Changes in Circulating Levels of 25-hydroxyvitamin D3 in Breast Cancer Patients Receiving Chemotherapy

Figures & data

Table 1. Description of the study population.

	Breast cancer patient group (n = 95)	Comparison group (n = 52)	P-value^g
General characteristics
Age (years), mean (SD)	52.0 (8.8)	53.4 (8.9)	0.355
Body mass index (kg/m^2), median (IQR)^a	25.2 (22.5–27.9)	23.3 (21.7–27.1)	0.075
Smoking status, n (%)^b			0.048
Current	18 (19%)	4 (8%)
Former	40 (42%)	18 (35%)
Never	35 (37%)	29 (56%)
Menopausal status, n (%)^b			0.988
Pre-menopausal	53 (56%)	29 (56%)
Post-menopausal	40 (42%)	22 (42%)
Educational level, n (%)			0.154
Low	7 (7%)	3 (6%)
Medium	36 (38%)	13 (25%)
High	49 (52%)	36 (69%)
Unknown	3 (3%)	–
Use of dietary supplements containing vitamin D at start of the study (T1)^c (yes), n (%)	30 (32%)	16 (31%)	0.802
Season of drawing first blood sample (T1), n (%)			0.927
Spring (21 March–21 May)	21 (22%)	11 (21%)
Summer (21 June–21 August)	16 (17%)	11 (21%)
Autumn (21 September–21 November)	18 (19%)	10 (19%)
Winter (21 December–21 February)	40 (42%)	20 (39%)
Season of drawing last blood sample (T3), n (%)			0.023
Spring (21 March–21 May)	17 (18%)	8 (15%)
Summer (21 June–21 August)	12 (13%)	14 (27%)
Autumn (21 September–21 November)	29 (31%)	6 (12%)
Winter (21 December–21 February)	37 (39%)	24 (46%)
Adherence to recommendation for physical activity (T1)^d (yes), n (%)	57 (60%)	33 (64%)	0.686
Adherence to recommendation for physical activity (T3)^e (yes), n (%)	46 (48%)	33 (64%)	0.075
Clinical characteristics
Tumor stage, n (%)			–
I	32 (34%)	NA
II	52 (55%)	NA
III	11 (12%)	NA
Timing of chemotherapy, n (%)			–
Neoadjuvant	33 (35%)	NA
Adjuvant	62 (65%)	NA
Type of chemotherapy, n (%)			–
TAC	35 (37%)	NA
FEC/DOC	31 (33%)	NA
ACPT	11 (12%)	NA
AC/DOC/T	6 (6%)	NA
Other	12 (13%)	NA
Circulating vitamin D levels
Serum 25OHD at baseline (T1) (nmol/L), mean (SD)	54.1 (22.8)	66.1 (23.5)	0.003
Serum 25OHD directly after CTx (T2)^f (nmol/L), mean (SD)	52.4 (21.4)	70.5 (25.5)	<0.001
Serum 25OHD 6 months after CTx (T3)^f (nmol/L), mean (SD)	64.9 (24.5)	69.0 (21.2)	0.304

Data are presented as mean (standard deviation), median (interquartile range) or numbers (percentage). ^aData missing for one patient.^bData missing for one participant from the comparison group and two patients. ^cMultivitamins or specific dietary supplements containing vitamin D. Data missing for two participants from the comparison group and seven patients. ^dDutch recommendations for physical activity referring to ≥ 150 min moderate intensive physical activity per week. Data missing for one participant from the comparison group and two patients. ^eData missing for three participants from the comparison group and six patients. ^fComparable time points for women without cancer refer to 6 months (T2) and 12 months after baseline (T3). ^gCalculated through Mann–Whitney U tests, Student’s t-tests or chi-square tests. CTx, chemotherapy; TAC, docetaxel, doxorubicin, cyclophosphamide; FEC/DOC, 5-fluorouracil, epirubicin, cyclophosphamide and docetaxel; ACPT, doxorubicin, cyclophosphamide, paclitaxel and trastuzumab; AC/DOC/T, doxorubicin, cyclophosphamide, docetaxel and trastuzumab; NA, not applicable.

Figure 1. Percentage of participants with a sufficient, insufficient or deficient vitamin D status. Vitamin D status in breast cancer patients (n = 95) and women without cancer (n = 52) according to the time of sample collection. Baseline samples were collected before start of chemotherapy (CTx) for patients with breast cancer.

Figure 2. Changes in circulating 25(OH)D₃ levels. Estimated marginal means (95% confidence intervals) of the circulating 25(OH)D₃ levels throughout the course of chemotherapy (CTx) in patients with breast cancer and at comparable time points for women from the comparison group based on a linear mixed model analysis. The analyses were adjusted for age and season of each blood withdrawal. ^aStatistically significant interaction for time*group in the linear mixed model analysis. *Indicates a statistically significant difference (Sidak-adjusted P < 0.05) for the comparison between patients and women without cancer identified through a pairwise post-hoc analysis. **Indicates a statistically significant change over time in the patients with breast cancer (Sidak-adjusted P < 0.05). A] All patients with breast cancer (n = 95) and women without cancer (n = 52), B] Patients receiving adjuvant chemotherapy (n = 62) and women without cancer (n = 52), C] Patients receiving neoadjuvant chemotherapy (n = 33) and women without cancer (n = 52), D] Pre-menopausal patients (n = 53) and women without cancer (n = 29), E] Post-menopausal patients (n = 40) and women without cancer (n = 22).

Table 2. Changes in 25OHD levels over time.

Overall analyses
	Breast cancer patient group (n = 95)			Comparison group (n = 52)
	Estimated mean change (nmol/L)	95% confidence interval	P-value^a	Estimated mean change (nmol/L)	95% confidence interval	P-value^a
T2–T1	–5.1	–10.7 ; 0.5	0.082	1.5	–5.8 ; 8.9	0.945
T3–T2	16.0	10.4 ; 21.7	<0.001	1.1	–6.3 ; 8.5	0.978
Stratified analysis for menopausal status: pre-menopausal^b
	Breast cancer patient group (n = 53)			Comparison group (n = 29)
T2–T1	–6.8	–14.9 ; 1.3	0.125	–1.2	–11.7 ; 9.3	0.990
T3–T2	18.3	10.1 ; 26.6	<0.001	1.3	–9.2 ; 11.9	0.987
Stratified analysis for menopausal status: post-menopausal^b
	Breast cancer patient group (n = 40)			Comparison group (n = 22)
T2–T1	–4.5	–12.1 ; 3.0	0.386	6.4	–4.2 ; 17.1	0.377
T3–T2	14.3	6.5 ; 22.0	<0.001	0.3	–10.4 ; 10.9	1.000
Sensitivity analysis^c
	Breast cancer patient group (n = 56)			Comparison group (n = 40)
T2–T1	–7.9	–13.8 ; -2.1	0.004	0.8	–6.0 ; 7.6	0.987
T3–T2	12.8	6.9 ; 18.6	<0.001	0.7	–6.2 ; 7.5	0.994

Estimated mean changes in 25(OH)D₃ levels over time calculated using a linear mixed model analysis adjusted for age and season of blood withdrawal. Time points indicate T1: before start of chemotherapy, T2: directly after chemotherapy and T3: 6 months after chemotherapy for patients and T1: baseline, T2: 6 months after baseline and T3: 12 months after chemotherapy for women without cancer in the comparison group. ^aAdjusted for multiple comparisons using the Sidak procedure in the pairwise post-hoc analysis. ^bAnalyses stratified for menopausal status. Menopausal status unknown for two patients and one participant from the comparison group. ^cSensitivity analysis excluding participants reporting inconsistent use of dietary supplements (starters and stoppers) and the participants for whom it is unknown whether they used dietary supplements at the indicated time points.

Figure 3. Use of dietary supplements containing vitamin D. Dietary supplements with vitamin D as well as multivitamins containing vitamin D were considered. Use of these supplements was reported by the participants at start of the study (T1) and 6 months after the end of chemotherapy for patients (i.e. 12 months after start of the study for the comparison group) (T3). Consistency is reflecting use or nonuse of these supplements at the indicated time points, whereas inconsistency refers to changes in dietary supplement use (i.e., starting of stopping use of dietary supplements containing vitamin D). A] Patients with breast cancer (n = 95), B] Women without cancer from the comparison group (n = 52).