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Considering the difficulty in detecting primary breast cancers using whole-body positron emission tomography (WBPET) owing to its limited spatial resolution, we aimed to evaluate the detectability of breast cancer by ring-type dedicated breast PET (DbPET) on the World Health Organization (WHO) histological classification in comparison with WBPET.A total of 938 patients with breast cancer underwent WBPET and ring-type DbPET, and 1021 lesions were histologically assessed based on the WHO classification of tumors of the breast. The findings of WBPET and DbPET were retrospectively evaluated and compared.The size-related sensitivity of DbPET was superior to that of WBPET for subcentimetric tumors (81.9% vs. 52.4%, P 0.001). The histological distribution was as follows: 11 lobular carcinoma in situ, 158 ductal carcinoma in situ, 738 infiltrating duct carcinoma not otherwise specified (NOS), 12 lobular carcinoma NOS, 40 mucinous adenocarcinoma, 13 tubular carcinoma, 36 invasive breast carcinoma others, and 13 papillary neoplasms. WBPET had low sensitivity for lobular carcinoma in situ, ductal carcinoma in situ, lobular carcinoma NOS, mucinous adenocarcinoma, and tubular carcinoma. DbPET showed improved sensitivity for all the above except lobular and tubular carcinoma. The maximum standardized uptake values (SUVmax) of DbPET were significantly higher than those of WBPET for histological types, excluding lobular carcinoma in situ. The SUVmax of papillary neoplasms was high regardless of low-grade histology and Ki-67 labeling index.DBPET was found to have high sensitivity and SUVmax values for all histologic types that showed low sensitivity of detection on WBPET, except lobular carcinoma in situ.

This study aimed to assess the clinical effect of the pathological axillary assessment method in breast cancer without clinical lymph node metastasis. Data of patients with clinically node-negative breast cancer were retrospectively reviewed. The study period was divided into early (January 2000–July 2007) and late (August 2007–December 2014) periods based on the pathological assessment method used (single-sectional and detailed multi-sectional lymph node processing). In the late period, lymph nodes were evaluated at six levels including immunohistochemistry on each 1.5–2 mm interval section. The axillary diagnostic accuracy and role of chemotherapy were assessed. In 1698 patients, 27 isolated tumor cells (ITCs), 39 micrometastases, and 205 macrometastases were noted. The sensitivity for pathological N0 diagnosis was dependent on clinical T stage, Tis (97.8%), T1 (83.0%), T2 (74.2%), T3 (54.5%), and T4 (63.6%). ITCs and micrometastases were detected only in the late period, and 84.7% and 91.6% of cases in the early and late period, respectively, did not have macrometastases. The 5-year disease-free interval (DFI) rates were 95.2% in node-negative cases, 98.4% in ITCs/micrometastases, and 91.4% in macrometastases (P

This study compares the sensitivity of dedicated breast positron emission tomography (DbPET) and whole body positron emission tomography (WBPET) in detecting invasive breast cancer based on tumor size and biology. Further, we explored the relationship between maximum standardized uptake value (SUVmax) of DbPET and biological features of the tumor. A total of 639 invasive breast cancer lesions subjected to both DbPET and WBPET before surgery, between January 2016 and May 2019, were included in the study. The sensitivity of DbPET and WBPET in detection and the biology of the tumor according to the clinicopathological features were retrospectively evaluated. The overall sensitivity of DbPET was higher than that of WBPET (91.4% vs. 80.3%, p

The telomere G‐tail (G‐tail) plays an essential role in maintaining chromosome stability. In this study, we assessed the leukocyte G‐tail length of breast cancer (BC) patients and cancer‐free individuals and evaluated the association between the G‐tail length and the presence of BC. A significant shortening of the median G‐tail length was observed in BC patients compared with cancer‐free individuals and was found in the early phase of BC. Our study indicated that the leukocyte G‐tail length might be a potential biomarker for BC detection., Telomere G‐tail length correlates with the presence of breast cancer.

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.

Purpose Anorexia induced by cytotoxic chemotherapy on delayed phase is a highly frequent adverse event. We aimed to determine the effects of rikkunshito (RKT) on chemotherapy-induced anorexia (CIA) in patients with lung cancer. Methods This prospective, randomized, cross-over pilot trial included 40 lung cancer patients scheduled to undergo cisplatin-based chemotherapy and randomized to either a group given RKT 7.5 g/day for 14 days (Group A, N = 20) or not (Group B, N = 20), then the treatments were switched. All patients received dexamethasone, palonosetron hydrochloride and aprepitant regardless of group assignment. Rescue drugs were allowed as required. The primary and key secondary endpoints were changes in caloric intake and in plasma acylated ghrelin (AG) levels, respectively. Average daily caloric intake during days 3 to 5 was compared with that on day 1 of each course. Results The primary and key secondary endpoints were analyzed in 31 patients (per protocol population) completing the study. Reduction rate of caloric intake was lower in RKT, than in control courses (18% vs. 25%, P = 0.025). Plasma AG levels significantly declined between days 1 and 3 in RKT (12.3 vs. 7.5 fmol/mL, P

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: We investigated whether contrast-enhanced ultrasonography (CEUS) scores can predict lymphocyte-predominant breast cancer (LPBC). Patients and Methods: We evaluated 75 patients who underwent US and CEUS. LPBC was defined as tissues with ≥50% stromal tumour-infiltrating lymphocytes (TILs) preoperatively. Characteristic US images predicting LPBC were evaluated using TIL-US scores via three ultrasonic tissue characteristics: Shape, internal echo level, and posterior echoes. TIL-CEUS was evaluated based on TIL-US plus CEUS. Results: TIL-US and TIL-CEUS cut-offs for predicting LPBC were 4 and 6 (area under the curve=0.93 and 0.96, respectively) points based on receiver operating characteristics curves. Sensitivity, specificity, and accuracy values (95% confidence intervaI) were 0.94 (0.77-0.99), 0.75 (0.70-0.77), and 0.80 (0.72-0.82); and 0.94 (0.78-0.99), 0.86 (0.81-0.87), and 0.88 (0.80-0.90) for TIL-US and TIL-CEUS, respectively. TIL-CEUS score was a significant single predictor for LPBC in multivariate logistic regression (p=0.001). Conclusion: TIL-CEUS can be used for preoperative LPBC prediction and detection.

Microsatellite instability-high/mismatch repair deficiency is one of biomarkers predicting the response to pembrolizumab, an immune checkpoint inhibitor for metastatic solid tumors. A 44-year-old woman with stage IIIC right breast cancer was treated with mastectomy and axillary node dissection after primary systemic chemotherapy followed by radiation, chemotherapy, and hormonal therapy. Eighteen months after surgery, recurrent diseases were revealed and refractory to multiple treatments. The recurrent site biopsy showed microsatellite instability-high, and programmed cell death ligand-1 inhibitor pembrolizumab was administrated. FDG PET/CT showed complete metabolic response over 12 months and is useful to monitor the response of active immunotherapy.

Febrile neutropenia (FN) incidence during docetaxel and cyclophosphamide (TC) chemotherapy, known as a high-risk regimen, differs among countries. The role of prophylactic granulocyte colony-stimulating factor (G-CSF) in FN is unclear. This study aimed to investigate FN frequency and relative dose intensity (RDI) of TC chemotherapy in patients with breast cancer and identify the correct population requiring prophylactic G-CSF. In total, 205 patients with breast cancer were scheduled for TC chemotherapy (docetaxel/cyclophosphamide 75/600 mg/m2, every 3 weeks, 4 cycles) as adjuvant chemotherapy. Trastuzumab (8 mg/kg; continued with 6 mg/kg) was administrated intravenously for human epidermal growth factor receptor 2 (HER2)-positive cancer. Fifty-five patients received primary prophylactic measures (G-CSF: 20 and antibiotics: 35). We investigated the frequency of FN and hospitalization, RDI, and the factors related to FN, adverse events, hospitalization, and RDI. FN occurred in 70 patients (35.7%). FN incidence was noted in 41.1% without any prophylactic measures and in 5.0% with prophylactic G-CSF. In multivariate analysis, the independent risk factors of FN were older age (≥ 60 years, P = 0.017) and without primary prophylactic G-CSF (P = 0.011). Eleven patients (5.6%) were hospitalized of which 8 (72.7%) were elderly. The median RDIs of docetaxel and cyclophosphamide were 96.7% and 99.7%, respectively. FN frequency during TC chemotherapy was high, and primary prophylactic G-CSF reduced FN incidence. Primary prophylactic G-CSF is an effective therapy for preventing FN during TC chemotherapy. However, prophylactic G-CSF should be considered for elderly patients based on the low hospitalization rate and the high RDI.

AIM To investigate the usefulness of classification of ring-type dedicated breast positron-emission tomography (dbPET) findings in detection of breast cancer. PATIENTS AND METHODS A total of 709 patients with breast cancer underwent dbPET before treatment. Each finding was morphologically categorized as a focus (uptake size ≤5 mm), mass (>5 mm), or non-mass (multiple uptakes not belonging to a three-dimensional mass or without distinct mass features). Non-mass uptakes were additionally classified as linear, focal, segmental, regional, or diffuse distributions. Lesion-to-background ratios were calculated. RESULTS Among 910 abnormal findings, 700 (76.9%) were malignant and 210 (23.1%) were benign. Morphologically, 198 (21.8%) lesions were foci, 431 (47.4%) were masses, and 281 (30.9%) were non-masses. In multivariate analysis, mass, focal and segmental distributions of non-mass lesions and high lesion-to-background ratio were significantly related to breast cancer (all p

AIM To investigate whether tumor-infiltrating lymphocyte (TIL) scoring based on 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) can predict the pathological response to neoadjuvant chemotherapy. PATIENTS AND METHODS A total of 261 patients with breast cancer underwent complete resection after neoadjuvant chemotherapy. PET-TIL score was calculated using tumor size, Ki-67 labeling index, and maximum standardized uptake value (SUVmax) on FDG PET/CT. The efficacy of the PET-TIL score in predicting the pathological complete response (pCR) was retrospectively evaluated. RESULTS pCR rates were 11.4%, 58.6%, and 38.8% in luminal, human epidermal growth factor receptor 2 (HER2)-positive, and triple-negative breast cancer, respectively. The corresponding median PET-TIL scores were 28, 37, and 45. pCR rates were 20.0% and 44.2% in the low and high PET-TIL score groups, respectively (p

Dedicated breast positron emission tomography (DbPET) provides detailed high-resolution images and can detect intratumoral heterogeneity using 18F-fluorodeoxyglucose (FDG). We aimed to evaluate the correlation between FDG uptake on DbPET and the clinicopathological features of breast cancer, particularly those with an intratumoral heterogeneous distribution of FDG on DbPET. We evaluated 195 consecutive patients with invasive breast cancer who underwent preoperative whole-body PET (WBPET) and DbPET concurrently between January 2016 and March 2017. The relationships between clinicopathological factors and the maximum standard uptake values (SUVmax) of DbPET and WBPET, including clinical stage, nuclear grade, Ki67 proliferation index, estrogen receptor (ER) and human epidermal growth factor receptor type 2 (HER2) statuses, and the intratumoral heterogeneous distribution of FDG on DbPET, were evaluated. The SUVmax of DbPET was significantly correlated with clinical T stage, N stage, nuclear grade, and Ki67 proliferation index (all p

Hypocalcemia is a significant adverse effect of denosumab. We herein report a case of prolonged hypocalcemia in a patient with multiple risk factors for hypocalcemia, including gastrectomy, increased bone turnover, and a poor performance status. Hypocalcemia developed after denosumab treatment for diffuse bone metastasis of gastric cancer, despite oral supplementation with vitamin D and calcium. To avoid serious prolonged hypocalcemia, a thorough assessment of the bone calcium metabolism is required before initiating denosumab treatment.

Background The telomere G-tail, located at the terminal 3’-end, plays an important role in the maintenance of chromosome stability. Telomere G-tail length has been shown to be related to the presence of various cancers; however, the association between telomere G-tail length and breast cancer has remained unclear. Methods We measured the length of the leukocyte telomere G-tail using the hybridization protection assay, which has the advantages of being simple to perform, accurate and highly sensitive for G-tails as short as 20 nucleotides. The association between telomere G-tail length and presence of breast cancer was estimated by comparing breast cancer patients (n=70) and cancer-free individuals (n=83). We recruited cStage I-III breast cancer patients who underwent surgery between November 2016 and December 2017 at Hiroshima University Hospital. Cancer-free individuals included age-matched female individuals with no previous or current history of any cancer. Results The median telomere G-tail length was significantly shorter in breast cancer patients (11,886.70 ± 2,008.74 RLU/μg DNA) than in cancer-free individuals (13,336.00 ± 2,072.31 RLU/μg DNA; p < 0.01). Shortening of the telomere G-tail length was observed in the phase of ductal carcinoma in situ, and this trend was observed with or without shortening of the total telomere length. Spearman’s rank correlation analysis showed that there was no significant association between telomere G-tail length and total telomere length in breast cancer patients (ρ = -0.09; p = 0.48). In contrast, a significant correlation was found between telomere G-tail length and total telomere length in cancer-free individuals (ρ = 0.29; p = 0.01). Conclusions Our study indicated that leukocyte telomere G-tail length may serve as a novel potential biomarker for detection of breast cancer. Citation Format: Yumiko Koi, Yasuhiro Tsutani, Yukie Nishiyama, Shinsuke Sasada, Norio Masumoto, Takayuki Kadoya, Ryou-u Takahashi, Morihito Okada, Hidetoshi Tahara. Telomere G-tail length correlates with the presence of breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-04-01.

Background: Contrast-enhanced ultrasonography (CEUS) allows a thorough visualization of the intra-tumoral blood flow. This study aimed to determine if CEUS can predict the early effects of neoadjuvant chemotherapy (NAC) on breast cancer. Patients and Methods: We evaluated 93 patients with triple-negative type (ER-negative and HER2-negative, n= 30), HER2-positive (HER2-positive and any ER, n= 34), and luminal type (ER-positive and HER2-negative, n= 29) invasive breast cancer who underwent NAC between September 2012 and March 2019. Ultrasonography (US) and CEUS were performed before NAC and after two cycles of NAC. All patients underwent either mastectomy or breast-conserving surgery after NAC. To objectively evaluate CEUS findings, the ascending slope (AS) in perfusion parameters of CEUS was calculated using time-intensity curves based on enhancement intensity and temporal changes. The changes of maximum tumor diameter in US (ΔUS) and the changes of AS in perfusion parameters of CEUS (ΔAS) were measured in the primary tumor. Results: Thirty-seven (39.8%) patients achieved pathological complete response (pCR). In triple-negative breast cancer, both of ΔUS and ΔAS showed a significant decline with pCR, but there were no significant differences in ΔUS and ΔAS in the luminal-type and HER2-positive breast cancer. We set cutoffs of the ΔUS (-37%, AUC 0.742) and ΔAS (-26%, AUC 0.823) for predicting pCR on the basis of their ROC curves. ΔUS (OR 8.75, p=0.017) and ΔAS (OR 21.3, p=0.0001) in univariate analysis and ΔAS (OR 16.1, p=0.009) in multivariate analysis were significant predictors for pCR in triple-negative breast cancer. The sensitivity, specificity, and accuracy for predicting pCR in triple-negative breast cancer were 0.70, 0.79, and 0.76 in ΔUS and 0.80, 0.84, and 0.83 in ΔAS, respectively. The sensitivity, specificity, and accuracy of ΔAS were greater than those of ΔUS for predicting pCR. Conclusions: CEUS may serve as a new important diagnostic modality when planning therapeutic strategies, for patients with triple-negative breast cancer who received NAC. univariate analysis and multivariate analysis for pCR in triple-negative breast cancerCharacteristicUnivariate logistic analysisMultivariate logistic analysisOR95%CIpOR95%CIpAge, Citation Format: Mai Nishina, Norio Masumoto, Akiko Kanou, Kayo Fukui, Yuri Kimura, Ai Amioka, Tomoko Itagaki, Shinsuke Sasada, Akiko Emi, Takayuki Kadoya, Morihito Okada. Contrast-enhanced ultrasonography after two cycles of chemotherapy predicts the outcome of neoadjuvant chemotherapy in triple-negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-02-04.

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.

The objective of this paper is to investigate the detectability of breast tumors having various histological types in excised breast tissues of total mastectomy. The tumor images measured by a portable impulse-radio-ultra-wideband (IR-UWB)-radar-based breast cancer detector are compared with both pathological images and images of dedicated breast positron emission tomography. It is found that the detector can detect invasive-ductal-carcinomas and extensive intraductal component in the dense breast. The density of the breast has a correlation to the effective permittivity derived from the reconstructed confocal images. The results show that the IR-UWB-radar-based breast cancer detector has a potential as a portable modality for early-stage breast cancer screening.

Background The prognosis of lepidic predominant lung adenocarcinoma is favorable. We postulated that lepidic predominant tumors might not require postoperative adjuvant chemotherapy. The present study aims to determine whether lepidic component occupancy affects overall survival after postoperative adjuvant chemotherapy for lung adenocarcinoma. Methods Clinical and pathologic data were collected from a database and from the medical records of 964 patients with completely resected lung adenocarcinoma. We assessed the influence of lepidic component occupancy in the tumor on the outcomes of adjuvant chemotherapy. Results Among the patients, 270 received adjuvant chemotherapy and 694 did not, and 415 and 549 had lepidic predominant and non-lepidic predominant tumors, respectively. Adjuvant chemotherapy contributed to better overall survival compared with observation in non-lepidic predominant tumors ( p = 0.025). Multivariate analyses revealed age, sex, stage, lepidic component occupancy, and adjuvant chemotherapy as independent prognostic factors for overall survival. The overall survival was significantly longer for patients with non-lepidic predominant tumors at stages IA, IB, and II-III under adjuvant chemotherapy compared with observation ( p = 0.040, p = 0.007, and p = 0.012, respectively), whereas survival rates were similar for patients with all stages of lepidic predominant tumors even after propensity score matching study. Conclusions Lepidic component occupancy reflected the effect of adjuvant chemotherapy for lung adenocarcinoma. Adjuvant chemotherapy did not have much impact for lepidic predominant tumors and could be considered for non-lepidic predominant tumors even at stage IA.

Background Mammography is the standard examination for breast cancer screening; however, it is associated with pain and exposure to ionizing radiation. Microwave breast imaging is a less invasive method for breast cancer surveillance. A bistatic impulse radar–based breast cancer detector has recently been developed. Objective This study aims to present a protocol for evaluating the diagnostic accuracy of the novel microwave breast imaging device. Methods This is a prospective diagnostic study. A total of 120 participants were recruited before treatment administration and divided into 2 cohorts: 100 patients diagnosed with breast cancer and 20 participants with benign breast tumors. The detector will be directly placed on each breast, while the participant is in supine position, without a coupling medium. Confocal images will be created based on the analyzed data, and the presence of breast tumors will be assessed. The primary endpoint will be the diagnostic accuracy, sensitivity, and specificity of the detector for breast cancer and benign tumors. The secondary endpoint will be the safety and detectability of each molecular subtype of breast cancer. For an exploratory endpoint, the influence of breast density and tumor size on tumor detection will be investigated. Results Recruitment began in November 2018 and was completed by March 2020. We anticipate the preliminary results to be available by summer 2021. Conclusions This study will provide insights on the diagnostic accuracy of microwave breast imaging using a rotational bistatic impulse radar. The collected data will improve the diagnostic algorithm of microwave imaging and lead to enhanced device performance. Trial Registration Japan Registry of Clinical Trials jRCTs062180005; https://jrct.niph.go.jp/en-latest-detail/jRCTs062180005 International Registered Report Identifier (IRRID) DERR1-10.2196/17524

The presence of tumor-infiltrating lymphocytes (TILs) is a prognostic factor for breast cancer. However, because of tumor tissue heterogeneity, an accurate and simple evaluation method is needed. We determined if preoperative characteristic ultrasonography (US) image findings are predictive of lymphocyte-predominant breast cancer (LPBC). We evaluated 191 patients with invasive breast cancer treated by curative surgery between January 2014 and December 2017. Stromal lymphocytes in surgical pathological specimens were evaluated. Fifty-two patients with ≥ 50% stromal TILs were defined as having LPBC. Preoperative US images were examined for indicators of TILs. The US images with characteristic TILs were scored for prediction of LPBC. Shape (more lobulated), internal echo level (weaker), and posterior echoes (stronger) were predictors of LPBC and used to assign the TILs-US scores (0–7 points); the score cutoff for predicting LPBC was 4 points (sensitivity, 0.73; specificity, 0.87; accuracy, 0.83) based on the receiver operating characteristics (ROC) curves (AUC 0.88). Multivariate logistic regression analysis identified nuclear grade (NG), OR 3.4; estrogen receptor (ER), OR 5.7; human epidermal growth factor receptor type-2 (HER2), OR 4.1; and TILs-US score, OR 14.9 as LPBC predictors (all, p

Background Small RNAs are multiple classes of short non-coding RNAs (ncRNAs) that include microRNAs (miRNAs), transfer RNA fragments (tRFs), and other ncRNA fragments that play essential role in gene regulation. Small RNAs exist in blood circulation within extracellular vesicles (EVs), which have been the center of the attention at cell-to-cell communication tools, or bound to proteins or lipid. Recent studies have shown that the expression levels of small RNAs are different between patients with breast cancer (BC) and cancer-free individuals. Thus, circulating small RNAs have attracted as valuable biomarkers for cancer detection. Methods First, we assessed and the expression level of circulating small RNAs in the serum of BC patients (n = 78) and cancer-free volunteers (control) (n = 72) using next generation sequencer. By comparing those expression level, we identified some small RNAs that have signifficant difference between 2 groups as biomarker candidates for BC detection. We constructed a diagnostic model using some small RNAs from biomarker candidates. To test the possibilities that those candidates are released from cancer cells, we next profiled small RNAs within EVs that isolated from the serum of participants in this study and from breast cancer cells (MCF-7 and MDA-MB-231) and normal epithelial cells (184-h TERT). Results Twelve circulating small RNAs that expressed significantly higher in BC patients compared to control were identified, indicating potential biomarkers for BC detection. A diagnostic model using 4 small RNAs including isoforms of miRNAs (isomiRs) and tRFs was. The ROC curve analysis revealed that our model showed a high diagnostic accuracy of AUC 0.945 and achieved discriminating stage 0 BCs from control. Importantly, significantly different expression in serum-EVs was observed in 4 small RNAs between BC patients and control. Furthermore, 4 small RNAs were also observed in EVs derived from cell culture media in breast cancer cells and normal epithelial cells and those expressions were aberrant as the same as those of serum-EVs. Conclusions These findings suggests circulating small RNAs in serum serve as potential biomarkers for BC detection that enables to include the molecular movement of cancer cells. Legal entity responsible for the study Hidetoshi Tahara. Funding Has not received any funding. Disclosure H. Tahara: Advisory / Consultancy: MiRTeL.

We analyzed and validated the prognostic utility of the new International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) for clinical stage IA lung adenocarcinoma (ADC) classification of adenocarcinoma (ADC).We retrospectively reviewed 347 patients with clinical stage IA nonmucinous ADC, who had undergone complete resection. The histological subtype was classified according to the predominant subtype, as proposed by the new IASLC/ATS/ERS ADC classification.The histopathological subtypes, defined according to the new IASLC/ATS/ERS ADC classification, were ADC in situ (AIS) in 56 patients (16.1%), minimally invasive ADC (MIA) in 15 (4.3%), lepidic-predominant ADC in 109 (31.4%), papillary-predominant ADC in 70 (20.2%), acinar-predominant ADC in 61 (17.6%), solid-predominant ADC in 30 (8.6%), and micropapillary-predominant ADC in 6 (1.7%). The 5-year disease-free survival (DFS) rate was 100% for both AIS and MIA. All cases of recurrence involved invasive ADC. The 5-year DFS for lepidic-predominant ADC was 99.0%; acinar-predominant ADC, 82.4%; papillary-predominant ADC, 80.8%; solid-predominant ADC, 73.6%; and micropapillary-predominant ADC, 33.3%. The predominant subtype of ADC was significantly correlated with DFS (P0.0001). Multivariate analysis indicated that the pathological stage was an independent predictor of DFS (P=0.031). Other independent predictors of increased risk of recurrence were the presence of vascular or lymphatic invasion (HR=4.96, P=0.001), and a pathological stage more advanced than IB (HR=2.87, P=0.010). The coincidence between the clinical stage and pathological stage was 79.8%. The stage migration was found in 53.3% of solid-predominat ADC and in 83.3% of micropapillary-predominant ADC.The new IASLC/ATS/ERS ADC classification has prognostic value in predicting the recurrence and survival of patients with clinical stage IA ADC. The frequency of stage migration was found in more than half of solid and micropapillary predominant ADCs.

OBJECTIVES There is uncertainty as to which factors determine the aggressiveness of lung adenocarcinoma with a micropapillary pattern (MPP). The present study aimed to clarify the influence of a MPP on the malignant aggressiveness of clinical stage IA lung adenocarcinoma. METHODS We retrospectively examined 347 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete resection. We defined MPP-positive as accounting for ≥5% of the entire tumour. RESULTS Forty-eight (14%) and 299 (86%) patients were MPP-positive and negative, respectively. Lymphatic (P = 0.003) and vessel (P = 0.029) invasion as well as lymph node metastasis (P = 0.002) were more frequent in the MPP-positive than negative group. Five-year disease-free survival (DFS) rates were significantly lower in the MPP-positive than negative group (69.7 vs 89.3%, P < 0.001). Multivariate analysis for DFS showed that MPP (P = 0.048), lymphatic invasion (P = 0.003) and vessel invasion (P = 0.002) were independent poor prognostic factors. In addition, higher proportions (

The present study investigates the malignant significance of lepidic component presence in predominantly invasive lung adenocarcinoma that comprise less than 50% lepidic growth of the tumor.Among 347 consecutive patients with completely resected clinical stage IA lung adenocarcinoma, we excluded those with adenocarcinoma in situ, minimally invasive, and lepidic predominant invasive adenocarcinoma. We finally assessed 167 patients with predominantly invasive lung adenocarcinoma. We analyzed the clinicopathologic characteristics and prognoses of patients with 49 pure invasive tumors without lepidic growth and 118 partially invasive tumors with lepidic growth.Pure invasive tumors were associated with being male, small tumor size, high maximum standardized uptake, and pleural as well as lymphatic invasion. Nonetheless, the invasive component size of both tumor types was similar. The predominant subtypes of pure and partially invasive tumors, respectively, were papillary, 17 (34.7%) and 53 (44.9%); acinar, 10 (20.4%) and 51 (43.2%); solid, 19 (38.8%) and 11 (9.3%), and micropapillary 3 (6.1%) and 3 (2.5%; p0.001). Recurrence-free survival was significantly worse for patients with pure, compared with partially, invasive tumors (p = 0.045).Among predominantly invasive stage IA lung adenocarcinomas, the malignant potential was higher for pure invasive tumors, and the prognosis was poorer than for partially invasive tumors when the invasive components were of equal sizes. The presence or absence of a lepidic component reflects a difference in subtype predominance and can help to decide the malignant grade of lung adenocarcinoma.

In this report, a hand-held impulse-radar breast cancer detector is presented and the detectability of malignant breast tumors is demonstrated in the clinical test at Hiroshima University Hospital, Hiroshima, Japan. The core functional parts of the detector consist of 65-nm technology 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) with the pulse width of 160 ps and single port eight throw (SP8T) switching matrices for controlling the combination of 4 × 4 cross-shaped dome antenna array. The detector is designed to be placed on the breast with the patient in the supine position. The detectability of malignant tumors is confirmed in excised breast tissues after total mastectomy surgery. The three-dimensional positions of the tumors in the imaging results are consistent with the results of histopathology analysis. The clinical tests are conducted by a clinical doctor for five patients at the hospital. The malignant tumors include invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS). The final confocal imaging results are consistent with those of Magnetic Resonance Imaging (MRI), demonstrating the feasibility of the hand-held impulse-radar detector for malignant breast tumors.

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.

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.

Background Ring-type dedicated breast positron emission tomography (DbPET) can detect small breast cancers; however, there are no category classifications of abnormal findings on DbPET such as BI-RADs (mammography, ultrasonography, and magnetic resonance imaging). We investigated whether the classification of DbPET findings was useful for detecting breast cancer. Methods A total of 674 patients with breast cancers underwent ring-type DbPET using FDG before treatment between January 2016 and March 2019. Findings were morphologically categorized as a focus (uptake size ≤5 mm), mass (>6 mm), or non-mass (multiple uptakes). Non-mass uptakes were additionally classified based on the distribution: focal, linear, regional, segmental, and diffuse. Maximum standardized uptake value (SUVmax) and tumor-to-normal tissue ratio (TNR) were calculated. The final diagnosis was pathologically evaluated based on biopsy or surgical specimens, and lesions of category 2 or lower by conventional examinations were determined benign. Results Among 867 abnormal findings, 668 (77%) were malignant and 199 (23%) were benign. Morphologically, 187 (21.6%) lesions were foci, 413 (47.6%) were masses, and 267 (30.8%) were non-masses. Among non-mass lesions, 131 focal, 1 linear, 15 regional, 115 segmental, and 5 diffuse distributions were presented. The median SUVmax was 5.0 and TNR was 2.8. The area under the curve values of SUVmax and TNR for predicting malignancy were 0.824 and 0.855, respectively. In a multivariate analysis, mass, focal and segmental distributions of non-mass lesions, high TNR were significantly related with breast cancer (all P Conclusions Classification using morphological findings and TNRs on DbPET are useful to detect breast cancer. The DbPET classification should be considered for breast cancer screening. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

[Purpose] Tumor-infiltrating lymphocytes (TILs) is a prognostic factor for breast cancer, however, an accurate and simple evaluation method remains elusive. Therefore, we focused on findings characteristic of lymphocyte-predominant breast cancer (LPBC) in ultrasound (US) images. In this study, the application of preoperative US image assessment to diagnostic prediction of LPBC evaluated from postoperative pathological specimens, was appraised. [Methods] We evaluated 191 patients with invasive breast cancer between January 2014 and December 2017. All patients were treated by either mastectomy or breast-conserving surgery. Stromal lymphocytes were evaluated on surgical pathological specimens. Breast cancer samples with ≥ 50% stromal TILs were defined as LPBC. Preoperative US was performed in all cases and images were examined for characteristics indicative of TILs. Scores were given to US images with characteristic TILs and these TILs-US scores were assessed for their application to predict LPBC. [Results] There were 39 cases of LPBCs and 122 cases of non-LPBCs in surgical pathological specimens. The characteristic US image findings predicting LPBC were shape (more lobulated), internal echo level (weaker) and posterior echoes (stronger). The TILs-US scores were given based on these three ultrasound tissue characterizations.We set TILs-US score cut-offs for predicting LPBC at 4 points (Sensitivity, 0.73; specificity, 0.87; accuracy, 0.83) based on the receiver operating characteristics (ROC) curves (AUC, 0.88). There were significant predictors for LPBC in maltivariate logistic analysis (Nuclear Grade (NG): OR3.4, p=0.02; ER: 5.7, p =0.007;HER-2: OR4.1, p=0.04; TILs-US score2: OR14.9, p The sensitivity, specificity and accuracy of predicting LPBCPerformance measureTILs-US score (95%CI)NGER or HER-2P, TILs-US score vs. NG,P, TILs-USscore vs. ER or HER-2Sensitivity0.73 (0.63-0.81)0.75 (0.64-0.84)0.327 (0.24-0.39)0.08 Conclusions LPBC has characteristic ultrasound tissue characterizations in US images. Thus, TILs-US scores based on US may be applicable to accurate and convenient preoperative diagnosis of LPBC. Citation Format: Fukui K, Masumoto N, Shiroma N, Kanou A, Yokozaki M, Sasada S, Emi A, Kadoya T, Arihiro K, Okada M. Characteristics of lymphocyte-predominant breast cancer in ultrasound images and their application to diagnostic prediction [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 P6-02-06.

[Purpose] Tumor-infiltrating lymphocytes (TILs) has been shown to be useful for predicting outcomes after surgery in breast cancer, and while TILs can be evaluated in preoperative biopsy tissue, heterogeneous distribution of TILs requires examination of all biopsied tissue samples. We gave scores to preoperative ultrasonography (US) images with characteristics indicative of lymphocyte-predominant breast cancer (LPBC) and attempted to apply these for diagnostic prediction of LPBC. In this study, TILs-US scores based on preoperative US were assessed for their usefulness in predicting LPBC, the diagnosis of which was confirmed with postoperative pathology. [Methods] We evaluated 161 patients with invasive breast cancer between January 2014 and December 2017. All patients were treated by either mastectomy or breast-conserving surgery. Stromal lymphocytes were evaluated on preoperative biopsy tissues and surgical pathological specimens. Breast cancer samples with ≥ 50% stromal TILs were defined as pre-LPBC (preoperative biopsy tissues) and LPBC (surgical pathological specimens). TILs-US score was calculated from US before curative surgery. Based on clinicopathological factors including TILs-US scores based on preoperative US and pre-LPBC indicators, determinants useful for prediction of LPBC were examined. [Results] There were 39 cases of LPBCs and 122 cases of non-LPBCs in surgical pathological specimens. We set TILs-US score cut-offs for predicting LPBC at 4 points based on the receiver operating characteristics (ROC) curves (AUC, 0.88). There were significant predictors for LPBC in maltivariate logistic analysis (TILs-US score: OR26.8, p The sensitivity, specificity and accuracy of predicting LPBCPerformance measureTILs-US score (95%CI)Preoperative biopsyHER-2P, TILs-US score vs. Preoperative biopsyP, TILs-USscore vs. HER-2Sensitivity0.74 (0.62-0.84)0.51 (0.42-0.55)0.28 (0.19-0.36)0.04 [Conclusions] TILs-US scores are an important factor that can predict LPBC preoperatively. The TILs-US score has particularly high sensitivity and may be an applicable index in the preoperative evaluation for LPBC. Citation Format: Kanou A, Masumoto N, Shiroma N, Fukui K, Sasada S, Emi A, Kadoya T, Yokozaki M, Arihiro K, Okada M. The TILs-US scores based on ultrasonography can predict lymphocyte-predominant breast cancer before surgery [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 P6-02-11.

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.

Metabolomics has developed as an important new tool in cancer research. It is expected to lead to the discovery of biomarker candidates for cancer diagnosis and treatment. The current study aimed to perform a comprehensive metabolomic analysis of the intracellular dynamic responses of human gastric cancer cells to 5-fluorouracil (5-FU), referencing the mechanisms of drug action and drug resistance. Small metabolites in gastric cancer cells and 5-FU-resistant cells were measured by liquid chromatography-mass spectrometry. Candidates for drug targets were selected according to the presence or absence of resistance, before and after 5-FU treatment. In addition, the gene expression of each candidate was assessed by reverse transcription-polymerase chain reaction. The number of metabolites in cancer cells dramatically changed during short-term treatment with 5-FU. Particularly, proline was reduced to one-third of its original level and glutamate was increased by a factor of 3 after 3 h of treatment. The metabolic production of glutamate from proline proceeds by proline dehydrogenase (PRODH), producing superoxide. After 5-FU treatment, PRODH mRNA expression was upregulated 2-fold and production of superoxide was increased by a factor of 3. In 5-FU-resistant cells, proline and glutamate levels were less affected than in non-resistant cells, and PRODH mRNA expression and superoxide generation were not increased following treatment. In conclusion, the authors identified a candidate biomarker, PRODH, for drug effects using a meta-bolomic approach, a result that was confirmed by conventional methods. In the future, metabolomics will play an important role in the field of cancer research.

The role of adjuvant chemotherapy for stage I lung cancer is unknown. Some Japanese trials demonstrated that tegaful-uracil chemotherapy improved the prognosis of stage I lung cancer over 2 cm.

Fibrinogen/thrombin-based collagen fleece (TachoSil) can be applied to repair pleural injury, however, little is known about the impact of its use on lung.

Purpose: Wnt signaling occurs in β-catenin-dependent pathways, through β-catenin regulates the expression of many genes, and in the β-catenin-independent planar cell polarity (PCP) and Wnt/Ca2+ pathways. Wnt5a is a key ligand in activation of β-catenin-independent pathways, involved in cell motility and polarity through downstream signaling (e.g., JNK phosphorylation). Wnt5a expression correlates significantly with malignancy and stage of progression in malignant melanoma, gastric cancer, prostate cancer, lung cancer, and pancreatic cancer. In contrast, Wnt5a is a tumor suppressor in colorectal cancer, thyroid cancer, liver cancer, and malignant lymphoma. Thus, the effect of Wnt5a expression differs between organs. The role of Wnt5a expression in breast cancer remains elusive. In this study, we examined significance of Wnt5a expression in breast cancer. Experimental design: The relationships between Wnt5a expression and clinicopathologic factors were assessed in 178 consecutive cases of invasive breast cancer resected in Hiroshima University Hospital between January 2011 and February 2014. In addition, altered gene expression following Wnt5a addition was mapped as possible Wnt5a-induced transformation pathways. Results: Wnt5a was positively expressed in 69 of 178 cases (39%) of invasive breast cancer. Wnt5a expression was strongly correlated with estrogen receptor (ER)-positive (P < 0.001). Analysis of the relationship between Wnt5a expression and malignancy in 153 cases of ER-positive breast cancer revealed significant correlations with lymph node metastasis, nuclear grade, and lymphatic invasion. Relapse-free survival was shorter in cases of Wnt5a-positive breast cancer compared to Wnt5a-negative breast cancer cases (P = 0.024). Constitutive expression of Wnt5a in MCF7 cells enhanced migratory capacity, whereas knockdown of Wnt5a reduced this capacity. DNA microarray analysis identified activated leukocyte cell adhesion molecule (ALCAM) as the molecule which is primarily induced by Wnt5a. ALCAM was expressed in 69% of Wnt5a-positive breast cancers but only 27% of Wnt5a-negative breast cancers in 153 cases of ER-positive breast cancer, showing a statistical correlation between Wnt5a and ALCAM expressions. Inhibition of ALCAM in MCF7 constitutively expressing Wnt5a cells reverted the effect of Wnt5a, confirming the important of this molecule in migration of ER-positive breast cancer cells. Conclusions: In ER-positive breast cancer, Wnt5a expression is related with high malignancy and poor prognosis. We speculate that Wnt5a expression increases malignancy in breast cancer by enhancing migratory capacity of cancer cells through induction of ALCAM expression. Wnt5a may be useful as a predictor of malignancy, a therapeutic target, and a prognostic indicator in ER-positive breast cancer. Citation Format: Yoshie Kobayashi, Takayuki Kadoya, Ai Amioka, Hideaki Hanaki, Shinsuke Sasada, Norio Masumoto, Koji Arihiro, Akira Kikuchi, Morihito Okada. Effect of Wnt5a on aggressiveness of estrogen receptor-positive breast cancer and cancer cell migration through ALCAM pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 30.

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...

Autonomic nerve preservation in a gastrectomy for gastric cancer improves the postoperative quality of life. We retrospectively examined the survival of patients treated by an autonomic nerve-preserving gastrectomy in comparison to the survival of the patients treated by a conventional gastrectomy.The survival of 385 patients treated by an autonomic nerve-preserving gastrectomy for clinical early gastric cancer (the ANP group) was compared with that of 285 patients treated by a conventional gastrectomy (non-ANP group).Among the ANP group, the numbers of patients with tumor invasion to the mucosa, submucosa, and muscularis propria were 210, 166, and 9, respectively, whereas the numbers of patients with lymph node metastasis grades of N0, N1, and N2 were 360, 21, and 4, respectively. The overall 5-year survival rate of the ANP group was 94.7%, which was superior to that of the non-ANP group (90.4%; P = 0.003). The 5-year survival rates of patients with lymph node metastasis were 94.9% and 91.8% in the ANP and non-ANP groups, respectively (P = 0.733). Only 3 patients in the ANP group died from gastric cancer.The survival of patients treated by an autonomic nerve-preserving gastrectomy was equivalent to that of patients treated by a conventional gastrectomy, thus suggesting that an autonomic nervepreserving gastrectomy could be a useful procedure for the treatment of early gastric cancer.

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.