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 13, Number 6, December 2022, pages 379-386

Advanced Stage Is a Risk for Severe Neutropenia in Breast Cancer Patients Undergoing Neoadjuvant Adriamycin/Cyclophosphamide/Docetaxel Chemotherapy

Figure 1. The CONSORT diagram with inclusion and exclusion criteria. Eighty-three patients were included for analysis. AC: adriamycin/cyclophosphamide; DTX: docetaxel; FEC: fluorouracil/epirubicin hydrochloride/cyclophosphamide; PTX: paclitaxel; TC: docetaxel/cyclophosphamide.

Figure 2. The comparison of responses after chemotherapy between patients treated with neoadjuvant chemotherapy and those treated with adjuvant chemotherapy. There were plenty of TME-derived soluble and bioactive factors (cytokines, growth factors, exosomes, and chemokines) during neoadjuvant chemotherapy, whereas there were no TME in adjuvant chemotherapy. TME: tumor microenvironment.

**Table 1.** Univariate and Multivariate Analyses of the Factors Which Associated With Severe Neutropenia Among 83 Patients
Variables	No.	Univariate	Multivariate
cStage: clinical stage; CR: complete response; HR: hormone receptor; HER-2: human epidermal growth factor receptor 2; PR: partial response; RECIST: Response Evaluation Criteria in Solid Tumors; SD: stable disease; OR: odds ratio; CI: confidence interval; CA15-3: cancer antigen 15-3; CEA: carcinoembryonic antigen.
Age				0.379
Median (range)	51 (27 - 74)	49 (27 - 69)	53 (34 - 74)
Tumor size				0.081
cT1 - 3	77 (93%)	15 (83%)	62 (95%)		1
cT4	6 (7%)	3 (17%)	3 (5%)		11.805 (1.090 - 127.885)	0.042
Lymph node metastasis				0.290
cN0 - 1	71 (86%)	14 (78%)	57 (88%)
cN2 - 3	12 (14%)	4 (22%)	8 (12%)
Cancer stage				0.134
cStage II	62 (74%)	11 (61%)	51 (78%)
cStage III	21 (26%)	7 (39%)	14 (22%)
HR status				0.437
Negative	44 (53%)	11 (61%)	33 (51%)
Positive	39 (47%)	7 (39%)	32 (49%)
HER-2 status				0.583
Negative	46 (55%)	11 (61%)	35 (54%)
Positive	37 (45%)	7 (39%)	30 (46%)
Ki-labeling index				0.256
Ki ≥ 30%	58 (70%)	13 (72%)	45 (69%)
Ki < 30%	19 (23)	2 (11%)	17 (26%)
Unknown	6 (7%)	3 (17%)	3 (5%)
RECIST				0.155
cCR + cPR	76 (84%)	15 (83%)	61 (94%)
cSD	7 (16%)	3 (17%)	4 (6%)
Pegfilgrastim for primary prophylaxis				0.023
Absence	61 (73%)	17 (94%)	44 (68%)		1
Presence	22 (27%)	1 (6%)	21 (32%)		0.063 (0.005 - 0.770)	0.030
CEA (cutoff 5.8)				0.302
Negative	67 (81%)	13 (72%)	54 (83%)
Positive	16 (19%)	5 (28%)	11 (17%)
CA15-3 (cutoff 23)				0.290
Negative	71 (86%)	14 (78%)	57 (88%)
Positive	12 (14%)	4 (22%)	8 (12%)

Table 1. Univariate and Multivariate Analyses of the Factors Which Associated With Severe Neutropenia Among 83 Patients

Variables

No.

Univariate

Multivariate

Total (n = 83)

With neutropenia (n = 18)

Without neutropenia (n = 65)

P value

OR (95% CI)

P value

cStage: clinical stage; CR: complete response; HR: hormone receptor; HER-2: human epidermal growth factor receptor 2; PR: partial response; RECIST: Response Evaluation Criteria in Solid Tumors; SD: stable disease; OR: odds ratio; CI: confidence interval; CA15-3: cancer antigen 15-3; CEA: carcinoembryonic antigen.

Age

0.379

Median (range)

51 (27 - 74)

49 (27 - 69)

53 (34 - 74)

Tumor size

0.081

cT1 - 3

77 (93%)

15 (83%)

62 (95%)

cT4

6 (7%)

3 (17%)

3 (5%)

11.805 (1.090 - 127.885)

0.042

Lymph node metastasis

0.290

cN0 - 1

71 (86%)

14 (78%)

57 (88%)

cN2 - 3

12 (14%)

4 (22%)

8 (12%)

Cancer stage

0.134

cStage II

62 (74%)

11 (61%)

51 (78%)

cStage III

21 (26%)

7 (39%)

14 (22%)

HR status

0.437

Negative

44 (53%)

11 (61%)

33 (51%)

Positive

39 (47%)

7 (39%)

32 (49%)

HER-2 status

0.583

Negative

46 (55%)

11 (61%)

35 (54%)

Positive

37 (45%)

7 (39%)

30 (46%)

Ki-labeling index

0.256

Ki ≥ 30%

58 (70%)

13 (72%)

45 (69%)

Ki < 30%

19 (23)

2 (11%)

17 (26%)

Unknown

6 (7%)

3 (17%)

3 (5%)

RECIST

0.155

cCR + cPR

76 (84%)

15 (83%)

61 (94%)

cSD

7 (16%)

3 (17%)

4 (6%)

Pegfilgrastim for primary prophylaxis

0.023

Absence

61 (73%)

17 (94%)

44 (68%)

Presence

22 (27%)

1 (6%)

21 (32%)

0.063 (0.005 - 0.770)

0.030

CEA (cutoff 5.8)

0.302

Negative

67 (81%)

13 (72%)

54 (83%)

Positive

16 (19%)

5 (28%)

11 (17%)

CA15-3 (cutoff 23)

0.290

Negative

71 (86%)

14 (78%)

57 (88%)

Positive

12 (14%)

4 (22%)

8 (12%)

**Table 2.** Univariate and Multivariate Analyses for Severe Neutropenia Among 61 Patients Without Pegfilgrastim for Primary Prophylaxis
Variables	No.	Univariate	Multivariate
cStage: clinical stage; CR: complete response; HR: hormone receptor; HER-2: human epidermal growth factor receptor 2; PR: partial response; RECIST: Response Evaluation Criteria in Solid Tumors; SD: stable disease; OR: odds ratio; CI: confidence interval; CA15-3: cancer antigen 15-3; CEA: carcinoembryonic antigen.
Age				0.559
Median (range)	49 (27 - 74)	49 (27 - 69)	53 (34 - 74)
Tumor size				0.004
cT1 - 3	58 (95%)	14 (82%)	44 (100%)
cT4	3 (5%)	3 (18%)	0 (0%)
Lymph node metastasis				0.067
cN0 - 1	54 (89%)	13 (76%)	41 (93%)
cN2 - 3	7 (11%)	4 (24%)	3 (7%)
Cancer stage				0.009
cStage II	49 (80%)	10 (59%)	39 (89%)		1
cStage III	12 (20%)	7 (41%)	5 (11%)		5.194 (1.288 - 20.946)	0.021
HR status				0.437
Negative	31 (51%)	10 (59%)	21 (48%)
Positive	30 (49%)	7 (41%)	23 (52%)
HER-2 status				0.929
Negative	40 (66%)	11 (65%)	29 (66%)
Positive	21 (34%)	6 (35%)	15 (34%)
Ki-labeling index				0.158
Ki ≥ 30%	39 (64%)	12 (71%)	27 (61%)
Ki < 30%	16 (26%)	2 (12%)	14 (32%)
Unknown	6 (10%)	3 (17%)	3 (7%)
RECIST				0.203
cCR + cPR	56 (92%)	14 (82%)	42 (95%)
cSD	5 (8%)	3 (18%)	2 (5%)
CEA (cutoff 5.8)				0.088
Negative	51 (84%)	12 (71%)	39 (89%)
Positive	10 (16%)	5 (29%)	5 (11%)
CA15-3 (cutoff 23)				0.026
Negative	55 (90%)	13 (76%)	42 (95%)		1
Positive	6 (10%)	4 (24%)	2 (5%)		6.074 (0.904 - 40.819)	0.063

Table 2. Univariate and Multivariate Analyses for Severe Neutropenia Among 61 Patients Without Pegfilgrastim for Primary Prophylaxis

Variables

No.

Univariate

Multivariate

Total (n = 61)

With neutropenia (n = 17)

Without neutropenia (n = 44)

P value

OR (95% CI)

P value

Age

0.559

Median (range)

49 (27 - 74)

49 (27 - 69)

53 (34 - 74)

Tumor size

0.004

cT1 - 3

58 (95%)

14 (82%)

44 (100%)

cT4

3 (5%)

3 (18%)

0 (0%)

Lymph node metastasis

0.067

cN0 - 1

54 (89%)

13 (76%)

41 (93%)

cN2 - 3

7 (11%)

4 (24%)

3 (7%)

Cancer stage

0.009

cStage II

49 (80%)

10 (59%)

39 (89%)

cStage III

12 (20%)

7 (41%)

5 (11%)

5.194 (1.288 - 20.946)

0.021

HR status

0.437

Negative

31 (51%)

10 (59%)

21 (48%)

Positive

30 (49%)

7 (41%)

23 (52%)

HER-2 status

0.929

Negative

40 (66%)

11 (65%)

29 (66%)

Positive

21 (34%)

6 (35%)

15 (34%)

Ki-labeling index

0.158

Ki ≥ 30%

39 (64%)

12 (71%)

27 (61%)

Ki < 30%

16 (26%)

2 (12%)

14 (32%)

Unknown

6 (10%)

3 (17%)

3 (7%)

RECIST

0.203

cCR + cPR

56 (92%)

14 (82%)

42 (95%)

cSD

5 (8%)

3 (18%)

2 (5%)

CEA (cutoff 5.8)

0.088

Negative

51 (84%)

12 (71%)

39 (89%)

Positive

10 (16%)

5 (29%)

5 (11%)

CA15-3 (cutoff 23)

0.026

Negative

55 (90%)

13 (76%)

42 (95%)

Positive

6 (10%)

4 (24%)

2 (5%)

6.074 (0.904 - 40.819)

0.063

**Table 3.** Association Between Clinical Stage and Period of Observed Severe Neutropenia in 17 Patients Without Pegfilgrastim for Primary Prophylaxis
Observed neutropenia	During AC	During DTX	Total	P value
AC: adriamycin and cyclophosphamide; DTX: docetaxel; cStage: clinical stage.
cStage II	4 (40%)	6 (60%)	10	0.059
cStage III	6 (86%)	1 (14%)	7
Total	10	7	17

Table 3. Association Between Clinical Stage and Period of Observed Severe Neutropenia in 17 Patients Without Pegfilgrastim for Primary Prophylaxis

Observed neutropenia

During AC

During DTX

Total

P value

AC: adriamycin and cyclophosphamide; DTX: docetaxel; cStage: clinical stage.

cStage II

4 (40%)

6 (60%)

0.059

cStage III

6 (86%)

1 (14%)

Total