Pretreatment Circulating Albumin, Platelet, and RDW-SD Associated with Worse Disease-Free Survival in Patients with Breast Cancer

Figures & data

Table 1 Descriptive Baseline Characteristics of the Study Participants by Disease Recurrence Status

Variable	Total	Disease Recurrence		p-value
		Present	Absent
No	559	86(15.4)	473(84.6)
Age (year)	55.6±12.0	54.5±12.3	55.8±11.9	0.369
Body mass index (kg/m^2)	25.2±4.7	24.2±4.5	25.3±4.7	0.036
Systolic BP (mmHg)	130±20	126±19	130±20	0.099
Diastolic BP (mmHg)	77±12	74±11	78±12	0.024
Smoking	14(2.5)	3(3.5)	11(2.3)	0.530
Drinking	12(2.2)	1(1.2)	11(2.3)	0.491
Diabetes mellitus	79(14.1)	11(12.8)	68(14.4)	0.693
Hypertension	158(28.3)	20(23.3)	138(29.2)	0.258
Hyperlipidemia	30(5.4)	4(4.7)	26(5.5)	0.746
Age (year)
<50	139(24.9)	23(26.7)	116(24.5)	0.661
≥50	420(75.1)	63(73.3)	357(75.5)
Surgery type
Breast-conserving surgery	226(40.4)	22(25.6)	204(43.1)	0.002
Total mastectomy	231(41.3)	38(44.2)	193(40.8)	0.558
Others	102(18.3)	26(30.2)	76(16.1)	0.002
Histopathology
Invasive ductal carcinoma	331(59.2)	51(59.3)	280(59.2)	0.985
Invasive lobular carcinoma	30(5.4)	6(7.0)	24(5.1)	0.471
Mucinous carcinoma	20(3.6)	0(0.0)	20(4.2)	0.052
Others	178(31.8)	29(33.7)	149(31.5)	0.684
Tumor site
Bilateral	1(0.2)	0(0.0)	1(0.2)	0.670
Right	270(48.3)	42(48.8)	228(48.2)	0.914
Left	288(51.5)	44(51.2)	244(51.6)	0.943
Tumor size
<2 cm	379(67.8)	57(66.3)	322(68.1)	0.743
2–5 cm	135(24.1)	23(26.7)	112(23.7)	0.541
>5 cm	45(8.1)	6(7.0)	39(8.3)	0.691
Clinical tumor stage
T0-1	363(64.9)	51(59.3)	312(66.0)	0.305
T2	162(29.0)	24(27.9)	138(29.1)	0.793
T3-T4	34(6.1)	11(12.8)	23(4.9)	0.010
Tumor grade
1	100(17.9)	8(9.3)	92(19.4)	0.099
2	304(54.4)	44(51.2)	260(55.0)	0.688
3	155(27.7)	34(39.5)	121(25.6)	0.046
AJCC stage
I–II	440(78.7)	33(38.4)	407(86.0)	<0.0001
III	119(21.3)	53(61.6)	66(14.0)
Ki67 status
<14%	226(40.4)	22(25.6)	204(43.1)	0.009
≥14%	333(59.6)	64(74.4)	269(56.9)
Estrogen receptor
Negative	108(19.3)	25(29.1)	83(17.6)	0.023
Positive	451(80.7)	61(70.9)	390(82.4)
Progesterone receptor
Negative	188(33.6)	41(47.7)	147(31.1)	0.004
Positive	371(66.4)	45(52.3)	326(68.9)
HER2
Negative	297(53.1)	38(44.2)	259(54.8)	0.073
Positive	262(46.9)	48(55.8)	214(45.2)
Radiotherapy
Yes	253(45.3)	41(47.7)	212(44.8)	0.625
No	306(54.7)	45(52.3)	261(55.2)
Chemotherapy
Yes	271(48.5)	60(69.8)	211(44.6)	<0.0001
No	288(51.5)	26(30.2)	262(55.4)
Hormone therapy
Yes	365(65.3)	69(80.2)	296(62.6)	0.002
No	194(34.7)	17(19.8)	177(37.4)

Notes: Data are presented as means ± SD or number (percentage). AJCC, American Joint Committee on Cancer.

Abbreviation: HER2, human epithelial growth factor receptor-2.

Table 2 Descriptive Baseline Biochemical Data at Primary Diagnosis of the Study Participants by Disease Recurrence Status

Variable	Total	Disease Recurrence		p-value
		Present	Absent
No	559	86(15.4)	473(84.6)
Carcinoembryonic antigen (ng/mL)	1.9(1.3–3.2)	2.3(1.4–5.6)	1.8(1.2–2.8)	0.005
CA153 (U/mL)	9.9(7.1–16.6)	13.8(8.1–36.6)	9.7(6.9–15.0)	<0.0001
HbA1C (%)	6.8±1.4	6.8±1.0	6.9±1.5	0.893
Fasting glucose (mg/dl)	119.8±41.1	114.8±23.5	120.5±43.2	0.516
Total cholesterol (mg/dl)	196.3±42.1	194.3±41.6	196.6±42.3	0.790
Triglycerides (mg/dl)	115.0(75.0–175.3)	106.0(77.0–201.5)	118.0(74.0–175.0)	0.039
HDL-cholesterol (mg/dl)	61.1±15.7	57.0±16.4	61.6±15.5	0.172
LDL-cholesterol (mg/dl)	111.0±38.7	106.7±35.8	111.5±39.2	0.565
Uric acid (mg/dl)	5.5±1.4	6.0±1.6	5.4±1.3	0.170
Aspartate aminotransferase (U/L)	22.0(19.0–29.0)	23.0(18.0–31.5)	22.0(19.0–29.0)	0.003
Alanine aminotransferase (U/L)	19.0(14.0–27.0)	18.0(13.0–32.0)	19.0(14.5–27.0)	0.276
Alkaline phosphatase (U/L)	214.0(171.0–269.5)	217.0(167.0–302.0)	214.0(171.0–267.0)	0.105
Creatinine (mg/dl)	0.9±0.6	0.9±0.4	0.9±0.7	0.627
eGFR (mL/min/1.73m^2)	114.0±39.0	110.7±43.7	114.6±38.1	0.397
Albumin (g/dl)	4.3±0.6	3.9±0.6	4.4±0.6	0.0001
White blood cell (10^9/l)	6.600(5.330–7.970)	6.630(5.330–7.920)	6.510(5.300–8.463)	0.013
Neutrophil count (10^9/l)	4090(3189–5367)	4542(3298–6117)	3977(3173–5219)	0.001
Monocyte count (10^9/l)	351(289–468)	359(289–508)	349(289–457)	0.017
Lymphocyte count (10^9/l)	1771(1352–2185)	1642(1110–2027)	1788(1418–2210)	0.063
Eosinophil count (10^9/l)	91.0(48.8–156.4)	63.0(31.7–128.1)	97.8(50.1–161.8)	0.385
Basophil count (10^9/l)	32.6(20.5–51.7)	33.1(20.5–51.7)	31.4(19.5–51.9)	0.025
Red blood cell (10^6/μL)	4.41±0.53	4.36±0.63	4.42±0.51	0.383
Hemoglobin (g/dl)	12.6±1.6	12.2±1.7	12.7±1.6	0.010
Hematocrit (%)	38.3±4.4	37.4±4.4	38.5±4.4	0.030
Mean corpuscular volume (fL)	87.4±8.2	86.5±9.3	87.6±8.0	0.228
MCH (pg/cell)	28.8±3.4	28.3±3.9	28.9±3.3	0.126
MCHC (g/dL)	32.9±1.4	32.6±1.6	32.9±1.4	0.068
Platelet (10^3/μL)	254.0(211.0–306.5)	275.5(225.0–333.3)	249.0(210.0–299.0)	0.0003
RDW-SD (fL)	42.7±4.7	44.0±6.1	42.5±4.4	0.013
RDW-CV (%)	13.7±2.3	14.2±2.4	13.6±2.3	0.035
Leptin (ng/mL)	11.2(7.9–16.0)	9.9(7.4–13.1)	11.4(7.9–16.1)	0.796
Sarcopenia ratio	8.2±2.4	8.9±3.3	8.1±2.3	0.132

Note: Data are means ± SD.

Abbreviations: HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular- hemoglobin concentration; RDW, red cell distribution width; SD, standard deviation; CV, coefficient of variation.

Table 3 Cox Proportional Hazard Model of Baseline Clinical Risk Factors for Breast Cancer Recurrence in the Whole Cohort

Baseline Data	Univariate Analysis HR (95% CI)	p-value	Multivariate Analysis* HR (95% CI)	p-value
Age	0.98 (0.99–1.02)	0.023
Body mass index	0.95 (0.99–1.05)	0.036
Smoking	1.58 (0.39–4.23)	0.467
Drinking	0.51 (0.03–2.29)	0.452
Diabetes mellitus	0.89 (0.45–1.60)	0.715
Hypertension	0.74 (0.44–1.20)	0.229
Hyperlipidemia	0.70 (0.21–1.67)	0.453
Surgery type
Total mastectomy	Reference
Breast-conserving surgery	0.50 (0.30–0.80)	0.003
Others	2.68 (1.65–4.25)	0.0001
Histopathology
Invasive ductal carcinoma	Reference
Invasive lobular carcinoma	1.20 (0.47–2.53)	0.678
Others	1.47 (0.93–2.29)	0.099
Tumor site
Right	Reference
Left	0.87 (0.57–1.33)	0.525
Tumor size
<2 cm	Reference
2–5 cm	1.27 (0.77–2.02)	0.333
>5 cm	1.30 (0.50–2.76)	0.550
Clinical tumor stage
T0-1	Reference
T2	0.99 (0.58–1.64)	0.984
T3-T4	2.55 (1.17–4.91)	0.021
Tumor grade
1	Reference
2	1.02 (0.64–1.59)	0.937
3	2.18 (1.30–3.51)	0.004
AJCC stage
I–II	Reference
III	6.31 (3.91–10.34)	<0.0001	4.84 (2.88–8.22)	<0.0001
Ki67 status
<14%	Reference
≥14%	2.34 (1.36–4.24)	0.002	2.23 (1.23–4.33)	0.007
Estrogen receptor
Positive	Reference
Negative	1.76 (1.08–2.79)	0.025
Progesterone receptor
Positive	Reference
Negative	1.91 (1.24–2.93)	0.003
HER2
Negative	Reference
Positive	1.24 (0.80–1.94)	0.329
Radiotherapy
No	Reference
Yes	0.85 (0.55–1.30)	0.451
Chemotherapy
No	Reference
Yes	1.89 (1.20–3.05)	0.005
Hormone therapy
No	Reference
Yes	1.51 (0.91–2.66)	0.117

Notes: *The model was included variables with a p-value <0.1 in univariate analysis.

Abbreviation: HR, Hazard ratio.

Table 4 Cox Proportional Hazard Model of Baseline Biochemical Risk Factors for Breast Cancer Recurrence in the Whole Cohort

Baseline Data	Univariate Analysis HR (95% CI)	p-value	Multivariate Analysis* HR (95% CI)	p-value
Carcinoembryonic antigen	1.00 (1.00–1.00)	0.016
CA153	1.00 (1.00–1.00)	0.006
HbA1C	0.97 (0.50–1.54)	0.922
Fasting glucose	1.00 (0.98–1.01)	0.470
Total cholesterol	1.00 (0.99–1.01)	0.638
Triglycerides	1.00 (0.99–1.00)	0.277
HDL-cholesterol	0.99 (0.96–1.01)	0.359
LDL-cholesterol	1.00 (0.99–1.01)	0.506
Uric acid	1.45 (0.92–2.18)	0.106
Aspartate aminotransferase	1.01 (1.00–1.02)	0.039
Alanine aminotransferase	1.00 (0.99–1.01)	0.497
Alkaline phosphatase	1.00 (0.99–1.00)	0.195
Creatinine	0.92 (0.46–1.24)	0.698
eGFR	1.01 (1.00–1.01)	0.047
Albumin	0.17 (0.10–0.32)	<0.0001	0.23 (0.13–0.45)	<0.0001
White blood cell	1.10 (1.05–1.15)	0.001
Neutrophil count	1.00 (1.00–1.00)	0.0003
Monocyte count	1.00 (1.00–1.00)	0.044
Lymphocyte count	0.99 (0.99–1.00)	0.155
Eosinophil count	1.00 (0.99–1.00)	0.084
Basophil count	1.00 (0.99–1.00)	0.093
Red blood cell	0.88 (0.58–1.33)	0.551
Hemoglobin	0.87 (0.77–0.99)	0.030
Hematocrit	0.96 (0.92–1.01)	0.083
Mean corpuscular volume	0.99 (0.96–1.01)	0.269
MCH	0.96 (0.91–1.02)	0.159
MCHC	0.88 (0.77–1.02)	0.083
Platelet	1.01 (1.00–1.01)	0.0003	1.00 (1.00–1.01)	0.037
RDW-SD	1.06 (1.01–1.09)	0.017	1.10 (1.00–1.18)	0.041
RDW-CV	1.09 (1.01–1.15)	0.030
Leptin	0.78 (0.39–1.50)	0.462
Sarcopenia ratio	1.07 (0.91–1.21)	0.394

Note: *The model was included variables with a p-value <0.1 in univariate analysis.

Abbreviations: HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular-hemoglobin concentration; RDW, red cell distribution width; SD, standard deviation; CV, coefficient of variation.

Figure 1 Receiver operating characteristic (ROC) curves of albumin, platelet, and RDW-SD to detect the risk of disease recurrence. A threshold value of <4.1 g/dl was associated with the risk of disease recurrence with a sensitivity of 55.9% and specificity of 24.5% for albumin (A). A threshold value of >253 10^3/μL was associated with the risk of disease recurrence with a sensitivity of 65.5% and specificity of 48.1% for platelet (B). A threshold value of >44 fL was associated with the risk of disease recurrence with a sensitivity of 36.6% and specificity of 21.7% for red cell distribution width-standard deviation (RDW-SD) (C).

Figure 2 Comparison of disease-free survival between albumin <4.1 g/dl group and albumin ≥4.1 g/dl group (A), platelet >253 10^3/μL group and platelet ≤253 10^3/μL group (B), and red cell distribution width-standard deviation (RDW-SD) >44 fL group and RDW-SD ≤44 fL group (C) in patients with breast cancer.

Figure 3 Structural equation model for disease recurrence in patients with breast cancer. Comparative fit index (CFI), 1.000; goodness of fit index (GFI), 0.980; root mean square error of approximation (RMSEA), 0.000; standardized root mean square residual (SRMR), 0.049. *p<0.05, **p<0.01, and ***p<0.001. Path loadings are standardized coefficients. Abbreviations: AST, aspartate aminotransferase; WBC, white blood cell; RDW-SD, red cell distribution width-standard deviation; AJCC, American Joint Committee on Cancer.