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HER2 positive

Timothy Kwang Yong Tay, Aye Aye Thike, Nirmala Pathmanathan, Ana Richelia Jara-Lazaro, Jabed Iqbal, Adeline Shi Hui Sng, Heng Seow Ye, Jeffrey Chun Tatt Lim, Valerie Cui Yun Koh, Jane Sie Yong Tan, Joe Poh Sheng Yeong, Zi Long Chow, Hui Hua Li, Chee Leong Cheng, Puay Hoon Tan
Background: Ki67 positivity in invasive breast cancers has an inverse correlation with survival outcomes and serves as an immunohistochemical surrogate for molecular subtyping of breast cancer, particularly ER positive breast cancer. The optimal threshold of Ki67 in both settings, however, remains elusive. We use computer assisted image analysis (CAIA) to determine the optimal threshold for Ki67 in predicting survival outcomes and differentiating luminal B from luminal A breast cancers...
February 20, 2018: Oncotarget
Fernanda Ramos-Gomes, Julia Bode, Alyona Sukhanova, Svetlana V Bozrova, Mara Saccomano, Miso Mitkovski, Julia Eva Krueger, Anja K Wege, Walter Stuehmer, Pavel S Samokhvalov, Daniel Baty, Patrick Chames, Igor Nabiev, Frauke Alves
Early detection of malignant tumours and, especially, micrometastases and disseminated tumour cells is still a challenge. In order to implement highly sensitive diagnostic tools we demonstrate the use of nanoprobes engineered from nanobodies (single-domain antibodies, sdAbs) and fluorescent quantum dots (QDs) for single- and two-photon detection and imaging of human micrometastases and disseminated tumour cells in ex vivo biological samples of breast and pancreatic metastatic tumour mouse models expressing human epidermal growth factor receptor 2 (HER2) or carcinoembryonic antigen (CEA)...
March 15, 2018: Scientific Reports
Volkmar Müller, Michael Clemens, Jacek Jassem, Nedal Al-Sakaff, Petra Auclair, Eveline Nüesch, Debbie Holloway, Mona Shing, Yung-Jue Bang
BACKGROUND: Trastuzumab (Herceptin® [H]) is the standard of care for HER2-positive locally advanced/metastatic breast cancer and gastric/gastroesophageal junction (GEJ) cancer. However, there is a paucity of data available on long-term H treatment of patients. The Rollover Protocol (ROP) Study was conducted to report safety data for patients with HER2-positive locally advanced/metastatic breast and gastric/GEJ cancer who have received long-term H therapy (≥ 5 years and ≥ 3 years for breast and gastric/GEJ cancer, respectively)...
March 15, 2018: BMC Cancer
Michael Untch, Gunter von Minckwitz, Bernd Gerber, Christian Schem, Mahdi Rezai, Peter A Fasching, Hans Tesch, Holm Eggemann, Claus Hanusch, Jens Huober, Christine Solbach, Christian Jackisch, Georg Kunz, Jens-Uwe Blohmer, Maik Hauschild, Tanja Fehm, Valentina Nekljudova, Sibylle Loibl
Purpose The GeparQuinto phase III trial demonstrated a lower pathologic complete response (pCR; pT0 ypN0) rate when lapatinib was added to standard anthracycline-taxane chemotherapy compared with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer. Here, we report the long-term outcomes. Methods Patients with HER2-positive tumors (n = 615) received neoadjuvant treatment with epirubicin (E) plus cyclophosphamide (C), followed by docetaxel (T) in combination with either lapatinib (L) or trastuzumab (H; ECH-TH arm: n = 307; ECL-TL arm: n = 308)...
March 15, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Kelly Kyker-Snowman, Bracha Erlanger Avigdor, Mansoor Nasim, Ashley Cimino-Mathews, Sarah J Wheelan, Pedram Argani, Ben Ho Park
BACKGROUND/PURPOSE: Tumor heterogeneity is a now well-recognized phenomenon that can affect the classification, prognosis and treatment of human cancers. Heterogeneity is often described in primary breast cancers based upon histologic subtypes, hormone- and HER2-receptor status, and immunolabeling for various markers, which can be seen within a single tumor as mixed cellular populations, or as separate discrete foci. EXPERIMENTAL DESIGN/METHODS: Here, we present a case report of a patient's primary breast cancer that had two separate but adjacent histologic components, one that was estrogen receptor (ER) positive, and the other ER negative...
March 15, 2018: Breast Cancer Research and Treatment
Hua Ye, Xuyu Chai, Xiaoyu Wang, Qi Zheng, Dingcheng Zheng, Feng Wu, Cheng Zheng, Ping Chen
The autophagy involved in the occurrence, development and prognosis of human epidermal growth factor receptor 2 (HER2) gene-amplified cancer also controls the resistance of this type of cancer to the monoclonal antibody, trastuzumab (Tzb). In the present study, Tzb resistance was established in HER2-positive NCI-N87 cell lines (Tzb-refractory cells). The cell viability, clonogenic assay, ratios of light chain 3 II/I, sequestosome 1 expression, and the phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR) were investigated in the parental and Tzb-refractory cells...
April 2018: Oncology Letters
Mi Hwa Heo, Hee Kyung Kim, Hansang Lee, Ji-Yeon Kim, Jin-Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Background/Aims: We conducted a retrospective analysis of the clinical activity of fulvestrant in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) previously treated with endocrine therapy and/or chemotherapy. Methods: We reviewed the medical records of all patients with MBC treated at Samsung Medical Center between January 2009 and August 2016. Patients received fulvestrant 250 mg intramuscularly every 28 days (from January 2009 to November 2010) or 500 mg intramuscularly every 28 days (from December 2010 to August 2016)...
March 16, 2018: Korean Journal of Internal Medicine
Tanaya Vaidya, Robert M Straubinger, Sihem Ait-Oudhia
PURPOSE: Trastuzumab combined with Doxorubicin (DOX) demonstrates significant clinical activity in human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC). However, emergence of treatment resistance and trastuzumab associated cardiotoxicity remain clinical challenges. In an effort to improve patient outcome, we have developed and evaluated novel tri-functional immunoliposomes (TFIL) that target HER2-receptors on BC cells and CD3-receptors on T-lymphocytes, and deliver DOX...
March 13, 2018: Pharmaceutical Research
Jiaolong Shi, Fengping Li, Xingxing Yao, Tingyu Mou, Zhijun Xu, Zheng Han, Siyu Chen, Wende Li, Jiang Yu, Xiaolong Qi, Hao Liu, Guoxin Li
Trastuzumab is the only target to be approved as the first-line treatment of HER2 positive metastatic gastric cancer, but ubiquitous resistance decreases its therapeutic benefit. In this study, we found HER4, phosphorylation HER4 (p-HER4) and the mesenchymal marker Vimentin increased in trastuzumab-resistant cells (MKN45TR and NCI-N87TR), while epithelial markers expressions in trastuzumab-resistant cell lines and animal models decreased. Additionally, silencing HER4 prevented the epithelial-mesenchymal transition and led to decreased proliferation and migration in vitro and in vivo...
March 14, 2018: Oncogene
Jeff Sperinde, Weidong Huang, Aki Vehtari, Ahmed Chenna, Pirkko-Liisa Kellokumpu-Lehtinen, John Winslow, Petri Bono, Yolanda Lie, Christos J Petropoulos, Jodi Marie Weidler, Heikki Joensuu
PURPOSE: Expression of p95HER2 (p95), a truncated form of the HER2 receptor, which lacks the trastuzumab binding site but retains kinase activity, has been reported as a prognostic biomarker for poor outcomes in trastuzumab-treated HER2-positive metastatic breast cancer. The impact of p95 expression on trastuzumab treatment efficacy in early HER2-positive breast cancer is less clear. In the current study, p95 was tested as a predictive marker of trastuzumab treatment benefit in the HER2-positive subset of the FinHer adjuvant phase III trial...
March 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Diana David, Arun Surendran, Jissa V Thulaseedharan, Asha S Nair
BACKGROUND: Smurf2 E3 ubiquitin ligase physically associates with and regulate the stability of distinct cellular protein substrates. The multi-functional scaffold protein Connector enhancer of kinase suppressor of ras 2 (CNKSR2) plays a key role in regulating cell proliferation, and differentiation through multiple receptor tyrosine kinase pathways. The aim of this study was to investigate whether the interaction between Smurf2 and CNKSR2 has any significant role in the post transcriptional regulation of CNKSR2 expression in breast cancer...
March 13, 2018: BMC Cancer
Eunpi Cho, Qian Wu, Lena Rubinstein, Hannah Linden, Julie Gralow, Jennifer Specht, Vijayakrishna Gadi, Georgiana Ellis
Many studies have sought to optimize the dosing schedule of adjuvant chemotherapy in early-stage breast cancer. Here, we assessed the use of continuous metronomic weekly doxorubicin plus daily oral cyclophosphamide (AC) with continuous G-CSF growth factor support for 12 weeks followed by weekly nab-paclitaxel (nP) for 12 weeks. A nonrandomized phase II clinical trial was designed to assess (1) DFS at 2 years, (2) dose delivered, (3) use of nP in the adjuvant setting, and (4) toxicities. The dosing of A was 24 mg/m2 IV weekly and C was 60 mg/m2 oral daily (with scheduled filgrastim 5mcg/kg 6 days/week); nP, 100 mg/m2 IV weekly...
March 13, 2018: Breast Journal
A Mukherjee, R Russell, Suet-Feung Chin, B Liu, O M Rueda, H R Ali, G Turashvili, B Mahler-Araujo, I O Ellis, S Aparicio, C Caldas, E Provenzano
The integration of genomic and transcriptomic profiles of 2000 breast tumours from the METABRIC [Molecular Taxonomy of Breast Cancer International Consortium] cohort revealed ten subtypes, termed integrative clusters (IntClust/s), characterised by distinct genomic drivers. Central histopathology ( N  = 1643) review was undertaken to explore the relationship between these ten molecular subtypes and traditional clinicopathological features. IntClust subtypes were significantly associated with histological type, tumour grade, receptor status, and lymphocytic infiltration ( p  < 0...
2018: NPJ Breast Cancer
Saranya Chumsri, Jeff Sperinde, Heshan Liu, Joseph Gligorov, Jean-Philippe Spano, Martine Antoine, Alvaro Moreno-Aspita, Winston Tan, John Winslow, Christos J Petropoulos, Ahmed Chenna, Michael Bates, Jodi Marie Weidler, Weidong Huang, Amylou C Dueck, Edith A Perez
BACKGROUND: p95HER2 is a truncated form of human epidermal growth factor receptor 2 (HER2) that confers resistance to trastuzumab in vitro, but clinical results have been conflicting to date. Given that p95HER2 levels correlate with total HER2 expression levels, which confer better outcomes, we sought to evaluate the p95HER2/HER2 ratio in the North Central Cancer Treatment Group N0337 and N98-32-52 trials. METHODS: The HERmark assay and VeraTag technology (Monogram Biosciences) were used to measure total HER2 and p95HER2 expression levels in 91 patient samples...
March 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Martin Filipits, Urania Dafni, Michael Gnant, Varvara Polydoropoulou, Margaret Hills, Astrid Kiermaier, Evandro De Azambuja, Denis P Larsimont, Federico Rojo, Giuseppe Viale, Masakazu Toi, Nadia Harbeck, Kathleen I Pritchard, Richard D Gelber, Phuong Dinh, Dimitrios Zardavas, Brian Leyland-Jones, Martine Piccart-Gebhart, Mitch Dowsett
PURPOSE: To assess the prognostic and predictive value of selected biomarkers involved in cell cycle regulation or proliferation in HER2-positive early breast cancer patients. METHODS: Protein expression of TOP2A, Ki67, cyclin D1 and p27 was immunohistochemically determined in tissue microarrays of surgical specimens from 862 patients randomized to trastuzumab (1 or 2 year; N=561) and observation (N=301) arms of the HERA trial. The primary analysis endpoint was disease-free survival (DFS)...
March 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Alex C Herskovic, Xian Wu, Paul J Christos, Himanshu Nagar
PURPOSE: We used the National Cancer Data Base to analyze practice patterns of adjuvant breast radiotherapy (RT) in elderly patients to see if a difference in overall survival (OS) could be detected. Additionally, we investigated factors that affected OS in these patients. PATIENTS AND METHODS: Women aged ≥ 65 years with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative pathologic T1-T2N0M0 invasive breast cancer measuring up to 3 cm who were treated with breast conservation and adjuvant endocrine therapy without adjuvant chemotherapy were identified and stratified by use of adjuvant RT...
February 20, 2018: Clinical Breast Cancer
Scott Kizy, Jing Li Huang, Schelomo Marmor, Anne Blaes, Jianling Yuan, Heather Beckwith, Todd M Tuttle, Jane Yuet Ching Hui
CONTEXT: - The 21-gene recurrence score (RS) provides a probability of distant recurrence for estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers. The utility of RS for rarer histologic subtypes of breast cancer is uncertain. OBJECTIVE: - To determine the distribution of RS among various histologic subtypes using a population database. DESIGN: - Women between the ages of 18 and 75 with estrogen receptor-positive, HER2-negative breast cancer and known RS results were identified using the Surveillance, Epidemiology, and End Results database...
March 12, 2018: Archives of Pathology & Laboratory Medicine
Shinya Sakata, Yasumiko Sakamoto, Akira Takaki, Shiho Ishizuka, Sho Saeki, Kazuhiko Fujii
Pseudomesotheliomatous carcinoma of the lung is very rare, and reversible restrictive lung disease with pseudomesotheliomatous carcinoma has not yet been previously reported. We herein report a patient with HER2-positive non-small-cell lung cancer (NSCLC) showing pseudomesotheliomatous carcinoma who was successfully treated with bevacizumab combination chemotherapy. A 56-year-old Japanese woman with advanced NSCLC presented with dyspnea. We administered chemotherapy with cisplatin (75 mg/m2 ) plus pemetrexed (500 mg/m2 ) plus bevacizumab (15 mg/kg), followed by pemetrexed plus bevacizumab...
March 9, 2018: Internal Medicine
Kimberly Blackwell, Joseph Gligorov, Ira Jacobs, Chris Twelves
Trastuzumab improves survival outcomes for patients with HER2-positive (HER2+ ) breast cancer, yet not all such women receive this important therapy. Trastuzumab was approved by the US Food and Drug Administration in 1998 and the European Medicines Agency in 2000 as treatment for HER2+ metastatic breast cancer (MBC). Observational studies between 2000 and 2015 in patients with HER2+ MBC suggest that nearly 12% in the United States, 27% to 54% in Europe, and 27.1% to 49.2% in China did not receive trastuzumab or any other HER2-targeted agent as first- and/or later-line for treatment of metastatic disease...
February 2, 2018: Clinical Breast Cancer
Yanchun Li, Mateusz Opyrchal, Song Yao, Xuan Peng, Li Yan, Hossam Jabbour, Thaer Khoury
PURPOSE: The purpose of the study is to investigate the prognostic significance of programmed death ligand-1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in HER2+ breast cancer (BC). METHODS: HER2+ BC cases (n  = 191) were collected between 1996 and 2013. Tissue microarray (TMA) slides were stained with two clones of PD-L1 antibodies (28-8 and 22C3) and the percentage of positive membranous staining was scored. TILs of the full sections were also scored using percentage scale...
March 9, 2018: Breast Cancer Research and Treatment
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