Early cardiotoxicity after adjuvant concomitant treatment with radiotherapy and trastuzumab in patients with breast cancer

		All N = 175 (100%)	Left BC group N = 84 (48%)	Right BC group N = 91 (52%)	p value
Age in years (Median [Q1–Q3])		58 (49–64)	59 (52–67)	55 (46–63)	0.0096
*Menopause status*	Premenopause	90 (51.4%)	38 (45.2%)	52 (57.1%)	0.155
	Pomenopause	85 (48.5%)	46 (54.8%)	39 (42.9%)
*Histological type*	Ductal invasive	168 (96%)	81 (96.4%)	87 (95.6%)	1
	Lobular invasive	4 (2.3%)	2 (2.4%)	2 (2.2%)
	Other	3 (1.7%)	1 (1.2%)	2 (2.2%)
**Histo-pathological grade**	G 1	2 (1.1%)	0	2 (2.2%)	0.337
	G 2	48 (27.4%)	21 (25%)	27 (29.7%)
	G 3	125 (71.5%)	63 (75%)	62 (68.1%)
*Hormonal receptors*	ER positive	97 (55.4%)	53 (63%)	44 (48.3%)	0.851
	PR positive	82 (46.8%)	43 (51.2%)	39 (42.8%)
	ER in PR negative	73 (41.7%)	28 (33.3%)	45 (49.4%)
*Concomitant disease*	Smoking	33 (19%)	13 (15%)	20 (22%)	0.365
	Arterial hypertension	35 (20%)	21 (25%)	14 (15.4%)	0.161
	Diabetes	3 (1.7%)	3 (3.4%)	0	0.108
	Hyperlipidemia	30 (17.1%)	16 (19%)	14 (15.4%)	0,658
	Known heart disease*	4 (2.3%)	1 (1.2%)	3 (3.3%)	0.621

BC = breast cancer; ER = estrogens receptor; PR = progesterone receptor; Q1–Q3 = quartiles

* All diseases had been already present at diagnosis of breast cancer. Group 1: mild aortic stenosis; Group 2: mitral valve prolapse; compensated hypertonic heart and symptomatic angina pectoris; undefined cardiomyopathy

Table 2

Systemic treatment and surgical characteristics

	All (N = 175) (%)	Left BC Group (N = 84) (%)	Right BC Group (N = 91) (%)	P value
*Anthracyclines*
Cumulative dose- mg/m² BSA
(Median [Q1–Q3])	350 (292–499)	352 (295–497)	349 (290–499)	0.799
*Taxanes*
Cumulative dose- mg/m² BSA	297	297	298	0.783
(Median [Q1–Q3])	(276–594)	(281–422)	(273–768)	0.783
*Cyclophosphamide*
Cumulative dose- mg/m² BSA	2316	2344	2268	0.482
(Median [Q1–Q3])	(1758–2924)	(1763–2992)	(1758–2829)	0.482
*CT Scheme*
AC/EC/FAC/FEC + taxanes	95 (54.3%)	40 (47.6%)	55 (60.4%)	0.235
AC/EC/FAC/FEC without taxanes	69 (39.4%)	38 (45.3%)	31 (34.1%)
Other	11 (6.3%)	6 (7.1%)	5 (5.5%)
*Endocrine therapy*
Tamoxifen	39 (22.3%)	21 (25%)	18 (19.8%)	0.652
Aromatase inhibitor	45 (25.7%)	26 (30.9%)	19 (20.8%)
Other	10 (5.7%)	7 (8.3%)	3 (3.3%)
*Trastuzumab*
Cumulative dose- mg/kg BSA	105 (97–114)	105 (97–116)	105 (97–112)	0.658
(Median [Q1–Q3])	105 (97–114)	105 (97–116)	105 (97–112)
*Type of surgery*
Mastectomy	91 (52%)	38 (45.2%)	53 (58.2%)	0.116
Breast conserving surgery	84 (48%)	46 (54.8)	38 (41.8%)

[i] AC = doxorubicin, cyclophosphamide; BC = breast cancer; BSA = body surface area (The Du Bois formula was used for the calculation); CT = chemotherapy; EC = epirubicin, cyclophosphamide; FAC = 5-FU, doxorubicin, cyclophosphamide; FEC = 5-FU, epirubicin, and cyclophosphamide; Q1–Q3 = quartiles

Table 3

Radiotherapy treatment features

	All (N = 175) (%)	Left BC group (N = 84) (%)	Right BC group (N = 91) (%)	p value
*RT field**
Breast	70 (40%)	38 (45.3%)	32 (35.2%)	0.434
Breast + scl	17 (9.7%)	9 (10.7%)	8 (8.8%)
Thoracic wall	17 (9.7%)	8 (9.5%)	9 (9.9%)
Thoracic wall + scl	71 (40.6%)	29 (34.5%)	42 (46.1%)
*RT technique*
2D RT	139 (79.4%)	69 (82.1%)	70 (76.9%)	0.256
3D CRT	25 (14.3%)	12 (14.3%)	13 (14.3%)
Electrons +/- photons	11 (6.3%)	3 (3.6%)	8 (8.8%)
*RT scheme*
25 × 2 Gy	14 (84.6%)	73 (86.9%)	75 (82.4%)	0.540
17 or 18 × 2.5 Gy	27 (15.4%)	11 (13.1%)	16 (17.6%)	0.540

BC = breast cancer; RT = radiotherapy; scl = periclavicular nodes; 2D RT = two-dimensional radiotherapy; 3D CRT = three-dimensional conformal radiotherapy

* parasternal lymph nodes were not included in the irradiated area

Table 4

Analysis of the difference in left ventricular ejection fractions (Δ LVEF)

	All (N = 175)	Left BC Group (N = 84)	Right BC Group (N = 91)	P value
**LVEF₀ (%)**	65 (60–69)	65 (61–70)	63 (59.5–67)	0.0208
(Median [Q1–Q3])		65 (61–70)	63 (59.5–67)	0.0208
**LVEF₁ (%)**	66 (62–70)	67 (64–70)	65 (60–70.5)	0.117
(Median [Q1–Q3])
*Analysis of Δ LVEF*	(n = 149)	(n = 70)	(n = 79)	0.562
LVEF₀ (%)-LVEF₁(%) = Δ LVEF	-2.22 (8.69)	-1.78 (7.85)	-2.60 (9.4)	95% CI: -2.004 – 3.648
(Mean [SD])

[i] BC = breast cancer; CI = confidental interval; LVEF₀ = measurement of LVEF before RT; LVEF₁-measurement of LVEF after the adjuvant treatment with T; Q1–Q3 = quartiles; SD = standard deviation

Table 5

Echocardiografic parameters (n = 175)

	Left BC Group (n = 84) (median [Q1–Q3])	Right BC Group (n = 91) (median [Q1–Q3])	p value
LV EDD (cm)	4.6 (4.4–4.9)	4.6 (4.4–4.8)	0.913
LV EDD (cm)	4.6 (4.4–4.9)	4.6 (4.4–4.8)	95% CI (-0.10-0.10)
LV ESD (cm)	2.9 (2.6–3.1)	2.8 (2.5–3.2)	0.541
LV ESD (cm)	2.9 (2.6–3.1)	2.8 (2.5–3.2)	95% CI (-0.19–0.10)
LA tr (cm)	3.4 (3.2–3.8)	3.4 (3.2–3.7)	0.830
LA tr (cm)	3.4 (3.2–3.8)	3.4 (3.2–3.7)	95% CI (-0.10–0.10)
LA long (cm)	4.4 (4.0–4.8)	4.5 (4.2–4.6)	0.979
LA long (cm)	4.4 (4.0–4.8)	4.5 (4.2–4.6)	95% CI (-0.10–0.10)
RA tr (cm)	3.2 (3.0–3.6)	3.4 (3.0–3.7)	0.298
RA tr (cm)	3.2 (3.0–3.6)	3.4 (3.0–3.7)	95% CI (-0.20–0.00)
RA long (cm)	4.1 (3.8–4.4)	4.3 (3.9–4.4)	0.226
RA long (cm)	4.1 (3.8–4.4)	4.3 (3.9–4.4)	95% CI (-2.0–3.00)
LVEF (%)	68.5 (64–74.2)	68.0 (63.0–72.5)	0.758
LVEF (%)	68.5 (64–74.2)	68.0 (63.0–72.5)	95% CI (-2.0–3.00)
E/A	1.07 (0.80–1.23)	1.08 (0.87–1.32)	0.113
E/A	1.07 (0.80–1.23)	1.08 (0.87–1.32)	95% CI (-0.18–0.02)
E/E_m	7.15 (6.27–9.26)	7.40 (6.18–8.68)	0.918
E/E_m	7.15 (6.27–9.26)	7.40 (6.18–8.68)	95% CI (-0.52–0.66)
s/d	1.368 (1.065–1.600)	1.149 (0.94–1.35)	0.002
s/d	1.368 (1.065–1.600)	1.149 (0.94–1.35)	95% CI ( 0.07–0.29)
TDI Sm (cm/s)	8.0 (7.0–9.1)	8.0 (7.0–9.1)	0.985
TDI Sm (cm/s)	8.0 (7.0–9.1)	8.0 (7.0–9.1)	95% CI (-0.50–0.50)
TDI Em (cm/s)	10.0 (7.82–11.37)	10.0 (8.05–11.8)	0.547
TDI Em (cm/s)	10.0 (7.82–11.37)	10.0 (8.05–11.8)	95% CI (-0.10–0.50)

[i] CI = confidental interval; E/A = mitral valve annulus ratio of early diastolic and atrial flow velocities; E/E_m = ratio between the early diastolic blood flow velocitiy on the mitral valve annulus and early diastolic tissue Doppler velocity at the mitral ring; LA long – left atrial longitudinal diameter; LA tr = left atrial transversal diameter; LV EDD = left ventricular end diastolic diameter; LVEF = left ventricular ejection fraction; LV ESD = left ventricular end systolic diameter; Q1–Q3 = quartiles; RA long – right atrial longitudinal diameter; RA tr = right atrial transversal diameter; s/d = ratio of systolic and diastolic blood flow velocities in the pulmonary vein, TDI Sm - systolic tissue Doppler velocity at the mitral ring; TDI Em = early diastolic tissue Doppler velocity at the mitral ring

Table 6

Pericardial effusion

	ECHO	All (N = 174) (%)	Left BC Group (N = 83) (%)	Right BC Group (N = 91) (%)	p value
Pericard	Normal	164 (94.3%)	74 (89%)	90 (99%)	0.007
Pericard	Effusion	10 (5.7%)	9 (11%)	1 (1%)	0.007

[i] BC = breast cancer; ECHO = echocardiography

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DOI: https://doi.org/10.2478/raon-2018-0011 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099

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Language: English

Page range: 204 - 212

Submitted on: Dec 4, 2017

Accepted on: Dec 12, 2017

Published on: Feb 25, 2018

Published by: Association of Radiology and Oncology

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

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© 2018 Tanja Marinko, Simona Borstnar, Rok Blagus, Jure Dolenc, Cvetka Bilban-Jakopin, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Volume 52 (2018): Issue 2 (June 2018)