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 14, Number 1, February 2023, pages 60-66

Estradiol Levels and Chemotherapy in Breast Cancer Patients: A Prospective Clinical Study

Figure 1. The distribution of breast cancer patients based on chemotherapy regimens. AC: anthracycline cyclophosphamide. TA: paclitaxel, anthracycline. TA + H: paclitaxel, anthracycline and trastuzumab.

**Table 1.** Subjects’ Characteristics
Characteristics	Total (n = 194)	Chemotherapy	P-value
^aIndependent t-test. ^bMann-Whitney U. ^cChi-square/Fisher exact test. *Statistically significant (α = 5%). EBC: early breast cancer; LABC: locally advanced breast cancer; ABC: advanced breast cancer; LVI: lymphovascular invasion; HER2: human epidermal growth factor receptor 2.
Age^a (years)	51.63 ± 10.01	51.47 ± 13.02	51.64 ± 9.72	0.946
Menarche^b (years)	12.77 ± 1.41	12.65 ± 1.73	12.78 ± 1.38	0.793
Cancer stage^b				0.033*
EBC	42 (21.6%)	7 (41.2%)	35 (19.8%)
LABC	100 (51.5%)	8 (47.1%)	92 (52.0%)
ABC	52 (26.8%)	2 (11.8%)	50 (28.2%)
Cancer grading^b				0.332
I	13 (6.7%)	3 (17.6%)	10 (5.6%)
II	64 (33.0%)	5 (29.4%)	59 (33.3%)
III	117 (60.3%)	9 (52.9%)	108 (61.0%)
LVI^c				0.366
Negative	61 (31.4%)	7 (41.2%)	54 (30.5%)
Positive	133 (68.6%)	10 (58.8%)	123 (69.5%)
Subtype^c				0.004*
Luminal A	46 (23.7%)	10 (58.8%)	36 (20.3%)
Luminal B	41 (21.1%)	4 (23.5%)	37 (20.9%)
HER2 overexpression	50 (25.8%)	0 (0.0%)	50 (28.2%)
Triple-negative	36 (18.6%)	2 (11.8%)	34 (19.2%)
Triple-positive	21 (10.8%)	1 (5.9%)	20 (11.3%)
Ki67^c				0.888
Negative	111 (57.2%)	10 (58.8%)	101 (57.1%)
Positive	83 (42.8%)	7 (41.2%)	76 (42.9%)
Menopausal status^c				0.675
Premenopause	112 (57.7%)	9 (52.9%)	103 (58.2%)
Menopause	82 (42.3%)	8 (47.1%)	74 (41.8%)
Marital status^c				0.570
Unmarried	9 (4.6%)	1 (5.9%)	8 (4.5%)
Married	185 (95.4%)	16 (94.1%)	169 (95.5%)
Number of kid(s)^b				0.959
None	19 (9.8%)	1 (5.9%)	18 (10.2%)
1 - 2	111 (57.2%)	11 (64.7%)	100 (56.5%)
≥ 2	64 (33.0%)	5 (29.4%)	59 (33.3%)
Breastfeeding^c				0.128
No	42 (21.6%)	1 (5.9%)	41 (23.2%)
Yes	152 (78.4%)	16 (94.1%)	136 (76.8%)
Contraception^c				0.312
Hormonal	74 (38.1%)	9 (52.9%)	65 (36.7%)
Nonhormonal	57 (29.4%)	5 (29.4%)	52 (29.4%)
None	63 (32.5%)	3 (17.6%)	60 (33.9%)
Family history of cancer^c				0.318
Present	35 (18.0%)	1 (5.9%)	34 (19.2%)
Absent	159 (82.0%)	16 (94.1%)	143 (80.8%)

Table 1. Subjects’ Characteristics

Characteristics

Total (n = 194)

Chemotherapy

P-value

No (n = 17)

Yes (n = 177)

^aIndependent t-test. ^bMann-Whitney U. ^cChi-square/Fisher exact test. *Statistically significant (α = 5%). EBC: early breast cancer; LABC: locally advanced breast cancer; ABC: advanced breast cancer; LVI: lymphovascular invasion; HER2: human epidermal growth factor receptor 2.

Age^a (years)

51.63 ± 10.01

51.47 ± 13.02

51.64 ± 9.72

0.946

Menarche^b (years)

12.77 ± 1.41

12.65 ± 1.73

12.78 ± 1.38

0.793

Cancer stage^b

0.033*

EBC

42 (21.6%)

7 (41.2%)

35 (19.8%)

LABC

100 (51.5%)

8 (47.1%)

92 (52.0%)

ABC

52 (26.8%)

2 (11.8%)

50 (28.2%)

Cancer grading^b

0.332

13 (6.7%)

3 (17.6%)

10 (5.6%)

64 (33.0%)

5 (29.4%)

59 (33.3%)

III

117 (60.3%)

9 (52.9%)

108 (61.0%)

LVI^c

0.366

Negative

61 (31.4%)

7 (41.2%)

54 (30.5%)

Positive

133 (68.6%)

10 (58.8%)

123 (69.5%)

Subtype^c

0.004*

Luminal A

46 (23.7%)

10 (58.8%)

36 (20.3%)

Luminal B

41 (21.1%)

4 (23.5%)

37 (20.9%)

HER2 overexpression

50 (25.8%)

0 (0.0%)

50 (28.2%)

Triple-negative

36 (18.6%)

2 (11.8%)

34 (19.2%)

Triple-positive

21 (10.8%)

1 (5.9%)

20 (11.3%)

Ki67^c

0.888

Negative

111 (57.2%)

10 (58.8%)

101 (57.1%)

Positive

83 (42.8%)

7 (41.2%)

76 (42.9%)

Menopausal status^c

0.675

Premenopause

112 (57.7%)

9 (52.9%)

103 (58.2%)

Menopause

82 (42.3%)

8 (47.1%)

74 (41.8%)

Marital status^c

0.570

Unmarried

9 (4.6%)

1 (5.9%)

8 (4.5%)

Married

185 (95.4%)

16 (94.1%)

169 (95.5%)

Number of kid(s)^b

0.959

None

19 (9.8%)

1 (5.9%)

18 (10.2%)

1 - 2

111 (57.2%)

11 (64.7%)

100 (56.5%)

≥ 2

64 (33.0%)

5 (29.4%)

59 (33.3%)

Breastfeeding^c

0.128

42 (21.6%)

1 (5.9%)

41 (23.2%)

Yes

152 (78.4%)

16 (94.1%)

136 (76.8%)

Contraception^c

0.312

Hormonal

74 (38.1%)

9 (52.9%)

65 (36.7%)

Nonhormonal

57 (29.4%)

5 (29.4%)

52 (29.4%)

None

63 (32.5%)

3 (17.6%)

60 (33.9%)

Family history of cancer^c

0.318

Present

35 (18.0%)

1 (5.9%)

34 (19.2%)

Absent

159 (82.0%)

16 (94.1%)

143 (80.8%)

**Table 2.** Estradiol Levels Before and After Therapy Based on Subtypes
Subtype	Estradiol	N	Mean	SD	Min.	Max.	P value
*Uji Wilcoxon: there was a statistically significant difference in estradiol levels between before and after chemotherapy based on subtype (P < 0.05). HER2: human epidermal growth factor receptor 2; SD: standard deviation.
Luminal A	Before therapy	46	78.63	65.37	0	377	0.003*
	After therapy	46	73.36	79.61	0	357
Luminal B	Before therapy	41	83.30	59.98	23	267	0.008*
	After therapy	41	68.86	47.13	16	222
Triple-negative	Before therapy	36	87.47	67.652	28	350	0.002*
	After therapy	36	72.42	58.194	27	315
Triple-positive	Before therapy	21	98.37	63.899	33	260	0.001*
	After therapy	21	60.88	41.182	1	175
HER2 overexpression	Before therapy	50	77.69	57.59	12	315	0.001*
	After therapy	50	54.31	23.78	5	112

Table 2. Estradiol Levels Before and After Therapy Based on Subtypes

Subtype

Estradiol

Mean

Min.

Max.

P value

*Uji Wilcoxon: there was a statistically significant difference in estradiol levels between before and after chemotherapy based on subtype (P < 0.05). HER2: human epidermal growth factor receptor 2; SD: standard deviation.

Luminal A

Before therapy

78.63

65.37

377

0.003*

After therapy

73.36

79.61

357

Luminal B

Before therapy

83.30

59.98

267

0.008*

After therapy

68.86

47.13

222

Triple-negative

Before therapy

87.47

67.652

350

0.002*

After therapy

72.42

58.194

315

Triple-positive

Before therapy

98.37

63.899

260

0.001*

After therapy

60.88

41.182

175

HER2 overexpression

Before therapy

77.69

57.59

315

0.001*

After therapy

54.31

23.78

112

**Table 3.** Effects of Chemotherapy on Estrogen Levels
Regimen	Estradiol before (mean ± SD; pg/mL)	Estradiol after (mean ± SD; pg/mL)	P-value	Decrease (%)
^aWilcoxon rank test for comparison of two population means (paired samples). ^bKruskal-Wallis for comparison of more than two population means (unpaired samples). *Statistically significant (α = 5%). AC: anthracycline cyclophosphamide; TA: paclitaxel, anthracycline. TA + H: paclitaxel, anthracycline and trastuzumab; SD: standard deviation.
No chemotherapy (n = 17)	106.83 ± 97.59	99.44 ± 94.90	0.163^a	-6.9%
AC (n = 42)	78.25 ± 51.79	61.51 ± 42.06	0.011^a*	-21.4%
TA (n = 91)	81.81 ± 61.65	65.25 ± 54.85	< 0.001^a*	-20.2%
TA + H (n = 22)	83.43 ± 56.42	56.96 ± 32.29	0.006^a*	-31.7%
Platinum (n = 22)	79.46 ± 56.22	60.64 ± 40.38	0.016^a*	-23.7%
P-value	0.937^b	0.730^b

Table 3. Effects of Chemotherapy on Estrogen Levels

Regimen

Estradiol before (mean ± SD; pg/mL)

Estradiol after (mean ± SD; pg/mL)

P-value

Decrease (%)

^aWilcoxon rank test for comparison of two population means (paired samples). ^bKruskal-Wallis for comparison of more than two population means (unpaired samples). *Statistically significant (α = 5%). AC: anthracycline cyclophosphamide; TA: paclitaxel, anthracycline. TA + H: paclitaxel, anthracycline and trastuzumab; SD: standard deviation.

No chemotherapy (n = 17)

106.83 ± 97.59

99.44 ± 94.90

0.163^a

-6.9%

AC (n = 42)

78.25 ± 51.79

61.51 ± 42.06

0.011^a*

-21.4%

TA (n = 91)

81.81 ± 61.65

65.25 ± 54.85

< 0.001^a*

-20.2%

TA + H (n = 22)

83.43 ± 56.42

56.96 ± 32.29

0.006^a*

-31.7%

Platinum (n = 22)

79.46 ± 56.22

60.64 ± 40.38

0.016^a*

-23.7%

P-value

0.937^b

0.730^b