Inflammatory Blood Markers as Prognostic and Predictive Factors in Early Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Patients’ Characteristics
2.2. Predictive Factors for Pathological Complete Response
2.3. Prognostic Factors for RFS
2.4. Prognostic Factors for OS
2.5. Sub Group Analyses
2.6. Predictive Factors for Febrile Neutropenia
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Pathological Assessments
4.3. Treatments
4.4. Endpoints
4.5. Ethical Statement
4.6. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Characteristics | No (%) |
---|---|
Age (median) | 50.3 (25.3–76.6) |
Menopausal status | |
Yes | 103 (36.8) |
No | 177 (63.2) |
T stage (before NACT) | |
T0 | 2 (0.7) |
T1 | 22 (7.9) |
T2 | 165 (58.9) |
T3 | 47 (16.8) |
T4 | 43 (15.4) |
Missing | 1 (0.3) |
Node status (before NACT) | |
N- | 129 (46.1) |
N+ | 145 (51.8) |
Missing | 6 (2.1) |
Inflammatory BC | |
Yes | 39 (14.2) |
No | 241 (85.8) |
Histology | |
Ductal | 235 (84) |
Lobular | 27 (9.6) |
Other | 18 (6.4) |
Histological grade | |
1 | 5 (1.8) |
2 | 123 (43.9) |
3 | 146 (52.2) |
Missing | 6 (2.1) |
Differentiation (N = 215) | |
1 | 1 (0.5) |
2 | 21 (9.8) |
3 | 193 (89.7) |
Nucleus (N = 216) | |
1 | 3 (1.4) |
2 | 77 (35.6) |
3 | 136 (63) |
Mitosis (N = 216) | |
1 | 70 (32.4) |
2 | 70 (32.4) |
3 | 76 (35.2) |
HER2 status | |
Positive | 81 (28.9) |
Negative | 199 (71.1) |
HR status | |
Positive | 168 (60) |
Negative | 112 (40) |
Molecular subtype | |
HR+/HER2₋ | 127 (45.4) |
HR+/HER2+ | 41 (14.6) |
HR₋/HER2+ | 40 (14.3) |
HR₋/HER2₋ | 72 (25.7) |
Baseline biology: median (range) | |
Hemoglobin (g/dl) | 13.6 (8.0–15.4) |
Platelets (G/L) | 264 (124–452) |
White blood cell count (G/L) | 6.8 (1.5–30) |
Lymphocyte count (G/L) | 1.9 (0.6–26) |
PNN (G/L) | 3.9 (1.4–11.6) |
NLR | 2.0 (0.1–17.3) |
PLR | 132.3 (6.9–514.9) |
PCR | Univariate | Multivariate | ||||
---|---|---|---|---|---|---|
Variable | No | Yes | Total | p | Odd Ratio (95%CI) | p |
Age (year) | 0.278 | |||||
<50.25 | 99 (48.1%) | 41 (55.4%) | 140 (50%) | |||
≥50.25 | 107 (51.9%) | 33 (44.6%) | 140 (50%) | |||
cT | 0.895 | |||||
T 0/2 | 140 (68.0%) | 49 (67.1%) | 189 (67.7%) | |||
T 3/4 | 66 (32.0%) | 24 (32.9%) | 90 (32.3%) | |||
cN | 0.093 | |||||
Negative | 88 (44.0%) | 41 (55.4%) | 129 (47.1%) | 1 | 0.010 | |
Positive | 112 (56.0%) | 33 (44.6%) | 145 (52.9%) | 0.43 (0.23–0.82) | ||
Inflammatory BC | 0.967 | |||||
No | 174 (85.7%) | 61 (85.9%) | 235 (85.8%) | |||
Yes | 29 (14.3%) | 10 (14.1%) | 39 (14.2%) | |||
Histological grade | 0.001 | |||||
1 | 1 | |||||
2 | 106 (52.5%) | 22 (30.6%) | 128 (46.7%) | 0.13 (0.07–0.27) | <0.001 | |
3 | 96 (47.5%) | 50 (69.4%) | 146 (53.3%) | 0.28 (0.12–0.63) | 0.002 | |
Histologic type | 0.233 | |||||
Ductal | 168 (81.5%) | 67 (90.5%) | 235 (83.9%) | |||
Lobular | 23 (11.2%) | 4 (5.4%) | 27 (9.7%) | |||
Others | 15 (7.3%) | 3 (4.1%) | 18 (6.4%) | |||
Hormone receptor | <0.001 | |||||
Negative | 65 (31.6%) | 47 (63.5%) | 112 (40.0%) | |||
Positive | 141 (68.4%) | 27 (36.5%) | 168 (60.0%) | |||
Molecular subtype | <0.001 | |||||
HR+HER2₋ | 116 (56.3%) | 11 (14.9%) | 127 (45.4%) | 1 | ||
HR+HER2+ | 25 (12.1%) | 16 (21.6%) | 41 (14.6%) | 7.98 (3.13–20.34) | <0.001 | |
HR₋HER2+ | 18 (8.8%) | 22 (29.7%) | 40 (14.3%) | 11.94 (4.76–29.91) | <0.001 | |
HR₋HER2₋ | 47 (22.8%) | 25 (33.8%) | 72 (25.7%) | 4.65 (1.98–10.89) | <0.001 | |
Platelet count | 0.068 | |||||
<264 G/L | 97 (47.1%) | 44 (59.5%) | 141 (50.4%) | |||
≥264 G/L | 109 (52.9%) | 30 (40.5%) | 139 (49.6%) | |||
White blood cell count | 0.058 | |||||
<6.75 G/L | 96 (46.6%) | 44 (59.5%) | 140 (50.0%) | |||
≥6.75 G/L | 110 (53.4%) | 30 (40.5%) | 140 (50.0%) | |||
Neutrophil count | 1.000 | |||||
<1.5 G/L | 1 (0.5%) | 0 (0.0%) | 1 (0.4%) | |||
≥1.5 G/L | 205 (99.5%) | 74 (100.0%) | 279 (99.6%) | |||
Lymphocyte count | 0.685 | |||||
<1 G/L | 7 (3.4%) | 1 (1.4%) | 8 (2.9%) | |||
≥1 G/L | 199 (96.6%) | 73 (98.6%) | 272 (97.1%) | |||
NLR | 0.550 | |||||
<2 | 103 (50.0%) | 34 (45.9%) | 137 (48.9%) | |||
≥2 | 103 (50.0%) | 40 (54.1%) | 143 (51.1%) | |||
PLR | 0.617 | |||||
<150 | 132 (64.1%) | 45 (60.8%) | 177 (63.2%) | |||
≥150 | 74 (35.9%) | 29 (39.2%) | 103 (36.8%) |
RFS | Univariate | Multivariate | ||
---|---|---|---|---|
Variable | Hazard Ratio (95%CI) | p | Hazard Ratio (95%CI) | p |
Age (year) | ||||
<50.25 | 1 | |||
≥50.25 | 1.50 (0.91–2.46) | 0.111 | ||
cT | ||||
T 0/2 | 1 | 1 | ||
T 3/4 | 2.01 (1.23–3.26) | 0.005 | 2.07 (1.26–3.39) | 0.004 |
cN | ||||
Negative | 1 | |||
Positive | 1.61 (0.97–2.69) | 0.066 | ||
Inflammatory BC | ||||
No | 1 | |||
Yes | 2.34 (1.33–4.12) | 0.003 | ||
Histological grade | ||||
1/2 | 1 | 1 | ||
3 | 1.12 (0.68–1.84) | 0.657 | 0.84 (0.47–1.51) | 0.65 |
Histologic type | ||||
Ductal | 1 | |||
Lobular | 0.93 (0.40–2.16) | 0.866 | ||
Others | 1.84 (0.84–4.06) | 0.129 | ||
HR | ||||
Negative | 1 | |||
Positive | 0.48 (0.29–0.78) | 0.003 | ||
Molecular subtype | ||||
HR+HER2₋ | 1 | 1 | ||
HR+HER2+ | 1.135 (0.505–2.551) | 0.759 | 1.55 (0.73–3.33) | 0.253 |
HR₋HER2+ | 1.378 (0.634–2.993) | 0.418 | 1.89 (0.86–4.14) | 0.111 |
HR₋HER2₋ | 2.669 (1.511–4.714) | 0.001 | 4.11 (2.28–7.42) | <0.001 |
PCR | ||||
No | 1 | 1 | ||
Yes | 0.37 (0.18–0.78) | 0.009 | 0.27 (0.12–0.56) | 0.001 |
Platelet count | ||||
<264 G/L | 1 | |||
≥264 G/L | 1.73 (1.05–2.84) | 0.031 | ||
White blood cell count | ||||
<6.75 G/L | 1 | |||
≥6.75 G/L | 1.14 (0.70–1.86) | 0.593 | ||
Neutrophil count | ||||
<1.5 G/L | 1 | 1 | ||
≥1.5 G/L | 0.06 (0.01–0.48) | 0.007 | 0.06 (0.03–0.12) | <0.001 |
Lymphocyte count | ||||
<1 G/L | 1 | |||
≥1 G/L | 0.89 (0.22–3.64) | 0.871 | ||
NLR | ||||
<2 | 1 | |||
≥2 | 1.02 (0.63–1.66) | 0.930 | ||
PLR | ||||
<150 | 1 | 1 | ||
≥150 | 1.65 (1.01–2.69) | 0.044 | 1.91 (1.15–3.16) | 0.012 |
OS | Univariate | Multivariate | ||
---|---|---|---|---|
Variable | Hazard Ratio (95%CI) | p | Hazard Ratio (IC95%CI) | p |
Age (year) | ||||
<50.25 | 1 | |||
≥50.25 | 1.60 (0.91–2.83) | 0.103 | ||
cT | ||||
T 0/2 | 1 | 1 | ||
T 3/4 | 2.15 (1.24–3.73) | 0.006 | 2.43 (1.37–4.30) | 0.002 |
cN | ||||
Negative | 1 | |||
Positive | 1.42 (0.80–2.51) | 0.232 | ||
Inflammatory BC | ||||
No | 1 | |||
Yes | 2.21 (1.17–4.16) | 0.014 | ||
Histological grade | ||||
1/2 | 1 | |||
3 | 1.00 (0.57–1.76) | 0.993 | ||
Histologic type | ||||
Ductal | 1 | |||
Lobular | 0.76 (0.27–2.12) | 0.604 | ||
Others | 1.20 (0.43–3.33) | 0.732 | ||
HR | ||||
Negative | 1 | |||
Positive | 0.37 (0.21–0.65) | 0.001 | ||
Molecular subtype | ||||
HR+HER2₋ | 1 | 1 | ||
HR+HER2+ | 1.33 (0.15–3.47) | 0.555 | 1.77 (0.72–4.34) | 0.211 |
HR₋HER2+ | 1.15 (0.41–3.20) | 0.785 | 1.44 (0.50–4.13) | 0.501 |
HR₋HER2₋ | 4.15 (2.16–7.96) | <0.001 | 6.59 (3.34–13.01) | <0.001 |
PCR | ||||
No | 1 | 1 | ||
Yes | 0.43 (0.20–0.97) | 0.041 | 0.29 (0.13–0.66) | 0.003 |
Platelet count | ||||
<264 G/L | 1 | |||
≥264 G/L | 1.76 (1.00–3.09) | 0.049 | ||
White blood cell count | ||||
<6.75 G/L | 1 | |||
≥6.75 G/L | 1.39 (0.80–2.41) | 0.248 | ||
Neutrophil count | ||||
<1.5 G/L | 1 | 1 | ||
≥1.5 G/L | 0.16 (0.02–1.17) | 0.071 | 0.12 (0.06–0.24) | <0.001 |
Lymphocyte count | ||||
<1 G/L | 1 | |||
≥1 G/L | 0.70 (0.71–2.89) | 0.624 | ||
NLR | ||||
<2 | 1 | |||
≥2 | 0.96 (0.55–1.66) | 0.890 | ||
PLR | ||||
<150 | 1 | 1 | ||
≥150 | 1.49 (0.85–2.60) | 0.160 | 1.83 (1.03–3.24) | 0.039 |
Febrile Neutropenia | Univariate | Multivariate | ||||
---|---|---|---|---|---|---|
Variable | No | Yes | Total | p | Odd Ratio (95%CI) | p |
Age (year) | 1 | |||||
<50.25 | 124 (52.3%) | 16 (37.2%) | 40 (50.0%) | |||
≥50.25 | 113 (47.7%) | 27 (62.8%) | 140 (50.0%) | 0.068 | ||
cT | ||||||
T 0/2 | 156 (66.1%) | 33 (76.7%) | 189 (67.7%) | 1 | ||
T 3/4 | 80 (33.9%) | 10 (23.3%) | 90 (32.3%) | 0.170 | 0.43 (0.20–0.91) | 0.028 |
cN | ||||||
Negative | 107 (46.3%) | 22 (21.2%) | 129 (47.1%) | |||
Positive | 124 (53.7%) | 21 (48.8%) | 145 (52.9%) | 0.559 | ||
Inflammatory BC | ||||||
No | 200 (85.8%) | 35 (85.4%) | 235 (85.8%) | |||
Yes | 33 (14.2%) | 6 (14.6%) | 39 (14.2%) | 0.936 | ||
Histological grade | 0.228 | |||||
1 | ||||||
2 | 112 (48.3%) | 16 (38.1%) | 128 (46.7%) | |||
3 | 120 (51.7%) | 26 (61.9%) | 146 (53.3%) | |||
Histologic type | ||||||
Ductal | 198 (82.5%) | 37 (86.0%) | 235 (83.9%) | |||
Lobular | 23 (9.6%) | 4 (9.3%) | 27 (9.6%) | |||
Others | 16 (7.9%) | 2 (4.7%) | 18 (6.5%) | 1.000 | ||
HR | ||||||
Negative | 86 (36.3%) | 26 (60.5%) | 112 (40.0%) | |||
Positive | 151 (63.7%) | 17 (39.5%) | 168 (60.0%) | 0.003 | ||
Molecular subtype | ||||||
RH+HER2₋ | 112 (47.3%) | 15 (34.5%) | 127 (45.5%) | 1 | ||
RH+HER2+ | 39 (16.5%) | 2 (4.8%) | 41 (14.6%) | 0.21 (0.05–0.93) | 0.039 | |
RH₋HER2+ | 28 (11.7%) | 12 (27.9%) | 40 (14.3%) | 2.18 (0.93–5.11) | 0.072 | |
RH₋HER2₋ | 58 (24.5%) | 14 (32.8%) | 72 (25.6%) | 0.007 | 1.09 (0.51–2.34) | 0.826 |
Platelet count | ||||||
<264 G/L | 112 (47.3%) | 29 (67.4%) | 141 (50.4%) | 1 | ||
≥264 G/L | 125 (52.7%) | 14 (32.6%) | 139 (49.6%) | 0.014 | 0.40 (0.21–0.75) | 0.004 |
White blood cell count | ||||||
<6.75 G/L | 109 (46.0%) | 31 (72.1%) | 140 (50.0%) | 1 | ||
≥6.75 G/L | 128 (54.0%) | 12 (27.9%) | 140 (50.0%) | 0.002 | 0.35 (0.17–0.72) | 0.004 |
Neutrophil count | ||||||
<1.5 G/L | 0 (0.0%) | 1 (2.3%) | 1 (0.4%) | |||
≥1.5 G/L | 237 (100.0%) | 42 (97.7%) | 279 (99.6%) | 0.154 | ||
Lymphocyte count | ||||||
<1 G/L | 7 (3.0%) | 1 (2.3%) | 8 (2.9%) | 1.000 | ||
≥1 G/L | 230 (97.0%) | 42 (97.7%) | 272 (97.1%) | |||
NLR | ||||||
<2 | 106 (44.7%) | 31 (72.1%) | 137 (48.9%) | 1 | ||
≥2 | 131 (55.3%) | 12 (27.9%) | 143 (51.1%) | 0.001 | 0.28 (0.13–0.58) | 0.001 |
PLR | ||||||
<150 | 148 (62.4%) | 29 (67.4%) | 177 (63.2%) | |||
≥150 | 89 (37.6%) | 14 (32.6%) | 103 (36.8%) | 0.532 |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Corbeau, I.; Thezenas, S.; Maran-Gonzalez, A.; Colombo, P.-E.; Jacot, W.; Guiu, S. Inflammatory Blood Markers as Prognostic and Predictive Factors in Early Breast Cancer Patients Receiving Neoadjuvant Chemotherapy. Cancers 2020, 12, 2666. https://doi.org/10.3390/cancers12092666
Corbeau I, Thezenas S, Maran-Gonzalez A, Colombo P-E, Jacot W, Guiu S. Inflammatory Blood Markers as Prognostic and Predictive Factors in Early Breast Cancer Patients Receiving Neoadjuvant Chemotherapy. Cancers. 2020; 12(9):2666. https://doi.org/10.3390/cancers12092666
Chicago/Turabian StyleCorbeau, Ileana, Simon Thezenas, Aurelie Maran-Gonzalez, Pierre-Emmanuel Colombo, William Jacot, and Severine Guiu. 2020. "Inflammatory Blood Markers as Prognostic and Predictive Factors in Early Breast Cancer Patients Receiving Neoadjuvant Chemotherapy" Cancers 12, no. 9: 2666. https://doi.org/10.3390/cancers12092666