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Shear Wave Speed of the Lesion in Preoperative Breast Ultrasonography

Rationale and Objectives

We aimed to investigate the relationship between shear wave speed (SWS) of the lesion on preoperative breast ultrasonography (US) and disease-free survival of patients with primary operable invasive breast cancer.

Materials and Methods

This retrospective study was approved by our Institutional Review Board. The requirement for informed consent was waived. A total of 195 consecutive newly diagnosed invasive breast cancer patients (age 33–83 years; mean 54.0 years) with preoperative breast US with SWS measurement of the lesion were identified. They underwent surgery between May 2012 and May 2013. SWS was measured at the center and three marginal zones in the main tumors, and the maximum value was used for analyses. For 35 patients who underwent primary systemic therapy (PST), the maximum SWS before PST was used. Cox proportional hazards modeling was used to identify the relationship between clinical-pathologic factors and disease-free survival.

Results

Fourteen recurrences occurred at 6–47 months (mean 22.3 months) after surgery. On multivariate analysis, a positive history of PST (hazard ratio [HR] = 4.93; 95% confidence interval [CI]: 1.66, 14.70; P = .004), adjuvant chemotherapy (HR = 3.67; 95% CI: 1.11, 12.1; P = .033), and higher maximum SWS (HR = 1.55; 95% CI: 1.07, 2.23; P = .020) were associated with poorer disease-free survival.

Conclusion

Higher maximum SWS on preoperative US, in addition to a positive history of PST and adjuvant chemotherapy, was significantly associated with poorer disease-free survival of patients with invasive breast cancer.

Introduction

Breast cancer is one of the most common malignancies and a leading cause of cancer mortality among women. Although a multidisciplinary approach including the development of screening and adjuvant therapy has improved the mortality rate , there are still more than 500,000 women who die from this malignancy per year worldwide . In planning therapeutic options for each breast cancer patient, it is beneficial to develop a prognosis. Studies have shown that information acquired from preoperative images including breast magnetic resonance imaging (MRI) can be used as prognostic factors .

Shear wave elastography is a method of quantitatively measuring tissue elasticity during breast ultrasonography (US) examinations. Focused acoustic radiation force pushing pulses of short duration and the speed of the shear waves that are propagated in a direction orthogonal to the direction of the tissue are measured . The shear wave speed (SWS) of the lesion reflects tissue stiffness. SWS can easily be measured in clinical settings, and its use has been reported to improve accuracy in differentiating breast cancers and benign lesions when used in addition to B-mode ultrasound during breast screening and diagnosis. In addition, several studies have shown that shear wave elastography of breast cancer lesions is significantly associated with prognostic factors, including tumor size, immunohistochemical biomarkers, lymph node metastasis, and vascular and lymphovascular invasion . From these results, it is plausible that shear wave elastography could be useful for predicting outcomes, including tumor recurrence and metastasis, although these correlations have not been evaluated in previous investigations.

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Materials and Methods

Study Population

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Figure 1, The patients' enrollment criteria. SWS, shear wave speed.

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Preoperative US Examinations

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Figure 2, A 47-year-old woman with invasive breast carcinoma of no specific type of the right breast, an example of measuring maximum SWS of a breast cancer lesion. SWS was measured at first at the center of the lesion ( a ), and then at three (superficial and two lateral) marginal zones ( b ) of the lesion using a 5 × 5 mm region of interest. SWS measurements were conducted three times at each spot, and the maximum value was used for analyses. In this case, maximum SWS of 3.70 m/s was measured at the lateral marginal zone of the lesion ( b , square ). The patient underwent surgery without primary systemic therapy and was free from recurrence for 57 months. SWS, shear wave speed.

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Clinical-Pathologic Evaluation

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Statistical Analyses

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Results

Study Subjects

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Table 1

Characteristics of the Study Subjects According to Recurrence Status

Total

( N = 195) Nonrecurrence Group

( n = 181) Recurrence Group

( n = 14)P Age (y) \* 33–83 (54.0) 33–83 (54.3) 34–82 (49.4) .078 Lesion size (mm) \* 4–53 (19.0) 4–53 (18.3) 11–42 (27.4) .001 Maximum SWS (m/s) \* 2.07–8.38 (5.39) 2.07–8.38 (5.29) 4.38–8.24 (6.71) .005 Lymphadenopathy .10 Positive 37 32 5 Negative 158 149 9 Nuclear grade .098 1 or 2 169 (86.7) 159 (81.5) 10 (5.1) 3 26 (13.3) 22 (11.3) 4 (2.1) ER status .045 Positive 165 (84.6) 156 (80.0) 9 (4.6) Negative 30 (15.4) 25 (12.8) 5 (2.6) PgR status .011 Positive 144 (73.8) 138 (70.8) 6 (3.1) Negative 51 (26.2) 43 (22.1) 8 (4.1) HER2 overexpression .021 Positive 25 (12.8) 20 (10.3) 5 (2.6) Negative 170 (87.2) 161 (82.6) 9 (4.6) PST .001 Performed 35 (17.9) 27 (13.8) 8 (4.1) Not performed 160 (82.1) 154 (79.0) 6 (3.1) Type of surgery .59 Lumpectomy 85 (43.6) 80 (41.0) 5 (2.6) Mastectomy 110 (56.4) 101 (51.8) 9 (4.6) Adjuvant chemotherapy .001 Performed 59 (30.3) 49 (25.1) 10 (5.1) Not performed 136 (69.7) 132 (67.7) 4 (2.1) Adjuvant hormone therapy .004 Performed 150 (76.9) 144 (73.8) 6 (3.1) Not performed 45 (23.1) 37 (19.0) 8 (4.1) Adjuvant radiation therapy 1.0 Performed 90 (46.2) 84 (43.1) 6 (3.1) Not performed 105 (53.8) 97 (49.7) 8 (4.1)

ER, estrogen receptor; HER2, human epidermal growth factor receptor-2; PgR, progesterone receptor; PST, primary systemic therapy; SWS, shear wave speed

Unless otherwise noted, data are numbers of patients, with percentages in parentheses.

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Cox Proportional Hazard Model Analyses

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Table 2

Results of Univariate Cox Proportional Hazard Analysis

HR 95% CI_P_ Age 0.96 0.91, 1.01 .123 Maximum diameter of lesion 1.074 1.03, 1.12 .001 Maximum SWS 1.62 1.12, 2.36 .011 Lymphadenopathy 2.61 0.87, 7.78 .086 Positive compared to negative Nuclear grade 2.65 0.83, 8.45 .10 1 or 2 compared to 3 ER status 3.01 1.01, 8.99 .048 Negative compared to positive PgR status 3.68 1.28, 10.62 .016 Negative compared to positive HER2 overexpression 4.14 1.38, 12.36 .011 Positive compared to negative PST 6.80 2.36, 19.62 <.001 Performed compared to not performed Type of surgery 1.40 0.47, 4.18 .547 Lumpectomy vs mastectomy Adjuvant chemotherapy 6.22 1.95, 19.83 .002 Performed compared to not performed Adjuvant hormone therapy 5.05 1.75, 14.57 .003 Not performed compared to performed Adjuvant radiation therapy 0.83 0.29, 2.39 .73 Performed compared to not performed

CI, confidence interval; ER, estrogen receptor; HER2, human epidermal growth factor receptor-2; HR, hazard ratio; PgR, progesterone receptor; PST, primary systemic therapy; SWS, shear wave speed.

Figure 3, A 45-year-old woman with invasive breast carcinoma of no specific type of the left breast. ( a ) Maximum SWS of 7.29 m/s was measured at the lateral marginal zone of the lesion ( square ). The patient underwent lumpectomy after receiving primary systemic therapy, followed by adjuvant chemotherapy and radiation therapy. She palpated a recurrent lump 22 months after surgery. ( b ) Positron emission tomography revealed locoregional recurrence of the ipsilateral breast ( arrow ), distant metastases to the right costal bone ( white arrowhead ), and the right cervical lymph node ( black arrowhead ). SWS, shear wave speed.

Table 3

Results of Multivariate Cox Proportional Hazard Analysis

HR 95% CI_P_ PST 4.93 1.66, 14.70 .004 Performed compared to not performed Adjuvant chemotherapy 3.67 1.11, 12.1 .033 Performed compared to not performed Maximum SWS 1.55 1.07, 2.23 .020

CI, confidence interval; HR, hazard ratio; PST, primary systemic therapy; SWS, shear wave speed.

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Disease-free Survival Analysis

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Figure 4, Receiver operating characteristic curve for the association between maximum SWS and recurrence. Optimal maximum SWS value to assess the association with disease-free survival was 6.08 m/s (sensitivity 85.7%, specificity 62.4%), and the area under the curve was 0.73 (95% confidence interval, 0.63, 0.82). SWS, shear wave speed.

Figure 5, Kaplan-Meier curve for survival analysis. The graph shows that patients with tumors with maximum SWS higher than 6.08 m/s had poorer disease-free survival compared to those with maximum SWS ≤6.08 m/s ( P < .001). SWS, shear wave speed.

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Discussion

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