Quality of life in elderly patients with localized breast cancer treated with radiotherapy. A prospective study

Quality of life in elderly patients with localized breast cancer treated with radiotherapy. A prospective study

The Breast 26 (2016) 46e53 Contents lists available at ScienceDirect The Breast journal homepage: www.elsevier.com/brst Original article Quality o...

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The Breast 26 (2016) 46e53

Contents lists available at ScienceDirect

The Breast journal homepage: www.elsevier.com/brst

Original article

Quality of life in elderly patients with localized breast cancer treated with radiotherapy. A prospective study Juan Ignacio Arraras a, b, *, Ana Manterola a, Gemma Asin a, Jose Juan Illarramendi b, ~ ez c, Josu Delfrade d, Esteban Salgado b, Uxue Zarandona a, b, Susana de la Cruz b, Berta Iban c b Koldo Cambra , Ruth Vera , Miguel Angel Dominguez a a

Complejo Hospitalario de Navarra, Radiotherapeutic Oncology Department, Irunlarrea 3, 31008 Pamplona, Spain Complejo Hospitalario de Navarra, Medical Oncology Department, Irunlarrea 3, 31008 Pamplona, Spain n Miguel Servet-NavarraBiomed, Red de Investigacio n en Servicios Sanitarios en Enfermedades Cro nicas (REDISSEC), Irunlarrea 3, 31008 Fundacio Pamplona, Spain d Instituto Salud Pública, CIBER Salud Pública, Leyre 3, 31003 Pamplona, Spain b c

a r t i c l e i n f o

a b s t r a c t

Article history: Received 3 August 2015 Received in revised form 12 December 2015 Accepted 17 December 2015 Available online xxx

Purpose: There is a debate on the role of adjuvant Radiotherapy (RT) in elderly breast cancer patients. The aim is to study Quality of Life (QL) throughout the treatment and follow-up periods in early stages breast cancer patients who have started radiotherapy, and to compare the QL of axillary surgery groups. Methods: 173 patients, 65 years completed the EORTC QLQ-C30 and QLQ-BR23, and the Interview for Deterioration in Daily Living Activities in Dementia(IDDD) questionnaires three times throughout treatment and follow-up periods. Linear mixed effect models were used to evaluate longitudinal changes in QL, and whether these changes differed among axillary surgery groups. Results: QL scores were high (>70/100 points) in most QL areas, with moderate limitations (>30) in sexual functioning and enjoyment, future perspective and global QL. In six areas there was a decline at the RT sessions end, that after 6 weeks was recovered. For three areas, there was an improvement in the follow-up measurement compared to the previous assessments. Changes in seven areas were <5 points. Axillary node dissection patients had a body image decrease (6 points) in the follow up period. The lymphadenectomy group had more fatigue (10 points, p ¼ 0.078) than the other two axillary surgery groups. Conclusions: Results orientate towards good patients' adaptation to their disease and treatments, and to administering RT in early stages breast cancer patients. QL differences between the axillary surgery groups and in their evolutions were few but have appeared in key QL areas. © 2015 Elsevier Ltd. All rights reserved.

Keywords: Quality of life Breast cancer Elderly Radiotherapy EORTC

Introduction Elderly patients constitute the largest group in oncologic medical practice [1]. Breast cancer is most prevalent in elderly patients [2,3], as the risk of breast cancer increases significantly with age [4,5]. Its management is becoming more important [3]. The number

Abbreviations: RT, radiotherapy; QL, quality of life; ALND, axillary node dissection; SLNB, sentinel node surgery. * Corresponding author. Complejo Hospitalario de Navarra, Oncology Departments, Irunlarrea 3, 31008 Pamplona, Spain. Tel.: þ34 848422751; fax: þ34 848422730. E-mail address: [email protected] (J.I. Arraras). http://dx.doi.org/10.1016/j.breast.2015.12.008 0960-9776/© 2015 Elsevier Ltd. All rights reserved.

of older women with breast cancer who may be eligible for adjuvant irradiation is rising [6]. There is considerable controversy about what constitutes appropriate care for older breast cancer patients. This controversy is reflected in the persistence of age-dependent variations in care, with older women being less likely to receive standard therapies such as adjuvant Radiotherapy (RT) [6e8]. Physicians' and patients' assumptions might be misleading, including that elderly patients are unable to withstand treatments. Ballinger et al. [5] consider that older patients are a heterogeneous group, and that other variables, like functional and cognitive abilities, may be a more useful indicator for suitable treatments than age. Browall et al. [9] consider that age should not be used in isolation in decisions about adjuvant

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treatment in elderly breast cancer patients. Age based differences have been found in some Quality of Life(QL) dimensions in breast cancer patients [10,11], not necessarily indicating elderly people have more limitations than younger ones. Elderly patients(>70) are usually excluded from clinical trials [5,7]. More clinical research is considered necessary in elderly breast cancer patients [8,12e14]. QL is considered a key aim in elderly patients [8]. QL assessment has an important role in elderly breast cancer patients, as it can be helpful in aspects like determining the optimal adjuvant regimens for this patient population or offering better supportive care [2,5,15,16]. There has been a debate in the last years about the possible negative role of adjuvant RT in elderly breast cancer patients' QL [7]. Several studies have shown that omission of RT might not increase elderly breast cancer patients' QL [5]. More studies on QL in adjuvant RT are needed to provide a more robust basis for RT practice [2,6]. QL studies on surgery in elderly breast cancer patients are considered useful: more evidence-based surgical options in elderly cancer patients might lead to an increase in their overall cancer survival and QL [17,18]. Axillary node dissection (ALND) was initially compared with no surgery in the axille in elderly patients, and was associated with limitations in QL and no clear clinical benefits [19,20]. Sentinel node surgery (SLNB) is agreed to be an important advance in breast cancer in general, which may cause fewer long-term adverse outcomes than ALND: lower arm morbidity and better QL [21,22]. More research in QL after different axillary procedures is advised [23], especially in elderly patients, as they are not frequently included in these studies. Comprehensive Geriatric Assessment is an interdisciplinary evaluation of the heterogeneity of elderly patients. It includes measurements that are related to QL. Its use with cancer patients is recommended [5,24e26]. A preliminary study was carried out by our group in a small part of the present sample, which we aim to confirm [27]. The aims of the present study were to assess QL in a sample of elderly early stages breast cancer patients treated with adjuvant RT; to evaluate their QL changes throughout the treatment period, and the differences between axillary surgery groups. We expected QL scores to be high, with small limitations in emotional and physical areas and with small changes during the treatment period, that improved in the follow-up. We expected differences in the axillary surgery groups to appear in a few emotional and physical areas.

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Treatment Patients initiated radiotherapy with or without endocrine therapy. They may have previously undergone surgery for breast cancer (breast conserving surgery or mastectomy). Radiotherapy was given with conventional fractionation organized into three main groups: (1) breast/chest wall local irradiation; (2) breast/chest wall and supraclavicular and axillary level III nodal area irradiation if axillary node affection; (3) regional exclusive in selected relapses. Patients treated with endocrine therapy had, as a general rule, already started this treatment before beginning radiotherapy. Patients could have received surgery in the breast, radical or conservative, combined or not with a mode of surgery in the axille (SLNB, ALND). Measures All patients completed the EORTC questionnaires QLQ-C30 version 3.0 [29] and QLQ-BR23 [30], which had been translated into Spanish following the EORTC Quality of Life Group translation procedure [31] and that our group have validated for use in our country [32,33]. The structure of these questionnaires is shown in Table 1. QLQ-C30 evaluates areas common to different tumour sites and treatments, whereas QLQ-BR23 evaluates the areas associated with breast cancer and its treatments. Questionnaires with less than 70% of the items answered were excluded. A scale of daily activities (DA), the Interview for Deterioration in Daily Living Activities in Dementia (IDDD) [34] and a physician's assessment of limiting comorbidity were added to approximate the QL evaluation to Comprehensive geriatric assessment. The IDDD scale evaluates patients' views on their personal care and complex DA. Values from 33 to 36 are considered normal. The treating physician assessed toxicity levels through selected items from the National Cancer Institute (NCI) Common Toxicity Criteria version 4.0 scale [35], and performance status using the Karnofsky scale [36]. Data collection procedures Those patients who provided informed consent were invited to complete the QL and DA questionnaires at three points during the treatment and follow-up periods: the first and final day of radiotherapy, and the follow-up consultation, 6 weeks after finalizing treatment. This study followed the recommendations of the Declaration of Helsinki, and was approved by the Ethics Committee of the Complejo Hospitalario of Navarra. Statistical analysis

Materials and methods Participants A consecutive sample of breast cancer patients who initiated treatment in the Radiotherapeutic Oncology Department of the Complejo Hospitalario of Navarra (Spain) between December 2004 and December 2011 were invited to participate in the study. Inclusion criteria were breast cancer in stages IeIII, 65 years of age or older, and starting radiotherapy. Two main groups of patients were selected: newly diagnosed, and those with exclusively local or regional relapses, with a negative extension search and without having undergone radiotherapy previously in the area. For the latter, data regarding the treatment for the relapse were recorded. The criteria for exclusion were treatment that included chemotherapy, cognitive state that did not permit treatment evaluation, or a life expectancy of less than 3 months.

Descriptive statistics such as means with standard deviations and frequencies with percentages were used to summarize the sample characteristics. Statistical tests such as Anova, Kruskalwallis, X2 test and Fisher test (depending on the nature of the variable) were used to carry out to compare the characteristics of the axillary surgery groups (SLNB, ALND or without surgery) in patients with conservative surgery. Linear mixed effect models were used to evaluate longitudinal changes in QL for the global sample, including time as fixed effect and individual as random effect to account for the intra-correlation structure of the data. When significant, age was also included as an adjusting variable. To evaluate if longitudinal changes in QL differed among groups of axillary surgery in patients with conservative surgery, the same methodology was used, adding to the time effect the fixed effect of type of axillary surgery, and an interaction term between them. When the interaction term was significant, it was

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Table 1 Content of the general questionnaire and the breast cancer module. General EORTC questionnaire QLQ-C30 Functional scalesa Symptom scales and/or itemsb

Scales of physical, role, cognitive, emotional, social, global quality of life. Scales of fatigue, nausea and vomiting, pain. Individual items on dyspnoea, sleep disturbance, appetite loss, constipation, diarrhoea, financial impact.

EORTC module QLQ-BR23 Functioning scales and/or itemsa Symptoms scales and/or itemsb a b

Scales of body image, sexual functioning. Individual items on sexual enjoyment, future perspective. Scales of arm symptoms, breast symptoms, systemic therapy side effects. Individual item on upset by hair loss.

The scores range from 0 to 100, where a higher score represents a higher functional level. The scores range from 0 to 100, where a higher score represents a greater degree of symptoms.

maintained, otherwise, it was removed and p-values for group and time for the additive model without interaction are given. Osoba et al. [37] and Cocks et al. [38] criteria were used to interpret clinically significant changes, and Cocks et al. [39] axillary surgery group differences.

Results 173 patients From 180 candidates were evaluated. The reasons for not filling in the questionnaires were administrative failure (5 cases) and patient refusal (2 cases). 173 patients filled in the second questionnaire and 168 the third. The reason for not completing the third questionnaire was administrative failure (changes in the days programmed for follow-up interviews). All questionnaires had more than 70% of the items answered. The sociodemographic and clinical characteristics of the patients are presented in Table 2. Married patients and those with a level of education below primary level predominate in this sample.

Most patients received a first diagnosis of breast cancer. Conservative surgery, SLNB, local radiotherapy and hormotherapy predominated. One patient had regional RT. Neither rest nor reduction of radiotherapy dosages was necessary. Most patients had limiting comorbidities: arterial hypertension (63 patients; 36.4%), arthrosis (59; 34.1%), heart failure (15; 8.7%), chronic obstructive pulmonary disorder (10; 5.8%) and hip fracture (4; 2.3%). Performance status mean values in the three measurements corresponded to high levels. Mean scores in the DA scale were located within the normal range, with the highest values corresponding to a patient with a hip fracture. Five patients showed in the second measurement toxicity grade 3 in skin, one in dyspnoea, and another in fatigue, and one patient in the third measurement in dyspnoea. In the group of patients with conservative therapy (n ¼ 148), no differences in demographic and clinical characteristics were found among groups of patients classified by axillary surgery, except in RT modality (higher proportion of locoregional in lymphadenectomy

Table 2 Descriptive statistics global sample and Axillary Surgery groups.

Age. Median (range) Level of studies. n(%)

Civil status. n(%) Breast surgery. n(%) Limiting comorbidity. N(%) Radiotherapy n(%) Endocrine therapy. N (%) Diagnostic group. N (%) Performance status. Mean (SD)

DA. mean (SD)

Toxicity level 3 (N) 2nd assessment

3rd assessment

Total

Axillary surgeryd

(n ¼ 173)

ALND (n ¼ 22)

SLNB (n ¼ 92)

No surgery (n ¼ 34)

Less than primary Primary Secondary or university Married Mastectomy Conservative Yes Local Locoregional Yes Newly diagnosed Local or regional relapses 1st assessment 2nd assessment 3rd assessment 1st assessment 2nd assessment 3rd assessment

73 (65e90) 73(42.2%) 66(38.2%) 15(8.7%) 91(52.6%) 24(13.9%) 148(85.0%) 122(70.5%) 133(76.9%) 38(22.0%) 144(83.2%) 160(92.5%) 8(4.6%) 92.5 (8.2) 90.1 (6.9) 92.9 (7.5) 33.9 (3.1) 34.1 (3.1) 33.6 (2.1)

76.0(65e80) 12(54.5%) 5(22.7%) 3(13.6%) 11(50.0%)

70(65e90) 31(36.7%) 41(44.1%) 10(10.9%) 53(53.6%)

70(65e87) 16(47.1%) 12(35.3%) 2(5.9%) 17(50.0%)

0.067c 0.222a

13(59.1%) 13(59.1%) 9(40.9%) 22(100%) 21(95.5%) 1(4.5%) 90.9(8.9) 87.7(8.1) 91.1(8.1) 34.2(3.9) 34.6(4.1) 34.0(2.3)

61(66.3%) 84(91.3%) 7(7.6%) 80(87%) 87(94.6%) 3(3.3%) 93.8(6.1) 91.5(5.8) 94.1(7.2) 33.5(1.9) 33.34(1.8) 33.2(0.6)

26(76.5%) 32(94.1%) 2(17.9%) 22(64.7%) 34(100%) 0 92.7(10.9) 90.6(7.9) 93.7(7.1) 33.7(2.2) 33.8(2.6) 33.5(1.6)

0.449b <0.001a

Skin Dyspnoea Fatigue Dyspnoea

5 1 1 1

P: differences among axillary surgery patients. Types of axillary surgery: SLNB Sentinel node biopsy, ALND axillary node dissection. DA: Daily activities. IDDD (Interview for Deterioration in Daily Living Activities in Dementia) questionnaire. a Test de fisher. b Test ji cuadrado c Test Kruskal Wallis. d Breast conservative patients.

p-Value

0.666b

0.001b 0.510a 0.374c 0.094c 0.231c 0.346c 0.194c 0.926c

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patients) and administration of endocrine therapy (more frequent in sentinel node patients). QL mean scores in the whole sample were high in most QL areas (>80 points in Functioning, <20 in symptoms areas, Table 3). Moderate limitations (>30) occurred in sexual functioning and enjoyment (in the three assessments), future perspective (in the second and third), and global (in the second). Light affectation (between 20 and 29 points) appeared in sleep disturbance (in the three assessments), global (in the first and third), future perspective (in the first), and fatigue, pain and breast symptoms (in the second). Results of the evolution of QL for the three questionnaires are given in Table 3. For the EORTC QLQ-30, six out of the 15 items (Global QL, physical and role functioning, fatigue, nausea and vomiting, and pain) showed significant changes over time. In most cases (Global QL, physical functioning, pain, fatigue) the time trend was similar: at baseline, scores were above 70 (below 30 for those items with reverse direction), then they declined in the 2nd visit (moderate change in fatigue; less in the other areas), and after 6 weeks they had recovered and achieved the pre-treatment level. For nausea and vomiting and role functioning, differences between the last and the first measurements are statistically significant: nausea and vomiting decreases throughout the follow-up, whereas role functioning improves (less than a little in both scales). For the QLQ-BR-23, sexual function (less than little) and breast symptoms (moderate) worsen after the treatment, but for the third visit the baseline scores have been recovered in both cases. For arm symptoms, a significant linear decreasing trend indicates that results at the third visit are even better than before and during treatment (less than little). DA scores did not significantly change along time (Table 3). Results of the mixed models for EORTC QLQ-C30 scores in the group of patients with conservative surgery by axillary surgery

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modality are given in Table 4. For none of the 15 scores evolution in time differed among groups, the interaction term signification being above p ¼ 0.05 in all cases. Differences among groups were found to be marginally significant (p ¼ 0.078) for FA, with scores about 10 points (small difference) higher in the lymphadenectomy group than in the other two groups. No other significant differences were found among groups. For the EORTC QLQ-BR-23, different trend among groups were found only for Body Image (Table 5). Those patients with lymphadenectomy lost about 6 points (little change) along the follow up, whereas patients with sentinel node or without surgery maintained the same scores as before treatment. For the whole QLQBR23 areas and the DA scale, no differences among groups were depicted. Discussion The main results were QL scores in a sample of Spanish elderly early stages breast cancer patients were high in most QL areas, with moderate limitations in sexuality, future perspective and global QL. In six QL areas there was a similar time trend: at baseline, scores were high then they declined in the 2nd visit and after 6 weeks they had recovered. For three areas, there was an improvement in the third measurement compared to the previous assessments. Changes in most cases were of less than a little magnitude. Among conservative surgery patients, only ALND patients underwent a change: a little decrease in Body Image throughout the follow up. The clinical and biographical characteristics of the sample are representative of the patients treated at the Radiotherapeutical Department of the Complejo Hospitalario of Navarre. Performance status and DA values and the lack of rest or radiotherapy dosage reduction indicate the situation was positive.

Table 3 EORTC QLQ-C30, EORTC QLQ-BR-23 mean scores and evolution assessment using linear mixed models. Time

EORTC QLQ-C30 c Global QL c Physicala c Role c Emotional c Cognitive c Social d Fatigue d Nausea and vomiting d Pain d Dyspnoea d Sleep disturbance d Appetite loss d Constipation d Diarrhoea d Financial impact EORTC QLQ-BR-23 c Body image c Sexual functioninga c Sexual enjoymenta c Future perspective d Systemic therapy side effects d Breast symptoms d Arm symptoms d Upset by hair lossb Daily activities IDDD a b c d

Global Time p value

Time p value 2nd vs. 1st

Time p value 3rd vs. 1st

72.0 85.6 92.6 82.8 89.7 94.0 18.3 0.9 15.3 5.1 24.2 6.3 15.3 2.0 7.1

<0.001 0.001 0.001 0.423 0.755 0.087 <0.001 0.040 0.002 0.127 0.829 0.500 0.526 0.799 0.835

<0.001 0.006 0.146 0.617 0.457 0.317 <0.001 0.292 0.023 0.157 0.620 0.649 0.435 1.000 1.000

0.820 0.375 0.018 0.194 0.775 0.222 0.397 0.012 0.192 0.049 0.577 0.473 0.272 0.561 0.602

95.1 5.0 19.7 69.0 14.3 12.1 8.4 19.7 33.7

0.975 0.029 0.804 0.082 0.194 <0.001 0.028 0.583 0.060

0.873 0.017 0.791 0.049 0.071 <0.001 0.883 0.437 0.466

0.954 0.897 0.511 0.057 0.427 0.218 0.017 0.301 0.108

1st visit

2nd visit

3rd visit

71.7 84.6 88.4 80.9 90.1 92.3 16.8 2.5 17.7 8.1 22.9 7.5 17.5 1.5 6.4

66.2 81.8 85.9 81.7 89.1 90.9 27.9 1.8 22.0 6.0 24.1 8.3 16.0 1.5 6.4

95.1 5.1 25.7 73.4 13.6 13.9 11.1 12.0 34.0

94.9 2.7 25.4 68.9 15.2 26.5 11.0 17.4 34.1

Age-adjusted model. Upset by hair loss only in patients with hair loss. The scores range from 0 to 100, where a higher score represents a higher functional level. The scores range from 0 to 100, where a higher score represents a greater degree of symptoms.

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QL scores were generally satisfactory in the three measurements. Our scores in the first assessment are in line with the EORTC Reference Values [40] for the QLQ-C30 for the general population, and also the QLQ-C30 and QLQ-BR23 for 60-69 year-old patients (a variety of stages), who were starting treatment (though we observed better role functioning, fatigue, dyspnoea and future perspective, and lower sexual enjoyment). Moreover we observed better QL scores in the QLQ-C30 than 70 year-old breast cancer patients (different stages) in three functioning, four symptoms areas, and global QL. Our results are in line with those found in other QL studies of breast cancer patients in the same stages as in our sample, before starting RT, and in which the EORTC instruments have been administered: Browall et al. [9] also assessed 65 years patients and found just worse sleep disturbance and better sexual enjoyment; also in studies with patients of a variety of ages [2,11,41e44], with better social [41,43,44] and emotional functioning [41] and lower fatigue [42,43] and financial impact [41,42] in our case.

We have found limitations in sexuality areas, the scores being lower than those found in the previous studies [9,10,42e44]. Sexuality limitations have been found in other studies performed by our group [45], and could have a cross-cultural base. We found limitations in future perspective, but scores are higher than in the previous studies with patients in different age groups [10,42e44], indicating a better adaptation to their situation. Results of comparisons between the different measurements indicated primarily that the QL of patients in this sample, after a brief follow-up period, was in general as good as at the beginning of treatment. Reductions were mainly of low intensity and occurred in areas directly and indirectly related to radiotherapy toxicity, and were followed by an early recovery. These comparisons are in line with the fact that no significant differences are observed in the DA scale, and with the low toxicity levels. Improvements have appeared in the third measurement in areas related to surgery and to radiotherapy, something that could indicate a recovery after these treatment modalities.

Table 4 EORTC QLQ-C30 mean scores from time of baseline by surgery type in patients with conservative surgery using linear mixed models. QLQ-C30

Time

Areas

Independent

1st visit

2nd visit

3rd visit

QLQ

ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery

70.9 73.5 70.4 79.5 87.6 86.0 89.5 89.8 89.1 80.5 80.0 85.4 89.3 90.1 93.9 94.4 91.3 94.3 24.6 15.1 13.3 3.8 2.3 1.9 17.1 17.6 18.7 8.4 8.4 8.6 17.6 21.6 24.3 9.0 8.4 4.3 20.8 15.2 18.9 2.0 1.2 2.5 4.5 5.6 9.8

65.1 67.7 64.6 77.1 85.1 83.5 86.0 86.3 85.7 80.8 80.3 85.8 87.4 88.2 91.9 92.1 89.1 92.0 36.0 26.5 24.7 3.3 1.8 1.5 21.6 22.1 23.2 5.6 5.7 5.9 20.1 24.2 26.8 9.7 9.1 5.0 19.7 14.1 17.8 2.2 1.4 2.7 4.5 5.6 9.8

71.3 73.9 70.8 80.6 88.7 87.1 93.3 93.7 93.0 82.5 82.0 87.4 88.6 89.3 93.1 95.9 92.9 95.8 26.2 16.8 14.9 2.4 0.9 0.6 14.6 16.1 16.2 3.9 3.9 4.2 20.3 24.3 27.0 7.3 6.7 2.5 18.4 12.8 16.5 2.3 1.5 2.8 5.4 6.5 10.7

PF

RF

EF

CF

SF

FA

NV

PA

DY

SL

AP

CO

DI

FI

SLNB: sentinel node biops. ALND: axillary node dissection. a Signification of group effect and time in a model without interaction. b Age-adjusted model.

Interaction p-value

Time p valuea

Group p-valuea

0.911

<0.001

0.632

0.069

0.005b

0.210b

0.768

0.001

0.977

0.807

0.378

0.283

0.130

0.393

0.396

0.953

0.052

0.402

0.470

<0.001

0.078

0.709

0.164

0.300

0.690

0.004

0.944

0.525

0.019

0.993

0.486

0.494

0.549

0.643

0.380

0.254

0.421

0.554

0.451

0.141

0.904

0.353

0.553

0.818

0.377

J.I. Arraras et al. / The Breast 26 (2016) 46e53

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Table 5 EORTC QLQ-BR-23 and IDDD mean scores from time of baseline by surgery type in patients with conservative surgery using linear mixed models. QLQ-BR23

Time

Areas

Independent

1ª visit

2ª visit

3ª visit

Body ima

ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery ALND SLNB No surgery

94.4 95.9 96.8 4.7 6.4 5.1 12.4 27.0 19.5 66.6 76.9 80.8 14.3 10.4 10.3 15.9 14.3 11.0 16.5 13.6 10.5 22.4 15.3 16.1

96.8 94.8 99.0 1.9 3.6 2.3 14.1 28.7 21.2 60.7 71.0 74.9 13.4 9.4 9.3 28.0 26.4 23.0 18.0 15.1 12.1 21.6 14.5 15.3

88.5 96.4 97.4 4.2 5.9 4.6 9.3 23.9 16.4 60.9 71.1 75.1 10.9 7.0 6.8 14.4 12.7 9.4 17.4 14.4 11.4 24.1 17.0 17.9

ALND SLNB No surgery

34.3 33.5 33.8

34.3 33.5 33.8

34.0 33.2 33.5

Sexual f

Sexual e

Future p

Systemic t

Breast sym

Arm sym

Hair loss

Daily activities IDDD

Interaction p-value

Time p valuea

Group p-valuea

0.005

0.043

0.347

0.734

0.030b

0.753b

0.446

0.721b

0.345b

0.244

0.025

0.115

0.895

0.013

0.446

0.959

<0.001

0.271

0.576

0.272

0.188

0.628

0.905

0.735

0.438

0.122b

0.340b

SLNB: sentinel node biops. ALND: axillary node dissection. a Signification of group effect and time in a model without interaction if interaction not significant. b Age-adjusted model.

These results are in line with those studies carried out with patients in the same disease stages, a variety of ages, treated with RT, and in which the EORTC questionnaires have been administered [2,43,46e48]. A combination of our results in the QL and DA questionnaires, the changes in these scores, and toxicity values, might lead us to conclude RT was mildly toxic, appropriate toxicity control was applied, and had a small influence on the QL of these patients. Our results are in line with the ideas proposed by Kunkler et al. [6] who consider that postoperative radiotherapy after breast conserving surgery does not seem to compromise older patients' QL. In this sense, Williams et al. [49] found very few QL differences in early stages breast cancer patients 65 years old between those who were and were not treated with radiotherapy shortly after the RT sessions end (just in more fatigue and breast symptoms, and less insomnia and endocrine side effects in RT patients). Reimer and Geber [50] indicate the advent of innovative RT techniques has resulted in marked improvements in short-term tolerability together with reductions in the late normal tissue damage in elderly breast cancer patients. Few significant relations have been found between age and QL changes. This result agrees with the Browall et al. [2] study, and might support the idea that age should not be used in isolation in decisions about adjuvant RT for breast cancer in elderly women. QL differences between the three axillary surgery groups and in their evolutions were few but have appeared in key QL areas [51]. Our results partly support Reimer and Gerber's conclusions [50] that avoiding ALND and undergoing SLNB in elderly patients has been associated with better short-term QL. QL scores in the surgery related areas (specially in arm symptoms) were high in the three measurements and surgery groups. The few differences found and the high QL scores could be partly related to good surgery methodology and also to the fact that all patients had breast-conserving surgery. In this sense, Peintinger et al. [52] found differences just in

pain in patients with conservation surgery. It would be interesting to study these differences after a longer follow-up period, to see if a few more differences in favour of the SLNB are found, as in De Gournay et al. [53] and Steegers et al. [54] studies. Our results are also in line with those from some other short term studies performed with the EORTC QL questionnaires, (with patients in the same disease stages, with mastectomy or conservative surgery and a variety of ages), in which a few QL differences (better arm symptoms) in favour of SLNB were found [23,55]. Conclusions Early stages elderly patients have shown high QL scores throughout the treatment and follow-up assessments, with few differences among axillary surgery groups, indicating they have adapted well to their disease and treatments. Elderly patients' capacities for managing difficulties may have contributed to these high QL scores. Our data might orientate towards administering RT in early stages breast cancer patients, given these high QL scores and its low and brief influence on patients' QL. In this sense we agree with Vetter et al. [8] that it must be ensured that appropriate standard therapies are not routinely withheld in older patients based on erroneous perceptions of the disease and treatment. It would be interesting to study the effect of axillary surgery in patients with these characteristics after a longer follow-up. The results of present study confirm the ones found in our preliminary study performed with a small part of the present sample [28]. Conflict of interest statement The authors have no conflict of interest in relation to this manuscript.

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