Patient sampling
BCSs treated for stage II breast cancer between 1998 and 2002 at The Norwegian Radium Hospital (NRH), were invited to take part in a follow-up survey in 2004/2005. The survey consisted of a mailed questionnaire and an outpatient clinical examination. The inclusion criterias were: 1) Curatively intended surgery, followed by loco-regional radiotherapy; 2) No evidence of relapse since primary treatment; 3) No other malignant diagnosis; 4) Age ≤75 years at survey.
Among the 415 BCSs fulfilling the inclusion criteria, 23 (6%) declined to participate, and 43 (10%) did not respond, resulting in 349 BCSs (84%) returning questionnaires in 2004. Among them 318 (91%) also had the outpatient examination. Fifty-five (17%) BCSs with primary inoperable cT3-cT4 tumours, who received neo-adjuvant chemotherapy, were excluded in order to obtain a homogenously treated sample of BCSs. Thus, all included BCSs had pT1-pT2 tumours and axillary lymph node metastases. However, eight patients were omitted due to incomplete questionnaires, resulting in a 2004 sample of 255 BCSs. Among these, 195 women also took part in the 2007 follow-up survey (2007 longitudinal sample). A flowchart of the study is shown in Fig. 1.
Treatment modalities
Treatment was based on the guidelines of the Norwegian Breast Cancer Group (www.nbcg.no). All BCSs had either modified radical mastectomy or lumpectomy, and all had axillary lymph node dissection at level I–II. The target volume of radiotherapy included the breast after lumpectomy, and the chest wall after mastectomy. All BCSs had adjuvant radiotherapy to the regional lymph nodes, with 50 Gy in 25 fractions. From October 1999, patients who had removed ≥ 10 axillary nodes without perinodal infiltration had irradiation only to the axillary apex, as opposed to those with <10 nodes removed and those having radiotherapy before that time, who had radiotherapy to the entire axilla. Post-operative adjuvant chemotherapy with CMF or FEC and/or tamoxifen was given according to the patient’s age and the hormone receptor status of the tumour [15].
Measures
Demographic variables
Information on socio-demographic variables was obtained from the questionnaire and the medical records. Relationship status was dichotomized as paired (married/cohabiting) and non-paired (single/separated/divorced/widow) and level of education into ≤ 12 years or >12 years of basic education. Employment status was categorized as employed (full or part-time jobs or students), and not employed.
Cancer-related variables and BMI
Information on the type of breast cancer and its treatment was obtained from the medical records. Weight and height was collected at the 2004 survey, and the body mass index (BMI) was calculated as kg/m2.
Clinical assessments of shoulder mobility and lymphedema in 2004
At the clinical examination arm/shoulder mobility was assessed by two experienced physiotherapists. Goniometer-based measurements of flexion (forward elevation of the arm) and abduction (lateral elevation of the arm) were done on both arms. Based on clinical experience, a reduced range of motion of ≥ 25° difference between the operated side and the other was defined as impaired shoulder mobility either for flexion, abduction or both (n = 85).
Lymphedema was assessed by volumetric calculation using five circumferential measurements on both arms [16]. Lymphedema was defined as either: 1) a difference of ≥ 10% in volume between the operated side and the other; or 2) For BCSs with either current use of compression garment or received treatment for lymphedema and ≥ 2 cm increase of any circumference of the operated arm versus the other arm (n = 43).
Self-rating of ASPs in 2004
Self-rating was done by Kwan’s arm problem scale (KAPS) [8]. The KAPS consists of the Problem subscale rating arm/shoulder symptoms including pain, swelling, stiffness, use, and numbness, and the ADL subscale rating impairment in dressing and other daily activities. All 13 KAPS items were rated on five point Likert scales from 1 (no symptom or same as before) to 5 (severe symptom or unable to perform), and the KAPS score was the sum score of the items. The KAPS has shown good psychometric properties in our sample of BCSs [17]. Clinically significant self-rated ASPs were defined by a KAPS score of ≥ 21.5 [17], and that was present in 121 BCSs in 2004.
Definition of ASPs present (+) or absent (−) in 2004
We used the findings on the clinical assessment and the self-rated KAPS scores in 2004 to define two groups regarding ASPs in both the 2004 and 2007 samples. The ASPs+ (present) group fulfilled at least two of three criteria: 1) having impaired shoulder mobility; 2) having lymphedema; or 3) KAPS score ≥ 21.5. The ASP- (absent) group fulfilled one or none of these criteria.
Definition of self-rated ASPs in the longitudinal substudy (2004–7)
Since BCSs had filled in the EORTC QLQ-BR23 (BR23) a specific breast cancer module of QoL in both 2004 and 2007 [18], the ASPs questions of the BR23 was used for the longitudinal study of ASPs in relation to QoL domains over time. These questions were: During the past week: “Did you have pain in your arm or shoulder?”; “Did you have a swollen arm or hand?” and “Was it difficult to raise your arm or to move it sideways?” The items were rated on a four point Likert scale with the categories ‘not at all’ = 1, ‘a little’ = 2, ‘quite a bit’ = 3 and ‘very much’ = 4, which were used both as continuous measures and dichotomized as BR23-defined arm/shoulder pain, restricted mobility, and lymphedema present (quite a bit/very much) or absent (not at all/a little) [18].
The IOC version 1 (IOCv1)
The IOCv1 is a specific QoL instrument for long-term cancer survivors [13]. The IOCv1 covers six domains with 10 dimensional subscales, five positive (+) and five negative (−). The Physical Domain includes Health Awareness (+) and Body Changes (−). The Psychological Domain concerns Positive Self-evaluation (+) and Negative Self-evaluation (−). The Spiritual/Existential Domain covers Positive Life Outlook (+) and Negative Life Outlook (−). The Social Domain consists of Life Interference (−) and Values of Relationships (+). Meaning of Cancer (+) and Health Worries (−) are separate domains (10). All 41 IOC items are scored by five response categories: 1 (strongly disagree), 2 (disagree), 3 (neutral), 4 (agree) and 5 (strongly agree). The mean dimension score is calculated by summation of the dimensional item scores divided by the number of items, and mean scores <3 implies disagreement and >3 means agreement on the domains [13].
Ganz approved the use of the IOCv1 by our group. The translation of the IOC into Norwegian was made by professional translators with forward and backward translations. In the current study the Cronbach’s coefficient alphas were ≥0.75 for the positive domains and ≥0.85 for the negative ones.
The SF-36
The SF-36 is a generic QoL measure in common international use with well-documented psychometric properties and with normative data of the Norwegian general population [19]. The items are combined into four physical domain scales: Physical functioning, Physical role functioning, Bodily pain, General health, summarized as the Physical Component Summary Scale (PCS); and four mental domain scales: Vitality, Social functioning, Emotional role functioning and Mental health summarized as the Mental Component Summary Scale (MCS). The PCS and MCS are T-transformed so that the Norwegian general population mean scores were 50 [20].
Statistical analysis
Continuous variables were analyzed with t-tests and categorical variables with chi-square tests. In case of skewed distributions, non-parametric tests were applied. Statistically significant differences in continuous and 2 × 2 contingency tables were tested for clinical significance using effect sizes (ESs). For continuous variables we used Cohen’s coefficient d, and for 2 × 2 contingency tables we used differences between arcsine transformed proportions. ES values ≥ 0.40 were considered as clinically significant based on the recommendations of Cohen [21–23]. Changes of the BR-23 defined ASPs scores from 2004 to 2007 were tested with paired sample t-tests. Correlations were calculated with Spearman’s coefficient rho. Internal consistencies of scales and subscales were examined by Cronbach’s coefficient alpha.
Bivariate and multivariate logistic regression analyses were used to explore associations between demographic, cancer-related variables, and the SF-36 and IOCv1 domain scores as independent variables, and ASPs groups in 2004 and BR-23 defined arm/shoulder pain, restricted mobility, and lymphedema in 2004 and 2007 as dependent variables. The strength of the associations was expressed as odds ratios (OR) with 95% confidence intervals (95%CI). The analyses were done on SPSS for Windows, version 16.0. The level of significance was set at p < 0.01 due to multiple comparisons, and all tests were two-sided.
Ethical considerations
The study was approved by the Regional Ethical Committee of Health Region South of Norway and by the National Data Inspectorate. All patients gave written informed consent.