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Background Spontaneous regression (SR) is a rare phenomenon in which a cancer disappears or remits without treatment. We report a case of breast cancer that showed spontaneous tumor regression in the surgical specimen after core needle biopsy. Case presentation A 59-year-old woman came to our hospital complaining of a painful lump in the right breast. In the upper-outer quadrant of the right breast, a tumor with an unclear boundary, 30 mm in diameter, was palpable. In pathological findings from needle biopsy, the tumor was diagnosed as solid-type invasive ductal breast carcinoma. Partial coagulation necrosis was generated in estrogen receptor-negative, HER2-negative, and AE1/AE3-positive ductal carcinoma without infiltration of lymphocytes. Surgery for right breast cancer was then performed. Histological examination of the surgical specimen revealed the tumor was invasive ductal carcinoma with lymphocyte infiltration, coagulation necrosis, and fibrous tissue with hemosiderin. The tumor formed a solid nest, 3 mm in diameter, suggesting the possibility of SR. Conclusions Immune responses, infection, hormones, surgical stress, and ischemia have been reported as mechanisms of SR. The findings in this case strongly suggest that SR of breast cancer is associated with anti-tumor immune responses.

Background: Oncocytic carcinoma of the breast is extremely rare, and its molecular profile is poorly understood. The distinctive feature of oncocytic carcinoma of the breast is that the granular eosinophilic cytoplasm contains numerous mitochondria. Recently, microRNA-146a-5p has been identified as a contributor to carcinogenesis and as a mitochondria-related microRNA, which regulates the mitochondrial function affecting Bcl-2. Bcl-2 plays a role in mitochondrial apoptosis.Case presentation: We report the clinical features, histopathological features, and immunohistochemical and molecular findings of oncocytic carcinoma of the breast in a 76-year-old woman. Immunohistochemistry studies revealed that the tumor cells were positive for antimitochondrial antibody but negative for gross cystic disease fluid protein 15, which confirmed the diagnosis. For molecular profiling, expression of microRNA-146a-5p and Bcl-2 messenger RNA (mRNA), which are mitochondria-related small molecules, were evaluated using real-time reverse transcription polymerase chain reaction. We found that the expression of microRNA-146a-5p was significantly lower (p < 0.01) and that of Bcl-2 mRNA was significantly higher (p < 0.01) compared to the control group (with no specific type of breast cancer). Conclusions: The significant changes in the expression of microRNA-146a-5p and Bcl-2 are specific to oncocytic carcinoma of the breast. Therefore, we suggest that the use of microRNA-146a-5p to target Bcl-2 has a potential therapeutic effect on oncocytic carcinoma of the breast.

Postmastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) and breast cancer mortality for node-positive breast cancer, but its indication remains controversial in patients with 1–3 positive lymph nodes. We retrospectively analyzed LRR and survival rates in T1–2 breast cancer with 1–3 positive lymph nodes according to PMRT. The prognostic factors and the impact of the current standard systemic therapy (early period: 2000–2007 and late period: 2008–2015) were assessed because adjuvant trastuzumab has only been approved in 2008 in Japan. Between 2000 and 2015, 162 patients with T1–2N1 breast cancer underwent mastectomy, and 32 (19.8%) underwent PMRT. The 5-year LRR rates were 5.3% in the no PMRT group and 0% in the PMRT group (P = 0.272). Meanwhile, the disease-free survival rates were 80.6% in the no PMRT group and 96.6% in the PMRT group (P = 0.095), and the benefit of PMRT was low in the late period. The significant prognostic factors were larger tumor size (T2) and estrogen receptor negativity. PMRT tended to improve LRR and disease-free survival. The omission of PMRT is carefully determined.

18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) is related to the biological parameters and prognosis of breast cancer. However, whether whole-body PET (WBPET) and dedicated breast PET (DbPET) can reflect the tumor microenvironment is unclear. This study investigated the relationship between stromal tumor-infiltrating lymphocytes (TILs) and maximum standardized uptake value (SUVmax) in WBPET and DbPET. A total of 125 invasive breast cancers underwent WBPET and ring-type DbPET and resected specimens were pathologically assessed. The impact of SUVmax on the tumor biological parameters and TILs was retrospectively evaluated. SUVmax was classified as high and low relative to the median values (WBPET-SUVmax: 2.2 and DbPET-SUVmax: 6.0). SUVmax correlated with tumor size, nuclear grade, Ki-67 labeling index, and TILs in both WBPET and DbPET (all p

The aim of this study was to assess whether the retention index (RI) determined using dual-phase 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) reflects the malignant features of breast cancer. A total of 1,523 patients with breast cancer were retrospectively evaluated. PET/CT scans were performed at 1 h and 2 h after FDG administration before treatment. The maximum standardized uptake value (SUVmax) at both time points (SUVmax1 and SUVmax2) in the primary tumour and RI were calculated. Primary tumour tissues were evaluated in terms of biological features, such as histology, nuclear grade, lymphovascular invasion and molecular subtype. Of the 1,523 patients, 463 (30.4%) had luminal A-like, 661 (43.4%) had luminal B-like, 229 (15.0%) had human epidermal growth factor receptor 2-positive (HER2-positive), and 157 (10.3%) triple-negative breast cancer. The median SUVmax1, SUVmax2 and RI values were 2.2, 2.3 and 2.6%, respectively. These metabolic parameters were correlated with tumour size, nodal metastasis, histology, nuclear grade, lymphovascular invasion, and molecular subtype (all P

Background Breast cancer can be assessed preoperatively and postoperatively using 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). We prospectively analyzed the maximum baseline standardized uptake value (SUVmax) derived from FDG PET/CT to predict the outcomes after neoadjuvant chemotherapy (NAC) for breast cancer. Patients and Methods We assessed 130 consecutive female patients with primary breast cancer (mean age, 53.9 years) using PET/CT before and after NAC. The SUVmax before (pre-SUVmax) and after (post-SUVmax) NAC and the SUVmax reduction rates (ΔSUVmax) after NAC with sequential anthracyclines and a taxane were assessed to predict the pathologic complete response (pCR) and prognosis. Results Of the 130 patients, 30 (23.1%) achieved a pCR. The pCR rate of the patients with human epidermal growth factor receptor 2-positive (HER2 + ) and triple-negative (TN) breast cancer was 52.8% and 40.0%, respectively. In contrast, only 1.4% of those with estrogen receptor-positive and HER2 − cancer achieved a pCR. The post-SUVmax correlated closely with the pCR (area under the curve, 0.700) but not with the pre-SUVmax and ΔSUVmax (area under the curve, 0.414 and 0.589, respectively) in patients with HER2 + and TN breast cancer. The post-SUVmax was associated with the pCR ( P = .019), and multivariate analysis selected post-SUVmax as a significant prognostic factor ( P = .014). The post-SUVmax correlated significantly with recurrence-free survival and recurrence ( P = .026, log-rank test). Conclusion The SUVmax determined after NAC using FDG PET/CT can predict for the pCR and the prognosis of patients with operable HER2 + and TN breast cancer. In the future, additional chemotherapy will be applied according to the post-SUVmax after standard NAC to achieve a pCR or omit surgery.

OBJECTIVE. The aim of this study was to assess the diagnostic performance of dual-phase 18F-FDG PET/CT in detecting axillary lymph node metastasis in patients with breast cancer. MATERIALS AND METHODS. A total of 826 patients with breast cancer were retrospectively evaluated. PET/CT scans were performed 1 hour and 2 hours after FDG administration before treatment. The maximum standardized uptake value (SUVmax) in the axillary lymph node at both time points (hereafter referred to as SUVmax1 and SUVmax2, respectively) and the retention index (RI) were calculated. RESULTS. Axillary lymph node metastasis was detected in 285 of 826 patients (34.5%). The median axillary SUVmax1, SUVmax2, and RI in patients with nodal metastasis were higher than those in patients without metastasis (1.5 vs 0.6, 1.6 vs 0.5, and 7.7 vs -3.7, respectively; all p < 0.001). The diagnostic accuracy of axillary SUVmax1 and SUVmax2 was equivalent, and the sensitivity and specificity of SUVmax1 were 74.7% and 83.4%, respectively. Although the performance of the axillary RI was inferior to that of SUVmax1 and SUVmax2, both the SUVmax and the RI were independent predictors of nodal metastasis, and a positive RI suggested axillary lymph node involvement when the SUVmax1 was significantly high. Of 533 patients with category T1-2 breast cancer without lymph node swelling, 101 (19.0%) had pathologic lymph node involvement; the negative predictive value of axillary SUVmax1 was 86.8%. CONCLUSION. Delayed phase imaging identified axillary lymph node metastasis as accurately as standard PET/CT. A high negative predictive value of PET/CT for the detection of nodal metastasis is helpful to avoid surgical axillary assessment in patients with category T1-2 breast cancer without lymph node swelling.

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%) (p3.0 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 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) 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.

Background Prevention of letrozole–induced bone loss using oral risedronate has not been proved in the Japanese women. The aim of this study was to assess the effect of risedronate 17.5mg/week on bone mineral density (BMD) in postmenopausal, early breast cancer patients scheduled to receive adjuvant letrozole. Patients and Methods Postmenopausal women with hormone receptor–positive early breast cancer were assigned to one of two strata according to their baseline BMD T-score as being at low and high risk of osteoporosis. Patients with low risk (-2.5 ≤ T score) were randomly assigned to letrozole and risedronate (L+R) or to letrozole alone (L). Patients with high risk (-2.5 > T score) received letrozole and risedronate (L+R). Letrozole was given at a dosage of 2.5 mg/day while oral risedronate was given at 17.5mg/week. The primary end point was the change in lumbar spine (LS) BMD at 12 months. The secondary end points included change in total hip (HP) BMD and bone turnover markers. Results In the low risk group (N=103), treatment with L+R resulted in a significant increase in BMD at LS and at HP compared to treatment with L only at 12 months (1.8% vs -2.2%, P < 0.001, and -0.3% vs -2.9%, P = 0.001, respectively). In the L+R group, significant decreases in bone turnover makers, NTX and PINP, were recognized compared with L only at 12months (-11.1% vs. 27.5%, P Estimated Percentage Change From Baseline to 6 and 12 Months in Lumbar Spine and Total Hip BMD From Baseline to 6 MonthsFrom Baseline to 12 MonthsBMD areaRisk GroupTreatmentChange in BMD (%), 95% CIPChange in BMD (%), 95% CIPLumbar spineLow riskL+R1.7 (-1.3 to 4.7) Four patients (14.3%) improved from osteoporotic region to the osteopenic region with L+R treatment. Letrozole and risedronate were well tolerable and there was no serious adeverse event including osteonecrosis of jaw. Conclusions At 12 months, 17.5mg/week risedronate therapy prevented bone loss in postmenopausal women with breast cancer who were receiving adjuvant letrozole, of which results were compatible with previous findings of western populations. Citation Format: Kadoya T, Masumoto N, Shigematsu H, Emi A, Kajitani K, Kobayashi Y, Funakoshi M, Kawabuchi Y, Ohara M, Matsuura K, Noma M, Sasada T, Okada M. Prevention of letrozole–induced bone loss using risedronate in postmenopausal women with hormone receptor positive breast cancer: A multicenter randomized clinical trial. [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 P1-15-03.

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.

Distant metastases from breast cancer are frequently found in bones, lungs and the liver. Metastasis to the stomach is rare, and its clinical presentation remains unclear. The present report describes a case of isolated gastric metastasis from breast cancer identified by contrast-enhanced computed tomography (CT). A 45-year-old female patient underwent right mastectomy and axillary lymph node dissection after preoperative chemotherapy for right invasive lobular breast carcinoma T4bN2M0, stage IIIB. Postoperative radiotherapy and endocrine therapy with tamoxifen for 5 years were performed. CT for postoperative follow-up at 52 years old revealed thickening of the stomach wall. Although the patient was asymptomatic, erosive mucosa was observed on the gastric body during gastroscopy. The gastric lesion was immunohistochemically diagnosed as metastatic luminal disease from the breast cancer. Positron emission tomography/CT revealed no abnormal accumulation suggesting metastasis to other organs. Palbociclib and fulvestrant treatment were initiated for gastric metastasis. Invasive lobular breast carcinoma results in gastrointestinal metastasis, including the stomach, more frequently than invasive ductal breast carcinoma. However, most gastric metastases occur simultaneously with systemic metastases. Solitary metastasis to the stomach without symptoms as in this case has rarely been reported. The possibility of gastric metastasis should be considered among the differential diagnoses, even in the absence of symptoms, when gastrointestinal abnormalities are seen on CT in patients with a history of breast cancer.

Healthcare economics concerns with the way in which to distribute and allocate scarce resources that result in maximized outcome. When the expenditure on cancer medicine was examined using the macro data open to the public, it was found to have increased in parallel with the National Medical Care Expenditure. More specifically, the growth rates of the two showed a similar trend in the five years from 2011 to 2015. However, when looked more closely by excluding the patient share and separating the care settings, the result was different. The expenditure in outpatient care displayed a significant increase, implying the influence of chemotherapy shifting to take place more in the outpatient setting. Current discussion on introducing the concept of cost effectiveness into the fee schedule scheme should be based on multidimensional consideration.

Background It has been reported that tri-weekly Abraxane therapy has better outcomes in recurrent breast cancer than tri-weekly Cremophor-based taxol therapy, and that cyclophosphamide combined with taxane shows an enhanced antitumor effect. We conducted a phase II clinical trial of preoperative chemotherapy with a combination of TRI-ABC. Patients and Methods From September 2011 to September 2013, 4 cycles of preoperative chemotherapy with TRI-ABC followed by 4 cycles of FEC were administered in patients with resectable breast cancer. In patients with HER2-positive breast cancer, tri-weekly Trastuzumab was administered with TRI-ABC. The primary end point was the pathological complete response (pCR) rate in the breasts and lymph nodes. Results The treatment outcomes and safety were evaluated in 54 patients who received at least 1 dose of chemotherapy. All patients underwent radical surgery, and the overall pCR rate of 37% (20 of 54) was achieved. The pCR rates according to each subtype were 8% (2 of 24) in hormone receptor (HR)-positive HER2-negative breast cancer, 56% (5 of 9) in HR-positive HER2-positive breast cancer, 63% (5 of 8) in HR-negative HER2-positive breast cancer, and 62% (8 of 13) in triple-negative breast cancer. Multivariate analysis revealed that HR negativity and HER2 positivity were predictive factors of pCR. Clinical response was observed in 49 patients (91%). The safety profile was acceptable. Conclusion Preoperative chemotherapy with TRI-ABC followed by FEC showed high efficacy and excellent safety. Further clinical studies should be conducted to compare the efficacy of TRI-ABC followed by FEC with conventional taxane–anthracycline regimens.

Purpose Diagnostic methods to evaluate the response to neoadjuvant chemotherapy (NAC) for breast cancer have not been established. Dedicated breast PET (DbPET) is a high-resolution molecular breast imaging method, and we investigated the capability of DbPET to predict residual primary tumors after NAC compared with whole-body PET (WBPET). Methods Forty-five patients (47 tumors) underwent WBPET and ring-type DbPET after NAC, and the tumors were completely resected between January 2016 and March 2017. The pathological response was classified as complete remission (ypT0), residual intraductal disease (ypTis), or residual invasive disease (ypT ≥ 1). Standardized uptake value (SUV) and tumor-to-normal tissue ratio (TNR) were assessed. Results Twelve patients achieved ypT0 and five developed ypTis. DbPET detected all cases of ypTis, and WBPET detected only one case of ypTis. The sensitivity, specificity, and accuracy of WBPET for ypTis and/or ypT ≥ 1 were 54.3%, 83.3%, and 61.7%, respectively, and those of DbPET were 77.1%, 83.3%, and 78.7%, respectively. In the ypT0/ypTis/ypT ≥ 1 groups, the median WBPET-SUV, DbPET-SUV, and DbPET-TNR was 1.0/0.9/1.1, 1.7/1.8/2.2, and 1.0/1.6/1.7 (P = .134, .077, and 0.008), respectively. Areas under the curves of WBPET-SUV, DbPET-SUV, and DbPET-TNR for predicting ypTis and/or ypT ≥ 1 were 0.610, 0.648, and 0.807, respectively. Conclusions DbPET was more accurate than WBPET in detecting residual primary tumors after NAC, particularly intraductal carcinoma. TNR was the better parameter for pathological evaluation compared with SUV.

Breast cancer can be assessed preoperatively and postoperatively usingWe assessed 130 consecutive female patients with primary breast cancer (mean age, 53.9 years) using PET/CT before and after NAC. The SUVmax before (pre-SUVmax) and after (post-SUVmax) NAC and the SUVmax reduction rates (ΔSUVmax) after NAC with sequential anthracyclines and a taxane were assessed to predict the pathologic complete response (pCR) and prognosis.Of the 130 patients, 30 (23.1%) achieved a pCR. The pCR rate of the patients with human epidermal growth factor receptor 2-positive (HER2The SUVmax determined after NAC using FDG PET/CT can predict for the pCR and the prognosis of patients with operable HER2

Background: Neoadjuvant chemotherapy (NAC) is a standard treatment for operable breast cancer. However, imaging methods for evaluating treatment response have not been established. Previous studies reported that ring-type dedicated breast positron emission tomography (DbPET) detected residual tumors following NAC more accurately than whole-body PET/CT. This study assessed DbPET parameters for predicting pathological complete response (pCR) in patients with breast cancer. Patients and Methods: Among patients with breast cancer who underwent surgery after NAC, 61 were examined using ring-type DbPET before and after NAC. The maximum standardized uptake values (SUVmax) and tumor-to-normal-tissue ratio (TNR) were calculated before and after NAC (pre-SUVmax, pre-TNR, post-SUVmax and post-TNR, respectively). Moreover, the reduction rates (ΔSUVmax and ΔTNR) were determined. pCR was defined as complete remission of breast cancer. Results: The median patient age was 52 years. Forty patients (65.6%) were estrogen receptor (ER)-positive, whereas 25 patients (41.0%) were HER2-positive. Fifteen patients (24.6%) achieved pCR after NAC. The calculated values for the parameters of DbPET are summarized in Table 1. The most promising parameters for predicting pCR were ΔSUVmax (area under the curve [AUC]: 0.506) and post-TNR (AUC: 0.640). Although neither of these two parameters reflected the pathological response to NAC in patients with ER-positive disease, post-TNR showed the highest AUC (i.e., AUC: 0.750) for pCR in patients with ER-negative disease. The sensitivity and specificity of post-TNR in the ER-positive group were 85.7% and 39.4%, respectively. In the ER-negative group, these values were 100% and 58.3%, respectively [Table 2] Table 1.Diagnostic performance of dedicated breast positron-emission tomography for the prediction of pathological complete response after neoadjuvant chemotherapyParameterspCR Median (IQR)Non-pCR Median (IQR)PAUC (95% CI)Pre-SUVmax14.8 (9.2–17.7)14.4 (10.7–19.8)0.6040.454 (0.285–0.624)Post-SUVmax1.8(1.5–2.1)2.0 (1.6–3.4)0.2370.603 (0.460–0.746)ΔSUVmax (%)87.32 (81.5–91.8)88.6(82.8–91.8)0.9540.506 (0.329–0.682)Pre-TNR8.0 (5.3–9.2)7.3(5.9–10.2)0.7570.472 (0.297–0.647)Post-TNR1.7(1.0–1.1)1.2 (1.0–2.4)0.0980.640 (0.506–0.774)ΔTNR (%)87.3 (78.3–89.1)79.8 (62.7–86.7)0.1130.638 (0.472–0.803)pCR, pathological complete response; IQR, interquartile range; AUC, area under the curve; CI, confidence interval, SUV, standardized uptake value; TNR, tumor-to-normal-tissue ratio.Table 2.Diagnostic accuracy of post-TNR according to estrogen receptor status Sensitivity (%)Specificity (%)Accuracy (%)PPV (%)NPV (%)ER-positive85.739.447.523.192.9ER-negative10058.375.061.5100TNR, tumor-to-normal-tissue ratio; ER, estrogen receptor; PPV, positive predictive value; NPV, negative predictive value Conclusion: In DbPET, ΔSUVmax and post-TNR were shown to be promising parameters for predicting pathological response to NAC. Post-TNR provided the highest sensitivity for predicting pCR in patients with ER-negative breast cancer. Citation Format: Suzuki E, Sasada S, Sueoka S, Masumoto N, Goda N, Kajitani K, Emi A, Haruta R, Kadoya T, Kataoka T, Okada M. Diagnostic performance of dedicated breast PET for the prediction of pathological response after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-02-09.

Background: Microwave breast imaging, which using the difference in the dielectric properties between breast cancer and normal breast tissue, is a painless and non-radiation method. We have created a novel hand-held prototype of breast cancer detector using impulse-radar based imaging system, and conducted a pilot clinical study. Methods: The detector consists of complementary metal-oxide-semiconductor (CMOS) integrated circuits covering the ultrawideband width from 3.1 to 10.6 GHz, which enable the generation and transmission of Gaussian monocycle pulse (GMP) trains and single port eight throw switching matrices (SP8T-SW) for controlling a 4×4 cross-shaped dome antenna array. The size of the detector was 19.1 × 17.7 × 18.8 cm. After evaluation using a breast tumor phantom and the resected breast specimens obtained through mastectomy, we recruited 5 patients with histologically confirmed breast cancers in the clinical study. The detector was placed on the breast with the patient in a supine position. The primary endpoint was a detection rate of breast cancers, and the secondary endpoints were positional accuracy and adverse event. This study was registered with the UMIN Clinical Trials Registry (UMIN000026181). Results: The three-dimensional positions of the tumors in the imaging results using a phantom and resected specimens are consistent with the results of histopathology analysis. In the clinical study, all 5 targeted breast cancers were detected and were visualized at the sites confirmed by other diagnostic modalities. Among 5 tumors, one was not detected via mammography because of heterogeneously dense breast and another was a microinvasive carcinoma of invasive tumor size 0.5 mm. No study-related adverse events occurred. Conclusions: We succeeded in creating a new device of hand-held impulse-radar detector for breast cancer. The detector has sufficient detective capability, is safe for clinical use, and might detect an early stage breast cancer. In the future, we will proceed with the development to clinical application. Citation Format: Sasada S, Masumoto N, Song H, Goda N, Kajitani K, Emi A, Kadoya T, Arihiro K, Kikkawa T, Okada M. Hand-held impulse-radar detector for breast cancer: development and a pilot study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-02-17.

e12550Background: Dedicated breast positron emission tomography (DbPET) provides detailed high resolution images of the breast. We focused on breast cancer present with heterogeneous intratumoral d...

Background: Dedicated breast positron emission tomography (DbPET)provides detailed high resolution images of the breast and enables quantitative assessment using standard uptake values (SUVs). We aimed to determine whether DbPET can predict the pathological malignancy grade and neoplastic progress of breast cancer compared with whole body (WB) PET. Methods: We investigated 196 consecutive patients with invasive breast cancerwho underwent concurrent Db- and WB-PET from January 2016 to March 2017. All Db- and WB-PET were quantified based on SUVs. We also investigated pathological features of breast cancer who had a ring-like uptake (RU) without central FDG accumulation on DbPET. Results: The associations between the SUVs for DB- and WB-PET and the pathological factors in breast cancerCharacteristicSUV WBPETDbPET Mean ± SDpMean ± SDpall3.6 ± 3.4 9.4±7.9 Tumor size ≤2.0 cm2.2±1.62.0 cm5.5±4.1 13.3±9.2 LN Negative3.1±3.3 summarizes the association between SUVs for Db- and WB-PET and pathological factors inbreast cancer.SUVs on PET were significantly higher for the tumor size of >2.0 cm than for tumor size ≤2.0 cm (p The association between SUVs for breast cancer with and without RU on DbPETCharacteristicRU(-), nRU(+), npall17323 Tumor size ≤2.0 cm10952.0 cm6418 LN Negative1299 summarizes the association between SUVs for breast cancer with and without RU on DbPET. SUVs for breast cancer with RU on DbPET were significantly higher for the tumor size of >2.0 cm than for tumor size ≤2.0 cm, for LN -positive than for LN-negative (p Conclusions: SUVs for DbPET were equal or superiorto WBPET in predicting the pathological malignancy grade and neoplastic progress in tumors. Furthermore, the presence of RU on DbPET can provide excellent predictive value for high-grade malignancy and might help to determine appropriate therapeutic strategies. Citation Format: Masumoto N, Kadoya T, Nishina M, Kimura Y, Suzuki E, Sueoka S, Goda N, Sasada S, Kajitani K, Emi A, Haruta R, Kataoka T, Okada M. Evaluation of pathological malignancy grade and neoplastic progress of breast cancer using dedicated breast positron emission tomography [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-02-03.

Background: Whole body (WB) 18F-fluorodeoxyglucose positron emission tomography (PET) has a relatively poor spatial resolution (>1 cm), which limits the capability to detect small lesions. Therefore, small-sized breast cancers (≤1 cm) may not be visible on WBPET. To overcome these limitations, dedicated breast PET (DbPET) has been developed to improve spatial resolution. DbPET enables detailed high-resolution images within the breast. We aimed to determine whether DbPET can detect small-sized breast cancer compared to WBPET. Methods: We investigated 203 consecutive patients (217 tumors) (T1–3, N0–3a, M0) with breast cancer who underwent concurrent DbPET and WBPET between January 2016 and March 2017. All DbPET and WBPET images were semi-quantified based on standard uptake values. The diagnostic performance of each scanner was assessed in DbPET and WBPET. Tumors were classified based on pathological classification as follows: Tis, ductal carcinoma in situ (DCIS); T1a, ≤0.5 cm; T1b, 0.5–1 cm; and T1c, 1–2 cm; T2, 2–5 cm; T3, >5 cm. The sensitivities of DbPET and WBPET were compared in each size group. Results: Table 1 shows the detection rate of breast cancer in WBPET and DbPET The detection rate of breast cancer in WB- and Db-PET DbPETWBPETpTumor sizeDetection (-) n(%)Detection (+) n(%)Detection (-) n(%)Detection (+) n(%) Tis6(14.6)35(85.4)18(43.9)23(56.1)0.0030T1a2(8)23(92)7(28)18(72)0.0594T1b2(6.5)29(93.5)10(32.3)21(67.7)0.0077T1c5(8.2)56(91.8)11(18)50(82)0.1038T20(0)57(100)1(1.8)56(98.2)0.2375T30(0)2(100)0(0)2(100)-total15(6.9)202(93.1)47(21.7)170(78.3) . The overall detection rate in DBPET [93.1% (202/217)] was significantly higher than that of WBPET [78.3% (170/217)] (P < 0.001). For smaller tumors, DbPET was more sensitive than WBPET: Tis (85.4% vs. 56.1%), T1a (92% vs. 72%), T1b (93.5% vs. 67.7%), T1c (91.8% vs. 82%), T2 (100% vs. 98.2%), and T3 (100% vs. 100%). The sensitivity of DbPET was significantly higher than that of WBPET in Tis (P = 0.003) and T1b (P = 0.008) and tended to be higher than that of WBPET in T1a (P = 0.059). Conversely, no significant differences were observed in T1c (P = 0.103) and T2 (P = 0.238). Conclusion: The imaging sensitivity of DbPET was higher than that of WBPET. DbPET showed significant sensitivity in DCIS and tumors ≤1 cm, which is a weak point for WBPET. DbPET may serve as a new diagnostic modality to detect small-sized breast cancer. Citation Format: Sueoka S, Masumoto N, Nishina M, Kimura Y, Suzuki E, Goda N, Sasada S, Kajitani K, Emi A, Haruta R, Kadoya T, Kataoka T, Okada M. Detection ability of dedicated breast positron emission tomography for small-sized breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-03-08.

症例は56歳の男性で, 主訴は右下腹部痛, 嘔吐. 精査したところイレウス管からの造影で回腸末端に閉塞部位を認め, 小腸腫瘍による腸閉塞の診断で, イレウス解除術を施行した. 術中, 虫垂が腫大し回腸に癒着, 内腔を閉塞しており, 虫垂癌の診断で回盲部切除術を施行した. 組織学的には低分化腺癌を合併した虫垂杯細胞カルチノイドの診断であった. 術後の補助化学療法は行わず術後半年が経過している. 杯細胞性カルチノイドはカルチノイド腫瘍の一亜型とされているが, 悪性度が高く予後不良であり腺癌の一種とも考えられている. 我々の集計では杯細胞カルチノイドの本邦報告は71例と少なく, 治療法, 予後に対する一定の見解は定まっていない. さらに, 本症例のように腺癌を合併した例は少なく, 今後, 腫瘍の発生機序, 治療法を確立していく上で興味深いと考え, 若干の文献的考察を加えて報告する.

11614 Background: Wnt5a is a representative ligand that activates β-catenin-independent pathways and involved in cell motility and cell polarity, and the like, being mediated by JNK. We elucidated the implication of Wnt5a expression in breast cancer. Methods: One hundred seventy eight breast cancer patients (mean age ± SD: 60.0 ± 13.2 years) with clinical Stage I-III between January 2011 and February 2014, were prospectively evaluated. We examined relationships between Wnt5a expression and clinicopathological factors by immunohistochemical analyses. 5-year relapse-free survival rates and sites of recurrence were analyzed. In addition, molecules induced by Wnt5a in cultured cells were identified by DNA microarray analysis. 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 3.0 fold), involving activated leukocyte cell adhesion molecule (ALCAM). ALCAM is known to be related with apoptosis, invasion and prognosis of breast cancer. We focused on ALCAM and investigated its protein expression by Western blotting, and found remarkable increase of ALCAM in Wnt5a/MCF7 cells. Conclusions: Wnt5a expresses in ER-positive breast cancer and is associated with high-grade malignancy and a poor prognosis through JNK-ALCAM pathway. Wnt5a could be a novel prognostic factor of ER-positive breast cancer. [Table: see text]

e12097 Background: Unlike whole body (WB) 18F-fluorodeoxyglucose (FDG) PET, dedicated breast PET (DBPET) enables detailed high-resolution images within the breast and quantitative assessment using SUV. We aimed to determine whether DBPET can detect ductal carcinoma in situ (DCIS) and predict the malignancy and neoplastic progress of invasive breast cancer. Methods: We investigated 155 consecutive patients with breast cancer who underwent concurrent DB– and WB– PET (Elmammo®) between January and November 2016. All DB– and WB– PET images were quantified based on standard uptake values (SUV). We also assessed 12 patients with ring-like uptake (RU) without central FDG accumulation in invasive breast cancers on DBPET images. Results: The SUV (means ± SD) determined from DB– and WB– PET images of breast cancer were 8.2 ± 7.7 and 3.1 ± 3.3 respectively. We detected DCIS in DB- and WB– PET images from 22 (84.7%) and 15 (57.6%) of 26 among the 155 patients, respectively (p = 0.003). The SUV on WB– PET images was significantly higher for NG3 than for NG1-2 (p = 0.004), and for high (≥ 20%) than low ( < 20%) Ki67 (p = 0.003), and significantly lower for Luminal A than Luminal B, HER2 and triple-negative cancer (p < 0.05 for all three). The SUV for NG (p = 0.002), Ki67 (p = 0.001) and the luminal (p < 0.05) type also significantly differed in DBPET images. RU without central FDG accumulation was evident in DbPET images of 12 patients, all of whom had Ki67 ≥ 20 (p = 0.0001), two had NG1-2 and 10 had NG3 (p = 0.005), one had clinical T1, 11 had T2 (p = 0.0004), five had clinical N0 and seven had N1 (p = 0.03). RU was associated with high-grade malignancy and neoplastic progress. Conclusions: The detection rate of DBPET was excellent for DCIS. The RU on DBPET offers predictive value for high-grade malignancy and the neoplastic progress of invasive breast cancer. Thus, DBPET might help to determine therapeutic strategies.

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.

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 SUV max 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 SUV max to predict underestimation of invasive breast cancer was 1.6. The rates of underestimation were 61.5% for patients with a tumor of SUV max > 1.6 and 11.4% for patients with a tumor of SUV max ≤ 1.6 ( P max was significantly associated with symptomatic presentation ( P P P = .013), high Breast Imaging Reporting and Data System category ( P = .011), and core needle biopsy ( P = .007). In multivariate analysis, high SUV max was only a significant predictive factor of underestimation of invasive breast cancer (hazard ratio, 11.7; 95% confidence interval, 3.70-37.0; P Conclusion SUV max on FDG-PET/CT is useful for predicting the underestimation of invasive breast cancer in cases of DCIS at needle biopsy.

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). Table 1. Relationship between changes in temporal contrast over time as a perfusion parameter and clinicopathological factorsFactorn(%)Peak intensityMean ± SDpMean age ± SD (y)53.8 ± 13.5< 50 y30 (55.6)65.5 ± 25.40.50≥ 50 y24 (44.4)61.1 ± 21.5NG1 or 219 (35.2)65.8 ± 28.00.61335 (64.8)62.4 ± 21.2Ki67< 3024 (44.4)53.8 ± 22.40.006≥ 3030 (55.6)71.4 ±21.9ERNegative13 (31.7)58.2 ± 20.90.002Positive41 (68.3)80.5 ± 24.6HER2Negative47 (87.0)62.3 ± 24.00.32Positive7 (13.0)71.9 ± 20.5ER: estrogen receptor, HER2: human epidermal growth factor receptor 2, NG: nuclear grade. 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). Table 2. Relationship between signal intensity as a perfusion parameter and tumor subtypesTumor subtypenPeak intensitySubtypeMean ± SDp *Luminal3856.8 ± 20.9HER-2-positive771.9 ± 20.50.09Triple-negative985.7 ± 23.20.001 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.

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 Association between each preoperative variable and underestimation of invasive component in multivariate analysis in cases of DCIS diagnosed at needle biopsyVariables HR (95% CI)P valuePresentationsymptomatic vs. screening detected1.64 (0.43-6.22)0.47Palpableyes vs. no1.54 (0.36-6.69)0.58Lesion size< 2cm vs. ≥ 2cm1.23 (0.34-4.40)0.76Mass formationyes vs. no1.28 (0.36-4.44)0.7BI RADS category5 vs. 3, 42.92 (0.80-10.7)0.11Biopsy devicemammotome biopsy vs. CNB2.16 (0..64-7.30)0.21Nuclear gradehigh vs. not highhigh vs. not high 2.24 (0.51-9.78)0.29SUVmaxhigher vs. lower11.7 (3.70-37.0)< 0.001BI RADS, Breast Imaging Reporting and Data System; DCIS, ductal carcinoma in situ; IBC, invasive breast cancer; SUVmax, maximum standardized uptake value 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.

A resected case of complete response after treatment with S-1 for recurrent squamous cell carcinoma component of the breast is presented.A 65-year-old woman was admitted to another hospital because of a left breast tumor. A tumor approximately 6 cm in diameter was palpable in the subareolar-lower (DBE) region of the left breast; the diagnosis was breast cancer. We performed mastectomy and axillary lymph node dissection. The pathological diagnosis revealed squamous cell carcinoma of the left breast(pT3N1M0, Stage III A). FEC chemotherapy, a standard chemotherapy regimen for general breast cancer, was performed as first-line adjuvant therapy, but was withdrawn after 1 course due to sepsis shock. Weekly PTX chemotherapy as second-line treatment was also withdrawn after six courses due to interstitial pneumonia. Few skin rashes were observed along the incision scar of the left breast, but biopsy revealed skin invasion by local recurrence of squamous cell carcinoma of the breast. Treatment with S-1 was performed for 8 months, and she underwent resection of left skin, fat tissue, and underlying muscle, including the recurrent region. No residual primary carcinoma foci was found in the resected specimen; therefore, the pathological diagnosis revealed complete response for the squamous cell carcinoma component.

We report a case of HER-2-positive recurrent breast cancer showing a clinically complete response to trastuzumab-containing chemotherapy 6 years after primary treatment of triple-negative breast cancer. The primary tumor was negative for HER-2 as determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) (1+, and ratio, 1.1), but examination of the recurrent lymph node metastasis showed positivity for HER-2 by FISH (ratio, 5.2). No lesions were detected in either her left breast or in other organs, and the patient was diagnosed as having HER-2-positive recurrent disease. Combination chemotherapy using weekly paclitaxel and trastuzumab was initiated, and a clinically complete response was achieved. This report suggests the benefit of routine evaluation of HER-2 status in recurrent breast cancer with the introduction of HER-2-targeting agents.

We investigated the role of human natural killer (NK) cells in the peripheral blood (PB) and liver in controlling breast cancer. The proportion of NK cells among liver mononuclear cells was significantly higher than among PB mononuclear cells. Liver NK cells inductively expressed higher levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) than PB NK cells in response to interleukin-2 (IL-2). Liver NK cells displayed higher cytotoxicity against various breast cancer cell lines (MDA-MB231, MDA-MB453, MDA-MB468, and MCF-7) after IL-2 stimulation than did PB NK cells. Anti-HER2 monoclonal antibody (mAb) promoted the cytotoxicity of both the types of NK cells toward HER2-expressing cell lines. All breast cancer cell lines highly expressed death-inducing TRAIL receptors, death receptor 4, but did not express death-inhibitory receptors (DcR1 and DcR2). Both PB and liver NK cell-induced cytotoxicity was inhibited partially by anti-TRAIL mAb and more profoundly by the combination of anti-TRAIL mAb and concanamycin A, indicating that TRAIL and perforin are involved. IL-2-stimulated liver and PB NK cells exhibited upregulated expression of CXCR3, which bind to the chemokines CXCL9, CXCL10, and CXCL11 secreted by breast cancer cells. We also found that IFN-γ promoted the production of CXCL10 from breast cancer cells. The results of this study show that IFN-γ secreted from NK cells likely promotes the production of CXCL10 from breast cancer cells, which in turn accelerates the migration of CXCR3-expressing NK cells into the tumor site. These findings suggest the possibility of a therapeutic approach by either activation of endogenous PB and liver NK cells or adoptive transfer of in vitro-activated autologous NK cells.

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%; luminal B, 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). Relation of tumour characteristics and brightness intensityCharactersticNo. of PatientsIncreased rate of brightness (IRB)p-valueNG 1, 2122.6 ± 1.00.713113.9 ± 2.9 Ki-67 < 3092.4 ± 0.7P < 0.05≥ 30144.7 ± 2.9 ER status positive213.3 ± 2.2 negative29.1 Sub type Luminal A102.4 ± 0.8P < 0.05Luminal B124.2 ± 2.7 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.

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. table 1caseageStageSub typeMRIPET-CTpathological responseIncrease rate of brightness (IRB)167T2N1 IIBLuminal HER2PRCRCR1237T2N0 IIAHER2 positivePRCRCR1.1346T3N1 IIIAHER2 positiveCRCRCR1.2446T2N3c IIICLuminal HER2PRCRCR1.2564T2N0 IIAHER-2 positiveCRCRPR1.3658T2N1 IIBLuminal BCRCRPR1.6738T2N0 IIALuminal BPRCRPR1.8857T1cN0 ILuminal HER-2PRCRPR1.9939T2N1 IIBLuminalBSDCRSD2.51050T2N1 IIBTriple negativePRCRSD4.2 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.