Patient and tumor baseline characteristics
We identified 75 patients diagnosed with breast cancer who were treated with consecutive NACT. In the end, 67 patients who had pretreatment CBC were included in the study. The baseline characteristics are listed in Table 1. The median age at first diagnosis was 51 years (range 27–81). The majority of cases were in tumor stage G2 at diagnosis (62.7%), and the main histology was invasive ductal carcinoma (92.5%). The patients showed 11.9% Luminal A molecular subtype, 19.4% Luminal B/HER2-negative, 19.4% Luminal B/HER2-positive, 17.9% triple-negative and 31.3% HER2-enriched. Only 9.0% of tumors were well-differentiated (Gl), and 86.6% of patients expressed a Ki-67 proliferation index (≥ 14%).
Relationship between NLR/PLR and baseline characteristics
The NLR cutoff point according to the ROC curve analysis was 2.464 (Fig. 1: ROC curve of PLR and NLR predict PCR). This point allowed the identification of the following two categories: NLR low (≤ 2.464), 45 patients (67.2%), and NLR high (> 2.464), 22 patients (32.8%). Similarly, the ROC curve for the PLR deduced a cutoff value of 106.3, and the following two categories of patients were identified (Fig. 1): 19 patients (28.4%) in the PLRlow (≤ 106.3) group and 48 patients (71.6%) in the PLRhigh (> 106.3) group. The above data is shown in Table l. Following univariate analysis, Ki-67༜14% patients showed higher probability to be NLRhigh, while Ki-67 ≥ 14% patients showed a higher tendency to be NLRlow (p༜0.05). Interestingly, patients in the luminal B/HER2 + molecular subtype subgroup were more inclined to be PLRhigh (p = 0.028). No other baseline characteristics were significantly associated with either the PLR or NLR.
Table 1 Association of baseline characteristics to NLR or PLR.
Variable
|
N(%)(n=67)
|
NLR
|
PLR
|
Low(%)(n=45)
|
High(%)(n=22)
|
P value*
|
Low(%)(n=19)
|
High(%)(n=48)
|
P value*
|
Age (years)
|
|
|
|
0.516
|
|
|
0.610
|
≤50
|
25 (37.3)
|
18(72.0)
|
7(28.0)
|
|
8 (32.6)
|
17(68.0)
|
|
>50
|
42(62.7)
|
27(64.3)
|
15(35.7)
|
|
11 (26.2)
|
31(73.8)
|
|
Histologic type
|
|
|
|
0.624
|
|
|
0.169
|
Ductal
|
62 (92.5)
|
41(66.1)
|
21(33.9)
|
|
16 (25.8)
|
46(74.2)
|
|
Lobular
|
1 (1.5)
|
1(100.0)
|
0(0.0)
|
|
1 (100.0)
|
19(0.0)
|
|
Others
|
4 (6.0)
|
3(75.0)
|
1(25.0)
|
|
2 (50.0)
|
19(50.0)
|
|
Grade
|
|
|
|
0.087
|
|
|
0.269
|
G1
|
6 (9.0)
|
6(100.0)
|
0(0.0)
|
|
3 (50.0)
|
3(50.0)
|
|
G2
|
42(62.7)
|
29(69.0)
|
13(31.0)
|
|
12 (28.6)
|
30(71.4)
|
|
G3
|
15 (22.4)
|
8(53.3)
|
7(46.7)
|
|
4 (26.7)
|
11(73.3)
|
|
Uknowna
|
4 (6.0)
|
2(50.0)
|
2(50.0)
|
|
0 (0.0)
|
4(100.0)
|
|
Ki-67
|
|
|
|
0.034*
|
|
|
0.179
|
<14%
|
7 (10.4)
|
2(28.6)
|
5(71.4)
|
|
4 (57.1)
|
3(42.9)
|
|
≥14%
|
60 (89.6)
|
43(71.7)
|
17(28.3)
|
|
15 (25.0)
|
45(75.0)
|
|
Hormone Recepyor(HR)
|
|
|
|
0.545
|
|
|
0.846
|
Positive
|
34 (50.7)
|
24(70.6)
|
10(29.4)
|
|
9 (27.3)
|
24(72.7)
|
|
Negative
|
33 (49.3)
|
21(63.6)
|
12(36.4)
|
|
10 (29.4)
|
24(70.6)
|
|
Molecular Subtype
|
|
|
|
0.633
|
|
|
0.028*
|
Luminal A
|
8 (11.9)
|
5 (62.5)
|
3(37.5)
|
|
1 (12.5)
|
7(87.5)
|
|
Luminal B/HER2-
|
13 (19.4)
|
11 (84.6)
|
2(15.4)
|
|
8(61.5)
|
5(38.56)
|
|
Luminal B/HER2+
|
13 (19.4)
|
8 (61.5)
|
5(38.5)
|
|
1(7.7)
|
12(92.3)
|
|
HER2 enriched
|
21 (31.3)
|
13 (61.9)
|
8(38.1)
|
|
6(28.6)
|
16(71.4)
|
|
Triple Negative
|
12 (17.9)
|
8 (66.7)
|
4(33.3)
|
|
3(25.0)
|
9(75.0)
|
|
* Signifificant values are indicated in bold.
a Unknown not included in the analysis.
Association of the PLR/NLR and pCR in patients with breast cancer
For breast cancer with NLR and PLR, the pCR for patients with a high PLR was 19 and that of patients with a low PLR was 1, while the pCR for patients with a high and low NLR was 10. The results indicated that patients with a high NLR (p = 0.580) and high PLR (p = 0.007) had a higher pCR ratio than those with a low NLR and low PLR (Table 2).
Table 2 Association of patient/tumor characteristics to pCR in univariate analysis.
Variable
|
n(%)(n=67)
|
pCR(%)(n=20)
|
Odds ratio
|
95% CI
|
p value*
|
Age (years)
|
|
|
|
|
|
≤50
|
25 (37.3)
|
4 (16.0)
|
1.000
|
|
|
>50
|
42(62.7)
|
16(38.1)
|
0.481
|
0.099-1.187
|
0.083
|
Histologic type
|
|
|
|
|
|
Lobular
|
1 (1.5)
|
0 (0.0)
|
No
|
|
|
Others
|
3 (6.0)
|
1 (33.3)
|
1.000
|
No
|
No
|
Ductal
|
63 (94.0)
|
19(30.2)
|
1.020
|
0.140-14.609
|
1.000
|
Grade
|
|
|
|
|
|
Unknown
|
4 (6.0)
|
2 (50)
|
1.000
|
|
|
G1
|
6 (9.0)
|
2(33.3)
|
2.000
|
0.150-26.734
|
0.600
|
G2
|
42 (62.7)
|
11 (26.2)
|
3.200
|
0.398-25.733
|
0.274
|
G3
|
15 (22.4)
|
5(33.3)
|
2.000
|
0.214-18.687
|
0.543
|
Ki-67
|
|
|
|
|
|
<14%
|
7 (10.4)
|
1 (14.3)
|
1.000
|
|
|
≥14%
|
60 (89.6)
|
19(31.7)
|
0.392
|
0.040-3.200
|
0.665
|
Hormone Recepyor(HR)
|
|
|
|
|
|
Negative
|
33 (49.3)
|
14 (42.4)
|
1.000
|
|
|
Positive
|
34 (50.7)
|
6(17.6)
|
1.789
|
1.179-11.178
|
0.021
|
HER2
|
|
|
|
|
|
Negative
|
33 (49.3)
|
5(15.2)
|
1.000
|
|
|
Positive
|
34 (50.7)
|
15(44.1)
|
0.426
|
0.073-0.756
|
0.012
|
Molecular Subtype
|
|
|
|
|
|
Triple Negative
|
12 (17.9)
|
4(33.3)
|
1.000
|
|
|
Luminal A
|
8 (11.9)
|
0 (0.0)
|
No
|
No
|
No
|
Luminal B/HER2-
|
13 (19.4)
|
0(0.0)
|
No
|
No
|
No
|
Luminal B/HER2+
|
13 (19.4)
|
5 (38.5)
|
0.800
|
0.155-4.123
|
0.790
|
HER2 enriched
|
21 (31.3)
|
11(52.4)
|
0.550
|
0.126-2.403
|
0.427
|
Chemotherapy regimen
|
|
|
|
|
|
Chemio+Trastuzumab
|
28(41.8)
|
12(42.9)
|
1.000
|
|
|
Various
|
12(17.9)
|
1(8.3)
|
0.140
|
0.038-3.518
|
0.382
|
Antracycline and Taxane
|
25 (37.3)
|
5 (20.0)
|
1.364
|
1.016-2.247
|
0.038
|
Unknowna
|
2(3.0)
|
2 (100)
|
|
|
|
NLR
|
|
|
|
|
|
High
|
22 (32.8)
|
10 (45.5)
|
1.000
|
|
|
Low
|
45 (67.2)
|
10(22.2)
|
0.676
|
0.118-1.056
|
0.580
|
PLR
|
|
|
|
|
|
High
|
48 (71.6)
|
19 (37.5)
|
1.000
|
|
|
Low
|
19 (28.4)
|
1(10.5)
|
1.540
|
1.203-1.970
|
0.007
|
NLR/PLR
|
|
|
|
|
|
High/High
|
19 (28.4)
|
9 (47.4)
|
1.000
|
|
|
Low/High
|
30 (44.8)
|
9 (30.0)
|
2.100
|
0.638-6.916
|
0.222
|
High/Low
|
4 (6.0)
|
0 (0.0)
|
No
|
No
|
No
|
Low/Low
|
14 (20.9)
|
2 (24.3)
|
11.700
|
1.265-108.200
|
0.030
|
Surgery
|
|
|
|
|
|
Mastectomy
|
61 (91.0)
|
18 (29.5)
|
1.000
|
|
|
Breast-consercing surgery
|
6 (9.0)
|
2 (33.3)
|
1.175
|
0.201-7.114
|
1.000
|
* Signifificant values are indicated in bold.
a Unknown not included in the analysis.
A thorough investigation into the efficiency of the PLR was analyzed by anthracycline or taxane regimens. We found that patients with a high PLR had a higher PCR ratio than those with a low PLR when receiving the Chemo + Trastuzumab regimen. With the Chemo + Trastuzumab regimen, the results showed that the pCR for patients with a high PLR was 11 and that for patients with a low PLR was 1. Interestingly, it was easier to attain pCR in the NLRhigh/PLRhigh subgroup .
Relationship between pCR and baseline characteristics in patients with breast cancer
After NACT, 20 patients (29.9%) reached a pCR. High grade, Ki67 ≥ 14%, HER-2 positivity, and HR negativity are classical poor prognostic factors for breast cancer, and the univariate analysis results related to pCR are shown in Table 2. In particular, the pCR probability was higher in the HR-negative subgroup compared to the HR-positive subgroup (OR 3.630, 95% CI 1.179–11.178, p < 0.05), and the Chemo + Trastuzumab subgroup had a higher pCR rate (OR 1.364, 95% CI 1.016–2.247, p < 0.05). Similarly, compared to the HER-2-negative subgroup, the HER-2-positive subgroup had a greater than 4-fold pCR rate (OR 4.263, 95% CI 0.073–0.756, p < 0.05). Consistently, luminal B/HER2+, HER-2-enriched or triple-negative subtypes had higher pCR rates than luminal A subtypes, but there was not a significant difference (p = 0.069). Neither the age nor the type of surgery subgroup was suitable to predict pCR in our study.
The combined NLR and PLR analysis makes sense for pCR. Consistently, we found that patients in the NLRhigh/PLRhigh subgroup had the highest rate of pCR (47.4%), and those in the NLRlow/PLRlow subgroup had the lowest rate (24.3%). NLRhigh/PLRhigh subgroup patients were two times as likely to reach pCR than NLRlow/PLRlow subgroup patients (OR 2.98, 95% CI 1.265–108.200, p = 0.030).
By multivariate analysis, only Ki-67, the chemotherapy regimen, PLRhigh and NLRhigh/PLRhigh remained significant (Table 3). The Ki-67 ≥ 14% subgroup had a five-fold higher pCR than patients in the Ki-67 < 14% subgroup (OR 14.143, 95% CI 1.142–7.135, p = 0.019). Similarly, the NLRhigh and PLRhigh subgroup showed a more than 2-fold higher pCR rate than the NLRhigh and PLRhigh subgroup (OR 2.19, 95% CI 0.068–0.876, p = 0.008). Moreover, compared to the subgroup treated with the Chemo + Trastuzumab regimen, the pCR rate was higher (OR 1.719, 95% CI 1.020-10.889, p = 0.005). The same results were found for the PLR items (OR 2.150, 95% CI 1.972–5.639, p = 0.008).
Table 3
Association of patient/tumor characteristics to pCR in multivariate analysis.
Variable
|
OR
|
95% CI
|
P value*
|
TN/HER2 + vs Luminal HER2
|
1.930
|
0.038–98.076
|
0.058
|
Grading G2/G3 vs G1
|
0.552
|
0.003–21.505
|
0.263
|
Ki-67 ≥ 14% vs Ki-67༜14
|
14.143
|
1.142–7.135
|
0.019
|
NLRlow/PLRlow vs NLRhigh and/or PLRhigh
|
0.153
|
0.068–0.876
|
0.008
|
PLRlow vs PLRhigh
|
2.150
|
1.972–5.639
|
0.003
|
Hormone Recepyor(HR) Negative vs Positive
|
0.885
|
0.046–16.926
|
0.935
|
HER2 Positive vs Negative
|
0.301
|
0.030–3.064
|
0.311
|
Chemio + Trastuzumab
vs Chemio only
|
1.719
|
1.020-10.889
|
0.005
|
* Signifificant values are indicated in bold. |