Rumi Haruta

Estrogen receptors in gastric adenocarcinoma: A retrospective immunohistochemical analysis

Estrogen receptors (ER) in human gastric carcinomas were examined immunohistochemically using a specific monoclonal antibody to human ER. ER-immunoreactivity (ER-IR) was positive in 30 (27.8%) of the 108 gastric carcinomas examined. ER-IR was located in the nucleus of cancer cells. The incidence of ER-IR positive gastric carcinoma was not significantly different between male and female cases. However, the positive tumour cells were observed in 28 (39.4%) out of the 71 poorly differentiated adenocarcinoma, the incidence being significantly higher than that in well differentiated adenocarcinoma (p<0.01). There was no significant difference in the incidence of ER-IR between scirrhous carcinoma and non-scirrhous poorly differentiated adenocarcinoma. Synchronous expression of ER and epidermal growth factor receptor was found in 8 of the 26 scirrhous carcinomas (30.8%). Patients with ER-IR positive scirrhous gastric carcinomas showed a much worse prognosis than those with ER-IR negative scirrhous carcinomas.

Relation between Estrogen Receptor and Malignancy of Thyroid Cancer

The relationship between the histological grade of dedifferentiation of thyroid cancer and estrogen receptors (ER) was examined immunohistochemically. Thyroid cancers were from postmenopausal females of almost the same mean age (69‐73 years old) and within the same period of time (1974–1983). ER immunoreactivity located in the nucleus of the epithelium was found in all 6 well differentiated papillary cancers, and 5 of them (83.3%) showed ER‐immunoreactive (ER‐IR) cells amounting to 20 or more per visual field (x 100) under a light microscope. Of the 6 cases of poorly differentiated papillary cancer, 5 (83.3%) had 1‐19 ER‐IR cells per visual field. ER‐IR cells were negative in 5 out of 6 cases (83.3%) of anaplastic cancers. Thus, the number of ER‐IR cells tended to decrease with the degree of atypism of thyroid cancer (P < 0.001).

Abstract P4-02-06: Evaluation of contrast-enhanced ultrasonography for early prediction of response to neoadjuvant chemotherapy in triple negative breast cancer

Objectives We aimed to determine whether contrast-enhanced ultrasonography (CEUS) can predict the early effects of neoadjuvant chemotherapy on triple negative breast cancer. Methods The clinical responses of 20 consecutive patients with breast cancer (T1–2, N0–1, M0) to neoadjuvant chemotherapy between October 2012 and Feb 2016 were assessed using ultrasonography and contrast-enhanced ultrasonography before starting the therapy and after the treatment of 2 courses. Ascending slope (AS) of 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.We investigated whether rate of change of ascending slope (ΔAS) and tumor size (Δ US) could predict pCR. Results Eight (40.0%) of the 20 patients achieved pathological complete response. ΔAS were significantly higher (-25.5 ± 35.5 vs. 14.7 ± 33.2; P p = 0.02) and multivariate (odds ratio, 2.88; p = 0.03) analysis showed that ΔAS was the sole independent predictor of pCR. Conclusion ΔAS assessed with CEUS can help the physician to early predict the probability of achieving pCR or not. Citation Format: Masumoto N, Kadoya T, Murakami C, Gouda N, Sasada S, Emi A, Haruta R, Kataoka T, Okada M. Evaluation of contrast-enhanced ultrasonography for early prediction of response to neoadjuvant chemotherapy in triple negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-02-06.

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 P1-02-11: 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 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for predicting the underestimation of invasive breast cancer in cases of ductal carcinoma in situ (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 maximum standardized uptake value (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 (ROC) curve analysis showed the cutoff value of 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 SUV max ≤ 1.6 (p Conclusion: SUVmax on FDG-PET/CT is useful for predicting the underestimation of invasive breast cancer in cases of DCIS at needle biopsy. Citation Format: Hideo Shigematsu, Takayuki Kadoya, Noriko Yoshimura, Keiko Kajitani, Akiko Emi, Noriko Masumoto, Rumi Haruta, Tsuyoshi Kataoka, Morihito Okada. Role of FDG-PET/CT in prediction of underestimation of invasive breast cancer in cases of ductal carcinoma in situ diagnosed at needle biopsy [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 P1-02-11.

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.

Early Breast Cancer Following Treatment of Myelodysplastic Syndrome: Report of a Case

A 45-year-old woman was admitted to our hospital complaining of a mass in her left breast. She had previously been diagnosed with myelodysplastic syndrome (MDS), a type of refractory anemia, based on bone marrow findings and chromosome analysis. She received a preoperative transfusion of fresh packed platelets and a recombinant human granulocyte colony-stimulating factor (rhG-CSF) injection. Left partial mastectomy and axillary lymph nodes dissection were performed to treat early breast cancer. Postoperatively, prophylactic radiotherapy of the residual breast and administration of medroxyprogesterone acetate (MPA) were performed because the tumor tissue was positive for progesterone receptors. She has remained clinically stable, with no evidence of recurrence, for more than three years to date. We report a rare case of breast cancer with MDS, treated with breast-conserving therapy. The strategy of pre- or postoperative platelet transfusion, rhG-CSF injections, and hormonal therapy (AAPA) appears to be suitable treatment for progesterone receptor (PgR)-positive breast cancer patients with AADS.