Between 2011 and 2015 90 patients were randomized at 15 centers, 45 patients into each arm. 79 (88%) patients completed QoL assessment at least at baseline. 34 (76%) patients in the surgery arm and 41 (91%) in the no-surgery arm were included in the QoL analyses.(Table 1) A total of 289 QoL questionnaires were analysed 79 (88%) at baseline and 60 (76%), 54 (73%), 38 (56%), 32 (52%), at 6, 12, 18 and 24 months, respectively. QoL analysis covered the results of the five assessment time points (baseline and 6,12,18 and 24 months´ follow-up).
Except for tumour size, demographic and clinical characteristics in patients for whom QoL data were available and in those for whom they were not were similar (Table 2). Median age was 62.8 years and similar in both groups (61.7 vs 63.9).
Survival data have been reported previously[13]. Surgery did not provide an OS benefit (34.6 months vs 54.8 months, p=0.267; HR 0.691; 95% CI 0.358–1.333 ) or TTPd and TTPl ( HR 0.598, p=0.0668; HR 0.933, p=0.882)[13]. (Figure 2a and 2b)
QoL assessment as predictor for OS and TTPd
In the univariate and multivariate analyses the Global health status/QoL and physical functioning scales were predictors for overall OS. Patients with a higher score of global health status/QoL and higher score of physical functioning lived longer (HR 0.984; p=0.0250, HR 0.984; p=0.0225; HR 0.988 p=0.0355, HR0.988; p=0.0355)(Figure 3a; Figure 3b , Table 3). Although not statistically significant, patients with a higher score on the scale future perspective showed a tendency to longer OS in the univariate analyses (HR 0.987; p=0.0510). In the univariate analyses scales Global health status/QoL and social functioning scale were a predictor for a longer TTPd (HR 0.985, p=0.0244; HR 0.989, p=0.0140)( Table 4).
In the univariate and multivariate analyses, the scale future perspective was a predictor for longer TTPd (HR 0.988, p=0.020; HR 0.982, p=0.0123)(Table 4). In the multivariate analyses scale breast symptoms was a predictor for TTPd (HR 0.933, p=0.0438)( Table 4).
QoL assessment by therapy arm
Details of the systemic and local therapy in the surgical and no surgical arm are listed in the Table 2. There were no statistically significant differences in any of the scales of the QLQ-C30 and QLQ-BR23 questionnaires between the two groups over the time. (Table 5) Figure 4 presented QoL scale with statistically significant change (improvement or worsening) over the time in both groups .
QLQ C30
Global Health Status/QoL
At baseline, clinically relevant (>10 points differences) differences favouring the no-surgery arm were found in the Global Health Status/QoL scale (mean, 47.8 vs 61.6) (Table 5).These preferences disappeared at the first follow-up (6 months) and were not seen at further time points. Over time (up to 24 months follow up) patients in both arms had a clinically relevant and statistically significant improvement on the scale global health status (p=0.003). (Figure 4a)
Functional scales of the QLQ-C30
There were no statistically significant differences in any of the five functional scales of the QLQ-C30 [physical, role, emotional, cognitive and social functioning] at baseline, as well as over time. Patients reported significant improvement on the scale emotional functioning in both arms over time. (Figure 4b) In the surgical arm this improvement was clinically relevant. Cognitive functioning decreased over time in both groups, clinically relevant and statistically significant in the primary surgery arm and statistically significant without clinical relevance in the non-surgery arm. (Figure 4c)
Symptom scales/Items of the EORTC QLQ-C30
The mean scores of symptoms scales/items at baseline and during follow-up remained on the lower part of the 0-100 scale. Statistically significant worsening was found on the scale dyspnoea (p=0.025), but this difference was without clinical relevance in both arms (Figure 4d).
Over time patients reported more financial problems in both arms. (Figure 4e)
Functional scales of the QLQ-BR23
In both arms statistically significant and clinically relevant improvement was seen over time on the scale future perspective (p=0.009).(Figure 4f) In contrast, patients in both arms reported worsening symptoms on the body image scale, clinically relevant in the surgery arm (p=0.017, Figure 4g). At baseline women in the non-surgery arm reported a statistically significant and clinically relevant better mean score in the functional scale future perspective (mean 45.0 vs 21.4). In the following visits there were no differences in any of the functional scales between two arms ( Table 5).
QLQ-BR23 symptoms scales
In both arms, statistically significant and clinically relevant improvement was seen over time on the breast symptoms scale (p=0.006, Figure 4h). Symptom worsening was found on the scales symptoms of the systemic therapy and hair loss, but these differences were without clinical relevance in both arms. (p<0.001, Figure 4i, Figure 4j)
QoL assessment by age
The median age of our study population was 64 y (range 23y-85y). 64.5% of women were older than 60 years and only 14% were premenopausal. We compared women <60 and ≥60 years to assess a possible impact of age on QoL. There were no differences in the functional or symptomatic scales of the QLQ-C30 and QLQ –BR 23 between the two groups of women except in physical functioning scale (EORTC –QLQC30) and sexual functioning scale (EORTC BR 23). As expected, younger women had a statistically significant and clinical relevant better mean score of the physical functioning scale (p=0.039) and sexual functioning score (p=0.024) (Table 6).
QoL assessement by type of systemic therapy (chemotherapy vs. other, with or without surgery)
Overall, 79 women completed baseline QoL assessment and received chemotherapy (CTX) (N=25) or endocrine therapy (N= 54) as first-line systemic therapy. Women who received CTX reported baseline clinically better mean score on the scale physical functioning of the EORTC QLQC30 (Table 8).Over time those patients had statistically significant more diarrhoea (p=0.0014) (Table 7).
Qol by site of metastases
29 women with bone metastases only and 46 women with visceral ±bone metastases completed QoL assessments at baseline. Interestingly, women with bone metastases only reported worse physical functioning (59.8 vs 77.9; p=0.0079) and role functioning (55.9 vs 74.8; p=0.0412) on the functional scales of the QLQ-C30, as well as more pain (mean 52.0 vs 24.6; p=0.0066) compared to women with visceral ± bone metastases. All differences were statistically significant and clinical relevant. Differences at baseline were not visible anymore until the last visit at 24 months (Table 8).