Women with early breast cancer from hospitals across the UK were invited to join the study following surgery but before the start of adjuvant therapy. Exclusion criteria included advanced disease, previous treatment for any cancer, receiving neo-adjuvant chemotherapy, those with a previous history of stroke dementia, degenerative disease and alcohol or drug abuse. Of 224, 153 (68%) patients were recruited to the study; of the 69 who did not, 39 were not interested, 11 were not eligible owing to age (>75 years) or previous treatment history and 19 did not complete the baseline assessment before the start of treatment. The control group was a sample of convenience made up of friends and family of the patients and experimenters and from a local women's group.
Of 153, 100 women were scheduled to receive adjuvant chemotherapy and 53 to receive radiotherapy and/or endocrine therapy or no further treatment. Data are presented on 128 breast cancer patients (85 received chemotherapy, 43 did not) and 49 healthy controls. Of the 15 chemotherapy patients (five no longer wanted to take part, four could not be contacted, one owing to ill-health (unrelated), one owing to disease progression and four had died of their disease); 10 nonchemotherapy patients (four no longer wanted to take part, one was not contactable, two withdrew for unrelated health reasons, two because of disease progression and one had died of causes unknown to the authors) and three healthy controls (one for health reasons, one for family reasons and one emigrated) did not complete all assessments. A further six healthy controls were excluded prior to analyses in order to bring the groups into closer alignment for age and full-scale intelligence. The study had local ethics committee approvals and all participants gave full written consent.
shows the characteristics for the three participant groups. The nonchemotherapy group differed significantly from the healthy controls and chemotherapy group by age (F=22.74, P<0.0001; F=20.09, P<0.0001, respectively) and from the healthy control group by years spent in full time education (F=5.58, P=0.02). These differences are accounted for in the analyses. The chemotherapy group were less likely than the other groups to be peri- or postmenopausal at baseline (χ2=4.90, P=0.027; χ2=10.87, P=0.001 for healthy controls and nonchemotherapy, respectively) and the nonchemotherapy and control groups were not more likely to have used HRT.
Age (at baseline), IQ, years in education and psychological distress
details the tumour grade and type of surgery for both patient groups and chemotherapy regimen. In total, 59% of the chemotherapy and 14% of the nonchemotherapy patients were lymph node positive. Time between surgery and baseline assessment ranged from 21 to 83 days (mean 41.29 s.d. 13.30) in the chemotherapy group (date of surgery missing for six patients) and 22 to 92 days in the nonchemotherapy group (mean 53.21s.d. 16.03). Eighty eight percent (75 out of 85) of the chemotherapy and 74% (32 out of 43) of the nonchemotherapy patients were seen within 2 weeks of their second assessment and at T3, the proportions were 91% (77 out of 85) and 86% (37 out of 43), respectively.
Treatment details for both patient groups
At T1, 40 out of 43 (93%) nonchemotherapy patients had started endocrine therapy; 36 received tamoxifen and four anastrozole (one went on to have goserelin injections, six switched endocrine treatment during the study and one ceased endocrine treatment) and between T1 and T2 assessments, 36 out of 43 (84%) had completed a course of radiotherapy. By T2, 20 out of 85 (23%) chemotherapy patients had started endocrine therapy; 17 received tamoxifen, three letrozole and by T3, this had risen to 60 (71%); 46 tamoxifen, nine letrozole and five anastrozole (two patients switched from tamoxifen to anastrozole between assessments T2 and T3, and two received trastuzumab). Of the patients, 16 (19%) had started a course of radiotherapy by T2 and by T3, 71 (83.5%) had completed radiotherapy treatment. Out of 39, 32 premenopausal chemotherapy patients experienced a treatment-induced menopause.
Cognitive assessments were made at baseline (T1), 4 weeks after the final chemotherapy session (six months in the other groups) (T2), and 12 months after the final chemotherapy session (18 months in the other groups) (T3).
The cognitive test battery assesses several broad areas of cognitive function as outlined in . The tasks used are sensitive and have shown changes in a number of patient groups, including those suffering with AIDS, Parkinson's disease, head injury, and following cardiac surgery. They can provide information on a variety of cognitive processes including attention, learning, memory, planning and organisational strategies.
The tests were administered in the same order following the requirements of the Wechsler Memory Scale-III (Weschler, 1998
). All participants were screened for dementia, using the information and orientation subtest of the WMS III. The battery of standardised neuropsychological tests is briefly described below.
Intelligence was assessed using the National Adult Reading Test (Nelson, 1991
). Wechsler Adult Intelligence Scale FSIQ was predicted from this score.
WMS III logical memory part 1 and 2 indicate: immediate and delayed recall of a short paragraph, respectively. Rey Auditory-verbal learning test (Rey, 1964
) is a word list-learning task consisting of five verbal presentations with recall of a 15-word list. Three scores are reported from this test: supraspan score (number of words recalled from the first presentation of the list), total recall score (total words recalled from the first five presentations) and delayed recall score (total words recalled after half an hour delay).
Complex figure task with two alternate forms (Rey, 1941
) (Taylor, 1979
): copy, immediate and delayed recall of a complex geometric figure.
WMS III letter-number sequencing: sequences of letters and numbers must be reordered giving numbers first in ascending order and then letters in alphabetical order. WMS III digit span: strings of digits must be repeated in the same and then in the reverse order to presentation. WMS III spatial span: spatial patterns must be reproduced first in the same and then in the reverse order to presentation.
The Stroop task (Golden, 1978
) has three conditions, colour word reading, colour patch naming and the interference condition in which colour words are printed in incompatible ink colour. The participant names the colour of the ink, requiring the inhibition of the more salient word reading.
Processing speed and vigilance
Processing speed and vigilance are assessed using a letter cancellation task. A composite score is calculated based on both speed and accuracy.
All participants completed the General Health Questionnaire 12 (GHQ12
) and the Broadbent cognitive failures questionnaire (Broadbent et al, 1982
). The GHQ12
is a 12-item general health measure designed to screen for probable, nonpsychotic psychiatric disorder in community and medical settings (Goldberg and Williams, 1988
). The cognitive failures questionnaire comprises a series of 25 questions relating to lapses in attention in everyday life, such as forgetting what the person went into a room to do. Questions are rated on a five-point scale ranging from 0-‘never' to 5-‘very often'. As part of a structured interview (data to be presented elsewhere), patients were also asked at T2 and T3 whether they had noticed any changes in their memory and attention. Patients completed the Functional Assessment of Cancer Therapy questionnaire (Breast) (FACT B) (Brady et al, 1997
) and the fatigue (F) subscale (Yellen et al, 1997
). In addition, all participants completed a quality of life measure of endocrine symptoms (ES) (Fallowfield et al, 1999
The Statistical Package for the Social Sciences (SPSS) version 11.5 was used for all statistical analyses. Baseline cognitive performance on each measure was analysed using stepwise multiple regression with the predictor variables of treatment group, age, FSIQ, education, psychological distress and menopausal status. Group comparisons on cognitive performance on each measure and on self-reported cognitive failures were made at the three time points, using repeated measures ANOVA with group as the between-subjects factor and time point as the within-subject factor. Where significant main effects of group were found, any variable that had significantly predicted baseline performance on that task was covaried.
Such group comparisons do not identify impairment in subgroups of the population or account for practice effects. To examine performance at an individual level, we used the reliable change index (RCI) with a correction for observed practice effects on each measure (Sawrie et al, 1996
). By using the method put forward by Jacobson and Truax (1991)
, an RCI was calculated for each cognitive measure using the baseline and T2 and baseline and T3 data of the control subjects (see Appendix 1