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  • 1
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    Online Resource
    Recent Development of Sentinel Lymph Node Biopsy for Breast Cancer in Japan
    Elsevier BV ; 2004
    In:  Asian Journal of Surgery Vol. 27, No. 4 ( 2004-10), p. 275-278
    Details
    In: Asian Journal of Surgery, Elsevier BV, Vol. 27, No. 4 ( 2004-10), p. 275-278
    Type of Medium: Online Resource
    ISSN: 1015-9584
    URL: Article
    DOI: 10.1016/S1015-9584(09)60050-6
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2004
    detail.hit.zdb_id: 2031317-2
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  • 2
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    Thymidylate synthase expression as a predictive factor for response and progression-free survival in metastatic breast cancer patients.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 27_suppl ( 2012-09-20), p. 132-132
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 27_suppl ( 2012-09-20), p. 132-132
    Abstract: 132 Background: S-1, an oral fluoropyrimidine formulation that combines tegafur, 5-chloro-2,4-dihydroxypryidine, and potassium oxonate in a molar ratio of 1:0.4:1 has been widely used against solid cancers including gastric, colorectal, pancreatic, lung and breast cancer. In a phase II study, the response rate (RR) was 41.7% and the median survival was 872 days among taxane-pretreated patients with metastatic breast cancer (MBC). However, the predictive factor of S-1 in patients with MBC has not been determined yet. The purpose of this study is to investigate the correlation between 5-FU-related enzyme and clinical efficacy of S-1 in patients with MBC. Methods: Forty-eight patients with MBC were treated with S-1 twice daily at a dose of 80 mg/m 2 for 4 weeks, followed by a 2-week rest interval. Laser-captured microdissection was performed from the formalin-fixed, paraffin-embedded tumor sections at surgery and the expression of 5-FU-related enzyme including thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) was evaluated by RT-PCR. Results: The median age was 58 years. ER, PgR, HER2 was positive in 57, 28, and 14% of the entire patients, respectively. The median number of pretreated chemotherapy regimens was 2 (range 0-6). The sites of metastatic disease were the viceral in 25 patients, bone in 9 patients and soft tissue in 17 patients. The overall response rate (RR) was 22.9% (11/48) and clinical benefit rate was 41.7% (20/48). The median time to tumor progresssion (TTP) was 14.3 months (range 6.0 – 22.7). ER, PgR and HER2 status was not significantly correlated with RR. TS expression was significantly associated with clinical efficacy of S-1. Moreover, it is notable that triple negative breast cancer (TNBC) revealed lower TS expression than luminal type (TNBC vs luminal type = 80% (8/10) vs 36.4% (4/11), P= 0.054, OR 0.143, 95% CI 0.020-1.032). According to the correlation between metastatic sites and RR, better RR was noted for soft tissue metastases (soft tissue vs visceral = 25% (5/20) vs 84% (5/6), OR 15.0 (95%CI 1.40–161.05). Conclusions: This study demonstrated that TS is a significant predicitve factor of S-1 in patients with MBC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.27_suppl.132
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 3
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    A network meta-analysis assessing the comparative effectiveness of neoadjuvant therapy for HER2-positive breast cancer.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. e11598-e11598
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e11598-e11598
    Abstract: e11598 Background: The growing number of anti-HER2 agents suggests the eventual need for defining the optimal choice of neoadjuvant therapy for HER2-positive breast cancer. Multiple-treatments meta-analysis synthesizes information from a network of trials and combines direct and indirect evidence on the relative effectiveness. An indirect estimate of the benefit of A over B can be obtained by comparing trials of A v C with trials of B v C. In this study, we assessed the efficacy and safety of neoadjuvant therapy for HER2-positive breast cancer by conducting the direct and indirect comparisons from multiple RCTs. Methods: The primary outcome of the study was the number of the patients who achieved pathological complete response (pCR) defined as no invasive residual in breast or node. Secondary objectives were the number of patients who completed the treatment as planned and adverse events including diarrhea, neutropenia, cardiac events and skin disorder. Results: We identified 1047 articles by database search and 10 studies met our criteria. A total of 2247 patients in 7 different treatment arms were assessed; chemotherapy (CT) alone, CT with single or dual anti-HER2 agents and dual anti-HER2 agents without CT. Anti-HER2 agents evaluated were trastuzumab (T-mab), lapatinib, pertuzumab (P-mab). There was no significant difference between dual targeting treatment arms (CT + T-mab + lapatinib v CT + T-mab + P-mab, OR; 1.11, [0.42-2.86] , p=0.41), however, lapatinib reduced the treatment completion mainly due to adverse events. Patients in dual targeting arms had significantly higher incidence of pCR than in other treatment arms. (CT + T-mab + P-mab v CT + T-mab, OR; 2.29, [1.02-5.02], p=0.02) Surface under the cumulative ranking probability curve (SUCRA) also indicated that CT + T-mab + P-mab had the highest probability of being the best treatment arm for pCR followed by CT + T-mab + lapatinib and CT + T-mab. Conclusions: This study provides evidence that combining two anti-HER2 agents with chemotherapy are the most effective treatment arms. Considering the cost and limited medical resources, CT + T-mab showed a well-balanced profile for efficacy, completion and safety.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.e11598
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Investigation of potential salivary biomarkers for the diagnosis of breast cancer.
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 28_suppl ( 2015-10-01), p. 145-145
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 28_suppl ( 2015-10-01), p. 145-145
    Abstract: 145 Background: Saliva is an easily accessible and informative biological fluid which has high potential for the early diagnosis of diseases. Saliva-based diagnostics, particularly those based on metabolomics technology, offer a promising clinical strategy by characterizing the association between salivary analysts and a particular disease. The aim of this study is to investigate potential biomarkers in human saliva to facilitate the early diagnosis of breast cancer. Methods: We conducted a comprehensive metabolite analysis of saliva samples obtained from 60 breast cancer patients and 20 healthy controls, using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). Statistical analyses were performed by using a nonparametric Mann-Whitney U test, multiple logistic regression and the receiver operating characteristics (ROC) to evaluate the predictive power of biomarkers. Results: Forty-nine patients (81.7 %) had invasive ductal carcinoma (IDC) and 9 patients (15.0 %) had ductal carcinoma in situ. In 33 patients receiving neoadjuvant treatment, saliva samples were obtained just before surgery. After removing the concomitantly observed peaks and noise peaks, an average of 205 peaks were derived from the metabolites. Among these peaks, five potential salivary biomarkers demonstrated significantly higher concentrations in breast cancer patients comparing with healthy individuals (p 〈 0.05). Especially, salivary biomarkers obtained from patients with IDC before neoadjuvant treatments tended to be higher concentrations than those obtained after treatment. In these metabolites, the area under the ROC curves (AUCs) were 0.765 for substance A, 0.716 for substance B, 0.809 for substance C, 0.819 for substance D and 0.850 for substance E. Conclusions: Salivary metabolites are promising biomarkers for the early diagnosis of breast cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.28_suppl.145
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Machine learning methods with salivary metabolomics for breast cancer detection.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 3135-3135
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 3135-3135
    Abstract: 3135 Background: Saliva is non-invasively accessible and informative biological fluid which has high potential for the early diagnosis of various diseases. The aim of this study is to develop machine learning methods and to explore new salivary biomarkers to discriminate breast cancer patients from healthy controls. Methods: We conducted a comprehensive metabolite analysis of saliva samples obtained from 101 patients with invasive carcinoma (IC), 23 patients with ductal carcinoma in situ (DCIS) and 42 healthy controls, using capillary electrophoresis and liquid chromatography with mass spectrometry to quantify hundreds of hydrophilic metabolites. Saliva samples were collected under 9h fasting and were split into training and validation data. Conventional statistical analyses and artificial intelligence-based methods were used to access the discrimination abilities of the quantified metabolite. Multiple logistic regression (MLR) model and an alternative decision tree (ADTree)-based machine learning methods were used. The generalization abilities of these mathematical models were validated in various computational tests, such as cross-validation and resampling methods. Results: Among quantified 260 metabolites, amino acids and polyamines showed significantly elevated in saliva from breast cancer patients, e.g. spermine showed the highest area under the receiver operating characteristic curves (AUC) to discriminate IC from C; 0.766 (95% confidence interval [CI]; 0.671 – 0.840, P 〈 0.0001). These metabolites showed no significant difference between C and DICS, i.e., these metabolites were elevated only in the samples of IC. The MLR yielded higher AUC to discriminate IC from C; 0.790 (95% CI; 0.699 – 0.859, P 〈 0.0001). The ADTree with ensemble approach showed the best AUC; 0.912 (95% CI; 0.838 – 0.961, P 〈 0.0001). In the comparison of these metabolites in the analysis of each subtype, seven metabolites were significantly different between Luminal A-like and Luminal B-like while, but few metabolites were significantly different among the other subtypes. Conclusions: These data indicated the combination of salivary metabolomic profiles including polyamines showed potential ability to screening breast cancer in a non-invasive way.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.3135
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 6
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    Online Resource
    Mechanisms of resistance to trastuzumab as neoadjuvant therapy in women with HER2-overexpressing operable breast cancer.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e11060-e11060
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e11060-e11060
    Abstract: e11060 Background: Despite clinical usefulness of trastuzumab, intrinsic or acquired resistance is a common clinical phenomenon. Potential mechanisms of resistance include aberrant downstream signaling caused by loss of PTEN and/or PIK3CA mutation, alternative signaling from IGF-1R and masking with MUC4. Methods: Patients with operable breast cancer received 12 cycles of weekly paclitaxel (80 mg/m2 IV) plus weekly trastuzumab (4mg/kg loading dose followed by 2 mg/kg IV) before surgery. All tumors were HER2-positive by immunohistochemistry (IHC) or fluorescence in situ hybridization. Expressions of ER, PgR, Ki67, PTEN, phosphorylated IGF-1R (pIGF-1R) and MUC4 were performed by IHC in core needle biopsy samples at baseline. ER and PgR status was assessed using Allred score. For Ki67 labeling index, a total of 400 cells were counted from three consecutive high-power magnifications. PTEN, pIGF-1R and MUC4 expression level was scored semiquantitatively based on staining intensity. PIK3CA mutation status was evaluated by sequencing of PIK3CA exons 9 and 20 using PCR amplification and direct sequencing. Results: Thirty-seven patients were enrolled and assessable for clinical and pathologic responses. The pCR rate was 48.6% (18/37). ER and PgR were positive in 18 (48.6%) and 16 (43.2%) patients, respectively. Negative, moderate and strong membranous expression of MUC4 was observed in 3 (8.1%), 18 (48.6%) and 12 (32.4%) patients, respectively. Membranous staining for pIGF1-R was negative in 24 (64.9%) patients. PTEN loss was observed in 33.3% (8/24) of the tumor examined. PIK3CA sequence analysis of the 13 tumors identified 2 mutations in exon 20 and 2 mutations in exon 9, corresponding to a PIK3CA mutation frequency of 30.8%. MUC4 and pIGF1-R status did not affect the pCR rate. PTEN loss and/or PIK3CA mutation were not significantly associated with pCR rate. pCR rate was significantly correlated with PgR negativity (p=0.004) and higher Ki67 (p=0.01). Conclusions: These data indicate that aberrant downstream signaling caused by loss of PTEN and/or PIK3CA mutation, alternative signaling from IGF-1R and masking with MUC4 were not important mechanisms of resistance to trastuzumab.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.e11060
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Extent of lymph node involvement in breast cancer patients with sentinel lymph node metastasis.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 27_suppl ( 2012-09-20), p. 199-199
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 27_suppl ( 2012-09-20), p. 199-199
    Abstract: 199 Background: Axillary lymph node dissection (ALND) is a standard procedure in patients with positive sentinel lymph node (SLN). However, the appropriate level of ALND remains to be elucidated. The aim of this study is to determine the extent of lymph node involvement and predictors to assess non-SLN status in patients with metastatic SLNs. Methods: A prospective database of 235 breast cancer patients with metastases in SLNs who underwent ALND at Keio University Hospital from January 2001 to December 2011 was reviewed. Results: The median age of the patients was 54 years (range 28-86 years) and the mean tumor size was 2.08±0.74 cm. The mean total number of sentinel, level I, and level II lymph nodes removed was 2.72, 18.2, and 2.47, respectively. Other tumor factors include 66.5 % lymphatic invasion positive, 23.7% being nuclear grade 3, 89.4% estrogen receptor positive, and 83.2% progesterone receptor positive. Among 235 patients with SLN involvement, non-SLN metastases were identified in 72 (30.7%) patients and 13 (5.5%) patients had metastases at level II nodes.A univariate analysis showed a significant correlation between non-SLN involvement and number of tumor-involved SLNs. The mean number of tumor-involved SLNs in patients with positive non-SLNs was 1.86 compared with 1.33 in patients with negative non-SLNs (p=0.001). Patients with 2 or more positive SLNs showed a significantly higher rate of non-SLN metastases compared with patients with 1 positive SLNs (47.4% (37/78) vs. 22.3% (35/157), p 〈 0.001).The mean number of tumor-involved SLNs in patients with positive lymph nodes in level II was 2.08 compared with 1.46 in patients with negative lymph nodes in level II (p=0.016). Patients with 2 or more positive SLNs showed a significantly higher rate of metastases at level II nodes compared with patients with 1 positive SLNs (10.3% (8/78) vs. 3.2% (5/157), p=0.0026). Conclusions: Among 235 patients with SLN involvement, the positive rate of non-SLN metastases was 30.7%, whereas that of level II lymph nodes was 5.5%. The number of tumor-involved SLNs was a significant predictor of non-SLN involvement and level II lymph node metastases.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.27_suppl.199
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 8
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    HOXB9 Expression Promoting Tumor Cell Proliferation and Angiogenesis Is Associated with Clinical Outcomes in Breast Cancer Patients
    Springer Science and Business Media LLC ; 2012
    In:  Annals of Surgical Oncology Vol. 19, No. 6 ( 2012-6), p. 1831-1840
    Details
    In: Annals of Surgical Oncology, Springer Science and Business Media LLC, Vol. 19, No. 6 ( 2012-6), p. 1831-1840
    Type of Medium: Online Resource
    ISSN: 1068-9265 , 1534-4681
    URL: Article
    DOI: 10.1245/s10434-012-2295-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2012
    detail.hit.zdb_id: 2074021-9
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  • 9
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    Substrate Study for Dihydroxyboryl Astatine Substitution Reaction with Fibroblast Activation Protein Inhibitor (FAPI)
    The Chemical Society of Japan ; 2022
    In:  Chemistry Letters Vol. 51, No. 11 ( 2022-11-05), p. 1091-1094
    Details
    In: Chemistry Letters, The Chemical Society of Japan, Vol. 51, No. 11 ( 2022-11-05), p. 1091-1094
    Type of Medium: Online Resource
    ISSN: 0366-7022 , 1348-0715
    URL: Article
    DOI: 10.1246/cl.220391
    RVK:
    VA 3560
    Language: English
    Publisher: The Chemical Society of Japan
    Publication Date: 2022
    detail.hit.zdb_id: 2063626-X
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  • 10
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    Comprehensive assessment of cancer stem cell like cells in prediction of pathologic complete response to preoperative dual anti–HER2 therapy for HER2–positive primary breast cancer.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e12123-e12123
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e12123-e12123
    Abstract: e12123 Background: Chemotherapy for breast cancer destroys non–stem cells while sparing cancer stem cells (CSCs). In contrast, anti–HER2 therapy may eliminate resistant cells because HER2 may be a key driver of CSCs. CSC biomarkers have been found to be prognostic of poor outcome and predictive of resistance to therapy. However, there are no comprehensive studies of the impact of anti-HER2 therapies on CSC–related biomarkers. We conducted a prospective biomarker determination study of breast CSCs characterized by CD44v expression and increased aldehyde dehydrogenase 1 (ALDH1) enzymatic activity or expression. Methods: In a prospective trial (ClinicalTrials.gov: NCT01688609), 18 patients with operable primary HER2+ breast cancer (≥T2 excluding inflammatory, any N; median age of 54 yrs) were treated with preoperative anti–HER2 therapy following the NeoALTTO trial dual therapy arm regimen, with a goal of identifying novel predictive biomarkers for pCR. Proportions of tumor cells with CSC characteristics, defined as CD44v+ and ALDH1+, were estimated at baseline, at 6 weeks (after therapy with lapatinib/trastuzumab) and at 18 weeks (after therapy with lapatinib/trastuzumab and paclitaxel) to assess adaptive response. We determined changes in the quantity and characteristics of CSC–related biomarkers during preoperative therapy and correlated them to tumor response. Results: Out of 18 patients, 8 (44%) had a pCR; 5 of these 8 patients (62%) were positive for CD44v staining on tumor cells at baseline and none were positive on the 6–week biopsy. In contrast, 6 of the 10 patients without pCR exhibited persistent levels, or enrichment of CD44v proportion and expression at 6 and 18 weeks (p = 0.0128). ALDH1 expression and other biomarkers were not statistically significant predictors of pCR. Conclusions: Enrichment of CD44v+ tumor cells after double anti–HER2 therapy may predict poor response to dual anti–HER2 therapy with cytotoxic chemotherapy. A second biopsy after the start of preoperative therapy may reflect biological changes useful for the guidance and application of therapeutic strategies for patients with HER2+ breast cancer. Clinical trial information: NCT01688609.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.e12123
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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