Data-collection procedure
All women with a diagnosis of breast cancer, who underwent curative treatment at the Erasmus MC Cancer Institute in the Netherlands between November 1st, 2015, and January 1st, 2022 and who completed EQ-5D-5L and EORTC QLQ-C30 questionnaires pre-operatively (T0, baseline), 6 months post-surgery (T6) and 1-year post-surgery (T12) in the “patient data platform”, Erasmus MC’s online PROM collection tool, were included[34]. Patients who underwent proton therapy or palliative treatment, patients with recurrent breast cancer and patients with unavailable treatment data were excluded. The Institutional Review Board was consulted and concluded that informed consent was not needed since the value-based healthcare strategy is considered standard of care in Erasmus MC [34].
Health status/ QoL assessment
Health status/ QoL was evaluated with the EQ-5D-5L (5 level version) and the EORTC QLQ-C30 at T0, T6 and T12. The EQ-5D-5L consists of two items: a descriptive system and the EQ visual analogue scale (EQ VAS). Each dimension of the descriptive system (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) has five levels, ranging from no problems to extreme problems. When the scores of the five dimensions are combined, they create a 5-digit number that describes the patient's overall health state. A utility index can be calculated for each health state using country specific algorithms. The EQ-5D-5L index values typically range from 0 to 1, with 0 representing death and 1 representing perfect health. The EQ VAS is used to rate the patient's overall health on a scale of 0-100, with 0 being the best imaginable health and 100 being the worst imaginable health. Scores below 0 can occur, indicating that the person feels worse than being dead[14,16].
The EORTC QLQ-C30 consists of five functional scales (physical, role, cognitive, emotional, and social); nine cancer symptom scales (fatigue, pain, nausea and vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties); and a global health/ QoL scale[15]. The results of each domain from EORTC QLQ-C30 can be linearly transformed to a numeric score (range 0-100) by using manual scoring tables. For functional/ global QoL scales, higher scores indicate better functioning; for symptom scales, higher scores indicate greater symptom severity[15,35]. The EORTC QLQ-C30 summary score is calculated from the mean of 13 domains from the EORTC QLQ-C30, excluding the Global Quality of Life scale and the Financial Impact scale. Before determining the mean, symptom scales are reversed to ensure a consistent direction for all scales. Therefore, a higher summary score indicates higher HRQoL[36,37].
Data-analysis
Patient, tumor, and treatment characteristics of the breast cancer patients were described in Table 1. Descriptive statistics were used to describe EQ-5D-5L and EORTC QLQ-C30 scores on T0, T6 and T12. If normally distributed, the parametric paired t-test was used to compare the scores between T0 and T6 and between T0 and T12. If not normally distributed, the non-parametric paired Mann-Whitney U test was used.
Table 1
Baseline characteristics of study population
Characteristics | Patients (n = 333) | |
Age | | |
Mean (SD) | 54.0 (13.9) | |
Median [Min, Max] | 53.9 [26.1, 86.2] | |
BMI category |
< 25 | 161 (48.3%) | |
25–30 | 122 (36.6%) | |
> 30 | 50 (15.0%) | |
Type of breast surgery |
Mastectomy | 91 (27.3%) | |
BCS | 187 (56.2%) | |
Mastectomy + reconstruction | 55 (16.5%) | |
Receptor status |
Triple negative | 47 (14.1%) | |
HER2 positive | 38 (11.4%) | |
HR positive & HER2 negative | 225 (67.6%) | |
Unknown | 23 (6.9%) | |
T-stage | | |
pT0 | 29 (8.7%) | |
pT1 | 187 (56.2%) | |
pT2 | 69 (20.7%) | |
pT3 | 9 (2.7%) | |
pT4 | 0 (0%) | |
pTis | 33 (9.9%) | |
pTmi | 6 (1.8%) | |
N-stage | | |
pN0 | 249 (74.8%) | |
pN1 | 66 (19.8%) | |
pN2 | 14 (4.2%) | |
pN3 | 4 (1.2%) | |
Hormonal therapy |
No | 149 (44.7%) | |
Yes | 184 (55.3%) | |
Chemoimmunotherapy |
No | 196 (58.9%) | |
Yes | 137 (41.1%) | |
Axillary treatment | | |
SLNB / RISAS | 231 (69.4%) | |
ALND | 35 (10.5%) | |
SLNB / RISAS + Rtx | 27 (8.1%) | |
ALND + Rtx | 40 (12.0%) | |
*BCS; breast conserving surgery, HR; hormone receptor, RISAS; radioactive iodine seed localization in the axilla with sentinel node procedure, Rtx; radiotherapy, SLNB; sentinel |
lymph node biopsy. |
Mean and median differences of the EQ-5D-5L and EORTC QLQ-C30 between T0 and T6 (delta 1) and between T0 and T12 (delta 2) were calculated. Mean deltas of the EQ-5D-5L index and EORTC QLQ-C30 Global Quality of Life scale were compared to the minimal important clinical difference (MICD) of the EQ-5D-5L index (0.08) and the EORTC QLQ-C30 (5) to determine clinical significance[38,39]. For the EQ-5D-5L and functional domains of the EORTC QLQ-C30, negative deltas indicate a decline in health status/ QoL over time, while positive deltas indicate an increase in health status/ QoL. In contrast, for the symptom domains of the EORTC QLQ-C30, negative deltas indicate an improvement in QoL over time, while positive deltas indicate a decline in QoL.
To evaluate and compare the internal responsiveness of the two PROMs, effect sizes (ES) and standardized response means (SRM) were calculated. ES was defined as the mean delta (e.g., change in score from T0 to T6/T12), divided by the standard deviation of the T0 score. SRM was calculated as the mean delta, divided by the standard deviation of the delta[22,40]. Both the ES and SRM were classified as large (≥ 0.8), moderate (0.5–0.79), or small (< 0.5) based on previously established criteria[41–43]. ES and SRM are standardized indicators of change in health status/ QoL over time, regardless of the sample size[22,44].
To gain more insights into the internal responsiveness of the EQ-5D-5L and EORTC QLQ-C30 in different patient groups, a subgroup analysis was performed on patients receiving chemotherapy. This is because patients receiving chemotherapy usually have more advanced breast cancer compared to patients without chemotherapy[45]. The internal responsiveness of the EQ-5D-5L and EORTC QLQ-C30 might be larger for patients receiving chemotherapy (neoadjuvant, adjuvant or both), since chemotherapy has a significant effect on QoL[46]. For all statistical analyses, a two-sided p-value of 5% was considered significant. Statistical analyses were done using R statistical software version 4.2.2.[47].