Neuropsychological functioning in postmenopausal breast cancer patients treated with tamoxifen or exemestane after AC-chemotherapy: Cross-sectional findings from the neuropsychological TEAM-side study

Figures & data

Table I.  Summary of cognitive test measures and outcome variables

Cognitive domain	Cognitive tests	Outcome variable	Score range
Verbal memory	Rey auditory verbal learning test[21] (Dutch shortened version)	1. Total of 3 trials 2. Total for long delay trial	0-45 0–15
Visual memory	Wechsler Memory Scale revised – visual memory subtest[22] Visual Association Test[23]	3. Immediate recall 4. Delayed recall 5. Total of 2 trials	0–41 0–41 0–24
Working memory	WAIS III Letter-number sequencing[24]	6. Total correct trials	0–21
Attention/concentration	Stroop Card 1[25] Stroop Card 2[25] Trailmaking A[26]	7. Seconds to complete 8. Seconds to complete 9. Seconds to complete	0+ 0+ 0 +
Mental Flexibility	Stroop Card 3[25] Trailmaking B[26]	10. Seconds to complete 11. Seconds to complete	0+ 0 +
Speed of information processing	Fepsy Reaction times: [27] 1. dominant hand 2. non-dominant hand	12. Mean msec/30 trials 13. Mean msec/30 trials	0+ 0 +
Manual motor speed	Fepsy Finger tapping: [27] 1. dominant hand 2. non-dominant hand	14. Mean score of 5 trials of 10 seconds 15. Mean score of 5 trials of 10 seconds	0+ 0 +
Verbal fluency	Letter fluency (D,A,T) [29] Category Fluency (Animals/ professions)[28]	16. Total score of 3 letters/1 minute each 17. Total score animals/1 minute 18. Total score professions/1 minute	0+ 0+ 0 +

Table II.  Sociodemographic characteristics of patients and controls

	AC/Tam (n = 30)	AC/Exe (n = 50)	Controls (n = 48)	P-value
Mean age, yrs (SD) range	57.9 (3.9) 49–65	58.5 (5.4) 48–71	60.2 (5.1) 49–71	0.10
Level of education (%, n)
Low	20 (6)	12 (6)	13 (6)	0.46
Middle	67 (20)	68 (34)	58 (28)
High	13 (4)	20 (10)	29 (14)
IQ estimate	98.7 (13.7)	104.0 (17.6)	103.0 (15.6)	0.36
Current treatment for:
- high blood pressure (%, n)	13 (4)	22 (11)	25 (12)	0.46
- diabetes mellitus (%, n)	0 (0)	8 (4)	6 (3)	0.30
HRT use
- previous (%, n)	23 (7)	38 (19)	21 (10)	0.13
- current (%, n)	0 (0)	0 (0)	4 (2)
- never (%, n)	77 (23)	62 (31)	75 (36)
Current use of
- anti-depressive medication (%, n)	7 (2)	6 (3)	0 (0)	0.21
- benzodiazepines (%, n)	20 (6)	18 (9)	8 (4)	0.27
- cholesterol lowering agents (%, n)	7 (2)	4 (2)	13 (6)	0.28
Mean time since completion of chemotherapy (yrs, SD)	1.9 (0.5)	2.4 (0.7)	–	0.002
Past radiotherapy (%, n)	83 (25)	80 (40)	–	0.78

AC/Tam = doxorubicin/cyclophosphamide chemotherapy followed by tamoxifen; AC/Exe = doxorubicin/cyclophosphamide chemotherapy followed by exemestane; SD = standard deviation.

Table III.  Self reported cognitive problems in daily life^a.

	AC /Tam (n = 30)	AC /Exe (n = 50)	Controls (n = 48)	P-value
Memory (%, n)	28 (8) ^b	24 (12)	6 (3)	0.02
Concentration (%, n)	21 (6) ^b	18 (9)	13 (6)	0.60
Thinking (%, n)	7 (2)	6 (3)	2 (1)	0.55
Language (%, n)	17 (5)	10 (5)	2 (1)	0.34
CFQ ^c (mean; SD)	33.8 (9.3)	36.7 (11.2)	32.6 (7.6)	0.11

AC/Tam = doxorubicin/cyclophosphamide chemotherapy followed by tamoxifen; AC/Exe = doxorubicin/cyclophosphamide chemotherapy followed by exemestane; SD = standard deviation.

^aPatients who rated the frequency of their cognitive problem as at least 2 (‘regularly’) in a distinct domain were considered as having a complaint.

^bn = 29.

^cRange 0–100, higher scores means higher frequency of cognitive lapses in daily life

Table IV.  Health related quality of life (EORTC-QLQ-C30), Anxiety and Depression (HSCL), Fatigue (MFI) and Menopausal symptoms (FACT-B ES). Left side: AC/tamoxifen users versus AC/exemestane users; Right side: combined patient group versus healthy controls.

	AC/Tam	AC/Exe	P-value^f	Effect-	Combined patient group	Controls	P-value	Effect-
	(n = 30) Mean	(n = 50)		size^g	(n = 80)	(n = 48)		size^g
	(SD)	Mean (SD)			Mean (SD)	Mean (SD)
EORTC-QLQ-C30
Function Scales^a
Physical	83.8 (14.9)	86.7 (14.4)	.54	.14	85.6 (14.6)	87.2 (15.0)	.54	.11
Role	81.1 (23.0)	84.0 (23.6)	.83	.05	82.9 (23.3)	89.9 (19.7)	.08	.31
Cognitive	79.4 (23.0)	80.3 (20.9)	.86	.04	80.0 (21.6)	92.0 (12.9)	.001	.62
Emotional	84.7 (20.2)	84.3 (15.8)	.74	.08	84.5 (17.4)	85.8 (17.2)	.69	.07
Social	91.7 (21.3)	89.3 (18.1)	.56	.13	90.2 (19.2)	93.4 (14.9)	.33	.18
Global QoL	79.2 (17.6)	81.2 (17.2)	.99	.00	80.4 (17.3)	85.2 (16.7)	.12	.28
Symptom scales/items^b
Fatigue	28.5 (20.6)	23.8 (21.4)	.55	.14	25.6 (21.1)	15.0 (12.7)	.002	.56
Nausea and vomiting	6.1 (18.8)	3.3 (8.2)	.56	.13	4.4 (13.2)	1.4 (4.7)	.13	.27
Pain	22.2 (27.8)	18.3 (24.6)	.81	.05	19.8 (25.7)	19.1 (27.5)	.89	.03
Dyspnea	16.7 (21.0)	6.7 (16.5)	.05	.45	10.4 (18.8)	6.3 (14.8)	.19	.23
Sleep disturbance	37.8 (31.2)	31.3 (31.2)	.38	.20	33.8 (31.1)	18.8 (26.5)	.006	.50
Appetite loss	8.9 (19.4)	6.0 (17.4)	.46	.17	7.1 (18.1)	4.2 (16.3)	.36	.16
Constipation	4.4 (14.5)	7.3 (15.5)	.27	.25	6.3 (15.1)	4.2 (11.1)	.41	.15
Diarrhea	2.2 (8.5)	3.3 (15.4)	.36	.21	2.9 (13.2)	2.1 (8.2)	.69	.07
Financial impact	2.2 (8.5)	4.0 (12.8)	.27	.26	3.3 (11.3)	1.4 (6.7)	.28	.19
HSCL^b
Anxiety	14.7 (9.0)	10.2 (9.9)	.20	.29	11.9 (9.87)	9.9 (11.0)	.28	.19
Depression	13.5 (9.9)	13.1 (9.9)	.81	.06	13.2 (9.8)	9.8 (10.8)	.07	.33
MFI
General fatigue^c	10.6 (4.1)	9.2 (3.9)	.38	.20	9.7 (4.0)	7.6 (3.1)	.002	.56
Physical fatigue^c	9.6 (4.7)	8.7 (4.1)	.97	.01	9.0 (4.3)	7.9 (3.5)	.12	.28
Reduction of activities^c	9.2 (4.5)	9.2 (4.1)	.46	.17	9.2 (4.2)	7.3 (2.9)	.006	.49
Reduction of motivation^c	8.8 (3.4)	7.9 (3.4)	.56	.13	8.3 (3.4)	6.5 (3.0)	.004	.52
Mental fatigue^c	10.5 (4.1)	9.7 (4.5)	.85	.04	10.0 (4.3)	8.7 (3.8)	.10	.29
FACT-B ES total score^d	57.7 (8.2)	57.0 (9.1)	.38	.20	57.3 (8.7)	62.1 (6.1)	.001	.60

AC/Tam = doxorubicin/cyclophosphamide chemotherapy followed by tamoxifen; AC/Exe = doxorubicin/cyclophosphamide chemotherapy followed by exemestane; SD = standard deviation; EORTC = European Organization for Research an Treatment of Cancer; EORTC QLQ-C30 is a health-related quality of life questionnaire; HSCL (Hopkins Symptom Check-list-25) is a anxiety/depression symptom checklist; MFI = multi-dimensional fatigue inventory is a questionnaire addressing several dimensions of fatigue, FACT B ES the Endocrine Subscale of the Functional Assessment of Cancer Therapy – Breast questionnaire for assessment of menopausal symptoms (see ‘Materials and methods’ section for more details).

^a Higher scale means better functioning; scale 0–100. ^b Higher score means more serious complaints; scale 0–100. ^c Higher score means more serious complaints; scale 4–20. ^d Higher score means less serious complaints; scale 0–72. ^f P-value adjusted for time since completion of chemotherapy. ^gCohen's d: <.50: small effect, .50–.80: medium effect, >.80: large effect, range 0–2.

Table V.  Cognitive test scores (raw test scores). Left side: AC/tamoxifen users versus AC/exemestane users; Right side: combined patient group versus healthy controls.

Cognitive domains and tests	AC/Tam	AC/Exe	P-value *	Effect-	Combined	Controls	P-value **	Effect-sizeg
	(n = 30)	(n = 50)		Size^g	patient group	(n = 48)
(see table 1 for more details)	Mean (SD)	Mean (SD)			(n = 80)	Mean (SD)
					Mean (SD)
Verbal memory
RAVLT immediate ^#	21.2 (5.1)	22.8 (4.7)	.22	.29	22.2 (4.9)	23.5 (5.2)	.08	.31
RAVLT delayed ^¥	6.6 (2.2)	7.0 (2.2)	.42	.19	6.8 (2.2)	7.3 (2.9)	.21	.22
Visual memory
Visual Association Test^¥	20.5 (2.9)	21.5 (2.3)	.16	.33	21.1 (2.5)	21.3 (2.4)	.54	.11
WMS Visual memory immediate ^¥	32.9 (5.8)	32.6 (4.7)	.57	.13	32.7(5.1)	33.6 (4.4)	.16	.25
WMS Visual memory delayed ^¥	29.4 (7.3)	29.2 (6.8)	.36	.21	29.3 (7.0)	30.7 (5.3)	.10	.30
Working memory
Letter Number Sequencing ^¥	9.7 (2.1)	10.1 (2.4)	.64	.11	9.9 (2.3)	9.8 (2.4)	.79	.05
Attention/Concentration
Stroop Card 1^§	48.7 (8.1)	44.8 (6.1)	.13	.36	46.3 (7.2)	46.1 (7.5)	.86	.03
Stroop Card 2 ^§	62.2 (9.9)	58.1 (9.0)	.16	.33	60.0 (9.5)	60.1 (9.6)	.97	.01
Trailmaking A^§	36.5 (13.8)	40.3 (16.4)	.07	.43	38.9 (15.5)	36.0 (10.5)	.12	.28
Mental flexibility
Stroop Card 3 ^§	108.7 (22.0)	97.7 (22.5)	.07	.42	101.8 (22.8)	96.4 (18.2)	.02	.43
Trailmaking B ^§	82.6 (25.2)	86.8 (35.3)	.08	.40	85.2(31.8)	82.1 (31.7)	.21	.23
Information Processing Speed
RT - dominant hand ^‡	355 (84)	339 (66)	.62	.12	345 (73)	316(47)	.01	.47
RT - non-dominant hand ^‡	340 (98)	347 (68)	.74	.08	344 (80)	304 (53)	.002	.56
Motor Speed
Tapping dominant hand ^?	60.2 (8.3)	59.0 (8.4)	.24	.28	59.4 (8.3)	54.9 (8.2)	.01	.45
Tapping non-dominant hand ^?	53.9 (7.5)	53.2 (7.8)	.50	.16	53.4 (7.7)	50.4 (7.3)	.06	.34
Verbal Fluency
Category fluency – animals t	21.4 (4.1)	23.0 (5.6)	.42	.19	22.4 (5.2)	25.5 (6.3)	.001	.60
Category fluency – professions t	16.6 (4.0)	17.4 (4.6)	.66	.10	17.1 (4.4)	20.9 (6.0)	<.001	.80
Letter fluency (DAT)^tt	33.5 (9.3)	39.0 (10.9)	.14	.34	36.9(10.7)	39.5(11.9)	.14	.27

^aAC/Tam = doxorubicin/cyclophosphamide chemotherapy followed by tamoxifen; ^bAC/Exe = doxorubicin/cyclophosphamide chemotherapy followed by exemestane; SD = standard deviation; *adjusted for age/IQ/time since completion chemotherapy; **adjusted for age/IQ.

#total number of words after 3 trials; ^¥number of correct responses; § seconds to complete task (lower scores represent better performance); ‡milliseconds (lower scores represent better performance); ^!!mean of 5 trials of 10 seconds; ttotal of words produced in one minute; ^{t t}total number of words produced in 3 minutes (1 minute for each letter). ^g Cohen's d: <.50: small effect, .50–.80: medium effect, >.80: large effect, range 0–2.

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