In Early Breast Cancer, the Ratios of Neutrophils, Platelets and Monocytes to Lymphocytes Significantly Correlate with the Presence of Subsets of Circulating Tumor Cells but Not with Disseminated Tumor Cells
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Clinical Characteristics of Patients
2.2. Establishment of Cut-Off Values
2.3. Correlation of NLR, PLR and MLR with Clinical Characteristics
2.4. Mean Differences of CTC Subtypes, DTCs and Blood Values
2.5. Prognostic Role of Blood Cell Counts, Ratios, CTCs and DTCs
2.6. Prognostic Value of CTCs, DTCs in Combination with NLR, PLR and MLR
2.7. Univariate and Multivariate Analysis
3. Discussion
4. Patients and Methods
4.1. Study Population
4.2. Selection and Detection of CTCs
4.3. Selection and Detection of DTCs
4.4. Statistical Analysis
5. Limitations of the Study and Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Number of Patients | % | |
---|---|---|
Age (years) | ||
Median | 61 | |
Range | 31–83 | |
Menopausal Status | ||
Premenopausal | 32 | 18.7 |
Perimenopausal | 16 | 9.4 |
Postmenopausal | 123 | 71.9 |
Histology | ||
Ductal | 134 | 78.4 |
Lobular | 17 | 9.9 |
Others | 20 | 11.7 |
Tumor Size | ||
pT1 | 102 | 59.6 |
pT2 | 64 | 37.4 |
>pT2 | 5 | 2.9 |
Nodal Status | ||
pN0 | 101 | 59.1 |
pN1 | 66 | 38.6 |
pN2 and pN3 | 4 | 2.3 |
Grading | ||
I | 11 | 6.4 |
II | 100 | 58.5 |
III | 60 | 35.1 |
ER Status | ||
Negative | 37 | 21.6 |
Positive | 134 | 78.4 |
PR Status | ||
Negative | 52 | 30.4 |
Positive | 119 | 69.6 |
HER2 Status | ||
Negative | 144 | 84.2 |
Positive | 27 | 15.8 |
Immunohistochemical Subtype | ||
(ER−, PR−, HER2−) | 26 | 15.2 |
(ER−, PR−, HER2+) | 8 | 4.7 |
(ER+ and/or PR+, HER2−) | 118 | 69 |
(ER+ and/or PR+, HER2+) | 19 | 11.1 |
DTC | ||
Negative | 112 | 65.9 |
Positive | 58 | 34.1 |
n.d. | 1 | |
CTC | ||
Negative | 111 | 72 |
Positive | 44 | 28 |
n.d. | 16 | |
NLR | ||
>3.13 | 42 | 25 |
<3.13 | 127 | 75 |
n.d. | 2 | |
PLR | ||
>222.3 | 42 | 25 |
<222.3 | 129 | 75 |
MLR | ||
>0.39 | 47 | 28 |
<0.39 | 122 | 72 |
n.d. | 2 | |
Recurrent | 10 | 6 |
Deceased | 15 | 9 |
n | Mean | Median | Perc 25 | Perc 75 | SD | Min | Max | |
---|---|---|---|---|---|---|---|---|
NLR | 169 | 2.97 | 2.24 | 1.68 | 3.13 | 2.6 | 0.45 | 22.37 |
PLR | 170 | 193.6 | 161 | 124.5 | 222.3 | 135 | 30.2 | 1492.7 |
MLR | 169 | 0.33 | 0.29 | 0.22 | 0.39 | 0.17 | 0.03 | 0.99 |
Neutrophils (nL) | 169 | 4.45 | 4.03 | 3.13 | 5.31 | 2 | 0.25 | 11.8 |
Lymphocytes (nL) | 170 | 1.81 | 1.7 | 1.34 | 2.2 | 0.71 | 0.41 | 4.3 |
Platelets (nL) | 171 | 296.6 | 283 | 237 | 336 | 87.3 | 52 | 612 |
Monocytes (nL) | 169 | 0.55 | 0.53 | 0.4 | 0.67 | 0.23 | 0.02 | 1.36 |
Age (y) | 171 | 58.6 | 61 | 50 | 68 | 11.3 | 31 | 83 |
NLR (Cut-Off) | Sig $ | PLR (Cut-Off) | Sig $ | MLR (Cut-Off) | Sig $ | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
≥3.13 | <3.13 | ≥222.3 | <222.3 | ≥0.39 | <0.39 | |||||||||||
n | % | n | % | p-Value | n | % | n | % | p-Value | n | % | n | % | p-Value | ||
Age Grouped (60 y) | <60 | 25 | 58.1 | 66 | 52.4 | 0.513 | 25 | 58.1 | 67 | 52.8 | 0.54 | 26 | 61.9 | 65 | 51.2 | 0.227 |
≥60 | 18 | 41.9 | 60 | 47.6 | 18 | 41.9 | 60 | 47.2 | 16 | 38.1 | 62 | 48.8 | ||||
Total | 43 | 100 | 126 | 100 | 43 | 100 | 127 | 100 | 42 | 100 | 127 | 100 | ||||
Menopausal Status | Premenopausal | 9 | 20.9 | 22 | 17.5 | 0.399 | 8 | 18.6 | 23 | 18.1 | 0.997 | 7 | 16.7 | 24 | 18.9 | 0.426 |
Perimenopausal | 6 | 14 | 10 | 7.9 | 4 | 9.3 | 12 | 9.4 | 2 | 4.8 | 14 | 11 | ||||
Postmenopausal | 28 | 65.1 | 94 | 74.6 | 31 | 72.1 | 92 | 72.4 | 33 | 78.6 | 89 | 70.1 | ||||
Total | 43 | 100 | 126 | 100 | 43 | 100 | 127 | 100 | 42 | 100 | 127 | 100 | ||||
Histology | Ductal | 30 | 69.8 | 102 | 83.6 | 0.128 | 31 | 73.8 | 102 | 82.3 | 0.478 | 30 | 75 | 102 | 81.6 | 0.657 |
Lobular | 6 | 14 | 11 | 9 | 6 | 14.3 | 11 | 8.9 | 5 | 12.5 | 12 | 9.6 | ||||
Other | 7 | 16.3 | 9 | 7.4 | 5 | 11.9 | 11 | 8.9 | 5 | 12.5 | 11 | 8.8 | ||||
Total | 43 | 100 | 122 | 100 | 42 | 100 | 124 | 100 | 40 | 100 | 125 | 100 | ||||
pT | pT1 | 26 | 60.5 | 74 | 58.7 | 0.951 | 27 | 62.8 | 74 | 58.3 | 0.86 | 21 | 50 | 79 | 62.2 | 0.107 |
pT2 | 16 | 37.2 | 48 | 38.1 | 15 | 34.9 | 49 | 38.6 | 18 | 42.9 | 46 | 36.2 | ||||
pT3 pT4 | 1 | 2.3 | 4 | 3.2 | 1 | 2.3 | 4 | 3.1 | 3 | 7.1 | 2 | 1.6 | ||||
Total | 43 | 100 | 126 | 100 | 43 | 100 | 127 | 100 | 42 | 100 | 127 | 100 | ||||
pN | pN0 | 22 | 51.2 | 78 | 61.9 | 0.45 | 18 | 41.9 | 82 | 64.6 | 0.029 | 18 | 42.9 | 82 | 64.6 | 0.041 |
pN1 | 20 | 46.5 | 45 | 35.7 | 24 | 55.8 | 42 | 33.1 | 23 | 54.8 | 42 | 33.1 | ||||
pN2 pN3 | 1 | 2.3 | 3 | 2.4 | 1 | 2.3 | 3 | 2.4 | 1 | 2.4 | 3 | 2.4 | ||||
Total | 43 | 100 | 126 | 100 | 43 | 100 | 127 | 100 | 42 | 100 | 127 | 100 | ||||
Grading | G1 | 1 | 2.3 | 9 | 7.1 | 0.254 | 2 | 4.7 | 8 | 6.3 | 0.568 | 1 | 2.4 | 9 | 7.1 | 0.338 |
G2 | 23 | 53.5 | 76 | 60.3 | 23 | 53.5 | 77 | 60.6 | 23 | 54.8 | 76 | 59.8 | ||||
G3 | 19 | 44.2 | 41 | 32.5 | 18 | 41.9 | 42 | 33.1 | 18 | 42.9 | 42 | 33.1 | ||||
Total | 43 | 100 | 126 | 100 | 43 | 100 | 127 | 100 | 42 | 100 | 127 | 100 | ||||
ER Status | No | 13 | 30.2 | 23 | 18.3 | 0.098 | 10 | 23.3 | 27 | 21.3 | 0.784 | 9 | 21.4 | 27 | 21.3 | 0.982 |
Yes | 30 | 69.8 | 103 | 81.7 | 33 | 76.7 | 100 | 78.7 | 33 | 78.6 | 100 | 78.7 | ||||
Total | 43 | 100 | 126 | 100 | 43 | 100 | 127 | 100 | 42 | 100 | 127 | 100 | ||||
PR Status | No | 15 | 34.9 | 36 | 28.6 | 0.436 | 14 | 32.6 | 38 | 29.9 | 0.746 | 12 | 28.6 | 39 | 30.7 | 0.794 |
Yes | 28 | 65.1 | 90 | 71.4 | 29 | 67.4 | 89 | 70.1 | 30 | 71.4 | 88 | 69.3 | ||||
Total | 43 | 100 | 126 | 100 | 43 | 100 | 127 | 100 | 42 | 100 | 127 | 100 | ||||
HER2 Status | No | 35 | 81.4 | 107 | 84.9 | 0.586 | 33 | 76.7 | 110 | 86.6 | 0.126 | 33 | 78.6 | 109 | 85.8 | 0.266 |
Yes | 8 | 18.6 | 19 | 15.1 | 10 | 23.3 | 17 | 13.4 | 9 | 21.4 | 18 | 14.2 | ||||
Total | 43 | 100 | 126 | 100 | 43 | 100 | 127 | 100 | 42 | 100 | 127 | 100 | ||||
ER– PR– HER2– | No | 34 | 79.1 | 110 | 87.3 | 0.189 | 35 | 81.4 | 109 | 85.8 | 0.489 | 36 | 85.7 | 108 | 85 | 0.915 |
Yes | 9 | 20.9 | 16 | 12.7 | 8 | 18.6 | 18 | 14.2 | 6 | 14.3 | 19 | 15 | ||||
Total | 43 | 100 | 126 | 100 | 43 | 100 | 127 | 100 | 42 | 100 | 127 | 100 | ||||
ER– PR– HER2+ | No | 40 | 93 | 121 | 96 | 0.422 | 41 | 95.3 | 121 | 95.3 | 0.984 | 39 | 92.9 | 122 | 96.1 | 0.396 |
Yes | 3 | 7 | 5 | 4 | 2 | 4.7 | 6 | 4.7 | 3 | 7.1 | 5 | 3.9 | ||||
Total | 43 | 100 | 126 | 100 | 43 | 100 | 127 | 100 | 42 | 100 | 127 | 100 | ||||
ER + AND (PR + OR Her2–) | No | 13 | 30.2 | 29 | 23 | 0.344 | 11 | 25.6 | 32 | 25.2 | 0.96 | 10 | 23.8 | 32 | 25.2 | 0.857 |
Yes | 30 | 69.8 | 97 | 77 | 32 | 74.4 | 95 | 74.8 | 32 | 76.2 | 95 | 74.8 | ||||
Total | 43 | 100 | 126 | 100 | 43 | 100 | 127 | 100 | 42 | 100 | 127 | 100 | ||||
ER + AND (PR + OR Her2+) | No | 16 | 37.2 | 32 | 25.4 | 0.138 | 13 | 30.2 | 36 | 28.3 | 0.813 | 11 | 26.2 | 37 | 29.1 | 0.714 |
Yes | 27 | 62.8 | 94 | 74.6 | 30 | 69.8 | 91 | 71.7 | 31 | 73.8 | 90 | 70.9 | ||||
Total | 43 | 100 | 126 | 100 | 43 | 100 | 127 | 100 | 42 | 100 | 127 | 100 | ||||
DTC Status | Neg | 29 | 67.4 | 82 | 65.6 | 0.826 | 28 | 65.1 | 84 | 66.7 | 0.853 | 24 | 57.1 | 87 | 69 | 0.158 |
Pos | 14 | 32.6 | 43 | 34.4 | 15 | 34.9 | 42 | 33.3 | 18 | 42.9 | 39 | 31 | ||||
Total | 43 | 100 | 125 | 100 | 43 | 100 | 126 | 100 | 42 | 100 | 126 | 100 | ||||
CTC Status | Neg | 23 | 57.5 | 86 | 76.1 | 0.025 | 26 | 61.9 | 84 | 75 | 0.109 | 25 | 67.6 | 84 | 72.4 | 0.571 |
Pos | 17 | 42.5 | 27 | 23.9 | 16 | 38.1 | 28 | 25 | 12 | 32.4 | 32 | 27.6 | ||||
Total | 40 | 100 | 113 | 100 | 42 | 100 | 112 | 100 | 37 | 100 | 116 | 100 |
NLR | PLR | MLR | Neutrophils (nL) | Lymphocytes (nL) | Platelets (nL) | Monocytes (nL) | ||
---|---|---|---|---|---|---|---|---|
PFS | r | 0.073 | 0.143 | −0.067 | −0.096 | −0.130 | 0.101 | 0.144 |
p | 0.350 | 0.066 | 0.392 | 0.221 | 0.094 | 0.193 | 0.065 | |
n | 165 | 166 | 165 | 165 | 166 | 167 | 165 | |
OS | r | 0.053 | 0.150 | −0.085 | −0.085 | −0.146 | 0.083 | −0.163 |
p | 0.497 | 0.050 | 0.271 | 0.164 | 0.058 | 0.283 | 0.034 | |
n | 169 | 170 | 169 | 169 | 170 | 171 | 169 |
OS | PFS | |||||||
---|---|---|---|---|---|---|---|---|
Univariate | Multivariate | Univariate | Multivariate | |||||
HR (95% CI) | p-Value | HR (95% CI) | p-Value | HR (95% CI) | p-Value | HR (95% CI) | p-Value | |
Age (years) | ||||||||
< vs. > 60 | 4.195 (1.182–14.892) | 0.027 | 2.801 (0.552–14.203) | 0.214 | 4.784 (1.032–22.181) | 0.046 | 2.355 (0.375–14.782) | 0.361 |
Tumor size | ||||||||
T1 vs. >T1 | 2.182 (0.775–6.139) | 0.139 | 2.159 (0.672–6.932) | 0.196 | 2.533 (0.740–8.674) | 0.137 | 2.916 (0.669–12.705) | 0.154 |
Lymph node involvement | ||||||||
N0 vs. N+ | 3.889 (1.238–12.216) | 0.020 | 3.423 (0.999–11.730) | 0.050 | 3.836 (1.017–14.465) | 0.047 | 3.216 (0.752–13.746) | 0.115 |
Menopausal Status | ||||||||
Pre- and peri vs. postmenopausal | 2.785 (0.627–12.359) | 0.178 | 1.181 (0.169–8.235) | 0.866 | 4.266 (0.545–33.369) | 0.167 | 2.165 (0.185–25.378) | 0.538 |
NLR | ||||||||
< vs. ≥3.13 | 1.909 (0.678–5.373) | 0.221 | 2.073 (0.546–7.870) | 0.284 | 2.336 (0.711–7.667) | 0.162 | 2.696 (0.555–13.089) | 0.219 |
PLR | ||||||||
< vs. ≥222.3 | 0.671 (0.189–2.382) | 0.537 | 0.303 (0.069–1.326) | 0.113 | 0.608 (0.131–2.820) | 0.525 | 0.281 (0.049–1.618) | 0.155 |
MLR | ||||||||
< vs. ≥0.39 | 1.639 (0.559–4.805) | 0.368 | 1.500 (0.419–5.367) | 0.533 | 1.964 (0.572–6.745) | 0.284 | 1.575 (0.354–7.013) | 0.551 |
CTCs | ||||||||
Pos. vs. Neg. | 1.151 (0.360–3.677) | 0.813 | 0.981 (0.294–3.269) | 0.975 | 1.194 (0.308–4.628) | 0.797 | 0.904 (0.218–3.751) | 0.890 |
DTCs | ||||||||
Pos. Vs. neg. | 1.172 (0.416–3.305) | 0.764 | 0.825 (0.251–2.716) | 0.752 | 1.467 (0.446–4.828) | 0.528 | 0.959 (0.240–3.833) | 0.953 |
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Kasimir-Bauer, S.; Karaaslan, E.; Hars, O.; Hoffmann, O.; Kimmig, R. In Early Breast Cancer, the Ratios of Neutrophils, Platelets and Monocytes to Lymphocytes Significantly Correlate with the Presence of Subsets of Circulating Tumor Cells but Not with Disseminated Tumor Cells. Cancers 2022, 14, 3299. https://doi.org/10.3390/cancers14143299
Kasimir-Bauer S, Karaaslan E, Hars O, Hoffmann O, Kimmig R. In Early Breast Cancer, the Ratios of Neutrophils, Platelets and Monocytes to Lymphocytes Significantly Correlate with the Presence of Subsets of Circulating Tumor Cells but Not with Disseminated Tumor Cells. Cancers. 2022; 14(14):3299. https://doi.org/10.3390/cancers14143299
Chicago/Turabian StyleKasimir-Bauer, Sabine, Ebru Karaaslan, Olaf Hars, Oliver Hoffmann, and Rainer Kimmig. 2022. "In Early Breast Cancer, the Ratios of Neutrophils, Platelets and Monocytes to Lymphocytes Significantly Correlate with the Presence of Subsets of Circulating Tumor Cells but Not with Disseminated Tumor Cells" Cancers 14, no. 14: 3299. https://doi.org/10.3390/cancers14143299