Health-related quality of life during adjuvant treatment for breast cancer among postmenopausal women

Health-related quality of life during adjuvant treatment for breast cancer among postmenopausal women

ARTICLE IN PRESS European Journal of Oncology Nursing (2008) 12, 180–189 Available at www.sciencedirect.com journal homepage: www.elsevier.com/locat...

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ARTICLE IN PRESS European Journal of Oncology Nursing (2008) 12, 180–189

Available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/ejon

Health-related quality of life during adjuvant treatment for breast cancer among postmenopausal women Maria Browalla,b,, Karin Ahlberga, Per Karlssona,d, Ella Danielsona,e, Lars-Olof Perssona, Fannie Gaston-Johanssonc a

The Sahlgrenska Academy at Go ¨teborg University, Institute of Health and Care Sciences, Go ¨teborg, Sweden Department of Oncology, Division of Selected Clinical Specialties, Sahlgrenska University Hospital, Go ¨teborg, Sweden c School of Nursing, Johns Hopkins University, Baltimore, MD, USA d ¨lvsborg Hospital, Bora˚s, Sweden Department of Oncology, Southern A e ¨ stersund, Sweden Department of Health Science, Mid Sweden University, O b

KEYWORDS Quality of life; Chemotherapy; Radiotherapy; Breast cancer; Elderly

Summary The purpose of the present study was twofold: first, to describe changes of Health-Related Quality of Life (HRQoL) during the adjuvant treatment among postmenopausal women with breast cancer; second, in the same population to identify the best predictors of Overall Quality of Life (QoL) after treatment, from perceived functioning, symptoms, emotional distress and clinical/demographic variables measured at baseline. The study group was 150 women (X55 years of age) scheduled for adjuvant chemotherapy (CT, n ¼ 75) or radiotherapy (RT, n ¼ 75). They were examined before (baseline), during and after completing the treatment. Data about QoL, perceived functioning, symptoms and emotional distress were collected with the European Organisation for Research and Treatment of Cancer (EORTC)-QLQ-C30, BR23 and Hospital Anxiety and Depression Scale (HADS) questionnaires. The general finding was that the adjuvant treatments were associated with decrease in overall QoL, physical and role functioning, anxiety and body image, as well as with increase in fatigue, dyspnoea, pain, nausea/vomiting, constipation and systemic therapy side effects measured over time. For women receiving CT, better emotional functioning and less pain at baseline predicted better overall QoL at the end of the treatment. For women receiving RT, better physical and emotional functioning, less breast symptoms and lower tumour stage at baseline predicted better overall QoL at the end of the treatment. & 2008 Elsevier Ltd. All rights reserved.

Background Corresponding author at: The Sahlgrenska Academy at Go ¨teborg University, Institute of Health and Care Sciences, Go ¨teborg, Sweden. Tel.: +46 313427725. E-mail address: [email protected] (M. Browall).

1462-3889/$ - see front matter & 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejon.2008.01.005

The risk for breast cancer increases significantly with age, and in approximately 6900 women who developed the disease in Sweden during 2004 about 65% were postmenopausal and about 30% were aged 70 or older (National Board

ARTICLE IN PRESS Health-related quality of life during adjuvant treatment for breast cancer of Health and Welfare, 2004). The effects of adjuvant chemotherapy (CT) on breast cancer disease seem to be as good for both pre- and postmenopausal patients, at least for the hormone receptor-negative patients (EBCTCG, 2005). However, very few elderly patients have been included in the reported randomised studies (Talarico et al., 2004). Although adjuvant treatments have extended survival of women with breast cancer, the literature shows that such treatments and the disease itself may cause symptoms (Miaskowski et al., 2006; Schreier and Williams, 2004; Wood et al., 2006), and that experienced symptoms can cause decreased quality of life (QoL) (De Jong et al., 2002; Ganz et al., 2003, 2004; Given et al., 2001; Kurtz et al., 2001). However, since most studies have focused on long-term QoL (Engel et al., 2003; Peuckmann et al., 2007), there remains a knowledge gap regarding QoL effects during cancer treatment. Moreover, most studies investigating symptoms such as pain and fatigue (Beck et al., 2005; Dagnelie et al., 2007), sleep difficulties (Fortner et al., 2002), depression (Badger et al., 2004), nausea (Dibble et al., 2003) and QoL (Brandberg et al., 2003; Ganz et al., 2004; Hopwood et al., 2007) in patients treated for breast cancer with CT and/or radiotherapy (RT) primarily included younger and middleaged women. Older women were seldom included, and, even when so, they were very few in numbers (Rao and Cohen, 2004). The concept of QoL is broadly defined as an overall experience of life satisfaction (Fayers et al., 2000), while health-related quality of life (HRQoL), often used synonymously with subjective health status, is more precisely defined as the subjective impact of disease, impairments and their treatments (Carr et al., 2001; Spilker and Revicki, 1996). Commonly, many researchers studying medical populations have narrowed the concept further by defining and assessing a number of predefined core domains. For example, the European Organisation for Research and Treatment of Cancer (EORTC) has operationalised HRQoL in cancer diseases in terms of functional status, cancer and treatment-specific symptoms, psychological distress, social interaction, financial impact and overall QoL (Aaronson et al., 1993, 1996). In the present study, we have utilised their definitions and assessment tools of HRQoL in breast cancer. The different domains of HRQoL are likely to be influenced by age, sociodemographic and clinical variables, disease stage and type of adjuvant treatment (Armstrong, 2003; De Jong et al., 2002; Ganz et al., 2003, 2004). At present, there is a lack of knowledge about the subjective effects of adjuvant treatments for breast cancer in elderly women (Eaker et al., 2006; Witherby and Muss, 2005). A better understanding of how the two main types of adjuvant treatments (CT and RT) affect postmenopausal women with breast cancer is therefore an important issue for clinicians in the oncology setting. The purpose of the current study was twofold. First, to describe how HRQoL (perceived functions and symptoms) and emotional distress develops over time in postmenopausal women undergoing adjuvant CT and RT. Second, to identify the best predictors of global health and QoL (referred to as overall QoL in this article) after treatment, from perceived functioning, symptoms, emotional distress and clinical/demographic variables measured at baseline.

181

Methods Design The design for this descriptive study was longitudinal, predictive and correlational.

Sample and settings The sample consisted of 150 postmenopausal women aged 55 years or older with newly diagnosed, histologically confirmed stage I–IIIa breast carcinoma. Further inclusion criteria were: ability to give written consent, to read and speak Swedish, and to understand the purpose of the study. The exclusion criteria were: evidence of dementia, known history of psychiatric disorder, and history of any kind of cancer within the previous 5 years. Women aged 55 years and over were used to ensure that those participating in the study were homogeneous in regard to menopause. The age range was 55–80 years. Two groups of women were enrolled: (1) those scheduled to receive adjuvant CT (n ¼ 75) at one of the three hospitals in Sweden (two University Hospitals and one County Hospital) after surgery and (2) women (n ¼ 75) scheduled to receive adjuvant radiotherapy (RT) at one of the two University Hospitals after prior surgery. CT was offered to all patients with hormone receptor-negative breast cancer and to high-risk hormone receptor-positive patients (i.e. tumour size 450 mm and/or more than three positive lymph nodes). RT to the breast was offered to all women who had undergone breast-conserving surgery. RT to the chest wall was offered after mastectomy, if the tumour size was 450 mm. Both local (breast or chest wall) and lymph node RT were offered if more than three lymph nodes were involved, irrespective of the type of surgery to the breast.

Instruments The core questionnaires used were the cancer-specific EORTC QLQ-C30 (Aaronson et al., 1993) and the tumourspecific breast cancer module EORTC QLQ-BR23 (Sprangers et al., 1996). The QLQ-C30 consists of 30 items assessing five scales that evaluate physical, emotional, social, cognitive and role functioning, and eight symptom/problem scales measuring fatigue, pain, emesis, dyspnoea, sleep disturbance, appetite loss, diarrhoea, constipation and financial difficulties. Included in the questionnaire is a scale measuring the overall QoL. The QLQ-BR23 consists of 23 items covering four functioning scales (body image, sexual functioning, sexual enjoyment, and future perspective) and four symptom scales (arm symptoms, breast symptoms, side effects of systemic therapy, and being upset by hair loss). All scales in both questionnaires are transformed to a percentile scale ranging from 1 to 100. High scores in the functioning scales and overall QoL indicate high levels of functioning and overall QoL, whereas high scores in the symptom/problem scales indicate high levels of symptoms/ problems. The reliability of the Swedish version has been assessed in both healthy individuals and different groups of cancer patients with internal consistency (Cronbach’s alpha) ranging from 0.55 to 0.87 (Michelson et al., 2000).

ARTICLE IN PRESS 182 Emotional distress was measured with the 14-item Hospital Anxiety and Depression Scale (HADS) (Zigmond and Snaith, 1983). This questionnaire measures anxiety and depression. Scores on each subscale range from 0 (no symptoms of depression or anxiety) to 21 (numerous and severe symptoms). Cronbach’s alpha for the Swedish version of HADS is 0.84 for anxiety and 0.82 for depression (Lisspers et al., 1997).

Procedure Data were collected from November 2003 to 2005. For the CT group, all women meeting the inclusion criteria were consecutively invited to participate in the study. Information regarding women about to receive adjuvant treatment was collected through hospital charts and records by the first author at one of the University Hospitals. At the other University Hospital and County Hospital, due to long distance, two study-nurses identified the women and informed them of the study. Thereafter, the first author contacted each woman who consented to participate. The adjuvant CT regime used was mainly FEC (n ¼ 72) (fluorouracil 600 mg/m2 iv, epirubicin 75 mg/m2 iv, and cyclophosphamide 600 mg/m2 iv every third week for six courses), or CMF (n ¼ 3) (cyclophosphamide 100 mg/m2 p.o. on days 1–14 and methothrexate 40 mg/m2 iv, and fluorouracil 600 mg/m2 iv on days 1 and 8 (CMF) every 28th day for six courses). For each CT patient enrolled, a woman about to receive RT in the same age group was included. The target of the RT was mainly the breast, after breast-conserving surgery (n ¼ 69), but a few patients also had loco-regional RT after mastectomy (n ¼ 5). The prescribed absorbed dose for all patients was 2 Gy per daily fraction, 5 days per week for 5 weeks, with a total dose of 50 Gy. Baseline data were collected during the week prior to the start of the treatment. In the case of the CT group, women scheduled for treatment at one of the University Hospitals were interviewed and filled in the questionnaires either at the hospital or at home, whereas women treated at the County Hospital and the second University Hospital were interviewed by telephone because of the distance involved. At subsequent data collections (1 week after the first, third and last cycles of CT), the questionnaires, together with a pre-paid envelope and information explaining the procedures, was sent to the patients; furthermore, a telephone number at which the first author could be contacted was included. In the case of the RT group, women scheduled for RT at one of the University Hospitals were also interviewed and they filled in the questionnaires at baseline at the hospital and subsequent questionnaires (after 3 weeks of treatment and at 2 weeks after the completion of treatment) were administered by mail. The same data collection procedures as were used for the CT patients treated at the second University Hospital were used for the RT patients at that hospital. All demographic and clinical data were collected from the patient or from the hospital records. In order to ensure the logistics for the study, a pilot study was performed with 10 of the included 75 women about to receive CT. No adjustments were needed to the study design, instruments or data collection procedures.

M. Browall et al. Of the CT patients, a total of 10 women were lost between cycles one to six, 3 of whom had failed to send in the questionnaires and 7 who had withdrawn from adjuvant CT during the six cycles because of various medical conditions, such as diverticulitis, neutropenia, heart conditions, pulmonary embolism, or relapse. In addition, seven patients had a dose reduction due to symptoms such as nausea, low platelet count, neutropenia, or rash. Four women among the RT patients did not send in the questionnaires at the last data collection point (2 weeks after treatment). Of the 80 women about to receive CT who met the inclusion criteria and were invited to participate, only five refused. Among the women about to receive RT, 13 refused participation.

Data analysis To describe the development of HRQoL over time (aim 1), a regression coefficient was calculated for each patient and each subscale, with the number of weeks from baseline on the x-axis and the value of the subscale on the y-axis. Fisher’s test for pairwise comparisons was used to determine whether the regression coefficients were significantly different from zero, i.e. whether there were any trends with time from baseline during treatment within the two treatment groups. In the examination of potential predictors at baseline of overall QoL after treatment (aim 2), the scale asking about overall QoL in the QLQ-C30 was used as the dependent variable. All other scales provided by the QLQ-C30, BR23 and HADS as well as clinical and demographic variables were treated as potential predictors. In this explorative search for strong predictors, correlations were first computed between all potential predictors at baseline and overall QoL after treatment. Those variables showing significant correlations were then entered in multiple linear regression analyses (forward) to determine their unique predictive value for overall QoL. All analyses were performed within each treatment group. All tests were two-tailed and conducted at 5% significance level.

Ethics The study was performed in accordance with the ethical standards of the Helsinki Declaration and Good Clinical Practice guidelines (WMA, 2000). The Ethics Committees at the Gothenburg University and Stockholm University gave approval for the study. All patients received verbal and written information, and gave their written consent before inclusion.

Results Sample characteristics and background data Demographic and clinical characteristics of the total patient group of 150 women are presented in Tables 1 and 2, respectively. In the CT group (n ¼ 75), almost 50% of the women lived alone, 51% had a college or higher degree and 56% were retired (Table 1). Co-morbidities were relatively common

ARTICLE IN PRESS Health-related quality of life during adjuvant treatment for breast cancer

Table 1 Sociodemographic and characteristics of the patient groups

Age (years) 55–64 65–70 470 Mean (SD) Single/divorced/ widowed College/ graduate degree Employed, full time, or at least part time Old age retirement Swedish born

Table 2

Chemotherapy patients (n ¼ 75) n (%)

Radiotherapy patients (n ¼ 75) n (%)

36 26 13 65 35

37 26 12 64.5 21

(48) (35) (17) (5.8) (47)

(49) (35) (16) (6.1) (28)

38 (51)

35 (47)

28 (37)

25 (33)

42 (56)

44 (59)

60 (80)

68 (91)

Clinical characteristics of the patient groups

Co-morbidities One co-morbidity Two co-morbidity Three or more comorbidity Cardiovascular disorders (i.e., high/low blood pressure, ischaemic heart disease) Musculoskeletal problems (i.e., fibromyalgia, arthritis) Respiratory problems (i.e., asthma, chronic obstructive disease) Gastro-intestinal problems (i.e., diverticulitis) Depression Medication Cardiovascular Antidepressant/sedatives Analgesics Sleeping Respiratory Hormone replacement therapy

Chemotherapy patients (n ¼ 75) n (%)

Radiotherapy patients (n ¼ 75) n (%)

52 28 19 5

48 19 18 13

(69) (37) (25) (6)

(64) (25) (24) (17)

21 (28)

22 (29)

15 (20)

31 (41)

5 (7)

7 (9)

183

Table 2 (continued ) Chemotherapy patients (n ¼ 75) n (%) Endocrine therapy (i.e., nolvadex)

4 (5)

Radiotherapy patients (n ¼ 75) n (%) 28 (37)

Histopathology Invasive ductal cancer Invasive lobular Other Data missing

55 11 8 1

Surgery Total mastectomy Sector resection Missing

43 (57) 31 (41) 1 (1.3)

5 (7) 69 (92) 1 (1.3)

Axillary exploration Axillary clearance Sentinel node biopsy Positive receptor status Positive lymph nodes None 1–3 X3 Data missing

56 23 34 46 27 15 28 3

(75) (31) (45) (61) (36) (20) (50)c (4)

25 48 61 16 59 11 5 –

(33) (64) (81) (21) (79) (15) (7)

Tumour size 1–20 mm 21–50 mm 451 mm Data missing

28 30 13 4

(37) (40) (17) (5)

45 16 3 11

(60) (21) (4) (15)

Treatment Chemotherapy (CT)a CT+Radiotherapy (RT)a CT + RT + Endocrinea CT+ Endocrinea Radiotherapy (RT)b RT+Endocrineb Endocrine+RT+Endocrineb

2 26 33 4 – – –

(16) (35) (44) (5)

– – – – 39 (52) 8 (11) 28 (37)

Tumour stage Stage I Stage II Stage III Data missing

23 22 27 3

(31) (29) (36) (4)

46 22 6 1

(73) (15) (11) (1.3)

50 11 13 1

(67) (15) (18) (1.3)

(61) (29) (8) (1.3)

a

4 (5)

7 40 18 6 6 10 2 15

(9) (53) (24) (8) (8) (13) (3) (20)

4 (5)

3 48 21 3 21 6 5 13

(4) (64) (28) (4) (28) (8) (7) (17)

Treatment for chemotherapy (CT) group. Treatment for radiotherapy (RT) group. c Calculated from the 56 who had axillary clearance. b

(69%); 28% had cardiovascular disorders, and 24% received medication for these problems. Histopathological evaluation indicated that 73% had invasive ductal cancer, 57% underwent mastectomy and axillary clearance was performed in 75% (Table 2). Of the patients with axillary clearance, 28 had X3 positive lymph nodes. CT was combined with subsequent adjuvant RT and/or endocrine treatment in 84% of the patients. These subsequent treatments started about 1 month after the completion of the CT.

ARTICLE IN PRESS 184 Among the women who received RT (n ¼ 75), 28% lived alone, 47% had a college or higher degree, and 59% were retired (Table 1). Sixty-four percent had co-morbidities and 17% had X3 other diseases, the most common being musculoskeletal problems, followed by cardiovascular disorders. Sixty-four percent regularly received medication, of which endocrine therapy was the most common, followed by cardiovascular medication and analgesics. Breast-conserving surgery was performed in 92% of the cases and a sentinel node biopsy was used in 64% (Table 2). Most women (81%) had hormone receptor-positive disease. Invasive ductal cancer was the most common histopathology (67%). The majority was node negative (79%) and 60% had tumours less than 21 mm. Adjuvant endocrine treatment was part of the planned treatment for 30 out of the 75 RT patients. No endocrine treatment was used during RT; however, in 28 patients, endocrine treatment had been initiated while on the waiting list to start RT; these patients then discontinued endocrine treatment between 1 and 2 weeks before the start of RT until the end of RT (no concomitant treatment). Eight patients commenced endocrine treatment first after RT was completed.

The development of HRQoL over time The women receiving CT showed a significant decrease in the overall QoL, physical, role, social, and cognitive functioning, body image and anxiety between baseline and the completion of CT (cycle six). Fatigue, nausea/vomiting, dyspnoea, appetite loss, constipation, pain, systemic therapy side effects, hair loss, and depression increased significantly during the same period. There were no significant changes in emotional functioning, sleep, diarrhoea, or financial difficulties, sexual functioning, arm and breast symptoms, and future perspective during time from baseline to completion of the treatment (Table 3). For the women receiving RT, a significant decrease was observed for the overall QoL, role and physical functioning, body image and anxiety between baseline and 2 weeks after completion of the treatment. Significant increases were seen in fatigue and dyspnoea, nausea/vomiting, pain, financial difficulties, constipation, systemic therapy side effects, arm and breast symptoms during the same frame of time. There were no significant changes in emotional, social, and cognitive functioning, sleep, appetite loss, diarrhoea, sexual functioning, future perspective, upset by hair loss, or depression during time from baseline to completion of the treatment (Table 4).

Predictors of overall QoL after completed treatment For women who received CT, significant correlations were found between the overall QoL (after treatment) and ethnicity, muscular–skeletal problems, physical, role, emotional and social functioning, overall QoL, fatigue and pain, anxiety and depression measured at baseline (Table 5). In the subsequent multivariate linear regression analysis, emotional functioning (EF) (b ¼ 0.355) and pain (PA) (b ¼ 0.606) at baseline remained significant predictors

M. Browall et al. for the overall QoL after completion of the treatment (sixth cycle of CT). The resulting model to predict overall QoL was: overall QoL (sixth cycle) ¼ 37.798+0.355  EF0.606  PA. Thus, better emotional functioning and less pain at baseline predicted better overall QoL at the end of the treatment. Together, this model explained 24% of the total variance in overall QoL (R2 ¼ 0.24). For women who received RT, significant correlations were found between overall QoL (after treatment) and ethnicity, tumour stage, sleep medication, physical, emotional, role, social and cognitive functioning, overall QoL, fatigue, pain, dyspnoea, financial problems and future perspective, body image, systemic therapy side effects, breast and arm symptoms, anxiety and depression. In the subsequent multivariate linear regression analysis, tumour stage (TS) (b ¼ 10.779), physical functioning (PF) (b ¼ 0.619), emotional functioning (EF) (b ¼ 0.253) and breast symptoms (BS) (b ¼ 0.795) at baseline remained significant predictors for overall QoL after completion of the treatment (2 weeks after completing RT). The resulting model to predict overall QoL was: overall QoL (2 weeks after RT) ¼ 11.83610.779  TS+0.619  PF+0.253  EF0.795  BS. Thus, better physical and emotional functioning and less breast symptoms and lower tumour stage at baseline predicted better overall QoL at the end of the treatment (Table 5). Together, this model explained as much as 48% of the variance of overall QoL (R2 ¼ 0.48).

Discussion The purpose of the study was to examine how the predefined domains of HRQoL among postmenopausal women changed over time. Adjuvant treatments affected these breast cancer women in various ways during the treatment period. The treatments were associated with the decrease in overall QoL, physical and role functioning, anxiety and body image, as well as an increase in fatigue, dyspnoea, pain, nausea/ vomiting, constipation and systemic therapy side effects. Watters et al. (2003) found that younger women (p64) receiving CT appeared to decrease more in physical function than older women. Similar results were found in a study by Arora et al. (2001), where physical well-being had declined in a sample of younger women (p60 years). It is known that receiving CT is a very distressing and concern-provoking stage of the treatment (Ganz et al, 2002). In our study, those who received CT reported an increase in levels of depression and a decrease in social function. This is consistent with earlier studies on younger and middle-aged women which have shown that increased depressive symptoms tend to have a negative effect on QoL (Badger et al., 2004; Somerset et al., 2004) and worsen psychosocial adjustment in women with breast cancer (Kornblith et al., 2001). Our results that cognitive functioning decreased during adjuvant CT, therapy is consistent with results from several earlier studies in similarly treated younger and middle-aged women (Bender et al., 2006; Ahles et al., 2002; Tchen et al., 2003). Among the women who received RT, an increase was seen over time, in more localised symptoms (e.g., arm and breast symptoms) directly associated with their treatment and earlier surgery. These problems probably reflect the local

ARTICLE IN PRESS Health-related quality of life during adjuvant treatment for breast cancer

Table 3

185

Mean values (SD) of the EORTC QLQ-C30, BR-23 and HAD scales for the chemotherapy (CT) group Baseline m (sd)/n

First CT m (sd)/n

Third CT m (sd)/n

Sixth CT m (sd)/n

Overall QoL

76 (19)/75

63 (24)/71

61 (22)/69

58 (22)/65()

Functioning scalesa Physical function Role function Emotional function Social function Cognitive function

90 82 71 87 83

(14) (23) (20) (21) (21)

82 67 76 75 84

(16) (30) (22) (27) (19)

77 60 77 70 83

(17) (32) (23) (27) (20)

75 58 75 71 81

(18)() (30)() (19) (27)() (20)*()

Symptom scalesb Nausea and vomiting Fatigue Pain Dyspnoea Sleep Appetite loss Constipation Diarrhoea Financial difficulties

2 23 7 8 42 6 5 4 7

(6) (22) (13) (17) (41) (16) (16) (15) (18)

13 36 16 17 40 15 21 14 12

(17) (24) (20) (25) (34) (25) (27) (24) (22)

18 43 19 25 33 21 27 13 11

(20) (24) (26) (28) (26) (31) (33) (24) (23)

13 46 17 27 38 17 27 10 15

(18)(+) (24)(+) (25)(+) (25)(+) (30) (27)(+) (34)(+) (21) (27)

BR-23 functioning scalesa Body image Sexual functioning Sexual enjoyment Future perspective

90 12 89 62

(18)/75 (18) (19)/4 (23)

75 11 62 56

(30)/71 (18) (31)/15 (30)

68 11 47 56

(31)/69 (17) (25)/15 (32)

66 9 38 56

(30)/65() (15) (18)/13 (28)

BR-Symptom scalesb Systemic therapy side effects Breast symptoms Upset by hair loss Arm symptoms

7 9 00 9

(7) (12) (00) (12)

25 17 34 12

(17) (16) (38) (15)

35 15 49 12

(16) (16) (41) (18)

33 14 42 12

(18)(+) (15) (41)(+) (18)

HADSc Anxiety Depression

6.76 (4.91) 2.84 (3.21)

– –

4.36 (3.97) 4.13 (3.56)

4.74 (4.88)() 4.68 (4.16)(+)

Significant time effect po0.05; significant time effect po0.01; significant time effect po0.001. Significances marked in the sixth CT column indicate significant changes (regression) from baseline over the treatment period. () indicates a significant decrease in scores over time. (+) indicates a significant increase in scores over time. a Higher scores indicate higher perceived quality of life and better functioning. b Higher scores indicate more symptoms. c Higher scores indicate more anxiety and depression.

effect of the RT, which can produce a skin reaction and swelling of the irradiated area. Similar results have recently been reported by Knobf and Sun (2005) in a study of older women with breast cancer. For about one-third of these patients, breast oedema increased over time and even persisted after the treatment was completed. Wengstrom et al. (2000) found that skin problems steadily increased from the third week of the treatment and reached its peak at the completion of the therapy in middle-aged women receiving RT. A large percentage of women who received RT in our study reported musculoskeletal-related problems, which required the use of analgesics. A possible explanation for this is that several of these women had undergone endocrine treatment immediately prior to the initiation of their RT and would thus be expected to experience more musculoskeletal problems. These problems could possibly

explain the decreased physical functioning experienced by these women, and underscores the importance of taking into account other concomitant illnesses in order to gain a better understanding of experienced symptoms. The second purpose of the study concerned which variables, measured at baseline, were significant predictors of overall QoL at the end of treatment. For the women with CT, better emotional functioning and less pain at baseline were significant predictors of overall QoL at the end of treatment. Together, this model explained 24% of the total variance in overall QoL. For the women who received RT, better physical and emotional functioning, lower tumour stage and less breast symptoms were found to be predictors of better overall QoL at end of treatment. Together, this model explained 48% of the variance of overall QoL.

ARTICLE IN PRESS 186

Table 4

M. Browall et al.

Mean values (SD) of the EORTC QLQ-C30, BR-23 and HAD scales for the radiotherapy (RT) group Baseline m (sd)/n

3 w RT m (sd)/n

2 w after RT m (sd)/n

Overall QoL

78 (18)/75

71 (17)/75

70 (20)/70()

Functioning scalesa Physical function Role function Emotional function Social function Cognitive function

91 86 82 90 89

(12) (20) (21) (18) (17)

82 76 78 81 88

(16) (28) (20) (22) (17)

82 76 79 85 87

(17)() (29)() (20) (21) (19)

Symptom scalesb Nausea and vomiting Fatigue Pain Dyspnoea Sleep Appetite loss Constipation Diarrhoea Financial difficulties

45 (3) 19 (20) 14 (23) 7 (15) 40 (42) 5 (15) 3 (11) 1(9) 2 (10)

5 35 16 17 34 9 9 3 7

(13) (22) (18) (23) (36) (17) (18) (11) (16)

3 30 23 16 32 5 8 3 8

(7)(+) (20)(+) (23)(+) (24)(+) (35) (15) (18)(+) (12) (16)(+)

BR-23 functioning scalesa Body image Sexual functioning Sexual enjoyment Future perspective

94 13 50 71

(15)/75 (18) (28)/6 (22)

88 17 57 64

(18)/75 (23) (24)/21 (28)

87 16 51 67

(19)/71() (22) (23)/27 (26)

BR-23 symptom scalesb Systemic therapy side effects Breast symptoms Arm symptoms Upset by hair loss

10 4 5 1

(9) (8) (9) (12)

16 23 12 1

(13) (18) (18) (5)

15 (13)(+) 34 (24)(+) 15 (19)(+) 1(6)

HADSc Anxiety Depression

4.60 (4.47) 2.11 (2.88)

4.13 (3.84) 2.45 (2.87)

3.42 (3.53)() 2.49 (2.82)

Significant time effect po0.05; significant time effect po0.01; significant time effect po0.001. Significance marked in the 2 w after RT column indicate significant changes (regression) from baseline over the treatment period. () indicates a significant decrease in scores over time. (+) indicates a significant increase in scores over time. a Higher scores indicate higher perceived quality of life and better functioning. b Higher scores indicate more symptoms. c Higher scores indicate more anxiety and depression.

The result that emotional functioning predicts overall QoL is in line with available knowledge concerning emotional reactions. Emotions are seen as a fundamental aspect of the human psyche; it is also known that emotional reactions to stressful life events may lead to anxiety, tension and depression (Lazarus, 2006). Therefore, the current state of emotional functioning may become a major reference point for overall assessment of QoL. Due to this important knowledge, further research is required and, specifically, closer observations, considering the elderly group of women. The finding that almost twice as much of the variance in overall QoL could be explained in the RT group compared to the CT is interesting, but could be due to the fact that locally RT affects the body more predictably. Physical functioning, tumour stage and perceived breast symptoms

add to emotional functioning in this group. However, CT affects less locally and less predictably—emotional functioning and pain can only explain a minor part of the variation in overall QoL.

Strengths and limitations The strengths of the current study are the demographic and diagnostic homogeneity of the sample, the use of wellestablished self-report instruments, and the longitudinal design. It is, however, important to have in mind that results on a group level cannot be directly translated into an individual patient level. Also, the generalisation of the results must be interpreted with caution since this is a hospital-based study with consecutively treated

ARTICLE IN PRESS Health-related quality of life during adjuvant treatment for breast cancer

Table 5

187

Significant correlations between explanatory variables (at baseline) and overall QoL (at end of treatment)

Outcome variable

Overall QoL-CT treatment

Explanatory variables Ethnicity * Tumour stage ns

Overall QoL-RT treatment

Comments

* **

Swedish women have better overall QoL values than non-Swedish. Higher tumour stage at baseline, worse overall QoL at end of treatment. Muscular–skeletal problems at baseline, worse overall QoL than others at end of treatment. Sleep medication at baseline, better overall QoL than others at end of treatment. Better physical function at baseline, better overall QoL at end of treatment. Better role function at baseline, better overall QoL at end of treatment. Better emotional functions at baseline, better overall QoL at end of treatment. Better social function at baseline, better overall QoL at end of treatment. Better cognitive functions at baseline, better overall QoL at end of treatment. Better overall QoL at baseline, better overall QoL at end of treatment. More fatigue at baseline, worse overall QoL at end of treatment. Less pain at baseline, better overall QoL at end of treatment. More dyspnoea at baseline, worse overall QoL at end of treatment. More financial problems at baseline, worse overall QoL at end of treatment. Less systemic therapy side effects at baseline, better overall QoL at end of treatment. Less breast symptoms at baseline, better overall QoL at end of treatment. Less arm symptoms at baseline, better overall QoL at end of treatment. Better body image at baseline, better overall QoL at end of treatment. Better future perspective at baseline, better overall QoL at end of treatment. More anxiety at baseline, worse overall QoL at end of treatment. More depression at baseline, worse overall QoL at end of treatment.

Muscular–skeletal problems Sleep medication

*

ns

ns

*

Physical function

**

***

Role function

*

***

Emotional function

*

***

Social function

*

**

Cognitive function

ns

*

Overall QoL

**

***

Fatigue Pain Dyspnoea

** ** ns

*** ** *

Financial problems

ns

**

Systemic therapy side effects Breast symptoms

ns

*

ns

*

Arm symptoms

ns

*

Body image

ns

*

Future perspective

ns

**

Anxiety Depression

* *

*** **

*o0.05; **o0.01; ***o0.001. ns ¼ not significant. The 27 variables that were not significantly correlated with overall QoL were: age, education level, employed, retired, marital status, surgery, axillary exploration, tumour size, receptor status, sentinel node biopsy, cardiovascular disorders, respiratory problems, gastro-intestinal problems, depressive problems, hormone replacement therapy, cardiovascular medication, antidepressive/sedative medication, analgesics, respiratory medication, sleep, appetite loss, constipation, sexual enjoyment, sexual functioning, hair loss, nausea/vomiting, diarrhoea.

postmenopausal patients and we lack information about patients who were not referred for, not offered adjuvant CT or RT, or who declined participation. We also investigated whether or not the mode of questionnaire administration (personal interview at home/ at hospital versus telephone interview) correlated to responses in HRQoL. No significant differences were found (data not shown) between the modalities. The interview method did not affect response rate either. We lack information about patients who were not referred for,

were not offered adjuvant treatment or who declined participation.

Implications for nursing As shown, dimensions of HRQoL among these postmenopausal women were negatively affected in different ways by these adjuvant treatments over time. Several correlations were found between demographic, clinical and HRQoL

ARTICLE IN PRESS 188 dimensions and global ratings of overall QoL. This is important knowledge for understanding the relation between HRQoL and overall QoL in this relatively older population. Even if physical and emotional impairment is a somewhat expected reaction and pain and breast symptoms are common symptoms for breast cancer patients, the impact of these on QoL is still under-recognized. The results indicate that further studies among postmenopausal women’s experience of adjuvant treatments, with special focus on emotional and physical function, pain, tumour stage and breast symptoms at an early stage is important, in order to prevent decreases in overall QoL at the end of treatment. Since little is described in the literature about how elderly patients experience adjuvant treatments over time the knowledge about these predictors may increase the understanding of important areas of HRQoL, including symptom experience for postmenopausal women 55 years and older.

Acknowledgements This study was funded and supported by the King Gustav V Jubilee Clinic Cancer Research Foundation, Go ¨teborg, and The Sahlgrenska Academy at Go ¨teborg University, Institute of Health and Care Sciences, Go ¨teborg, Sweden. We are most grateful to all the women who took part in the study. We wish to thank Anders Oden, Professor in Biostatistics, for providing help and guidance with the statistical methods used in the data processing.

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