
FIGURE 1.
Study flow diagram.
HER2 = human epidermal growth factor receptor 2
TABLE 1.
Clinical characteristics and treatment of the study participants
| Variable | Value |
|---|---|
| No. of participants | 35 |
| Age, years* | 48.86 ± 10.34 |
| Height (cm)* | 160.97 ± 4.20 |
| Weight (kg)* | 62.61 ± 8.36 |
| Body surface area (m2)* | 1.63 ± 0.12 |
| Hypertension† | 5 (14%) |
| Chronic kidney disease | 0 |
| Current smoker or significant smoking history | 0 |
| Obesity (BMI > 30 kg/m2) † | 4 (11%) |
| Age 65–79 years† | 2 (6%) |
| Diabetes | 0 |
| Hyperlipidaemia | 0 |
| Prior cardiovascular disease | 0 |
| HFA-ICOS baseline cardiovascular toxicity risk stratification† | |
| Moderate risk (moderate risk factors with a total of 2–3 points) | 4 (11%) |
| Low risk | 31 (89%) |
| No risk factor | 18 (52%) |
| One moderate risk factor with a total of 1 point | 13 (37%) |
| Therapies† | |
| HER2-targeted therapies without anthracycline | 25 (71%) |
| Trastuzumab | 8 (23%) |
| Trastuzumab and pertuzumab | 17 (48%) |
| Anthracycline chemotherapy followed by a taxane plus trastuzumab plus pertuzumab | 10 (29%) |

FIGURE 2.
CMR imaging in a 44-year-old woman with human epidermal growth factor receptor 2 (HER2)-positive right-side breast cancer. The top row images (A, B, C, D) represent the baseline. The middle row images (E, F, G, H) correspond to the condition after 4 cycles of the TCbHP regimen (104 days after the baseline scan). The bottom row images (I, J, K, L) show the status after 9 cycles of the TCbHP regimen (203 days after the baseline scan). In the axial breast enhancement scan images (A, E, I), a decrease in the tumour size of the right breast is observed (arrow). The diastolic phase images of left ventricular two-chamber plane (B, F, J) demonstrate a slight increase in left ventricular systolic volume. T1 mapping images (C, G, I) reveal an increase in T1 value in the septum of the mid short-axis slice during follow-up 1, followed by a decrease during follow-up 2. The global radial, circumferential and longitudinal strain (GRS, GCS and GLS) curves before and after TCbHP treatment are presented (D, H, L).
CMR = cardiac magnetic resonance; GCS = global circumferential strain; GLS = global longitudinal strain; GRS = global radial strain; HER2 = human epidermal growth factor receptor 2; TCbHP = taxane plus carboplatin plus trastuzumab plus pertuzumab

FIGURE 3.
CMR imaging in a 68-year-old woman with HER2-positive right-side breast cancer. The upper images (A, B, C, D) depict the baseline condition. The lower images (E, F, G, H) represent the status after 4 cycles of the TCbHP regimen (106 days following the baseline scan). Axial breast enhancement scan images (A, E) exhibit a reduction in the tumour size of the right breast. Short-axis cine images reveal an enlargement in the left ventricular diastolic diameter (B, F). T1 mapping images (C, G) reveal an increase in T1 value in the septum of the mid short-axis slice during the follow-up. Strain curves demonstrate a reduction in the absolute values of global radial, circumferential and longitudinal strain (GRS, GCS and GLS) before and after treatment (D, H).
CMR = cardiac magnetic resonance; GCS = global circumferential strain; GLS = global longitudinal strain; GRS = global radial strain; HER2 = human epidermal growth factor receptor 2; TCbHP = taxane plus carboplatin plus trastuzumab plus pertuzumab
TABLE 2.
Cardiac magnetic resonance (CMR) parameter results at baseline and follow-up
| Variable | Follow-up 1 (n = 32) | Follow-up 2 (n = 16) | ||||
|---|---|---|---|---|---|---|
| Baseline 1 | Follow-up 1 | P Value | Baseline 2 | Follow-up 2 | P Value | |
| LV ejection fraction (%) | 64.03 ± 4.16 | 57.34 ± 5.32 | < 0.001 | 66.23 ± 4.19 | 57.45 ± 5.54 | < 0.001 |
| LV end-diastolic volume index (mL/m2) | 68.23 ± 12.41 | 65.63 ± 12.97 | > 0.057 | 68.20 ± 11.56 | 64.94 ± 14.01 | 0.275 |
| LV end-systolic volume index (mL/m2) | 24.53 ± 6.17 | 28.26 ± 9.15 | 0.001 | 22.91 ± 5.02 | 27.70 ± 7.60 | 0.002 |
| LV mass index (g/m2) | 37.17 (33.96, 43.69) | 38.24 (34.40, 41.45) | 0.369 | 39.23 ± 6.31 | 40.03 ± 6.78 | 0.261 |
| Stroke volume index (mL/m2) | 43.36 ± 8.12 | 37.10 ± 6.43 | < 0.001 | 44.84 ± 8.12 | 39.46 (30.13, 42.17) | 0.002 |
| Cardiac output index (L/min×m2) | 3.23 ± 0.58 | 2.91 ± 0.49 | 0.002 | 3.19 ± 0.38 | 2.65 ± 0.51 | 0.001 |
| Global radial strain | 33.59 ± 7.31 | 28.81 ± 6.37 | 0.001 | 37.16 ± 8.99 | 30.07 ± 6.18 | < 0.001 |
| Global circumferential strain | -18.86 ± 2.41 | -17.38 ± 2.31 | < 0.001 | -19.93 ± 2.81 | -17.23 ± 2.34 | < 0.001 |
| Global longitudinal strain | -16.12 ± 1.55 | -15.09 ±1.85 | 0.001 | -16.67 ± 1.28 | -14.88 ± 1.60 | 0.004 |
| T1 value (msec) | 1231.16 46.49 | 1255.81 ± 45.23 | 0.001 | 1222.00 ± 40.89 | 1237.13 ± 35.19 | 0.051 |
| T2 value (msec) | 47.86 ± 2.17 | 49.43 ± 2.71 | 0.001 | 48.13 ± 2.15 | 48.84 ± 1.75 | 0.306 |
| Heart rate during MR scan (bpm) | 74.50 ± 11.11 | 79.47 ± 13.40 | 0.048 | 72.50 ± 9.68 | 72.69 ± 12.28 | 0.928 |

FIGURE 4.
Box plot show changes in cardiac magnetic resonance (CMR) variables between the baseline and follow-up CMR examinations. The results of CMR variables at baseline (n = 35), follow-up 1 (n = 32) and follow-up 2 (n = 16) were shown in blue, yellow and red box plot. Left ventricular ejection fraction (LVEF) decreased significantly at follow-up 1 and follow-up 2. T1 and T2 value increased significantly at follow-up 1, but recovered to a level not significantly different from the baseline. Global longitudinal strain (GLS), global radial strain (GRS) and global circumferential strain (GCS) decreased significantly at follow-up 1 and follow-up 2.
TABLE 3.
Cardiac magnetic resonance (CMR) parameter results between follow-up 1 and follow-up 2 (n = 13)
| Variable | Follow-up 1 | Follow-up 2 | P Value |
|---|---|---|---|
| LV ejection fraction (%) | 58.45 ± 4.44 | 57.76 ± 5.53 | 0.545 |
| LV end-diastolic volume index (mL/m2) | 66.33 ± 11.13 | 62.32 ± 14.02 | 0.055 |
| LV end-systolic volume index (mL/m2) | 27.59 ± 6.20 | 26.35 ± 7.46 | 0.294 |
| LV mass index (g/m2) | 38.07 (36.22, 44.09) | 39.13 (35.77, 43.31) | 0.650 |
| Stroke volume index (mL/m2) | 39.37 (35.27, 43.55) | 39.44 (27.44, 40.83) | 0.101 |
| Cardiac output index (L/min×m2) | 3.01 ± 0.47 | 2.60 ± 0.54 | 0.022 |
| Global radial strain | 28.69 ± 8.12 | 29.70 ± 6.48 | 0.670 |
| Global circumferential strain | -17.70 ± 2.52 | -17.12 ± 2.30 | 0.172 |
| Global longitudinal strain | -15.01 ± 1.46 | -14.74 ±1.70 | 0.647 |
| T1 value (msec) | 1245.31 ± 22.46 | 1236.77 ± 40.36 | 0.486 |
| T2 value (msec) | 49.67 ± 2.19 | 49.11 ± 2.12 | 0.465 |
| Heart rate during MR scan (bpm) | 78.38 ± 14.67 | 73.92 ± 13.09 | 0.189 |

FIGURE 5.
The comparison of T1 value between the baseline and follow-up cardiac magnetic resonance (CMR) examinations. Bars represent median T1 value. Blue dots represent human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with no cardiovascular toxicity risk factor and orange dots represent patients with 1–3 risk factors.
TABLE 4.
Differences in CMR parameters at follow-up 1 between patients with and without baseline risk factors
| Variable | Patients with no risk factor (n = 16) | Patients with 1-3 risk factors (n = 16) | P Value |
|---|---|---|---|
| LV ejection fraction (%) | 57.92 ± 3.43 | 56.75 ± 6.79 | 0.543 |
| LV end-diastolic volume index (mL/m2) | 63.88 ± 10.89 | 67.39 ± 14.92 | 0.454 |
| LV end-systolic volume index (mL/m2) | 26.89 ± 5.66 | 29.63 ± 11.70 | 0.406 |
| LV mass index (g/m2) | 37.07 ± 6.68 | 43.03 ± 8.86 | 0.040 |
| Stroke volume index (mL/m2) | 36.60 ± 6.67 | 37.61 ± 6.36 | 0.665 |
| Cardiac output index (L/min×m2) | 2.84 ± 0.48 | 2.99 ± 0.49 | 0.387 |
| Global radial strain | 30.56 ± 5.40 | 27.07 ± 6.94 | 0.123 |
| Global circumferential strain | -17.94 ± 2.16 | -16.82 ± 2.37 | 0.174 |
| Global longitudinal strain | -15.11 ± 1.85 | -15.06 ± 1.90 | 0.938 |
| T1 value (msec) | 1235.06 ± 36.77 | 1276.56 ± 44.25 | 0.007 |
| T2 value (msec) | 48.95 ± 2.28 | 49.94 ± 3.07 | 0.318 |
| Heart rate during MR scan (bpm) | 77.56 ± 11.28 | 81.38 ± 15.37 | 0.430 |
TABLE 5.
CMR parameter results between patients treated with anthracycline-based and non-anthracycline-based antihuman epidermal growth factor receptor 2 (HER2) therapies at follow-up 1
| Variable | Anthracycline-based therapy (n = 10) | Non-anthracycline-based therapy (n = 22) | P Value |
|---|---|---|---|
| LV ejection fraction (%) | 57.01 ± 3.68 | 57.49 ± 5.99 | 0.816 |
| LV end-diastolic volume index (mL/m2) | 67.51 ± 12.83 | 64.78 ± 13.24 | 0.590 |
| LV end-systolic volume index (mL/m2) | 28.88 ± 6.01 | 27.98 ± 10.38 | 0.800 |
| LV mass index (g/m2) | 41.76 ± 7.91 | 39.28 ± 8.53 | 0.442 |
| Stroke volume index (mL/m2) | 38.58 ± 7.78 | 36.43 ± 5.80 | 0.389 |
| Cardiac output index (L/min×m2) | 3.13 ± 0.49 | 2.82 ± 0.46 | 0.094 |
| Global radial strain | 26.73 ± 6.62 | 29.76 ± 6.16 | 0.218 |
| Global circumferential strain | -17.09 ± 1.92 | -17.52 ± 2.49 | 0.637 |
| Global longitudinal strain | -15.36 (-16.56, -13.74) | -15.07 ± 2.05 | 1.000 |
| T1 value (msec) | 1280.90 ± 43.10 | 1244.41 ± 42.29 | 0.032 |
| T2 value (msec) | 49.65 (47.06, 53.10) | 49.04 ± 2.23 | 0.231 |
| Heart rate during MR scan (bpm) | 84.20 ± 18.44 | 77.32 ± 10.20 | 0.182 |