** | 0.234** | 0.352*** |
| CO | 0.406*** | 0.460*** | 0.395*** | 0.579*** | 0.521*** |
| DI | 0.388*** | 0.478*** | 0.572*** | 0.505*** | 0.565*** |
| FI | 0.482*** | 0.272** | 0.228** | 0.169* | 0.338*** |
| QL2 | − 0.519*** | − 0.419*** | − 0.269** | − 0.268** | − 0.433*** |
| QLQ-BR45 | F | K | P | E | SSS_sum |
|---|---|---|---|---|---|
| BI | − 0.447*** | − 0.437*** | − 0.393*** | − 0.322*** | − 0.469*** |
| FU | − 0.346*** | − 0.323*** | − 0.299*** | − 0.347*** | − 0.377*** |
| SX | − 0.076 | − 0.061 | − 0.066 | − 0.118 | − 0.114 |
| SE | − 0.416*** | − 0.283** | − 0.292** | − 0.342** | − 0.369*** |
| SYS | 0.707*** | 0.368*** | 0.212* | 0.249** | 0.438*** |
| HU | 0.093 | 0.093 | − 0.022 | − 0.047 | 0.061 |
| ARM | 0.417*** | 0.146 | 0.074 | 0.127 | 0.221** |
| BR | 0.226** | 0.118 | 0.144 | 0.114 | 0.162 |
| ET | 0.639* | 0.544 | 0.428 | 0.264 | 0.462 |
| SM | 0.534*** | 0.228** | 0.185* | 0.276** | 0.342*** |
| ES | 0.090 | 0.105 | − 0.109 | − 0.048 | 0.005 |
*p < 0.05, **p < 0.01, ***p < 0.001
Correlations used pairwise deletion, so valid N varied across coefficients. Scale-specific valid N values are presented in Table 8 and should be considered for conditional QLQ-BR45 scales
Discussion
This study provides the first cross-cultural adaptation and initial psychometric evaluation of the Latvian EORTC QLQ-C30 and QLQ-BR45 in women with breast cancer. Expert review and cognitive debriefing supported the linguistic, conceptual, and cultural appropriateness of the translations, while psychometric analyses provided preliminary support for several scales. The findings should be interpreted as initial validation evidence rather than confirmation of all measurement properties.
The expert review was deliberately framed as an assessment of translation equivalence and cultural appropriateness, not a re-evaluation of the established content validity of the original EORTC instruments. Translation-level refinements were most relevant for sensitive domains such as body image and sexuality, where wording can carry culturally specific meanings. Similar challenges have been reported in other QLQ-BR45 adaptations [20–22]. Importantly, no items were deleted and no constructs or scoring procedures were changed.
Reliability and multitrait scaling results were strongest for several QLQ-BR45 domains, particularly Body Image, Sexual Functioning, and Breast Symptoms. Some QLQ-C30 and QLQ-BR45 scales showed weaker internal consistency or scaling success. This may partly reflect short scales, smaller conditional subsamples, and clinical overlap among fatigue, pain, endocrine symptoms, skin/mucosal problems, arm symptoms, and functioning. Accordingly, individual reliability coefficients were interpreted together with item-scale correspondence and construct-validity evidence rather than as stand-alone proof of measurement quality [23, 24].
Construct-validity findings were broadly consistent with a priori expectations. Functioning and symptom scales generally correlated in theoretically plausible directions, and higher stress-related symptom burden was associated with poorer functioning and greater EORTC symptom burden. The Stress Symptom Scale is not cancer-specific and was therefore used only as a related external comparison measure, not as a criterion for cancer-specific HRQoL. Its use was justified by the limited availability of validated Latvian-language comparison measures and conceptual overlap in physical, cognitive, psychological, and emotional symptoms.
The six-month results showed clinically plausible deterioration in several functioning domains and increases in treatment-related symptoms, alongside relative stability in global health status and physical functioning. However, only 47 participants completed follow-up and several conditional scales had much smaller paired samples. These findings therefore indicate possible sensitivity to change but do not establish responsiveness. Additional longitudinal studies with better retention and adequate representation of treatment subgroups are required.
Several limitations remain. The study was conducted at a single specialised hospital using a convenience sample, and incomplete clinical/MDT information and small or unbalanced subgroups precluded robust known-groups comparisons. Attrition may have introduced selection bias, and conditional QLQ-BR45 scales reduced precision for reliability, correlations, and change analyses. The sample was also insufficient for confirmatory factor analysis or measurement invariance testing. Finally, the QLQ-BR45 was used because the final QLQ-BR42 was not available when the project began; future Latvian studies should evaluate transition to the updated module [6]. These limitations support the need for larger, multicentre studies examining internal structure, known-groups validity, measurement invariance, and responsiveness.
Conclusion
The Latvian EORTC QLQ-C30 and QLQ-BR45 were linguistically, conceptually, and culturally appropriate and showed acceptable preliminary psychometric performance in women with breast cancer. The findings provide initial support for cautious use in Latvian oncology research and clinical practice to assess HRQoL and breast cancer-specific symptoms. Larger multicentre and longitudinal studies are needed to evaluate additional measurement properties, particularly known-groups validity, internal structure, responsiveness, and transition to the EORTC QLQ-BR42.
Acknowledgements
We would like to thank all study participants.
Author contributions
All authors contributed to the conception and design of the study. Patient recruitment, data collection, and analysis were performed by Laura Rotberga, Jelena Maksimenko, Viktorija Pacukevica-Stope, Ingrida Trups Kalne. The first draught of the manuscript was written by Ingrida Trups Kalne, Lauma Springe, Elita Poplavska, Laura Nesaule, and Lubova Tihomirova and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Funding
This work was supported by the grant “Patient reported outcome measures in breast cancer patients: a pilot study” (RSU-PAG-2024/1–0016) within the project “Internal consolidation of RSU and external consolidation of RSU with LSPA” (No. 5.2.1.1.i.0/2/24/I/CFLA/005), financed by the European Union Recovery and Resilience Facility and the Latvian state budget.
Data availability
The data set generated and analysed during the current study is stored in a publicly accessible data repository (DOI: https://doi.org/10.48510/FK2/BJWIRG). The de‑identified data are available from the corresponding author on reasonable request.
Declarations
Competing interests
Ingrida Trups-Kalne, Laura Nesaule, Lauma Springe, Vita Steina, Jelena Maksimenko, Elita Poplavska, Laura Rotberga, and Viktorija Pacukevica-Stope declare no relevant financial or non-financial interests. Arvids Irmejs has received speaker honoraria from MSD and Novartis during the last two years. Lubova Tihomirova is employed by MSD.
Ethics approval
This study was approved by the Research Ethics Committee of Rīga Stradiņš University (No. 2-PĒK-4/479/2024). All participants received oral and written study information and provided informed consent before enrolment. Participants could withdraw at any time.
Consent to participate
Informed consent was obtained from all individual participants included in the study.
Patient, public or community engagement
People with lived experience were involved in the translation evaluation through cognitive debriefing, and the breast cancer patient association “Pārdzīvot” supported recruitment for this phase. Patients were not involved as coinvestigators in the study design, statistical analysis, or dissemination planning.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.International Agency for Research on Cancer (2024). Cancer Today [Data visualization interface]. https://gco.iarc.who.int/today/en/dataviz/pie?mode=cancer&types=0&sexes=2&populations=428
- 2.Tang, W. Z., Lu, Y. Q., Zhu, S. R., Teng, Y. J., Wei, T. F., Chen, G. L., & Jia, K. (2024). Quality of life and its predictors among breast cancer patients treated with surgery—a retrospective minimum 3-year follow-up study. Frontiers in Oncology. 10.3389/fonc.2024.1466625 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Holt-Kedde, I. L., Sadok, N., Krabbe-Timmerman, I. S., de Bock, G. H., Sidorenkov, G., & Werker, P. M. N. (2025). Quality of life after alloplastic versus autologous breast reconstruction: The influence of patient characteristics on outcomes. Breast Care, 20(2), 95–110. 10.1159/000543677 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.European Organisation for Research and Treatment of Cancer (n.d.). Questionnaires. https://qol.eortc.org/questionnaires/
- 5.Bjelic-Radisic, V., Cardoso, F., Cameron, D., Brain, E., Kuljanic, K., da Costa, R. A., Conroy, T., Inwald, E. C., Serpentini, S., Pinto, M., Weis, J., Morag, O., Lindviksmoen Astrup, G., Tomaszweksi, K. A., Pogoda, K., Sinai, P., Sprangers, M., Aaronson, N., Velikova, G., Greimel, E., Arraras, J., Bottomley, A., Bleiker, E., Bliem, B., Chie, W., Creutzberg, C., Deville, V., Duhoux, F., Eilf, K., Hartup, S., Koller, M., Nagele, E., Nicolatou-Galitis, O., Oberguggenberger, A., Schmalz, C., & Winters, Z. (2020). An international update of the EORTC questionnaire for assessing quality of life in breast cancer patients: EORTC QLQ-BR45. Annals of Oncology, 31(2), 283–288. 10.1016/j.annonc.2019.10.027 [DOI] [PubMed] [Google Scholar]
- 6.Bjelic-Radisic, V., Cardoso, F., Weis, J., Pogoda, K., Arraras, J. I., Greimel, E., Bottomley, A., Cameron, D., Brain, E., Hartup, S., da Costa Vieira, R. A., Hoefnagels, N., Huang, C. C., Shamieh, O., Pinto, M., Belay, Y. B., Serpentini, S., Bleiker, E., Nookala Krishnamurthy, M., Shimomura, A., Sturm-Inwald, E. C., Getu, M. A., Bliem, B., Astrup, G., Morag, O., Kikawa, Y., Kuljanic, K., Nevries, N., Sprangers, M., Aaronson, N. K., Sinai, P., Tomaszewski, K., Galalae, R., Conroy, T., Duhoux, F., Chie, W., & Velikova, G. (2025). An international Phase IV field study - psychometric properties of the updated module on assessing quality of life of patients with breast cancer EORTC QLQ-BR42. The Breast, 80, 103890. 10.1016/j.breast.2025.103890 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.EORTC Quality of Life Group (n.d.–a). EORTC translation procedure. https://qol.eortc.org/manuals/
- 8.Kuliś, D., Bottomley, A., Velikova, G., Greimel, E., & Koller, M. (2017). EORTC Quality of Life Group translation procedure (4 ed.). European Organisation for Research and Treatment of Cancer.
- 9.EORTC Quality of Life Group (n.d.–b). EORTC QLQ–BR45 scoring manual. https://qol.eortc.org/questionnaires/
- 10.Johnson, C., Aaronson, N., Blazeby, J. M., Bottomley, A., Fayers, P., Koller, M., Kuliś, D., Ramage, J., Sprangers, M., Velikova, G., & Young, T. (2011). EORTC Quality of Life Group guidelines for developing questionnaire modules (4 ed.). European Organisation for Research and Treatment of Cancer.
- 11.Fayers, P. M., Aaronson, N. K., Bjordal, K., Groenvold, M., Curran, D., & Bottomley, A. (2001). The EORTC QLQ-C30 scoring manual (3 ed.). European Organisation for Research and Treatment of Cancer.
- 12.Aaronson, N. K., Ahmedzai, S., Bergman, B., Bullinger, M., Cull, A., Duez, N. J., Filiberti, A., Flechtner, H., Fleishman, S. B., Haes, J. C. J. M., Kaasa, S., Klee, M., Osoba, D., Razavi, D., Rofe, P. B., Schraub, S., Sneeuw, K., Sullivan, M., & Takeda, F. (1993). The European Organization for research and treatment of cancer QLQ-C30: A quality-of-life instrument for use in international clinical trials in oncology. JNCI: Journal of the National Cancer Institute, 85(5), 365–376. 10.1093/jnci/85.5.365 [DOI] [PubMed] [Google Scholar]
- 13.EORTC Quality of Life Group [QLG] (n.d.). EORTC Quality of Life. https://qol.eortc.org/
- 14.Dudkina, A., & Perepjolkina, V. (2021). Development and initial validation of the Stress Symptoms Scale. SOCIETY INTEGRATION EDUCATION Proceedings of the International Scientific Conference, 7, 67–85. 10.17770/sie2021vol7.6426 [DOI] [Google Scholar]
- 15.Cronbach, L. J. (1951). Coefficient alpha and the internal structure of tests. Psychometrika, 16(3), 297–334. 10.1007/BF02310555 [DOI] [Google Scholar]
- 16.Dunn, T. J., Baguley, T., & Brunsden, V. (2014). From alpha to omega: A practical solution to the pervasive problem of internal consistency estimation. British Journal of Psychology, 105(3), 399–412. 10.1111/bjop.12046 [DOI] [PubMed] [Google Scholar]
- 17.McDonald, R. P. (1999). Test theory: A unified treatment. Lawrence Erlbaum Associates.
- 18.Lynn, M. R. (1986). Determination and quantification of content validity. Nursing Research, 35(6). [PubMed]
- 19.Polit, D. F., & Beck, C. T. (2006). The content validity index: Are you sure you know what’s being reported? Critique and recommendations. Research in Nursing & Health, 29(5), 489–497. 10.1002/nur.20147 [DOI] [PubMed] [Google Scholar]
- 20.Ehab, B. H., Hussein, R. R. S., Abdullah, E. A., Ahmed, Z. M., & Elsherbiny, R. M. (2022). Cultural adaptation and validation of the EORTC QLQ-BR45 to assess health-related quality of life of breast cancer patients. European Pharmaceutical Journal, 68(2), 41–48. 10.2478/afpuc-2021-0018 [DOI] [Google Scholar]
- 21.Getu, M. A., Wang, P., Kantelhardt, E. J., Seife, E., Chen, C., & Addissie, A. (2022). Translation and validation of the EORTC QLQ-BR45 among Ethiopian breast cancer patients. Scientific Reports, 12(1), 605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Kidayi, P. L., Pakpour, A. H., Saboonchi, F., Bray, F., Manhica, H., Mtuya, C. C., Serventi, F., Aune, R. E., Mahande, M. J., & Björling, G. (2023). Cross-Cultural Adaptation and Psychometric Properties of the Swahili Version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR45 among Breast Cancer Patients in Tanzania. Healthcare, 11, 2467. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Boateng, G. O., Neilands, T. B., Frongillo, E. A., Melgar-Quiñonez, H. R., & Young, S. L. (2018). Best practices for developing and validating scales for health, social, and behavioral research: A primer. Frontiers in Public Health, 6, 2018. 10.3389/fpubh.2018.00149 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Mokkink, L B., Elsman, E. B. M., & Terwee, C. B. (2024). COSMIN guideline for systematic reviews of patient-reported outcome measures version 2.0. Quality of Life Research, 33(11), 2929–2939. 10.1007/s11136-024-03761-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.OECD/European Observatory on Health Systems and Policies. (2019). Latvia: Country Health Profile 2019. 10.1787/4dd50c09-en [DOI]
- 26.Manrique-Hernandez, E. F., Goes, B., Hoyos Madera, E., Bermon, K., Hurtado-Ortiz, A., Licht-Ardila, A., M., & Nieves-Cuervo, G. M. (2024). Perspectives on quality of life in women with breast cancer. Indian Journal of Palliative Care, 30(4), 347–352. 10.25259/IJPC_37_2024 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Hasanah, U., Ahmad, M., Prihantono, P., Usman, A. N., Arsyad, A., & Agustin, D. I. (2024). The quality of life assessment of breast cancer patients. Breast Disease, 43(1), 173–185. 10.3233/BD-249008 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Vasanth, S., Lakshmana Kumar, V., Sopnajothi, S., Jeyaprakash, P., & Vijayabaskar, P. (2024). Carcinoma breast and quality of life: A prospective observational study. Global Journal for Research Analysis, 13(7), 1–2. 10.36106/gjra/7904909 [DOI] [Google Scholar]
- 29.Tadesse, D., Tadesse, F., Taye, G., Van Roey, T., Fayers, P., & Bjordal, K. (2022). Translation and validation of the EORTC QLQ–BR45 among Ethiopian breast cancer patients. Scientific Reports, 12, 12786. 10.1038/s41598-022-17088-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Abma, I. L., Rovers, M., & van der Wees, P. J. (2016). Appraising convergent validity of patient-reported outcome measures in systematic reviews: constructing hypotheses and interpreting outcomes. BMC Research Notes, 9(1), 226. 10.1186/s13104-016-2034-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Ashing-Giwa, K. T., & Lim, J. W. (2011). Examining emotional outcomes among a multiethnic cohort of breast cancer survivors. Oncology Nursing Forum, 38(3), 279–288. 10.1188/11.ONF.279-288 [DOI] [PubMed] [Google Scholar]
- 32.Calderon, C., Ferrando, P. J., Lorenzo-Seva, U., Ferreira, E., Lee, E. M., Oporto-Alonso, M., Obispo-Portero, B. M., Mihic-Góngora, L., Rodríguez-González, A., & Jiménez-Fonseca, P. (2022). Psychometric properties of the Spanish version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Quality of Life Research, 31(6), 1859–1869. 10.1007/s11136-021-03068-w [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Ministru Kabinets (2025). Par Veselības aprūpes pakalpojumu onkoloģijas jomā uzlabošanas plānu 2025.–2027. gadam. Ministru kabineta rīkojums Nr. 692. Latvijas Vēstnesis.
- 34.Neve, O. M., van Benthem, P. P. G., Stiggelbout, A. M., & Hensen, E. F. (2021). Response rate of patient reported outcomes: the delivery method matters. BMC Medical Research Methodology, 21(1), 220. 10.1186/s12874-021-01419-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data set generated and analysed during the current study is stored in a publicly accessible data repository (DOI: https://doi.org/10.48510/FK2/BJWIRG). The de‑identified data are available from the corresponding author on reasonable request.