The data of 3115 women were examined in this study. For the breast cancer group, the median age and the fT4, TSH, anti-TPO, and anti-TG levels were 49 years, 15,6 pmol/L, 1,57 µIU/ml, 42,1 IU/mL, and 49,4 IU/mL, respectively. The median age of the patients in the breast cancer groups was significantly different (p < 0.05), while the differences between the groups were not statistically significant in terms of fT4, TSH, or anti-TPO levels (p > 0.05). However, the median anti-TG antibody levels of women with breast cancer were significantly greater than those of women in the benign breast disease patient group and the control group (p < 0.05). A statistically significant difference was found between the median anti-TG levels in the breast cancer patient group and the benign breast disease group and between the median anti-TG levels in the breast cancer patient group and the control group (p = 0.002 and p = 0.000). The parameters of the participants are summarized in Table 1.
Table 1. Descriptive statistics of the study groups
Study Groups
|
Breast Cancer Median (IQR)
(N=44)
|
Benign Breast Disease
Median (IQR)
(N=144)
|
Control
Median (IQR)
(N=2927)
|
Significance
(p value)
|
Age
|
49 (43-61)
|
40 (36-48)
|
33 (29-39)
|
0.000
|
fT4 (pmol/L)
|
15.6 (14.3-17.3)
|
15.2 (14.2-16.8)
|
15.82 (15.5-17.8)
|
0.051
|
TSH (uIU/ml)
|
1.57 (0.65-2.54)
|
1.28 (0.81-1.97)
|
1.40 (0.38-2.08)
|
0.079
|
anti-TPO (IU/mL)
|
42.1 (28-876)
|
41.1 (28.0-581.2)
|
37(28-137)
|
0.705
|
anti-TG (IU/mL)
|
49.4 (15.0-235.1)
|
15 (1.30-158.5)
|
15 (14.9-83.1)
|
0.002
|
Abbreviations: fT4 Free Thyroxine, TSH Thyroid-stimulating hormone, anti-TPO Anti-Thyroid Peroxidase, anti-TG Anti-Thyroglobulin, IQR Interquartile range. The values shown in the table are given as median (interquartile) for continuous values
Furthermore, in the subgroup analysis consisting of peri-postmenopausal women, the median age and the fT4, TSH, anti-TPO, and anti-TG levels for the breast cancer group were 50 years, 15.6 µIU/ml, 1.53 µIU/ml, and 38.8, respectively. and 46.7 IU/ml, respectively. There was no significant difference in the fT4, TSH or anti-TPO values among the three groups (p > 0.05); however, when the three groups were compared, the median age and anti-TG level of the breast cancer patient group were greater than those of the benign breast disease group and the control group. A statistically significant difference in anti-TG levels was detected between the study groups (p=0.001). The descriptive statistics of the study groups for peri-postmenopausal women are given in Table 2.
Table 2: Descriptive statistics of the study groups of peri-postmenopausal women
Study Groups
|
Breast Cancer Median (IQR)
(N=40)
|
Benign Breast Disease
Median (IQR)
(N=79)
|
Control
Median (IQR)
(N=696)
|
Significance
(p value)
|
Age
|
50 (44-62)
|
46 (42-52)
|
48 (43-55)
|
0.04
|
fT4 (pmol/L)
|
15.6 (14.3-17.3)
|
15.5 (14.3-17.3)
|
15.2 (14.2-16.9)
|
0.747
|
TSH (uIU/ml)
|
1.53 (0.65-2.51)
|
1.30 (0.79-1.95)
|
1.5 (0.9-2.3)
|
0.396
|
anti-TPO (IU/mL)
|
38.8 (28-876)
|
42.2 (28.2-986.3)
|
38.3 (28-198.6)
|
0.236
|
anti-TG (IU/mL)
|
46.7 (15.0-284.4)
|
15 (1.30-103.5)
|
15 (1.3-50.5)
|
0.001
|
Abbreviations: fT4 Free Thyroxine, TSH Thyroid-stimulating hormone, anti-TPO Anti-Thyroid Peroxidase, anti-TG Anti-Thyroglobulin, IQR Interquartile range. The values shown in the table are given as median (interquartile) for continuous values.
The distributions of TSH, fT4, anti-TPO and anti-TG levels as categorical variables in peri-postmenopausal women were examined according to the study groups. The fT4 levels of 95% of the women in the breast cancer group, 97.5% of the women in the benign breast disease group and 85.3% of the women in the control group were within the normal range of the reference range. No statistically significant difference was detected between the distribution of fT4 categorical values of the three groups according to the study groups (p>0.05). However, 25%, 12.7%, and 15.3% of the patients in the breast cancer, benign breast disease and control groups, respectively, had TSH levels within the normal range. A statistically significant difference was found between the distribution of TSH categorical values of the three groups according to the study groups (p<0.05). The distributions of TSH and fT4 levels as categorical variables in peri-postmenopausal women according to study group are summarized in Table 3.
The prevalence of anti-TPO antibody positivity was 35.0%, 41.8%, and 34.9% in the breast cancer, benign breast disease and control groups, respectively. In contrast, the prevalence of anti-TG antibody positivity was 45.0%, 30.4% and 23.3% in the breast cancer, benign breast disease and control groups, respectively. There was no statistically significant difference in the distribution of patients with anti-TPO antibody positivity between the study groups (p = 0.52). (Table 3). The number of patients with anti-TG antibody levels ≥60 (anti-TG positive) in the breast cancer group was significantly greater than that in the benign breast disease group and the control group, and a significant difference was detected in the distribution of anti-TG antibody positivity between the study groups (p = 0.0012). The distributions of anti-TPO and anti-TG antibodies according to the study groups are given in Table 3.
Table 3. Distribution of fT4, TSH, anti-TPO, and anti-TG categorical values in peri-postmenopausal women according to study groups
|
Breast Cancer
(N=40)
|
Benign Breast Disease (N=79)
|
Control
(N=696)
|
fT4
>22,7 pmol/L
|
2 (5%)
|
2 (2.5%)
|
27 (3.9%)
|
TSH
>2,5 uIU/ml
|
10 (25%)
|
10 (12.6%)
|
150 (21.4%)
|
anti-TPO Positive
>60 IU/mL
|
14 (35%)
|
33 (41.8%)
|
243 (34.9%)
|
anti-TG Positive
>60 IU/mL
|
18 (45%)
|
24 (30.4%)
|
162 (23.3%)
|
Abbreviations: fT4 Free Thyroxine, TSH Thyroid-stimulating hormone, anti-TPO Anti-Thyroid Peroxidase, anti-TG Anti-Thyroglobulin
Table 4: Association between age, TSH, fT4, anti-TPO and anti-TG antibody levels and breast cancer risk analysis in Turkish women
|
Odds Ratio
(OR)
|
(95% CI)
Low Limit
|
(95%CI)
Upper Limit
|
Significance
(p value)
|
Age
|
1.119
|
1.091
|
1.146
|
<0.001
|
fT4
>22,7 pmol/L
|
1.407
|
0.291
|
6.810
|
0.671
|
TSH
>2,5 uIU/ml
|
5.103
|
0.265
|
98.295
|
0.280
|
anti-TPO Positive
>60 IU/mL
|
0.609
|
0.225
|
0.293
|
0.184
|
anti-TG Positive
>60 IU/mL
|
3.325
|
1.625
|
6.803
|
0.001
|
Abbreviations: fT4 Free Thyroxine, TSH Thyroid-stimulating hormone, anti-TPO Anti-Thyroid Peroxidase, anti-TG Anti-Thyroglobulin, OR odds ratios, CI confidence intervals
Binary logistic regression analysis was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for breast cancer patients. There was no overall statistically significant association between fT4, TSH, or anti-TPO levels and breast cancer in Turkish women (Table 4). The risk of breast cancer in anti-TG-positive women was 3.3 times greater than that in anti-TG-negative women. (OR = 3.325, 95% CI = 1.625-6.803, p = 0.001). (Table 4)
Table 5: Association between age, TSH, fT4, anti-TPO and anti-TG antibody levels and breast cancer risk analysis in peri-postmenopausal Turkish women
|
Odds Ratio
(OR)
|
(95% CI)
Low Limit
|
(95%CI)
Upper Limit
|
Significance
(p value)
|
Age
|
1.061
|
1.023
|
1.100
|
0.001
|
fT4
>22,7 pmol/L
|
1.23
|
0.267
|
5.657
|
0.790
|
TSH
>2,5 uIU/ml
|
1.198
|
0.557
|
2.576
|
0.644
|
anti-TPO Positive
>60 IU/mL
|
0.492
|
0.225
|
1.075
|
0.075
|
anti-TG Positive
>60 IU/mL
|
3.57
|
1.691
|
7.540
|
0.001
|
Abbreviations: fT4 Free Thyroxine, TSH Thyroid-stimulating hormone, anti-TPO Anti-Thyroid Peroxidase, anti-TG Anti-Thyroglobulin, OR odds ratios, CI confidence intervals
In peri-postmenopausal women, a significant association was also not found between fT4, TSH, or anti-TPO levels and breast cancer. (Table 5). However, a significant positive association was found between anti-TG antibody levels and breast cancer risk. Postmenopausal women who were anti-TG-positive had a 3.57-fold greater risk of developing breast cancer than women who were anti-TG-negative (OR = 3.57, 95% CI = 1.691-7.540, p = 0.001). (Table 5)
The relationship between thyroid antibody levels and breast cancer risk in peri-postmenopausal women was further evaluated via receiver operating characteristic (ROC) curve analysis. The ROC curves showing the sensitivity and specificity of the anti-TPO and anti-TG antibodies are provided in Figure 2.
The area under the curve (AUC) of the anti-TPO antibody was 52.1% (95% CI, 0.486-0.555), with a sensitivity of 25.0% (95% CI 12.7-41.2) and a specificity of 85.3% (95% CI 82.6 - 87.7) (p=0.662). The optimal cut-off value for the anti-TPO antibody level was 1290.2. The AUC of the anti-TG antibody was 67.3% (95% CI, 0.640-0.705), with a sensitivity of 65.0% (95% CI, 48.3-79.4) and a specificity of 66.8% (95% CI 63.4 - 70.1) (p=0.003). The optimal cut-off value for the anti-TG antibody level was 21. (Table 6)
Table 6. ROC analysis of anti-TPO and anti-TG antibodies
|
AUC (95% CI)
|
Cut-off Value
|
Sensitivity
(95% CI)
|
Specificity
(95% CI)
|
anti-TPO
|
0.521 (0.486 - 0.555)
|
1290.2
|
25 (12.7-41.2)
|
85,3 (82.6 - 87.7)
|
anti-TG
|
0.673 (0.640 - 0.705)
|
21
|
65 (48.3-79.4)
|
66,8 (63.4 - 70.1)
|
Abbreviations: anti-TPO Anti-Thyroid Peroxidase, anti-TG Anti-Thyroglobulin, AUC Area Under Curve, CI confidence intervals
According to the ROC analysis, the positive predictive values (PV+) for the anti-TPO and anti-TG antibody levels were 8.1% and 9.2%, respectively, and the negative predictive values (PV-) were 95.7% and 97.4%, respectively. The positive likelihood ratios (LRs) were 1.7 and 1.96 for anti-TPO and anti-TG, respectively, and the negative likelihood ratios (LRs) were 0.88 and 0.52, respectively. (Table 7).
Table 7. Results of +LR, -LR, PV+, and PV- values for anti-TPO and anti-TG
|
+LR
(95% CI)
|
-LR
(95% CI)
|
PV+
(95% CI)
|
PV-
(95% CI)
|
anti-TPO
|
1.7
(1.163 - 2.237)
|
0.88
(0.032 - 1.792)
|
8.1%
(6.23% - 9.97%)
|
95.7%
(94.3% - 97.1%)
|
anti-TG
|
1.96
(1.727 - 2.193)
|
0.52
(0.0744 - 0.9656)
|
9.2%
(7.22% - 11.18%)
|
97.4%
(96.3% - 98.5%)
|
Abbreviations: anti-TPO Anti-Thyroid Peroxidase, anti-TG Anti-Thyroglobulin, AUC Area Under Curve, CI confidence intervals, +LR Positive Likelihood Ratios, -LR Negative Likelihood Ratios, PV+ Positive Predictive Values, PV- Negative Predictive Values