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Quantitative Shear Wave Elastography

Rationale and Objectives

To correlate prognostic histologic features and immunohistochemical biomarkers of breast cancer with quantitative shear wave elastography (SWE) parameters.

Materials and Methods

B-mode ultrasound (US) and SWE were performed before core biopsy on 72 cancers in 68 patients. Mean cancer size was determined from US. Histologic grade, lymph node status, lymphovascular invasion (LVI), histologic type, and immunohistochemical biomarkers (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 [HER2]) were determined from surgical pathology reports. Correlation between these features and quantitative SWE parameters (mean elasticity [E mean], maximum elasticity [E max], and elasticity ratio [E ratio]) was made.

Results

There was significant correlation of mean cancer size with E mean, E max, and E ratio (correlation, 0.492, 0.500, and 0.435, respectively; all P < .001). Lymph node involvement was associated with significantly higher E max ( P = .040). LVI was associated with significantly higher E mean, E max, and E ratio ( P = .002, .004, and .042, respectively). There was no significant correlation of histologic grade with SWE parameters. HER2+ cancers were associated with significantly higher E ratio ( P = .030). In multivariate analysis, only mean cancer size was significantly correlated with E mean and E max ( P < .001).

Conclusions

There was significant correlation of cancer size with SWE parameters. There was significant correlation of lymph node status and LVI with SWE, but only on univariate analysis. SWE has the potential to provide prognostic information of breast cancer in a noninvasive manner, but further study is required.

Breast cancer is a heterogeneous disease, with different histologic types, clinical course, response to treatment, and prognosis. The prognostic histologic features of breast cancer include invasive size, lymph node status , histologic grade , lymphovascular invasion (LVI), and histologic type . Molecular profiling of breast cancer by gene expression array analysis classifies breast cancers into different subtypes. There is correlation of the different molecular subtypes with the response to systemic therapy . There is also a significant correlation between the different histologic types of breast cancer and their molecular subtypes . Because gene expression array analysis has strict tissue requirements and is not always available, immunohistochemical study is used as a surrogate with determination of the expression of the following cancer biomarkers: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) . Three major subtypes are defined: ER positive (ER+ [ER+, PR+/−, and HER2−/+]), HER2 positive (HER2+ [ER−, PR−, and HER2+]), and triple negative (TN [ER−, PR−, and HER2−]). These immunohistochemical subtypes correspond approximately to the molecular subtypes of luminal A (ER+, PR+/−, HER2−; low grade)/luminal B (ER+, PR+/−, HER2−; high grade or ER+, PR+/−, HER2+), HER2 enriched and basal-like, respectively. The luminal A subtype has the best prognosis and the basal-like subtype the worst prognosis .

Core biopsy is performed to obtain samples for analysis of histologic and immunohistochemical features of breast cancer. However, these limited biopsy samples are inadequate for assessment of the entire range of intratumoral heterogeneity, which can influence the course of tumor progression and treatment . Imaging of the entire tumor for prognostic features can potentially add useful information to that obtained from tissue biopsy.

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Materials and methods

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Statistical Analysis

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Results

Descriptive Statistics of Demographic and Clinical Characteristics

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Mean Cancer Size

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Histologic Grade

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Table 1

Correlation of Histologic Grade with SWE Parameters

SWE Parameter Grade_n_ Mean ± SD Range E mean 1 12 127.37 ± 76.82 26.90–286.30P ∗ = .247 2 29 131.48 ± 78.52 16.20–292.90 3 26 163.39 ± 77.86 32.70–300.00 E max 1 12 150.65 ± 86.33 29.80–300.00P = .241 2 29 156.60 ± 89.39 20.00–300.00 3 26 193.87 ± 89.15 37.10–300.00 E ratio 1 12 7.23 ± 3.34 2.30–13.01P = .152 2 29 12.28 ± 12.83 1.83–62.63 3 26 13.18 ± 9.48 2.55–41.43

E max, maximum elasticity; E mean, mean elasticity; E ratio, elasticity ratio; SD, standard deviation; SWE, shear wave elastography.

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Lymph Node Status

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Table 2

Correlation of Lymph Node Status with SWE Parameters

Variable Negative Lymph Node Status ( n = 36) Positive Lymph Node Status ( n = 22)P ∗ Value Mean ± SD Range Mean ± SD Range E mean 129.99 ± 76.41 16.20–292.90 169.85 ± 78.86 39.60–300.00 .062 E max 154.40 ± 87.21 20.00–300.00 204.07 ± 87.70 46.80–300.00 .040 E ratio 12.18 ± 12.62 1.83–62.63 12.40 ± 8.15 5.36–34.52 .941

E max, maximum elasticity; E mean, mean elasticity; E ratio, elasticity ratio; SD, standard deviation; SWE, shear wave elastography.

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Lymphovascular Invasion

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Table 3

Correlation of LVI with SWE Parameters

Variable Without LVI ( n = 43) With LVI ( n = 27)P ∗ Value Mean ± SD Range Mean ± SD Range E mean 121.15 ± 67.90 16.20–240.60 177.63 ± 80.44 42.50–300.00 .002 E max 146.96 ± 82.82 20.00–300.00 209.04 ± 86.33 53.30–300.00 .004 E ratio 9.23 ± 7.71 1.83–36.40 15.05 ± 12.98 5.36–62.63 .042

E max, maximum elasticity; E mean, mean elasticity; E ratio, elasticity ratio; LVI, lymphovascular invasion; SD, standard deviation; SWE, shear wave elastography.

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Immunohistochemical Biomarkers

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Table 4

Correlation of Immunohistochemical Biomarkers with SWE Parameters

Biomarker Variable Biomarker− Biomarker+ Mean ± SD Range Mean ± SD Range ER− ( n = 10), ER+ ( n = 57) E mean ( P ∗ = .438) 159.76 ± 63.66 59.60–237.00 142.35 ± 79.67 16.20–300.00 E max ( P = .629) 185.97 ± 74.95 71.80–283.40 171.06 ± 90.89 20.00–300.00 E ratio ( P = .941) 9.71 ± 5.14 2.55–15.34 12.06 ± 11.11 1.83–62.63 PR− ( n = 17), PR+ ( n = 50) E mean ( P = .980) 142.38 ± 66.19 48.90–237.00 145.75 ± 81.32 16.20–300.00 E max ( P = .930) 170.20 ± 78.03 57.80–300.00 174.27 ± 92.27 20.00–300.00 E ratio ( P = .700) 11.17 ± 7.52 2.55–33.24 11.90 ± 11.32 1.83–62.63 HER2− ( n = 53), HER2+ ( n = 14) E mean ( P = .259) 152.27 ± 78.54 16.20–300.00 123.06 ± 69.83 39.60–257.00 E max ( P = .162) 182.97 ± 89.19 20.00–300.00 143.46 ± 79.73 46.80–300.00 E ratio ( P = .030) 11.21 ± 11.15 1.83–62.63 14.08 ± 7.49 5.54–33.24

E max, maximum elasticity; E mean, mean elasticity; ER, estrogen receptor; E ratio, elasticity ratio; HER2, human epidermal growth factor receptor 2; PR, progesterone receptor; SD, standard deviation; SWE, shear wave elastography.

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Histologic Type

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Table 5

Correlation of Histologic Type with SWE Parameters

SWE Parameter Histologic Type_n_ Mean ± SD Range E mean DCIS 5 79.52 ± 56.07 32.70–177.00 P ∗ = .076 IDC 64 141.70 ± 75.79 16.20–300.00 ILC 1 286.30 286.30–286.30 IMC 2 219.10 ± 13.01 209.90–228.30 E max DCIS 5 95.36 ± 72.11 37.10–221.20P = .067 IDC 64 169.76 ± 86.94 20.00–300.00 ILC 1 300.00 300.00–300.00 IMC 2 270.65 ± 41.51 241.30–300.00 E ratio DCIS 5 4.92 ± 1.98 2.98–7.68P = .031 IDC 64 11.31 ± 10.30 1.83–62.63 ILC 1 13.01 13.01–13.01 IMC 2 27.12 ± 10.47 19.71–34.52

DCIS, ductal carcinoma in situ; E max, maximum elasticity; E mean, mean elasticity; E ratio, elasticity ratio; IDC, invasive ductal cancer; IMC, invasive mucinous carcinoma; SD, standard deviation; SWE, shear wave elastography.

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Multivariate Analysis

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Correlation of Cancer Size and Lymph Node Status

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Correlation of Cancer Size and LVI

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Discussion

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Figure 1, A 51-year-old woman with 5.1-mm, grade 1, invasive, ductal carcinoma (NOS) of the right breast. Shear wave elastography superimposed on ultrasound image ( top ) shows mean elasticity, 38.5 kPa; maximum elasticity, 47.8 kPa; and elasticity ratio, 5.45. Ultrasound image ( bottom ) shows the cancer with negative lymph node involvement (zero of four); negative lymphovascular invasion; estrogen receptor positive, progesterone receptor positive, and human epidermal growth factor receptor 2 negative; and luminal A subtype. This cancer was moderately hard.

Figure 2, A 59-year-old woman with 18-mm, grade 3, invasive, ductal carcinoma (NOS) of the right breast. Shear wave elastography superimposed on ultrasound image ( top ) shows mean elasticity, 167.2 kPa; maximum elasticity, 193.3 kPa; and elasticity ratio, 5.95. Ultrasound image ( bottom ) shows the cancer with positive lymph node involvement (five of eight); positive lymphovascular invasion; estrogen receptor positive, progesterone receptor negative, and human epidermal growth factor receptor 2 positive; and luminal B subtype. This cancer was very hard.

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Figure 3, A 70-year-old woman with 19.3-mm, grade 3, invasive, ductal carcinoma (NOS) of the left breast. Shear wave elastography superimposed on ultrasound image ( top ) shows mean elasticity, 237.0 kPa; maximum elasticity, 272.9 kPa; and elasticity ratio, 13.77. Ultrasound image ( bottom ) shows the cancer with unknown lymph node status; negative lymphovascular invasion; estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 positive; and human epidermal growth factor receptor 2 positive subtype. This cancer was extremely hard.

Figure 4, A 40-year-old woman with 12.3-mm, grade 3, invasive, ductal carcinoma (with medullary features) of the left breast. Shear wave elastography superimposed on ultrasound image ( top ) shows mean elasticity, 147.5 kPa; maximum elasticity, 165.5 kPa; and elasticity ratio, 15.29. Ultrasound image ( bottom ) shows the cancer with negative lymph node involvement (zero of four); negative lymphovascular invasion; estrogen receptor negative, progesterone receptor negative, human epidermal growth factor receptor 2 negative; triple negative subtype. This cancer was very hard.

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Figure 5, A 51-year-old woman with 8.0-mm, grade 2, ductal carcinoma in situ of the right breast. Shear wave elastography superimposed on ultrasound image ( top ) shows mean elasticity, 60.5 kPa; maximum elasticity, 75.3 kPa; and elasticity ratio, 5.53. Ultrasound image ( bottom ) shows the cancer with negative lymphovascular invasion. This cancer was moderately hard.

Figure 6, A 72-year-old woman with 14.0-mm, grade 2, invasive mucinous carcinoma of the left breast. Shear wave elastography superimposed on ultrasound image ( top ) shows mean elasticity, 209.9 kPa; maximum elasticity, 241.3 kPa; and elasticity ratio, 19.71. Ultrasound image ( bottom ) shows the cancer with negative lymph node involvement (zero of seven); negative lymphovascular invasion; estrogen receptor positive, progesterone receptor positive, and human epidermal growth factor receptor 2 negative; and indeterminate subtype. This cancer was extremely hard.

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