World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 15, Number 4, August 2024, pages 682-694

Accumulation of CD56⁺ CD16^- Natural Killer Cells in Response to Preoperative Chemotherapy for Breast Cancer

Figure 1. Box plots of pathological responses in primary tumors and peripheral natural killer cell activity before (a) and after (b) preoperative chemotherapy in 43 patients with breast cancer. The vertical axis represents peripheral natural killer cell activity. The box-plot analysis was performed using Excel software and individual data on pNK cell activity. The whiskers are error bars representing the minimum - maximum range, with the interquartile (25th - 75th percentile) range extended 1.5 times. The bottoms and tops of the boxes are the 25th and 75th percentiles, respectively, the lines in the boxes are the 50th percentiles (medians), and the Xs are the means. G: grade; NS: not significant.

Figure 2. Box plots of pathological responses in primary tumors and percentages of CD56⁺ CD16^- natural killer (NK) cells before (a) and after (b) preoperative chemotherapy in 43 patients with breast cancer. The vertical axis represents percentage of CD56⁺ CD16^- NK cells. The whiskers are error bars representing the minimum - maximum range, with the interquartile (25th - 75th percentile) range extended 1.5 times. The bottoms and tops of the boxes are the 25th and 75th percentiles, respectively, the lines in the boxes are the 50th percentiles (medians), outliers are shown as closed circles, and the Xs are the means. G: grade.

Figure 3. Model of the role of natural killer (NK) cells in the improvement of the effects of preoperative chemotherapy for breast cancer. Larger quantities of CD56⁺ CD16^- NK cells in peripheral blood before and after chemotherapy are recruited to primary tumor sites, where they are converted from this immunomodulatory state with poor cytolytic effects to CD56⁺ CD16⁺ cells with cytotoxic effects via the production of interferon gamma (IFN-γ), which can contribute to primary tumor shrinkage in crosstalk with CD4 and CD8 T cells. Conversely, the phenotype of tumor-associated CD56+ CD16^- NK cells is also involved in tumor growth and angiogenesis, derived from transforming growth factor beta (TGF-β) in the tumor microenvironment (TME). VEGF: vascular endothelial growth factor.

**Table 1.** Univariate Associations of Pathological Responses With Clinicopathological Factors in 43 Patients With Breast Cancer Who Received Preoperative Chemotherapy
Variable	Pathological response	P value
^aMann-Whitney test. ^bChi-squared test. ^cFisher’s exact test. ^dData were expressed as median (range). G1: grade 1; G2: grade 2; NS: not significant; HER-2: human epidermal growth factor receptor 2; TN: triple negative; EC: epirubicine/cyclophosphamide; PTX: paclitaxel; Tz: trastuzumab; ddEC: dose-dense EC; ddnab-PTX: dose-dense albumin-bound paclitaxel; TCHP: docetaxel/cyclophosphamide/trastuzumab/pertuzumab; Tz: trastuzumab; Pz: pertuzumab; pNK: peripheral natural killer; Pre-chemo: pre-chemotherapy; Post-chemo: post-chemotherapy.
Median age, years (range)	51 (43 - 76)	57 (31 - 71)	NS^a
Stage, n
I	0	1	NS^a
II	14	15
III	5	3
IV	1	4
Subtype, n
Luminal A	3	0	0.024^b
Luminal B	12	14
Luminal-HER-2	0	6
HER-2	0	1
TN	5	2
Histological type
IDC/NOS	18	20	NS^b
ILC	0	2
Others	2	1
Treatment regimen, n
EC/taxanes	16	22 (Tz: 6, Pz: 5)
EC/ddnab-PTX	1	0	NS^b
ddEC/nab-PTX	1	0
ddEC/ddnab-PTX	2	0
TCHP/ddEC	0	1 (Tz + Pz)
Tz, n
Tz-	20	16	0.008^c
Tz+	0	7
Pz, n
Pz-	20	17	0.017^c
Pz+	0	6
Nuclear grade, n
1	1	0	NS^a
2	9	6
3	20	17
Ki-67 positivity, n
< 15%	3	0	0.038^a
15-35%	11	10
> 35%	6	13
^dpNK
Pre-chemo	34.5 (6 - 49)	42.0 (9 - 65)	0.057^a
Post-chemo	36.0 (4 - 71)	35.0 (4 - 62)	NS^a
^dCD56⁺ CD16^-
Pre-chemo	3.3 (1.4 - 11.7)	5.1 (1.6 - 25.5)	0.054^a
Post-chemo	5.5 (2.1 - 17.6)	8.4 (2.7 - 31.8)	0.042^a
^dCD56^- CD16^-
Pre-chemo	82.0 (65.9 - 88.0)	73.1 (38.3 - 88.1)	NS^a
Post-chemo	63.3 (44.8 - 86.9)	62.5 (29.4 - 74.5)	NS^a
^dCD56^- CD16⁺
Pre-chemo	3.5 (1.1 - 12.6)	3.4 (0.9 - 13.2)	NS^a
Post-chemo	3.9 (1.2 - 11.7)	4.1 (1.1 - 14.3)	NS^a
^dCD56⁺ CD16⁺
Pre-chemo	12.3 (4.6 - 27.0)	14.4 (5.1 - 53.8)	NS^a
Post-chemo	20.5 (5.4 - 39.5)	18.3 (9.0 - 59.3)	NS^a
^dCD4
Pre-chemo	46.4 (29.6 - 66.2)	47.8 (23.4 - 57.6)	NS^a
Post-chemo	36.4 (21.5 - 55.8)	37.5 (18.6 - 55.1)	NS^a
^dCD8
Pre-chemo	31.4 (19.3 - 45.5)	31.2 (15.7 - 43.3)	NS^a
Post-chemo	40.1 (25.3 - 58.2)	38.9 (24.8 - 61.8)	NS^a
^dCD4/CD8
Pre-chemo	1.4 (0.7 - 2.9)	1.4 (0.5 - 3.6)	NS^a
Post-chemo	0.8 (0.5 - 2.2)	0.9 (0.4 - 1.8)	NS^a

Table 1. Univariate Associations of Pathological Responses With Clinicopathological Factors in 43 Patients With Breast Cancer Who Received Preoperative Chemotherapy

Variable

Pathological response

P value

Decreased (≤ G1, n = 20)

Increased (≥ G2, n = 23)

^aMann-Whitney test. ^bChi-squared test. ^cFisher’s exact test. ^dData were expressed as median (range). G1: grade 1; G2: grade 2; NS: not significant; HER-2: human epidermal growth factor receptor 2; TN: triple negative; EC: epirubicine/cyclophosphamide; PTX: paclitaxel; Tz: trastuzumab; ddEC: dose-dense EC; ddnab-PTX: dose-dense albumin-bound paclitaxel; TCHP: docetaxel/cyclophosphamide/trastuzumab/pertuzumab; Tz: trastuzumab; Pz: pertuzumab; pNK: peripheral natural killer; Pre-chemo: pre-chemotherapy; Post-chemo: post-chemotherapy.

Median age, years (range)

51 (43 - 76)

57 (31 - 71)

NS^a

Stage, n

NS^a

III

Subtype, n

Luminal A

0.024^b

Luminal B

Luminal-HER-2

HER-2

Histological type

IDC/NOS

NS^b

ILC

Others

Treatment regimen, n

EC/taxanes

22 (Tz: 6, Pz: 5)

EC/ddnab-PTX

NS^b

ddEC/nab-PTX

ddEC/ddnab-PTX

TCHP/ddEC

1 (Tz + Pz)

Tz, n

Tz-

0.008^c

Tz+

Pz, n

Pz-

0.017^c

Pz+

Nuclear grade, n

NS^a

Ki-67 positivity, n

< 15%

0.038^a

15-35%

> 35%

^dpNK

Pre-chemo

34.5 (6 - 49)

42.0 (9 - 65)

0.057^a

Post-chemo

36.0 (4 - 71)

35.0 (4 - 62)

NS^a

^dCD56⁺ CD16^-

Pre-chemo

3.3 (1.4 - 11.7)

5.1 (1.6 - 25.5)

0.054^a

Post-chemo

5.5 (2.1 - 17.6)

8.4 (2.7 - 31.8)

0.042^a

^dCD56^- CD16^-

Pre-chemo

82.0 (65.9 - 88.0)

73.1 (38.3 - 88.1)

NS^a

Post-chemo

63.3 (44.8 - 86.9)

62.5 (29.4 - 74.5)

NS^a

^dCD56^- CD16⁺

Pre-chemo

3.5 (1.1 - 12.6)

3.4 (0.9 - 13.2)

NS^a

Post-chemo

3.9 (1.2 - 11.7)

4.1 (1.1 - 14.3)

NS^a

^dCD56⁺ CD16⁺

Pre-chemo

12.3 (4.6 - 27.0)

14.4 (5.1 - 53.8)

NS^a

Post-chemo

20.5 (5.4 - 39.5)

18.3 (9.0 - 59.3)

NS^a

^dCD4

Pre-chemo

46.4 (29.6 - 66.2)

47.8 (23.4 - 57.6)

NS^a

Post-chemo

36.4 (21.5 - 55.8)

37.5 (18.6 - 55.1)

NS^a

^dCD8

Pre-chemo

31.4 (19.3 - 45.5)

31.2 (15.7 - 43.3)

NS^a

Post-chemo

40.1 (25.3 - 58.2)

38.9 (24.8 - 61.8)

NS^a

^dCD4/CD8

Pre-chemo

1.4 (0.7 - 2.9)

1.4 (0.5 - 3.6)

NS^a

Post-chemo

0.8 (0.5 - 2.2)

0.9 (0.4 - 1.8)

NS^a

**Table 2.** Univariate Associations of Disappearance of Axillary Lymph Node Metastasis With Clinicopathological Factors in 26 Patients With Breast Cancer Who Received Preoperative Chemotherapy
Variable	Axillary lymph node metastasis	P value
^aMann-Whitney test. ^bChi-squared test. ^cFisher’s exact test. ^dData were expressed as median (range). G1: grade 1; G2: grade 2; NS: not significant; HER-2: human epidermal growth factor receptor 2; TN: triple negative; IDC: invasive ductal carcinoma; NOS: not otherwise specified; ILC: invasive lobular carcinoma; EC: epirubicine/cyclophosphamide; PTX: paclitaxel; Tz: trastuzumab; ddEC: dose-dense epirubicine/cyclophosphamide; ddnab-PTX: dose-dense albumin-bound paclitaxel; TCHP: docetaxel/cyclophosphamide/trastuzumab/pertuzumab; Tz: trastuzumab; Pz: pertuzumab; pNK: peripheral natural killer; Pre-chemo: pre-chemotherapy; Post-chemo: post-chemotherapy.
Median age, years (range)	50.5 (46 - 76)	53 (31 - 67)	NS^a
Stage, n
II	11	7	NS^a
III	5	3
Subtype, n
Luminal A	1	0	NS^b
Luminal B	12	6
Luminal-HER2	0	2
HER-2	0	1
TN	3	1
Histological type
IDC/NOS	14	8	NS^b
ILC	1	0
Others	1	2
Treatment regimen, n
EC/taxanes	14	8 (Tz + Pz: 2)	NS^b
EC/ddnab-PTX	1	0
ddEC/ddnab-PTX	1	1
TCHP/ddEC	0	1 (Tz + Pz: 1)
Tz + Pz, n
Tz/Pz-	16	7	0.046^c
Tz/Pz+	0	3
Nuclear grade, n
1	1	0	NS^a
2	6	2
3	9	8
Ki-67 positivity, n
< 15%	2	0	0.040^a
15-35%	10	3
> 35%	4	7
^dpNK, n
Pre-chemo	36.5 (6 - 60)	27.5 (9 - 50)	NS^a
Post-chemo	34.0 (4 - 67)	31.0 (10 - 59)	NS^a
^dCD56⁺ CD16
Pre-chemo	4.2 (1.7 - 11.7)	5.3 (1.4 - 9.4)	NS^a
Post-chemo	5.6 (2.1 - 17.6)	10.2 (4.9 - 14.1)	NS^a
^dCD56^- CD16
Pre-chemo	72.4 (64.9 - 88.0)	82.4 (65.9 - 88.1)	NS^a
Post-chemo	63.0 (49.4 - 86.9)	67.2 (51.7 - 74.5)	NS^a
^dCD56^- CD16⁺
Pre-chemo	3.5 (1.2 - 13.2)	2.2 (0.9 - 6.7)	NS^a
Post-chemo	5.1 (1.2 - 14.3)	3.3 (1.1 - 11.7)	NS^a
^dCD56⁺ CD16⁺
Pre-chemo	14.9 (4.6 - 27.0)	10.6 (5.1 - 19.9)	NS^a
Post-chemo	22.3 (5.4 - 35.1)	17.9 (12.5 - 33.2)	NS^a
^dCD4
Pre-chemo	46.4 (29.6 - 66.2)	47.6 (34.0 - 57.1)	NS^a
Post-chemo	36.0 (24.6 - 55.8)	38.0 (21.5 - 55.1)	NS^a
^dCD8
Pre-chemo	32.9 (20.4 - 40.3)	25.9 (15.7 - 45.5)	NS^a
Post-chemo	42.3 (25.3 - 50.0)	37.7 (30.5 - 58.2)	NS^a
^dCD4/CD8
Pre-chemo	1.4 (0.7 - 2.9)	1.4 (0.5 - 3.6)	NS^a
Post-chemo	0.8 (0.5 - 2.2)	0.9 (0.4 - 1.8)	NS^a

Table 2. Univariate Associations of Disappearance of Axillary Lymph Node Metastasis With Clinicopathological Factors in 26 Patients With Breast Cancer Who Received Preoperative Chemotherapy

Variable

Axillary lymph node metastasis

P value

Not disappeared (n = 16)

Disappeared (n = 10)

^aMann-Whitney test. ^bChi-squared test. ^cFisher’s exact test. ^dData were expressed as median (range). G1: grade 1; G2: grade 2; NS: not significant; HER-2: human epidermal growth factor receptor 2; TN: triple negative; IDC: invasive ductal carcinoma; NOS: not otherwise specified; ILC: invasive lobular carcinoma; EC: epirubicine/cyclophosphamide; PTX: paclitaxel; Tz: trastuzumab; ddEC: dose-dense epirubicine/cyclophosphamide; ddnab-PTX: dose-dense albumin-bound paclitaxel; TCHP: docetaxel/cyclophosphamide/trastuzumab/pertuzumab; Tz: trastuzumab; Pz: pertuzumab; pNK: peripheral natural killer; Pre-chemo: pre-chemotherapy; Post-chemo: post-chemotherapy.

Median age, years (range)

50.5 (46 - 76)

53 (31 - 67)

NS^a

Stage, n

NS^a

III

Subtype, n

Luminal A

NS^b

Luminal B

Luminal-HER2

HER-2

Histological type

IDC/NOS

NS^b

ILC

Others

Treatment regimen, n

EC/taxanes

8 (Tz + Pz: 2)

NS^b

EC/ddnab-PTX

ddEC/ddnab-PTX

TCHP/ddEC

1 (Tz + Pz: 1)

Tz + Pz, n

Tz/Pz-

0.046^c

Tz/Pz+

Nuclear grade, n

NS^a

Ki-67 positivity, n

< 15%

0.040^a

15-35%

> 35%

^dpNK, n

Pre-chemo

36.5 (6 - 60)

27.5 (9 - 50)

NS^a

Post-chemo

34.0 (4 - 67)

31.0 (10 - 59)

NS^a

^dCD56⁺ CD16

Pre-chemo

4.2 (1.7 - 11.7)

5.3 (1.4 - 9.4)

NS^a

Post-chemo

5.6 (2.1 - 17.6)

10.2 (4.9 - 14.1)

NS^a

^dCD56^- CD16

Pre-chemo

72.4 (64.9 - 88.0)

82.4 (65.9 - 88.1)

NS^a

Post-chemo

63.0 (49.4 - 86.9)

67.2 (51.7 - 74.5)

NS^a

^dCD56^- CD16⁺

Pre-chemo

3.5 (1.2 - 13.2)

2.2 (0.9 - 6.7)

NS^a

Post-chemo

5.1 (1.2 - 14.3)

3.3 (1.1 - 11.7)

NS^a

^dCD56⁺ CD16⁺

Pre-chemo

14.9 (4.6 - 27.0)

10.6 (5.1 - 19.9)

NS^a

Post-chemo

22.3 (5.4 - 35.1)

17.9 (12.5 - 33.2)

NS^a

^dCD4

Pre-chemo

46.4 (29.6 - 66.2)

47.6 (34.0 - 57.1)

NS^a

Post-chemo

36.0 (24.6 - 55.8)

38.0 (21.5 - 55.1)

NS^a

^dCD8

Pre-chemo

32.9 (20.4 - 40.3)

25.9 (15.7 - 45.5)

NS^a

Post-chemo

42.3 (25.3 - 50.0)

37.7 (30.5 - 58.2)

NS^a

^dCD4/CD8

Pre-chemo

1.4 (0.7 - 2.9)

1.4 (0.5 - 3.6)

NS^a

Post-chemo

0.8 (0.5 - 2.2)

0.9 (0.4 - 1.8)

NS^a

**Table 3.** Univariate Associations of pNK Cell Activity With Clinicopathological Factors in 41 Patients With Breast Cancer Who Received Preoperative Chemotherapy
Variable	pNK cell activity	P value
^aMann-Whitney test. ^bChi-squared test. ^cFisher’s exact test. pNK: peripheral natural killer; NS: not significant; HER-2: human epidermal growth factor receptor 2; TN: triple negative; IDC: invasive ductal carcinoma; NOS: not otherwise specified; ILC: invasive lobular carcinoma; EC: epirubicine/cyclophosphamide; ddnab-PTX: dose dense albumin-bound paclitaxel; ddEC: dose dense EC; TCHP: docetaxel/cyclophosphamide/trastuzumab/pertuzumab; Tz: trastuzumab; Pz: pertuzumab; Pre-chemo: pre-chemotherapy; Post-chemo: post-chemotherapy.
Median age, years (range)	52.5 (31 - 66)	58 (33 - 76)	NS^a
pNK cell activity Pre-chemo	44 (6 - 65)	24 (8 - 55)	0.030^a
Post-chemo	24 (4 - 51)	42 (13 - 71)	0.005^a
Stage, n
I	1	0	NS^a
II	11	16
III	3	5
IV	1	4
Subtype, n
Luminal A	0	3	NS^b
Luminal B	10	14
Luminal-HER-2	4	2
HER-2	1	0
TN	1	6
Histological type
IDC/NOS	15	21	NS^b
ILC	0	2
Others	1	2
Treatment regimen, n
EC/taxanes	14 (Tz 4, Pz 3)	22 (Tz 2; Pz:2)	NS^b
EC/ddnab-PTX	0	1
ddEC/nab-PTX	0	1
ddEC/ddnab-PTX	1	1
TCHP/ddEC	1 (Tz 1, Pz 1)	0
Tz, n
Tz-	11	23	NS^c
Tz+	5	2
Pz, n
Pz-	12	23	NS^c
Pz+	4	2
Nuclear grade, n
1	0	1	NS^a
2	7	7
3	9	17
Ki-67 positivity, n
< 15%	0	3	NS^a
15-35%	10	10
> 35%	6	12
CD56⁺ CD16^-
Pre-chemo	3.2 (1.4 - 18.6)	4.2 (1.4 - 25.5)	NS^a
Post-chemo	6.2 (2.1 - 31.8)	8.4 (4.0 - 30.3)	NS^a
CD56^- CD16^-
Pre-chemo	72.4 (59.4 - 85.6)	78.5 (38.3 - 88.0)	NS^a
Post-chemo	62.4 (49.4 - 86.9)	62.6 (29.4 - 86.7)	NS^a
CD56^- CD16⁺
Pre-chemo	3.8 (0.9 - 12.6)	3.4 (0.9 - 13.2)	NS^a
Post-chemo	5.3 (1.2 - 14.3)	3.7 (1.3 - 11.1)	NS^a
CD56⁺ CD16⁺
Pre-chemo	14.2 (4.6 - 34.9)	9.9 (6.0 - 53.8)	NS^a
Post-chemo	18.1 (5.4 - 34.4)	19.8 (6.9 - 59.3)	NS^a
CD4
Pre-chemo	45.9 (29.6 - 59.7)	47.8 (23.4 - 66.2)	NS^a
Post-chemo	37.2 (24.6 - 55.1)	37.5 (21.5 - 55.8)	NS^a
CD8
Pre-chemo	32.2 (15.7 - 42.3)	31.2 (19.3 - 45.5)	NS^a
Post-chemo	41.0 (24.8 - 61.8)	39.7 (25.3 - 58.2)	NS^a
CD4/CD8
Pre-chemo	1.4 (0.7 - 3.6)	1.5 (0.5 - 2.9)	NS^a
Post-chemo	0.9 (0.4 - 1.8)	0.8 (0.5 - 2.2)	NS^a

Table 3. Univariate Associations of pNK Cell Activity With Clinicopathological Factors in 41 Patients With Breast Cancer Who Received Preoperative Chemotherapy

Variable

pNK cell activity

P value

Decrease (n = 16)

Increase (n = 25)

^aMann-Whitney test. ^bChi-squared test. ^cFisher’s exact test. pNK: peripheral natural killer; NS: not significant; HER-2: human epidermal growth factor receptor 2; TN: triple negative; IDC: invasive ductal carcinoma; NOS: not otherwise specified; ILC: invasive lobular carcinoma; EC: epirubicine/cyclophosphamide; ddnab-PTX: dose dense albumin-bound paclitaxel; ddEC: dose dense EC; TCHP: docetaxel/cyclophosphamide/trastuzumab/pertuzumab; Tz: trastuzumab; Pz: pertuzumab; Pre-chemo: pre-chemotherapy; Post-chemo: post-chemotherapy.

Median age, years (range)

52.5 (31 - 66)

58 (33 - 76)

NS^a

pNK cell activity Pre-chemo

44 (6 - 65)

24 (8 - 55)

0.030^a

Post-chemo

24 (4 - 51)

42 (13 - 71)

0.005^a

Stage, n

NS^a

III

Subtype, n

Luminal A

NS^b

Luminal B

Luminal-HER-2

HER-2

Histological type

IDC/NOS

NS^b

ILC

Others

Treatment regimen, n

EC/taxanes

14 (Tz 4, Pz 3)

22 (Tz 2; Pz:2)

NS^b

EC/ddnab-PTX

ddEC/nab-PTX

ddEC/ddnab-PTX

TCHP/ddEC

1 (Tz 1, Pz 1)

Tz, n

Tz-

NS^c

Tz+

Pz, n

Pz-

NS^c

Pz+

Nuclear grade, n

NS^a

Ki-67 positivity, n

< 15%

NS^a

15-35%

> 35%

CD56⁺ CD16^-

Pre-chemo

3.2 (1.4 - 18.6)

4.2 (1.4 - 25.5)

NS^a

Post-chemo

6.2 (2.1 - 31.8)

8.4 (4.0 - 30.3)

NS^a

CD56^- CD16^-

Pre-chemo

72.4 (59.4 - 85.6)

78.5 (38.3 - 88.0)

NS^a

Post-chemo

62.4 (49.4 - 86.9)

62.6 (29.4 - 86.7)

NS^a

CD56^- CD16⁺

Pre-chemo

3.8 (0.9 - 12.6)

3.4 (0.9 - 13.2)

NS^a

Post-chemo

5.3 (1.2 - 14.3)

3.7 (1.3 - 11.1)

NS^a

CD56⁺ CD16⁺

Pre-chemo

14.2 (4.6 - 34.9)

9.9 (6.0 - 53.8)

NS^a

Post-chemo

18.1 (5.4 - 34.4)

19.8 (6.9 - 59.3)

NS^a

CD4

Pre-chemo

45.9 (29.6 - 59.7)

47.8 (23.4 - 66.2)

NS^a

Post-chemo

37.2 (24.6 - 55.1)

37.5 (21.5 - 55.8)

NS^a

CD8

Pre-chemo

32.2 (15.7 - 42.3)

31.2 (19.3 - 45.5)

NS^a

Post-chemo

41.0 (24.8 - 61.8)

39.7 (25.3 - 58.2)

NS^a

CD4/CD8

Pre-chemo

1.4 (0.7 - 3.6)

1.5 (0.5 - 2.9)

NS^a

Post-chemo

0.9 (0.4 - 1.8)

0.8 (0.5 - 2.2)

NS^a

**Table 4.** Multivariate Associations of G2 and Better Therapeutic Effects With pNK Cell Activity Before Chemotherapy, CD56⁺ CD16^- NK Cell Subset Before and After Chemotherapy in 43 Patients With Breast Cancer Who Received Preoperative Chemotherapy
Dependent variable	Independent variable	OR (95% CI)	P value
Pre-chemo: pre-chemotherapy; Post-chemo: post-chemotherapy; G2: grade 2; pNK: peripheral natural killer; NK: natural killer; OR: odds ratio; CI: confidence interval.
G2 and better therapeutic effects	Pre-chemo pNK cell activity	0.96 (0.92 - 1.00)	0.067
	Pre-chemo CD56⁺ CD16^-	0.99 (0.70 - 1.39)	0.958
	Post-chemo CD56⁺ CD16^-	0.90 (0.70 - 1.15)	0.396

Table 4. Multivariate Associations of G2 and Better Therapeutic Effects With pNK Cell Activity Before Chemotherapy, CD56⁺ CD16^- NK Cell Subset Before and After Chemotherapy in 43 Patients With Breast Cancer Who Received Preoperative Chemotherapy

Dependent variable

Independent variable

OR (95% CI)

P value

Pre-chemo: pre-chemotherapy; Post-chemo: post-chemotherapy; G2: grade 2; pNK: peripheral natural killer; NK: natural killer; OR: odds ratio; CI: confidence interval.

G2 and better therapeutic effects

Pre-chemo pNK cell activity

0.96 (0.92 - 1.00)

0.067

Pre-chemo CD56⁺ CD16^-

0.99 (0.70 - 1.39)

0.958

Post-chemo CD56⁺ CD16^-

0.90 (0.70 - 1.15)

0.396