Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website https://www.cardiologyres.org

Original Article

Volume 13, Number 6, December 2022, pages 380-392

Anthracycline-Induced Cardiotoxicity in Breast Cancer Patients: A Five-Year Retrospective Study in 10 Centers

**Table 1.** Demographic and Clinical Profile of Patients (n = 341)
	Total (n = 341)	With AIC (n = 33)	Without AIC (n = 308)	P-value
Statistical test used: *Independent sample t-test; ^†Mann-Whitney U test; ^‡Chi-square/Fisher’s exact test. Data are expressed frequency (%) or median (range). AIC: anthracycline-induced cardiotoxicity; ARBs: angiotensin receptor blockers; BMI: body mass index; PTB: pulmonary tuberculosis; ACE: angiotensin converting enzyme; SGLT2: sodium-glucose cotransporter-2; HER2: human epidermal growth factor 2; LVEF: left ventricular ejection fraction.
Age, years	53.91 ± 10.84	59.06 ± 9.7	53.36 ± 10.83	0.004*
BMI, kg/m²	25.3 (11.3 - 45.06)	24 (11.7 - 34.71)	25.3 (11.3 - 45.06)	0.003^†
BMI category
Underweight (< 18.5)	12 (3.52)	2 (6.06)	10 (3.25)	0.336^‡
Normal (18.5 to < 23)	84 (24.63)	10 (30.3)	74 (24.03)
Overweight (23 to 27.5)	134 (39.3)	9 (27.27)	125 (40.58)
Obese (> 27.5)	111 (32.55)	12 (36.36)	99 (32.14)
Comorbidities
Any	154 (45.16)	27 (81.82)	127 (41.23)	< 0.001^‡
Hypertension	114 (33.43)	22 (66.67)	92 (29.87)	< 0.001^‡
Diabetes mellitus	57 (16.72)	7 (21.21)	50 (16.23)	0.464^‡
Dyslipidemia	36 (10.56)	3 (9.09)	33 (10.71)	> 0.999^‡
PTB	6 (1.76)	1 (3.03)	5 (1.62)	0.460^‡
Asthma	4 (1.17)	0	4 (1.3)	> 0.999^‡
Atrial fibrillation	3 (0.88)	2 (6.06)	1 (0.32)	0.026^‡
Coronary artery disease	3 (0.88)	1 (3.03)	2 (0.65)	0.264^‡
Chronic kidney disease	3 (0.88)	1 (3.03)	2 (0.65)	0.264^‡
Hyperthyroidism	3 (0.88)	1 (3.03)	2 (0.65)	0.264^‡
Hepatitis B	2 (0.59)	0	2 (0.65)	> 0.999^‡
Other	23 (6.74)	3 (9.09)	20 (6.49)	0.477^‡
Medications
Any medications	130 (38.12)	20 (60.61)	110 (35.71)	0.008^‡
Calcium channel blocker	55 (16.13)	8 (24.24)	47 (15.26)	0.211^‡
ARBs	53 (15.54)	13 (39.39)	40 (12.99)	< 0.001^‡
Statin	39 (11.44)	5 (15.15)	34 (11.04)	0.562^‡
Oral hypoglycemic agent	37 (10.85)	4 (12.12)	33 (10.71)	0.769^‡
Beta-blocker	19 (5.57)	6 (18.18)	13 (4.22)	0.006^‡
ACE inhibitor	7 (2.05)	3 (9.09)	4 (1.3)	0.022^‡
Anti-hypertensive	5 (1.47)	2 (6.06)	3 (0.97)	0.076^‡
Anti-platelet	5 (1.47)	1 (3.03)	4 (1.3)	0.401^‡
Exogenous insulin	5 (1.47)	0	5 (1.62)	> 0.999^‡
Exogenous thyroid medication	3 (0.88)	0	3 (0.97)	> 0.999^‡
Anticholesterol medication	3 (0.88)	0	3 (0.97)	> 0.999^‡
Vitamins	3 (0.88)	0	3 (0.97)	> 0.999^‡
Cardiometabolic drugs	3 (0.88)	1 (3.03)	2 (0.65)	0.264^‡
Anti-arrhythmic medication	2 (0.59)	1 (3.03)	1 (0.32)	0.184^‡
Anti-thyroid medication	2 (0.59)	0	2 (0.65)	> 0.999^‡
Novel oral anticoagulant	2 (0.59)	1 (3.03)	1 (0.32)	0.184^‡
Nutritional supplements	2 (0.59)	1 (3.03)	1 (0.32)	0.184^‡
SGLT2 inhibitors	2 (0.59)	1 (3.03)	1 (0.32)	0.184^‡
Anti-asthma medications	1 (0.29)	0	1 (0.32)	> 0.999^‡
Oral antimetabolite	1 (0.29)	0	1 (0.32)	> 0.999^‡
Anti-tuberculosis medications	1 (0.29)	0	1 (0.32)	> 0.999^‡
Low molecular weight heparin	1 (0.29)	0	1 (0.32)	> 0.999^‡
Mineralocorticoid receptor antagonists	0	0	0	-
Concurrent chemotherapeutic agents
Any	319 (93.55)	21 (63.64)	298 (96.75)	< 0.001^‡
Cyclophosphamide	262 (76.83)	12 (36.36)	250 (81.17)	< 0.001^‡
Taxanes	230 (67.45)	13 (39.39)	217 (70.45)	0.001^‡
HER-2 inhibitors	119 (34.9)	7 (21.21)	112 (36.36)	0.088^‡
5-fluorouracil	54 (15.84)	1 (3.03)	53 (17.21)	0.041^‡
Carboplatin	14 (4.11)	0	14 (4.55)	0.377^‡
Monoclonal antibodies	2 (0.59)	0	2 (0.65)	> 0.999^‡
Eribulin	2 (0.59)	1 (3.03)	1 (0.32)	0.184^‡
Vinorelbine	1 (0.29)	1 (3.03)	0	0.097^‡
Tyrosine kinase inhibitors	0	0	0	-
Radiation therapy				> 0.999^‡
No radiotherapy	303 (88.86)	30 (90.91)	273 (88.64)
Mediastinal radiotherapy	7 (2.05)	0	7 (2.27)
Left breast radiotherapy	19 (5.57)	2 (6.06)	17 (5.52)
Right chest wall radiotherapy	12 (3.52)	1 (3.03)	11 (3.57)
Baseline LVEF	67.53 ± 5.01	65.89 ± 5.84	67.71 ± 4.89	0.047*

Table 1. Demographic and Clinical Profile of Patients (n = 341)

Total (n = 341)

With AIC (n = 33)

Without AIC (n = 308)

P-value

Statistical test used: *Independent sample t-test; ^†Mann-Whitney U test; ^‡Chi-square/Fisher’s exact test. Data are expressed frequency (%) or median (range). AIC: anthracycline-induced cardiotoxicity; ARBs: angiotensin receptor blockers; BMI: body mass index; PTB: pulmonary tuberculosis; ACE: angiotensin converting enzyme; SGLT2: sodium-glucose cotransporter-2; HER2: human epidermal growth factor 2; LVEF: left ventricular ejection fraction.

Age, years

53.91 ± 10.84

59.06 ± 9.7

53.36 ± 10.83

0.004*

BMI, kg/m²

25.3 (11.3 - 45.06)

24 (11.7 - 34.71)

25.3 (11.3 - 45.06)

0.003^†

BMI category

Underweight (< 18.5)

12 (3.52)

2 (6.06)

10 (3.25)

0.336^‡

Normal (18.5 to < 23)

84 (24.63)

10 (30.3)

74 (24.03)

Overweight (23 to 27.5)

134 (39.3)

9 (27.27)

125 (40.58)

Obese (> 27.5)

111 (32.55)

12 (36.36)

99 (32.14)

Comorbidities

Any

154 (45.16)

27 (81.82)

127 (41.23)

< 0.001^‡

Hypertension

114 (33.43)

22 (66.67)

92 (29.87)

< 0.001^‡

Diabetes mellitus

57 (16.72)

7 (21.21)

50 (16.23)

0.464^‡

Dyslipidemia

36 (10.56)

3 (9.09)

33 (10.71)

> 0.999^‡

PTB

6 (1.76)

1 (3.03)

5 (1.62)

0.460^‡

Asthma

4 (1.17)

4 (1.3)

> 0.999^‡

Atrial fibrillation

3 (0.88)

2 (6.06)

1 (0.32)

0.026^‡

Coronary artery disease

3 (0.88)

1 (3.03)

2 (0.65)

0.264^‡

Chronic kidney disease

3 (0.88)

1 (3.03)

2 (0.65)

0.264^‡

Hyperthyroidism

3 (0.88)

1 (3.03)

2 (0.65)

0.264^‡

Hepatitis B

2 (0.59)

2 (0.65)

> 0.999^‡

Other

23 (6.74)

3 (9.09)

20 (6.49)

0.477^‡

Medications

Any medications

130 (38.12)

20 (60.61)

110 (35.71)

0.008^‡

Calcium channel blocker

55 (16.13)

8 (24.24)

47 (15.26)

0.211^‡

ARBs

53 (15.54)

13 (39.39)

40 (12.99)

< 0.001^‡

Statin

39 (11.44)

5 (15.15)

34 (11.04)

0.562^‡

Oral hypoglycemic agent

37 (10.85)

4 (12.12)

33 (10.71)

0.769^‡

Beta-blocker

19 (5.57)

6 (18.18)

13 (4.22)

0.006^‡

ACE inhibitor

7 (2.05)

3 (9.09)

4 (1.3)

0.022^‡

Anti-hypertensive

5 (1.47)

2 (6.06)

3 (0.97)

0.076^‡

Anti-platelet

5 (1.47)

1 (3.03)

4 (1.3)

0.401^‡

Exogenous insulin

5 (1.47)

5 (1.62)

> 0.999^‡

Exogenous thyroid medication

3 (0.88)

3 (0.97)

> 0.999^‡

Anticholesterol medication

3 (0.88)

3 (0.97)

> 0.999^‡

Vitamins

3 (0.88)

3 (0.97)

> 0.999^‡

Cardiometabolic drugs

3 (0.88)

1 (3.03)

2 (0.65)

0.264^‡

Anti-arrhythmic medication

2 (0.59)

1 (3.03)

1 (0.32)

0.184^‡

Anti-thyroid medication

2 (0.59)

2 (0.65)

> 0.999^‡

Novel oral anticoagulant

2 (0.59)

1 (3.03)

1 (0.32)

0.184^‡

Nutritional supplements

2 (0.59)

1 (3.03)

1 (0.32)

0.184^‡

SGLT2 inhibitors

2 (0.59)

1 (3.03)

1 (0.32)

0.184^‡

Anti-asthma medications

1 (0.29)

1 (0.32)

> 0.999^‡

Oral antimetabolite

1 (0.29)

1 (0.32)

> 0.999^‡

Anti-tuberculosis medications

1 (0.29)

1 (0.32)

> 0.999^‡

Low molecular weight heparin

1 (0.29)

1 (0.32)

> 0.999^‡

Mineralocorticoid receptor antagonists

Concurrent chemotherapeutic agents

Any

319 (93.55)

21 (63.64)

298 (96.75)

< 0.001^‡

Cyclophosphamide

262 (76.83)

12 (36.36)

250 (81.17)

< 0.001^‡

Taxanes

230 (67.45)

13 (39.39)

217 (70.45)

0.001^‡

HER-2 inhibitors

119 (34.9)

7 (21.21)

112 (36.36)

0.088^‡

5-fluorouracil

54 (15.84)

1 (3.03)

53 (17.21)

0.041^‡

Carboplatin

14 (4.11)

14 (4.55)

0.377^‡

Monoclonal antibodies

2 (0.59)

2 (0.65)

> 0.999^‡

Eribulin

2 (0.59)

1 (3.03)

1 (0.32)

0.184^‡

Vinorelbine

1 (0.29)

1 (3.03)

0.097^‡

Tyrosine kinase inhibitors

Radiation therapy

> 0.999^‡

No radiotherapy

303 (88.86)

30 (90.91)

273 (88.64)

Mediastinal radiotherapy

7 (2.05)

7 (2.27)

Left breast radiotherapy

19 (5.57)

2 (6.06)

17 (5.52)

Right chest wall radiotherapy

12 (3.52)

1 (3.03)

11 (3.57)

Baseline LVEF

67.53 ± 5.01

65.89 ± 5.84

67.71 ± 4.89

0.047*

**Table 2.** Chemotherapeutic Management (n = 341)
	Total (n = 341)	With AIC (n = 33)	Without AIC (n = 308)	P-value
Statistical test used: *Independent sample t-test; ^†Mann-Whitney U test. Data are expressed frequency (%) or median (range). AIC: anthracycline-induced cardiotoxicity.
Location of initiation chemotherapy				0.147^‡
In-patient/admitted	155 (45.45)	19 (57.58)	136 (44.16)
Outpatient	186 (54.55)	14 (42.42)	172 (55.84)
Dosage
5-fluorouracil, mg/m²	316.69 ± 1,081.76	92.03 ± 522.07	340.76 ± 1,123.2	0.210*
Epirubicin, mg/m²	65.13 ± 141.9	14.36 ± 45.24	70.57 ± 147.58	0.030*
Doxorubicin, mg/m²	96.82 ± 126.53	132.36 ± 127.24	93.02 ± 126.06	0.090*
Idarubicin, mg/m²	4.69 ± 63.07	0	5.19 ± 66.35	0.654*
Daunorubicin, mg/m²	0	0	0	-
Trastuzumab, mg	143.77 ± 627.86	57.03 ± 115.75	153.07 ± 659.01	0.405*
Docetaxel, mg/m²	96.98 ± 141.01	82.88 ± 154.53	98.49 ± 139.68	0.546*
Paclitaxel, mg/m²	69.77 ± 221.34	50.62 ± 171.5	71.83 ± 226.16	0.602*
Cyclophosphamide, mg	1,352.6 ± 1,247.64	1,447.39 ± 1,275.54	1,342.44 ± 1,246.3	0.647*
Carboplatin, mg/m²	19.38 ± 111.87	0 ± 0	21.46 ± 117.54	0.296*
Total duration of anthracycline chemotherapy cycles, months	4 (0 - 27)	4 (1 - 20)	4 (0 - 27)	0.081^†

Table 2. Chemotherapeutic Management (n = 341)

Total (n = 341)

With AIC (n = 33)

Without AIC (n = 308)

P-value

Statistical test used: *Independent sample t-test; ^†Mann-Whitney U test. Data are expressed frequency (%) or median (range). AIC: anthracycline-induced cardiotoxicity.

Location of initiation chemotherapy

0.147^‡

In-patient/admitted

155 (45.45)

19 (57.58)

136 (44.16)

Outpatient

186 (54.55)

14 (42.42)

172 (55.84)

Dosage

5-fluorouracil, mg/m²

316.69 ± 1,081.76

92.03 ± 522.07

340.76 ± 1,123.2

0.210*

Epirubicin, mg/m²

65.13 ± 141.9

14.36 ± 45.24

70.57 ± 147.58

0.030*

Doxorubicin, mg/m²

96.82 ± 126.53

132.36 ± 127.24

93.02 ± 126.06

0.090*

Idarubicin, mg/m²

4.69 ± 63.07

5.19 ± 66.35

0.654*

Daunorubicin, mg/m²

Trastuzumab, mg

143.77 ± 627.86

57.03 ± 115.75

153.07 ± 659.01

0.405*

Docetaxel, mg/m²

96.98 ± 141.01

82.88 ± 154.53

98.49 ± 139.68

0.546*

Paclitaxel, mg/m²

69.77 ± 221.34

50.62 ± 171.5

71.83 ± 226.16

0.602*

Cyclophosphamide, mg

1,352.6 ± 1,247.64

1,447.39 ± 1,275.54

1,342.44 ± 1,246.3

0.647*

Carboplatin, mg/m²

19.38 ± 111.87

0 ± 0

21.46 ± 117.54

0.296*

Total duration of anthracycline chemotherapy cycles, months

4 (0 - 27)

4 (1 - 20)

4 (0 - 27)

0.081^†

**Table 3.** Clinical Outcomes (n = 341)
	Total (n = 341)	With AIC (n = 33)	Without AIC (n = 308)	P-value
Statistical test used: ^‡Chi-square/Fisher’s exact test. Data are expressed as frequency (%) or median (range). AIC: anthracycline-induced cardiotoxicity; LVEF: left ventricular ejection fraction.
Mortality	17 (4.99)	2 (6.06)	15 (4.87)	0.674^‡
LVEF
At first follow-up	65.5 (55-92)	57 (39 - 80)	66 (55 - 92)
At second follow-up (n = 178)	64.4 (35 - 79)	50.8 (35 - 67)	65.1 (48.28 - 79)
At third follow-up (n = 109)	66 (27.6 - 86)	53.3 (27.6 - 81)	66.1 (55 - 86)

Table 3. Clinical Outcomes (n = 341)

Total (n = 341)

With AIC (n = 33)

Without AIC (n = 308)

P-value

Statistical test used: ^‡Chi-square/Fisher’s exact test. Data are expressed as frequency (%) or median (range). AIC: anthracycline-induced cardiotoxicity; LVEF: left ventricular ejection fraction.

Mortality

17 (4.99)

2 (6.06)

15 (4.87)

0.674^‡

LVEF

At first follow-up

65.5 (55-92)

57 (39 - 80)

66 (55 - 92)

At second follow-up (n = 178)

64.4 (35 - 79)

50.8 (35 - 67)

65.1 (48.28 - 79)

At third follow-up (n = 109)

66 (27.6 - 86)

53.3 (27.6 - 81)

66.1 (55 - 86)

**Table 4.** Unadjusted Odds Ratio for Factors Associated With Anthracycline-Induced Cardiotoxicity (n = 341)
	Crude odds ratio (95% CI)	P-value
Statistical test used: Firth logistic regression. BMI: body mass index; PTB: pulmonary tuberculosis; ACE: angiotensin converting enzyme; SGLT2: sodium-glucose cotransporter-2; HER2: human epidermal growth factor 2; LVEF: left ventricular ejection fraction; CI: confidence interval.
Age, years	1.05 (1.01 - 1.09)	0.005
BMI, kg/m²
Underweight (< 18.5)	1.689 (0.37 - 7.75)	0.500
Normal (18.5 to < 23)	1.0 (reference)	-
Overweight (23 to 27.5)	0.537 (0.21 - 1.35)	0.187
Obese (> 27.5)	0.891 (0.37 - 2.14)	0.796

Comorbidities
Any	6.023 (2.49 - 14.58)	< 0.001
Hypertension	4.579 (2.16 - 9.7)	< 0.001
Diabetes mellitus	1.449 (0.61 - 3.44)	0.401
Dyslipidemia	0.944 (0.3 - 3.02)	0.922
PTB	2.547 (0.4 - 16.06)	0.320
Asthma	1.01 (0.05 - 19.17)	0.995
Atrial fibrillation	16.27 (2.08 - 127.29)	0.008
Coronary artery disease	5.658 (0.72 - 44.23)	0.099
Chronic kidney disease	5.658 (0.72 - 44.23)	0.099
Hyperthyroidism	5.658 (0.72 - 44.23)	0.099
Hepatitis B	1.83 (0.09 - 38.92)	0.698
Other	1.615 (0.49 - 5.33)	0.431
Medications
Any medications	2.728 (1.32 - 5.63)	0.007
Calcium channel blocker	1.835 (0.8 - 4.23)	0.154
Angiotensin receptor blockers	4.366 (2.04 - 9.36)	< 0.001
Statin	1.535 (0.58 - 4.09)	0.391
Oral hypoglycemic agent	1.254 (0.44 - 3.6)	0.674
Beta-blocker	5.174 (1.88 - 14.26)	0.001
ACE inhibitor	7.765 (1.83 - 32.96)	0.005
Anti-hypertensive	6.927 (1.31 - 36.58)	0.023
Anti-platelet	3.123 (0.48 - 20.53)	0.236
Exogenous insulin	0.824 (0.04 - 15.22)	0.896
Exogenous thyroid medication	1.303 (0.07 - 25.77)	0.862
Anti-cholesterol medication	1.303 (0.07 - 25.77)	0.862
Vitamins	1.303 (0.07 - 25.77)	0.862
Cardiometabolic drugs	5.658 (0.72 - 44.23)	0.099
Anti-arrhythmic medication	9.462 (0.96 - 93.61)	0.055
Anti-thyroid medication	1.83 (0.09 - 38.92)	0.698
Novel oral anticoagulant	9.462 (0.96 - 93.61)	0.055
Nutritional supplements	9.462 (0.96 - 93.61)	0.055
SGLT2 inhibitors	9.462 (0.96 - 93.61)	0.055
Anti-asthma medications	3.06 (0.12 - 76.61)	0.496
Oral antimetabolite	3.06 (0.12 - 76.61)	0.496
Anti-tuberculosis medications	3.06 (0.12 - 76.61)	0.496
Low molecular weight heparin	3.06 (0.12 - 76.61)	0.496
Concurrent chemotherapeutic agents
Any	0.061 (0.02 - 0.15)	< 0.001
Cyclophosphamide	0.136 (0.06 - 0.29)	< 0.001
Taxanes	0.277 (0.13 - 0.57)	0.001
HER-2 inhibitors	0.494 (0.21 - 1.15)	0.101
5-fluorouracil	0.22 (0.04 - 1.16)	0.075
Carboplatin	0.303 (0.02 - 5.2)	0.410
Monoclonal antibodies	1.83 (0.09 - 38.92)	0.698
Eribulin	9.462 (0.96 - 93.61)	0.055
Vinorelbine	28.477 (1.14 - 713.39)	0.042
Radiation therapy
No radiotherapy	1.0 (reference)	^-
Left breast radiotherapy	0.598 (0.03 - 10.73)	0.727
Right chest wall radiotherapy	1.281 (0.32 - 5.08)	0.724
Mediastinal radiotherapy	1.17 (0.2 - 6.68)	0.860
Baseline LVEF	0.929 (0.86 - 1)	0.051
Chemotherapeutic agents dosage
5-fluorouracil, mg/m²	1 (0.99 - 1.0)	0.354
Epirubicin, mg/m²	0.991 (0.98 - 1)	0.050
Doxorubicin, mg/m²	1.002 (1 - 1)	0.076
Idarubicin, mg/m²	1.001 (1 - 1)	0.650
Daunorubicin, mg/m²	-	-
Trastuzumab, mg	1 (1 - 1)	0.988
Docetaxel, mg/m²	0.999 (1 - 1)	0.656
Paclitaxel, mg/m²	1 (0.99 - 1.0)	0.844
Cyclophosphamide, mg	1 (0.99 - 1.0)	0.574
Carboplatin, mg/m²	0.999 (0.99 - 1)	0.635
Total duration of anthracycline chemotherapy cycles, months	1.04 (0.97 - 1.11)	0.239

Table 4. Unadjusted Odds Ratio for Factors Associated With Anthracycline-Induced Cardiotoxicity (n = 341)

Crude odds ratio (95% CI)

P-value

Statistical test used: Firth logistic regression. BMI: body mass index; PTB: pulmonary tuberculosis; ACE: angiotensin converting enzyme; SGLT2: sodium-glucose cotransporter-2; HER2: human epidermal growth factor 2; LVEF: left ventricular ejection fraction; CI: confidence interval.

Age, years

1.05 (1.01 - 1.09)

0.005

BMI, kg/m²

Underweight (< 18.5)

1.689 (0.37 - 7.75)

0.500

Normal (18.5 to < 23)

1.0 (reference)

Overweight (23 to 27.5)

0.537 (0.21 - 1.35)

0.187

Obese (> 27.5)

0.891 (0.37 - 2.14)

0.796

Comorbidities

Any

6.023 (2.49 - 14.58)

< 0.001

Hypertension

4.579 (2.16 - 9.7)

< 0.001

Diabetes mellitus

1.449 (0.61 - 3.44)

0.401

Dyslipidemia

0.944 (0.3 - 3.02)

0.922

PTB

2.547 (0.4 - 16.06)

0.320

Asthma

1.01 (0.05 - 19.17)

0.995

Atrial fibrillation

16.27 (2.08 - 127.29)

0.008

Coronary artery disease

5.658 (0.72 - 44.23)

0.099

Chronic kidney disease

5.658 (0.72 - 44.23)

0.099

Hyperthyroidism

5.658 (0.72 - 44.23)

0.099

Hepatitis B

1.83 (0.09 - 38.92)

0.698

Other

1.615 (0.49 - 5.33)

0.431

Medications

Any medications

2.728 (1.32 - 5.63)

0.007

Calcium channel blocker

1.835 (0.8 - 4.23)

0.154

Angiotensin receptor blockers

4.366 (2.04 - 9.36)

< 0.001

Statin

1.535 (0.58 - 4.09)

0.391

Oral hypoglycemic agent

1.254 (0.44 - 3.6)

0.674

Beta-blocker

5.174 (1.88 - 14.26)

0.001

ACE inhibitor

7.765 (1.83 - 32.96)

0.005

Anti-hypertensive

6.927 (1.31 - 36.58)

0.023

Anti-platelet

3.123 (0.48 - 20.53)

0.236

Exogenous insulin

0.824 (0.04 - 15.22)

0.896

Exogenous thyroid medication

1.303 (0.07 - 25.77)

0.862

Anti-cholesterol medication

1.303 (0.07 - 25.77)

0.862

Vitamins

1.303 (0.07 - 25.77)

0.862

Cardiometabolic drugs

5.658 (0.72 - 44.23)

0.099

Anti-arrhythmic medication

9.462 (0.96 - 93.61)

0.055

Anti-thyroid medication

1.83 (0.09 - 38.92)

0.698

Novel oral anticoagulant

9.462 (0.96 - 93.61)

0.055

Nutritional supplements

9.462 (0.96 - 93.61)

0.055

SGLT2 inhibitors

9.462 (0.96 - 93.61)

0.055

Anti-asthma medications

3.06 (0.12 - 76.61)

0.496

Oral antimetabolite

3.06 (0.12 - 76.61)

0.496

Anti-tuberculosis medications

3.06 (0.12 - 76.61)

0.496

Low molecular weight heparin

3.06 (0.12 - 76.61)

0.496

Concurrent chemotherapeutic agents

Any

0.061 (0.02 - 0.15)

< 0.001

Cyclophosphamide

0.136 (0.06 - 0.29)

< 0.001

Taxanes

0.277 (0.13 - 0.57)

0.001

HER-2 inhibitors

0.494 (0.21 - 1.15)

0.101

5-fluorouracil

0.22 (0.04 - 1.16)

0.075

Carboplatin

0.303 (0.02 - 5.2)

0.410

Monoclonal antibodies

1.83 (0.09 - 38.92)

0.698

Eribulin

9.462 (0.96 - 93.61)

0.055

Vinorelbine

28.477 (1.14 - 713.39)

0.042

Radiation therapy

No radiotherapy

1.0 (reference)

Left breast radiotherapy

0.598 (0.03 - 10.73)

0.727

Right chest wall radiotherapy

1.281 (0.32 - 5.08)

0.724

Mediastinal radiotherapy

1.17 (0.2 - 6.68)

0.860

Baseline LVEF

0.929 (0.86 - 1)

0.051

Chemotherapeutic agents dosage

5-fluorouracil, mg/m²

1 (0.99 - 1.0)

0.354

Epirubicin, mg/m²

0.991 (0.98 - 1)

0.050

Doxorubicin, mg/m²

1.002 (1 - 1)

0.076

Idarubicin, mg/m²

1.001 (1 - 1)

0.650

Daunorubicin, mg/m²

Trastuzumab, mg

1 (1 - 1)

0.988

Docetaxel, mg/m²

0.999 (1 - 1)

0.656

Paclitaxel, mg/m²

1 (0.99 - 1.0)

0.844

Cyclophosphamide, mg

1 (0.99 - 1.0)

0.574

Carboplatin, mg/m²

0.999 (0.99 - 1)

0.635

Total duration of anthracycline chemotherapy cycles, months

1.04 (0.97 - 1.11)

0.239

**Table 5.** Multivariate Analysis for Factors Associated With Anthracycline-Induced Cardiotoxicity (n = 341)
	Adjusted odds ratio (95% CI)	P-value
Cox-Snell R²: 0.146; P < 0.001. LVEF: left ventricular ejection fraction; CI: confidence interval.
Age ≥ 65 years old	0.879 (0.28 - 2.8)	0.827
Any comorbidity	12.369 (3.58 - 42.74)	< 0.001
Any medications	0.369 (0.13 - 1.07)	0.065
Presence of any concurrent chemotherapy	0.07 (0.03 - 0.19)	< 0.001
Presence of concomitant radiation therapy	0.691 (0.17 - 2.84)	0.608
Baseline LVEF	0.954 (0.88 - 1.03)	0.245
Doxorubicin dosage > 250, mg/m²	1.497 (0.33 - 6.88)	0.604
Epirubicin dosage > 600, mg/m²	0.415 (0.02 - 8.2)	0.563

Table 5. Multivariate Analysis for Factors Associated With Anthracycline-Induced Cardiotoxicity (n = 341)

Adjusted odds ratio (95% CI)

P-value

Cox-Snell R²: 0.146; P < 0.001. LVEF: left ventricular ejection fraction; CI: confidence interval.

Age ≥ 65 years old

0.879 (0.28 - 2.8)

0.827

Any comorbidity

12.369 (3.58 - 42.74)

< 0.001

Any medications

0.369 (0.13 - 1.07)

0.065

Presence of any concurrent chemotherapy

0.07 (0.03 - 0.19)

< 0.001

Presence of concomitant radiation therapy

0.691 (0.17 - 2.84)

0.608

Baseline LVEF

0.954 (0.88 - 1.03)

0.245

Doxorubicin dosage > 250, mg/m²

1.497 (0.33 - 6.88)

0.604

Epirubicin dosage > 600, mg/m²

0.415 (0.02 - 8.2)

0.563