Ai Amioka

Ability of contrast-enhanced ultrasonography to determine clinical responses of breast cancer to neoadjuvant chemotherapy

OBJECTIVE We aimed to determine whether contrast-enhanced ultrasonography can predict the effects of neoadjuvant chemotherapy on breast cancer. METHODS The clinical responses of 63 consecutive patients with breast cancer (T1-4, N0-1, M0) to neoadjuvant chemotherapy between October 2012 and May 2015 were assessed using contrast-enhanced magnetic resonance imaging, positron emission tomography/computed tomography and contrast-enhanced ultrasonography. Perfusion parameters for contrast-enhanced ultrasonography were created from time-intensity curves based on enhancement intensity and temporal changes to objectively evaluate contrast-enhanced ultrasonography findings. The sensitivity, specificity and accuracy of contrast-enhanced ultrasonography, magnetic resonance imaging and positron emission tomography/computed tomography to predict a pathological complete response were compared after confirming the pathological findings of surgical specimens. RESULTS Twenty-three (36.5%) of the 63 patients achieved pathological complete response. The sensitivity, specificity and accuracy of contrast-enhanced ultrasonography for predicting pathological complete response were 95.7% (82.5-99.2%), 77.5% (69.9-79.5%) and 84.1% (74.5-86.7%). The sensitivity of contrast-enhanced ultrasonography was significantly greater than that of magnetic resonance imaging (95.7 vs. 69.6%, P = 0.047). The specificity and accuracy were significantly greater and tended to be greater, respectively, for contrast-enhanced ultrasonography than positron emission tomography/computed tomography (specificity, 77.5 vs. 52.5%, P = 0.02; accuracy, 84.1 vs. 69.8%, P = 0.057). CONCLUSIONS Contrast-enhanced ultrasonography might serve as a new diagnostic modality when planning therapeutic strategies for patients with breast cancer after neoadjuvant chemotherapy.

A Case of an Acute Cervicomediastinal Hematoma Secondary to the Spontaneous Rupture of a Parathyroid Adenoma

We herein report the case of a patient with an acute cervicomediastinal hematoma secondary to the spontaneous rupture of a parathyroid adenoma. A 47-year-old female presented with swelling and pain in the neck. She had no history of trauma or of having undergone any medical or odontological procedures. An ultrasound examination revealed the presence of an obscure mass located behind the right lobe of the thyroid gland. A computed tomography scan showed the presence of a low-density lesion extending from the retropharynx to the mediastinum, a high-density lesion located behind the right lobe of the thyroid gland and a right pleural effusion. Because the patients neck swelling and anemia gradually worsened, she underwent emergency surgery. The neck was found to be swollen due to a hematoma; however, no abscesses were detected in the operative field.Thoracoscopy of the right chest showed no active bleeding. The fragmented mass was histopathologically diagnosed as a parathyroid adenoma with acute hemorrhage, which is quite rare. Our experience suggests that, in patients with severe cervicomediastinal hematomas without any trauma or trigger, a diagnosis of spontaneous rupture of a parathyroid gland lesion should be considered.

Role of FDG-PET/CT in Prediction of Underestimation of Invasive Breast Cancer in Cases of Ductal Carcinoma In Situ Diagnosed at Needle Biopsy

BACKGROUND The aim of this study was to evaluate the significance of FDG-PET/CT for predicting the underestimation of invasive breast cancer in cases of DCIS at needle biopsy. PATIENTS AND METHODS Of 83 consecutive cases with diagnoses of DCIS at primary needle biopsy who underwent curative surgery between 2010 and 2013, the association between the SUVmax on FDG-PET/CT before excision and the underestimation of invasive breast cancer was examined. RESULTS There were 29 (34.9%) cases diagnosed to have invasive breast cancer at excision. Receiver operating characteristics curve analysis showed the cutoff value of the SUVmax to predict underestimation of invasive breast cancer was 1.6. The rates of underestimation were 61.5% for patients with a tumor of SUVmax > 1.6 and 11.4% for patients with a tumor of SUVmax ≤ 1.6 (P < .001). A high value of SUVmax was significantly associated with symptomatic presentation (P < .001), palpability (P < .001), mass formation (P = .013), high Breast Imaging Reporting and Data System category (P = .011), and core needle biopsy (P = .007). In multivariate analysis, high SUVmax was only a significant predictive factor of underestimation of invasive breast cancer (hazard ratio, 11.7; 95% confidence interval, 3.70-37.0; P < .001). CONCLUSION SUVmax on FDG-PET/CT is useful for predicting the underestimation of invasive breast cancer in cases of DCIS at needle biopsy.

Evaluation of Malignancy Grade of Breast Cancer Using Perflubutane-Enhanced Ultrasonography

Whether the contrast effects of perflubutane on contrast-enhanced ultrasonography can predict the malignancy grade of breast cancer is unknown. We analyzed associations between perfusion parameters created from time-intensity curves based on enhancement intensity and temporal changes in contrast-enhanced ultrasonography and clinicopathologic factors in 100 consecutive patients with invasive breast cancer. Values of perfusion parameters were significantly greater in estrogen receptor-negative than -positive tumors (peak intensity, p = 0.0002; ascending slope, p = 0.006; area under the curve, p = 0.0006). Variations in the peak intensity of Ki-67 were significantly correlated in all tumors (r = 0.54, p < 0.0001) and in luminal (r = 0.43, p = 0.0002), human epidermal growth factor receptor type 2-positive (r = 0.47, p = 0.047) and triple-negative (r = 0.55, p = 0.043) tumors. Perfusion parameters on contrast-enhanced ultrasonography can provide excellent predictive value for high-grade malignancy and might help to determine appropriate therapeutic strategies.

Wnt5a-induced cell migration is associated with the aggressiveness of estrogen receptor-positive breast cancer

Elevated expression of Wnt5a is associated with malignancy, cell invasion, and metastasis. The role of Wnt5a expression in breast cancer remains elusive. We investigated the significance of Wnt5a expression in breast cancer. The relationship between Wnt5a expression and clinicopathologic factors was assessed in invasive breast cancer (n = 178) resected at Hiroshima University Hospital between January 2011 and February 2014. Wnt5a was expressed in 69 of 178 cases (39%) of invasive breast cancer and correlated strongly with estrogen receptor (ER) expression (P < 0.001). Wnt5a expression in ER-positive breast cancer correlated significantly with lymph node metastasis, nuclear grade, and lymphatic invasion. The recurrence-free survival was shorter in breast cancer patients with Wnt5a expression than in those without (P = 0.024). The migratory capacity of ER-positive breast cancer cells increased with constitutive expression of Wnt5a and decreased with Wnt5a knockdown. DNA microarray analysis identified activated leukocyte cell adhesion molecule (ALCAM) as the primary gene induced by Wnt5a. ALCAM was expressed in 69% of Wnt5a-positive but only 27% of Wnt5a-negative cancers (κ = 0.444; P < 0.001). The inhibition of ALCAM reversed the enhanced migratory effect of Wnt5a, confirming the importance of this protein in the migration of ER-positive breast cancer cells. Wnt5a expression is related to high malignancy and a poor prognosis in ER-positive breast cancer. We suspect that Wnt5a expression increases the malignancy of breast cancer by increasing the migratory capacity of cancer cells through the induction of ALCAM expression.

Abstract P1-02-04: Impact of perflubutane-enhanced ultrasonography for evaluating malignancy grade of breast cancer

Objectives This study aimed to determine whether or not signal intensity caused by the contrast effects of Contrast-enhanced ultrasonography (CEUS) using perflubutane could predict malignancy grades of invasive breast cancer. Methods Fifty-four patients with clinical stages I – III breast cancer between April 2013 and April 2014 underwent CEUS using perflubutane. We analyzed the assciation between contrast-effect intensity and contrast time in CEUS and the prognostic factors based on tumor size, nodal status and immunohistochemical markers (ER, HER-2 status, nuclear grade, Ki-67) in breast cancer. Results Time to washout of time required to reach plateau intensity from the start of the maximum intensity was significantly associated with the Ki-67 value (p = 0.03). Also, A parameter of intratumoral blood perfusion, peak intensity (PI), was significantly associated with the Ki-67 value (p = 0.006) and ER status (p = 0.002) (Table 1), but not with tumor size (cT; p = 0.25, pT; 0.96), node status (p = 0.99), HER-2 status (p = 0.32) and nuclear grade (p = 0.61). Also, Thirty-eight, 7, and 9 patients had luminal, HER-2-positive and triple-negative tumors, respectively. The PI values for these tumors were 56.8 ± 20.9, 71.9 ± 20.5, and 85.7 ± 23.2, respectively. And, the PI value was significantly greater in the triple-negative, than in luminal tumors (p = 0.001). Furthermore, PI significantly correlated with the Ki-67 value (Spearman r = 0.54, P = 0.00002). Conclusions These findings indicated that PI has excellent predictive value for grade malignancy in breast cancer and might help to determine appropriate therapeutic strategies. Key points • Contrast-enhanced ultrasonography (CEUS) enables the real-time evaluation of detailed hemodynamics in breast cancer. • Peak intensity (PI) was significantly associated with Estrogen Receptors and Ki-67 assessed by immunohistochemistry. • PI significantly correlated with the Ki-67 value, indicating that PI reflects the grade of proliferative activity in tumors. • Analyses of contrast-effect intensity will be applied to evaluate grades of malignancy and determine treatment strategies. Citation Format: Noriko Yoshimura, Norio Masumoto, Ai Amioka, Keiko Kajitani, Hideo Shigematsu, Akiko Emi, Takayuki Kadoya, Tsuyoshi Kataoka, Rumi Haruta, Morihito Okada. Impact of perflubutane-enhanced ultrasonography for evaluating malignancy grade of breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-02-04.

Abstract P2-03-08: Usefulness of sonazoid-enhanced ultrasonography in the evaluation of the biological features of breast cancer

Background: Contrast-enhanced ultrasonography using Sonazoid (CEUS) has gained interest because of its ability to evaluate the vascularity of malignant tumors. This study aimed to investigate the relationship between biological marker expression and time-intensity curve values for signal intensity caused by the contrast effects of Sonazoid used during CEUS for breast cancer. Methods: We evaluated 32 patients with breast cancer (mean age, 45.4 years) using Sonazoid-enhanced ultrasonography between September 2012 and May 2013. Of these, 23 were diagnosed with invasive ductal carcinoma (IDC) and 9 were diagnosed with ductal carcinoma in situ (DCIS). Breast carcinoma was evaluated in terms of nuclear grade (NG), Ki-67 labeling index, and estrogen receptor (ER). Luminal types were categorized using the Ki-67 labeling index as follows: luminal A, ER-positive and Ki-67 30%. The HI VISION ASCENDUS (Hitachi Aloka Medical Corp.) was used for ultrasonography in this study. Tumors were observed 50 s after injection of 0.01 ml/kg of Sonazoid. Time–intensity curves for tumor signal intensity were drawn. The brightness in the tumor was digitized and the curves were created on the basis of changes in brightness over time. To indicate the intensity of brightness of breast cancer lesions on Sonazoid-enhanced ultrasonography, the increase rate of brightness (IRB) was calculated using the following formula: IRB = Maximum intensity x 1/Intensity before contrast. Results IRB was 1.6 ± 0.3 and 3.3 ± 2.2 in patients with DCIS and IDC, respectively, indicating a more significant increase in IDC patients ( P < 0.05). View this table: Relation of tumour characteristics and brightness intensity On classification of patients with IDC according to NG, Ki-67, and ER, it was found that IRB values were 2.6 ± 1.0 in patients with NG 1 and 2 tumors and 3.9 ± 2.9 in those with NG 3 tumors, 2.4 ± 0.7 in patients with Ki-67 < 30% and 4.7 ± 2.9 in those with Ki-67 ≥ 30%, and 9.1 in ER-negative patients and 3.3 ± 2.2 in ER-positive patients (table 1). Furthermore, comparison according to luminal subtype revealed that IRB values were 2.4 ± 0.8 and 4.2 ± 2.7 in luminal A and luminal B cases, respectively, indicating a significant difference ( P < 0.05) (table 1). Conclusions: The intensity of ultrasound brightness of breast cancer leasions, when digitized and analyzed, can be applied for the differential diagnosis of DCIS and IDC. Furthermore, brightness intensity may also exhibit correlations with NG, Ki-67 index, and luminal subtypes, suggesting that it can be applied in grading of malignancies. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-03-08.

Abstract P2-03-07: Prediction of the pathological response to neoadjuvant chemotherapy in patients with breast cancer using sonazoid-enhanced ultrasonography

Background: Altered blood flow in malignant tumors is evidenced by contrast-enhanced ultrasonography (CEUS) because of its image perfusion capabilities. This study aimed to investigate the value of CEUS in the evaluation of the response of breast cancer lesions to neoadjuvant chemotherapy (NAC). We evaluated whether the prediction of a pathological complete response (pCR) using CEUS was more precise than that using other standard evaluation methods such as magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT). Methods: Ten patients (mean age, 50.2 years) who underwent NAC for invasive breast cancer between September 2012 and April 2013 were eligible for this cohort study. Clinical tumor response was evaluated using contrast-enhanced MRI, PET/CT, and CEUS following NAC. A pCR was defined as the absence of invasive cancer in the breast and lymph nodes according to the Japanese Breast Cancer Society criteria. A clinically complete response (cCR) was defined as the absence of residual disease on MRI and PET/CT. The HI VISION ASCENDUS (Hitachi Aloka Medical Corp.) was used for ultrasonography. Tumors were observed 50 s after Sonazoid injection at a dose of 0.01 ml/kg. A time–intensity curve of tumor signal intensity was drawn. The brightness of the tumor was digitized and the curve was created on the basis of brightness changes over time. The intensity of brightness of the breast cancer lesions was calculated as the increased rate of brightness (IRB) using the following formula: maximal intensity/intensity before contrast. Results: Four (40%) of the 10 patients were diagnosed with pCR by NAC. Among 4 (40%) patients diagnosed with cCR by MRI, 1 (25%) achieved pCR. All patients were diagnosed with pCR by PET/CT. The IRB values of the 10 patients who received CEUS before surgery were 1.0, 1.1, 1.2, 1.2, 1.3, 1.6, 1.8, 1.9, 2.5, and 4.2. The IRB values of the 4 patients diagnosed with pCR were 1.0, 1.1, 1.2, and 1.2. IRB values were significantly lower in patients who achieved pCR than in those who did not (pCR vs. no pCR, 1.1 ± 0.9 vs. 2.2 ± 1.0, P < 0.05). Furthermore, among the patients who achieved pCR, the IRB values of 2 patients with no residual ductal carcinoma in situ (DCIS) were 1.0 and 1.1, whereas those of 2 patients with residual DCIS were both 1.2. In the 4 patients who achieved cCR as diagnosed by MRI and PET/CT, 3 with pathological residual disease had detectable IRB by CEUS. View this table: table 1 Conclusions: The prediction of pCR after NAC in patients with breast cancer is more precise with Sonazoid-enhanced ultrasonography than with standard methods such as MRI and PET/CT. Furthermore, CEUS may be useful for predicting residual DCIS on the basis of brightness intensity. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-03-07.