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 contrastenhanced 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.
The objective of the study was to investigate abnormalities of regional cerebral blood flow (rCBF) in young (age 33.076.3 years; range 21-45 years) non-diabetic and normolipidemic Asian Indians with hypertension. The rCBF was assessed with single-photon emission computed tomography (SPECT) in patients with hypertension (n ¼ 33) and healthy controls (n ¼ 20). The SPECT findings were normal in 41 subjects and showed abnormalities of cerebral perfusion in 10 subjects, all of which were hypertensive patients. These observations are extremely important for a vast number of young hypertensive patients in India. To prevent cerebrovascular accidents in future, patients with hypertension and decreased rCBF should be carefully monitored and their hypertension should be strictly controlled. These subjects may also be researched as potential candidates for preventive antiplatelet therapy.
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 < 0.02) in patients who achieved pCR than in those who did not. On the other hand, ΔUS of pCR and non-pCR did not significantly differ among tumors (-40.8 ± 22.4 vs. -21.4 ± 20.6; P = 0.06). The AUC values for ΔAS and ΔUS were 0.792 (95% CI, 0.579 -1.000, P = 0.03) and 0.729 (95% CI, 0.501 - 0.957;p = 0.09), respectively. We set ΔAS and Δ US cut-offs for predicting pCR at-20.08 and - 33.75 based on the ROC curves. Clinical and pathological characteristics of the 20 patients are summarized in Univariate (odds ratio, 2.71; p= 0.02) and multivariate (odds ratio, 2.88; p= 0.03) analysis showed that ΔAS was the sole independent predictor of pCR. Clinical and pathological characteristics of patients with breast cancer.CharacteristicpCR (n)Non pCR (n)pClinical T status T1110.71T2711 Clinical N status Negative570.85Positive35 Nuclear Grade 1 or 2340.85358 ΔUS (%) < -33.75390.09≥ -33.7553 ΔAS (%) < -20.082100.009≥ -20.0862 Univariate and multivariate logistic analysis of significant predictive factors for pCR in triple negative subtype Univariate analysisMultivariate analysis OR, 95% CI, pOR, 95% CI, pΔUS > -33.751.61, 0.72-34.7, 0.101.85, 0.51-79.1, 0.15≤-33.75 ΔAS > -20.082.71, 1.65-136.1, 0.022.88, 1.44-218.7, 0.03≤ -20.08 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.
Background: Wnt5a is a representative ligand that activates the β-catenin-independent pathways. The purpose of our study is to elucidate the implication of Wnt5a expression in breast cancer. Materials and methods: One hundred seventy eight breast cancer patients (mean age ± SD: 59.6 ± 13.2 years) with clinical Stage I∼III between January 2011 and February 2014, were prospectively evaluated. Patients who underwent operation without neoadjuvant therapy were enrolled to this study. The immunohistochemical analyses of Wnt5a protein was performed to evaluate relationships between Wnt5a expression and clinicopathological factors. MCF7 cells that stably express Wnt5a were generated and used for cDNA microarray analyses to investigate Wnt5a-dependent gene expression. Results: Wnt5a expression was significantly more frequent when estrogen receptor (ER) was present, 68/153 (44%) than when ER was absent, 1/25 (4%) (p<0.001). Wnt5a expression was also related with progesterone receptor (PgR) (P<0.001), but not with HER2 status (P=0.496). In ER-positive breast cancer, a significant interaction between expression of Wnt5a with lymph node metastasis (P<0.001), nuclear grade (P=0.004), lymphatic invasion (P=0.002), vessel invasion (P=0.050), and pStage (P<0.001). Microarray analyses identified several genes induced by Wnt5a (>3.0 fold), involving activated leukocyte cell adhesion molecule (ALCAM). ALCAM is known to be related with apoptosis, invasion and prognosis of breast cancer. Wnt5a expression levels correlated with those of ALCAM in ER-positive tumor samples from patients by immunohistochemical analyses (P<0.001). Relationship between Wnt5a expression and clinicopathological featureClinicopathological featuretotalWnt5a expressionP value (n=153)Negative (n=85)Positive (n=68) Age (median, range) 63, 35-8657.5, 34-870.065Age, n (%) ≤4528 (18)13 (46)15 (54) >45125 (82)72 (58)53 (42)0.282Menopausal status, n (%) Premenopausal58 (38)27 (47)31 (53) Postmenopausal95 (62)58 (61)37 (39)0.080Tumor size, n (%) pT1 ≤20mm104 (44)63 (61)41 (39) pT2/pT3 >20mm49 (56)22 (45)27 (55)0.069lymph node metastasis, n (%) Negative103 (67)72 (70)31 (30) Positive50 (33)13 (26)37 (74)<0.001Nuclear grade, n (%) 1/285 (56)56 (66)29 (34) 368 (44)29 (43)39 (57)0.004Lymphatic invasion, n (%) Negative101 (66)65 (64)36 (36) Positive52 (34)20 (38)32 (62)0.002Vessel invasion, n (%) Negative142 (93)82 (58)60 (42) Positive11 (7)3 (27)8 (73)0.050Ki-67, n (%) 0-2067 (44)43 (64)24 (36) 21-10086 (56)42 (49)44 (51)0.058pStage, n (%) pStage I80 (52)58 (73)22 (28) pStage II64 (42)27 (42)37 (58) pStage III9 (6)0 (0)9 (100)<0.001ALCAM, n (%) Negative85 (56)64 (75)21 (25) Positive68 (44)21 (31)47 (69)<0.001 Conclusions: Wnt5a express in ER-positive breast cancer and are associated with high-grade malignancy. Wnt5a could be a prognostic factor of ER-positive breast cancer. These results have implications that Wnt5a may become a preoperative and postoperative assessment tool for tumor malignancy grade and a potential therapeutic target except endocrine therapy in ER-positive breast cancer. In future studies, further research on Wnt5a are required to develop a novel treatment for more improved outcomes in a great variety of breast cancer. Citation Format: Kobayashi Y, Kadoya T, Gouda N, Kajitani K, Emi A, Shigematsu H, Masumoto N, Okada M. Wnt5a expression is associated with high-grade malignancy in ER-positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-17.
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