A nomogram integrating clinical data, B-mode ultrasound features, and super-resolution contrast-enhanced ultrasound characteristics to predict HER-2 positive breast cancer

doi:10.3877/cma.j.issn.1672-6448.2025.12.005

Abstract

Abstract:

Objective

To evaluate the utility of a nomogram model integrating clinical parameters, B-mode ultrasound features, and super-resolution contrast-enhanced ultrasound (SR-CEUS) characteristics for predicting human epidermal growth factor receptor 2 (HER-2) positive breast cancer.

Methods

We enrolled 132 patients with pathologically confirmed invasive breast cancer (55 HER-2 positive, 77 HER-2 negative) from the Second Hospital of Shanxi Medical University between March and September 2025. All patients underwent preoperative B-mode ultrasound and SR-CEUS examinations. Predictors were screened through univariate and multivariate logistic regression analyses. Three predictive models were constructed: Model 1 (clinical parameters + B-mode ultrasound features), Model 2 (SR-CEUS characteristics alone), and Model 3 (clinical parameters + B-mode ultrasound features + SR-CEUS characteristics). A nomogram was developed based on Model 3. Internal validation was performed using the bootstrap method. Model performance was assessed via receiver operating characteristic (ROC) curves, with area under the curve (AUC) differences compared using DeLong test. Calibration curves and the Hosmer-Lemeshow test were used to evaluate calibration and goodness-of-fit, while decision curve analysis (DCA) was performed to quantify clinical decision benefit.

Results

Univariate analysis revealed significant associations between HER-2 status and estrogen receptor (ER), progesterone receptor (PR), calcification, perfusion defects, vascular density, flow weighted vessel density (FWVD), perfusion index (PI), and blood flow velocity (OR=0.174, 0.149, 3.399, 2.837, 1.085, 1.104, 1.231, 1.081, all P＜0.05). Multivariate analysis identified PR negativity (odds ratio [OR]=0.211), calcification (OR=2.553), perfusion defects (OR=3.469), FWVD (OR=1.088), and PI (OR=1.184) as optimal predictors. The AUC values for Models 1, 2, and 3 in predicting HER-2 positive breast cancer were 0.763, 0.832, and 0.880, respectively. The combination model (Model 3) demonstrated a significantly higher AUC than Model 1 (P＜0.001) and Model 2 (P=0.039). Internal validation confirmed model stability. Calibration curves and the Hosmer-Lemeshow test indicated good calibration and fit. DCA showed superior net clinical benefit across a wide threshold probability range for the combination model.

Conclusion

The nomogram integrating clinical parameters, B-mode ultrasound features, and SR-CEUS characteristics effectively predicts HER-2 positive breast cancer.

Key words: Breast cancer, Human epidermal growth factor receptor 2, Contrast-enhanced ultrasound, Super resolution imaging, Nomogram

Yuhan Wang, Bojuan Wang, Jingzhu Xu, Tao Zhang, Xinghua Wang. A nomogram integrating clinical data, B-mode ultrasound features, and super-resolution contrast-enhanced ultrasound characteristics to predict HER-2 positive breast cancer[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2025, 22(12): 1130-1139.

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URL: https://chaosheng.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1672-6448.2025.12.005

https://chaosheng.cma-cmc.com.cn/EN/Y2025/V22/I12/1130

Figures/Tables 9

参数	HER-2阴性组（n=77）	HER-2阳性组（n=55）	统计值	P值
年龄（岁， $x ¯$ ±s）	56.21±11.30	55.85±10.22	t=0.187	0.852
身高[cm，M（Q₁，Q₃）]	160.00（157.00，162.00）	160.00（157.00，161.50）	Z=-0.210	0.833
体质量[kg，M（Q₁，Q₃）]	60.00（57.00，70.00）	60.00（57.00，65.00）	Z=-0.852	0.394
月经史[例（%）]			χ²=0.157	0.692
绝经	50（64.94）	33（60.00）
正常	27（35.06）	22（40.00）
ER[例（%）]			χ²=14.376	＜0.001
阴性	8（10.39）	22（40.00）
阳性	69（89.61）	33（60.00）
PR[例（%）]			χ²=22.858	＜0.001
阴性	15（19.48）	34（61.82）
阳性	62（80.52）	21（38.18）
Ki-67[例（%）]			χ²=0.842	0.359
阴性	31（40.26）	17（30.91）
阳性	46（59.74）	38（69.09）
淋巴结转移[例（%）]			χ²=0.174	0.677
无	46（59.74）	30（54.55）
有	31（40.26）	25（45.45）
最大径[例（%）]			χ²=0.786	0.375
≤2.0 cm	45（58.44）	27（49.09）
＞2.0 cm	32（41.56）	28（50.91）
边界[例（%）]			χ²=0.022	0.881
清晰	33（42.86）	22（40.00）
不清晰	44（57.14）	33（60.00）
形状[例（%）]			-	0.649
规则	2（2.60）	3（5.45）
不规则	75（97.40）	52（94.55）
内部回声[例（%）]			χ²=0.000	1.000
均匀	30（38.96）	21（38.18）
不均匀	47（61.04）	34（61.82）
后方回声[例（%）]			χ²=0.796	0.372
无改变	66（85.71）	43（78.18）
衰减	11（14.29）	12（21.82）
钙化[例（%）]			χ²=9.533	0.002
无	59（76.62）	27（49.09）
有	18（23.38）	28（50.91）
方位[例（%）]			χ²=0.181	0.670
平行	57（74.03）	38（69.09）
不平行	20（25.97）	17（30.91）
周围回声改变[例（%）]			χ²=0.217	0.642
无	28（36.36）	17（30.91）
有	49（63.64）	38（69.09）
灌注方式[例（%）]			χ²=0.828	0.363
离心/弥散	25（32.47）	13（23.64）
向心	52（67.53）	42（76.36）
灌注均匀性[例（%）]			χ²=1.477	0.224
均匀	14（18.18）	5（9.09）
不均匀	63（81.82）	50（90.91）
SR-CEUS形状[例（%）]			χ²=0.009	0.923
规则	22（28.57）	17（30.91）
不规则	55（71.43）	38（69.09）
灌注后范围扩大[例（%）]			χ²=0.094	0.760
无	18（23.38）	15（27.27）
有	59（76.62）	40（72.73）
灌注缺损[例（%）]			χ²=6.388	0.011
无	36（46.75）	13（23.64）
有	41（53.25）	42（76.36）
血管密度[%，M（Q₁，Q₃）]	63.64（54.77，75.05）	79.62（71.78，85.47）	Z=5.331	＜0.001
血流容积（ $x ¯$ ±s）	23.67±9.23	32.12±9.83	t=4.993	＜0.001
分形维数（ $x ¯$ ±s）	1.63±0.11	1.66±0.08	t=1.751	0.082
灌注指数[M（Q₁，Q₃）]	7.48（5.50，9.28）	10.93（8.52，15.10）	Z=5.430	＜0.001
血流速度[mm/s，M（Q₁，Q₃）]	11.03（9.03，14.12）	13.40（11.35，19.84）	Z=3.226	0.001
速度方差[M（Q₁，Q₃）]	23.58（14.30，54.76）	24.92（14.53，42.00）	Z=0.399	0.690
方向方差[M（Q₁，Q₃）]	1673.73（1314.24，2025.10）	1322.50（990.00，1746.46）	Z=-2.532	0.011

参数	HER-2阴性组（n=77）	HER-2阳性组（n=55）	统计值	P值
年龄（岁， $x ¯$ ±s）	56.21±11.30	55.85±10.22	t=0.187	0.852
身高[cm，M（Q₁，Q₃）]	160.00（157.00，162.00）	160.00（157.00，161.50）	Z=-0.210	0.833
体质量[kg，M（Q₁，Q₃）]	60.00（57.00，70.00）	60.00（57.00，65.00）	Z=-0.852	0.394
月经史[例（%）]			χ²=0.157	0.692
绝经	50（64.94）	33（60.00）
正常	27（35.06）	22（40.00）
ER[例（%）]			χ²=14.376	＜0.001
阴性	8（10.39）	22（40.00）
阳性	69（89.61）	33（60.00）
PR[例（%）]			χ²=22.858	＜0.001
阴性	15（19.48）	34（61.82）
阳性	62（80.52）	21（38.18）
Ki-67[例（%）]			χ²=0.842	0.359
阴性	31（40.26）	17（30.91）
阳性	46（59.74）	38（69.09）
淋巴结转移[例（%）]			χ²=0.174	0.677
无	46（59.74）	30（54.55）
有	31（40.26）	25（45.45）
最大径[例（%）]			χ²=0.786	0.375
≤2.0 cm	45（58.44）	27（49.09）
＞2.0 cm	32（41.56）	28（50.91）
边界[例（%）]			χ²=0.022	0.881
清晰	33（42.86）	22（40.00）
不清晰	44（57.14）	33（60.00）
形状[例（%）]			-	0.649
规则	2（2.60）	3（5.45）
不规则	75（97.40）	52（94.55）
内部回声[例（%）]			χ²=0.000	1.000
均匀	30（38.96）	21（38.18）
不均匀	47（61.04）	34（61.82）
后方回声[例（%）]			χ²=0.796	0.372
无改变	66（85.71）	43（78.18）
衰减	11（14.29）	12（21.82）
钙化[例（%）]			χ²=9.533	0.002
无	59（76.62）	27（49.09）
有	18（23.38）	28（50.91）
方位[例（%）]			χ²=0.181	0.670
平行	57（74.03）	38（69.09）
不平行	20（25.97）	17（30.91）
周围回声改变[例（%）]			χ²=0.217	0.642
无	28（36.36）	17（30.91）
有	49（63.64）	38（69.09）
灌注方式[例（%）]			χ²=0.828	0.363
离心/弥散	25（32.47）	13（23.64）
向心	52（67.53）	42（76.36）
灌注均匀性[例（%）]			χ²=1.477	0.224
均匀	14（18.18）	5（9.09）
不均匀	63（81.82）	50（90.91）
SR-CEUS形状[例（%）]			χ²=0.009	0.923
规则	22（28.57）	17（30.91）
不规则	55（71.43）	38（69.09）
灌注后范围扩大[例（%）]			χ²=0.094	0.760
无	18（23.38）	15（27.27）
有	59（76.62）	40（72.73）
灌注缺损[例（%）]			χ²=6.388	0.011
无	36（46.75）	13（23.64）
有	41（53.25）	42（76.36）
血管密度[%，M（Q₁，Q₃）]	63.64（54.77，75.05）	79.62（71.78，85.47）	Z=5.331	＜0.001
血流容积（ $x ¯$ ±s）	23.67±9.23	32.12±9.83	t=4.993	＜0.001
分形维数（ $x ¯$ ±s）	1.63±0.11	1.66±0.08	t=1.751	0.082
灌注指数[M（Q₁，Q₃）]	7.48（5.50，9.28）	10.93（8.52，15.10）	Z=5.430	＜0.001
血流速度[mm/s，M（Q₁，Q₃）]	11.03（9.03，14.12）	13.40（11.35，19.84）	Z=3.226	0.001
速度方差[M（Q₁，Q₃）]	23.58（14.30，54.76）	24.92（14.53，42.00）	Z=0.399	0.690
方向方差[M（Q₁，Q₃）]	1673.73（1314.24，2025.10）	1322.50（990.00，1746.46）	Z=-2.532	0.011

参数	单因素分析			多因素分析
参数	OR值	95%CI	P值	OR值	95%CI	P值
年龄	0.997	0.965~1.030	0.853
月经史	1.235	0.602~2.525	0.563
ER	0.174	0.066~0.417	＜0.001
PR	0.149	0.067~0.321	＜0.001	0.211	0.075~0.556	0.002
Ki~67	1.506	0.730~3.171	0.272
淋巴结转移	1.237	0.613~2.495	0.552
最大径	1.458	0.728~2.940	0.288
边界	1.125	0.558~2.287	0.743
形状	0.462	0.059~2.881	0.407
内部回声	1.033	0.508~2.117	0.928
后方回声	1.674	0.676~4.191	0.264
钙化	3.399	1.627~7.287	0.001	2.553	0.936~7.037	0.066
方位	1.275	0.589~2.746	0.534
周围回声改变	1.277	0.615~2.700	0.515
灌注方式	1.553	0.718~3.475	0.271
灌注均匀性	2.222	0.791~7.254	0.150
SR-CEUS形状	0.894	0.420~1.920	0.772
灌注后范围扩大	0.814	0.368~1.816	0.611
灌注缺损	2.837	1.342~6.266	0.008	3.469	1.308~9.925	0.015
血管密度	1.085	1.052~1.125	＜0.001
血流容积	1.104	1.058~1.161	＜0.001	1.088	1.024~1.163	0.009
分形维数	21.769	0.612~929.5	0.097
灌注指数	1.231	1.127~1.369	＜0.001	1.184	1.071~1.338	0.003
血流速度	1.081	1.027~1.146	0.005
速度方差	1.002	0.996~1.009	0.491
方向方差	1.000	0.999~1.000	0.195

模型	AUC（95%CI）	敏感度（%）	特异度（%）	准确性（%）
模型1	0.763（0.683~0.843）	80.00	64.94	71.21
模型2	0.832（0.765~0.898）	96.36	57.14	73.48
模型3	0.880（0.822~0.937）	85.45	77.92	81.06

参数	观察者内	观察者间
灌注方式	0.932（0.863~0.967）	0.934（0.867~0.968）
灌注均匀性	0.892（0.788~0.947）	0.873（0.753~0.937）
超声显微造影形状	0.843（0.699~0.922）	0.799（0.621~0.898）
灌注后范围扩大	0.921（0.841~0.961）	0.905（0.812~0.953）
灌注缺损	1.000	0.892（0.788~0.947）
血管密度	0.889（0.782~0.946）	0.896（0.789~0.950）
血流容积	0.836（0.687~0.918）	0.789（0.526~0.903）
分形维数	0.938（0.875~0.970）	0.915（0.821~0.960）
灌注指数	0.900（0.801~0.951）	0.925（0.843~0.964）
血流速度	0.937（0.873~0.969）	0.961（0.920~0.981）
速度方差	0.892（0.785~0.947）	0.833（0.663~0.919）
方向方差	0.841（0.693~0.921）	0.783（0.570~0.893）

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