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Her2 breast

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
Monica Samuel Avila, Silvia Moreira Ayub-Ferreira, Mauro Rogerio de Barros Wanderley Junior, Fatima das Dores Cruz, Sara Michelly Gonçalves Brandão, Vagner Oliveira Carvalho Rigaud, Marilia Higushi-Dos-Santos, Ludhmila Abrahão Hajjar, Roberto Kalil Filho, Paulo Marcelo Hoff, Marina Sahade, Marcela S M Ferrari, Romulo Leopoldo de Paula Costa, Max Senna Mano, Cecilia Beatriz Bittencourt Viana Cruz, Maria Cristina Abduch, Marco Stephan Lofrano Alves, Guilherme Veiga Guimaraes, Victor Sarli Issa, Marcio Sommer Bittencourt, Edimar Alcides Bocchi
BACKGROUND: Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with β-blockers remains controversial. OBJECTIVE: The aim of this prospective, randomized, double-blind, placebo-controlled study was to evaluate the role of carvedilol in preventing ANT cardiotoxicity. METHODS: We randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m2 ) to receive carvedilol or placebo until chemotherapy completion...
March 3, 2018: Journal of the American College of Cardiology
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
Ling Deng, Xuehua Zhu, Yun Sun, Jiemin Wang, Xiaorong Zhong, Jiayuan Li, Min Hu, Hong Zheng
Purpose: The prevalence of PIK3CA in Chinese breast cancer patients may be underestimated. Therefore, we investigated the distribution of somatic PIK3CA/AKT1 mutations in Chinese breast cancer patients and explored their roles in tumor phenotypes and disease prognosis. Materials and Methods: Tumors from five hundred and seven breast cancer patients were prospectively collected from the West China Hospital between 2008 and 2013. Whole exons of AKT1 and PIK3CA were detected in fresh-frozen tumors using next-generation sequencing, and correlations between PIK3CA/AKT1 mutations and clinicopathological features were analyzed...
March 15, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
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
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
Zhengyuan Zhou, Satish K Chitneni, Nick Devoogdt, Michael R Zalutsky, Ganesan Vaidyanathan
In a previous study, we evaluated a HER2-specific single domain antibody fragment (sdAb) 2Rs15d labeled with18 F via conjugation of a residualizing prosthetic agent that was synthesized by copper-catalyzed azide-alkyne cycloaddition (CuAAC). In order to potentially increase overall efficiency and decrease the time required for labeling, we now investigate the use of a strain-promoted azide-alkyne cycloaddition (SPAAC) between the 2Rs15d sdAb, which had been pre-derivatized with an azide-containing residualizing moiety, and an18 F-labeled aza-dibenzocyclooctyne derivative...
March 10, 2018: Bioorganic & Medicinal Chemistry
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
Hidejiro Torigoe, Kazuhiko Shien, Tatsuaki Takeda, Takahiro Yoshioka, Kei Namba, Hiroki Sato, Ken Suzawa, Hiromasa Yamamoto, Junichi Soh, Masakiyo Sakaguchi, Shuta Tomida, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka
Human epidermal growth factor receptor 2 (HER2) plays an important role in the pathogenesis of various cancers. HER2 alterations have been suggested to be a therapeutic target in non-small-cell lung cancer (NSCLC), just as in breast and gastric cancers. We previously reported that the pan-HER inhibitor afatinib could be a useful therapeutic agent as HER2-targeted therapy for patients with NSCLC harboring HER2 alterations. However, acquired resistance to afatinib was observed in the clinical setting, similar to the case for other HER inhibitors...
March 13, 2018: Cancer Science
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
Andreas H Scheel, Frédérique Penault-Llorca, Wedad Hanna, Gustavo Baretton, Peter Middel, Judith Burchhardt, Manfred Hofmann, Bharat Jasani, Josef Rüschoff
BACKGROUND: Detection of HER2/neu receptor overexpression and/or amplification is a prerequisite for efficient anti-HER2 treatment of breast and gastric carcinomas. Immunohistochemistry (IHC) of the HER2 protein is the most common screening test, thus precise and reproducible IHC-scoring is of utmost importance. Interobserver variance still is a problem; in particular in gastric carcinomas the reliable differentiation of IHC scores 2+ and 1+ is challenging. Herein we describe the physical basis of what we called the 'magnification rule': Different microscope objectives are employed to reproducibly subdivide the continuous spectrum of IHC staining intensities into distinct categories (1+, 2+, 3+)...
March 12, 2018: Diagnostic Pathology
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
Elena Ongaro, Lorenzo Gerratana, Marika Cinausero, Giacomo Pelizzari, Elena Poletto, Manuela Giangreco, Claudia Andreetta, Stefano Pizzolitto, Carla Di Loreto, Alessandro Marco Minisini, Mauro Mansutti, Stefania Russo, Gianpiero Fasola, Fabio Puglisi
AIM: Discordance between primary tumor and paired metastases biology has been widely detected in metastatic breast cancer. The aim of this study was to evaluate the prognostic impact of Ki67, estrogen receptor (ER), progesterone receptor (PR) and HER2 discordance. METHODS: We retrospectively analyzed a cohort of 544 patients affected by metastatic breast cancer. Variation in ER, PR, Ki67 and HER2 expression between primary site and recurrence was tested through the McNemar test...
March 12, 2018: Future Oncology
Wenjuan Ma, Yumei Zhao, Yu Ji, Xinpeng Guo, Xiqi Jian, Peifang Liu, Shandong Wu
RATIONALE AND OBJECTIVES: This study aimed to investigate whether quantitative radiomic features extracted from digital mammogram images are associated with molecular subtypes of breast cancer. MATERIALS AND METHODS: In this institutional review board-approved retrospective study, we collected 331 Chinese women who were diagnosed with invasive breast cancer in 2015. This cohort included 29 triple-negative, 45 human epidermal growth factor receptor 2 (HER2)-enriched, 36 luminal A, and 221 luminal B lesions...
March 8, 2018: Academic Radiology
Leticia Varella, Jame Abraham, Megan Kruse
Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor (VEGF) that interferes with VEGF binding to its receptor on vascular endothelium. Bevacizumab has been approved for the treatment of various malignant tumors, and has been studied in combination with several cytotoxic agents in the treatment of breast cancer. In 2008, the US Food and Drug Administration granted accelerated approval for the use of bevacizumab in combination with weekly paclitaxel for first-line treatment of HER2-negative metastatic breast cancer...
August 2017: Seminars in Oncology
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