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https://www.readbyqxmd.com/read/28092860/design-synthesis-and-biological-evaluation-of-quinazoline-phosphoramidate-mustard-conjugates-as-anticancer-drugs
#1
Songwen Lin, Yingbo Li, Yufen Zheng, Laichun Luo, Qi Sun, Zemei Ge, Tieming Cheng, Runtao Li
A series of novel compounds with phosphoramide mustard functionality incorporated into the quinazoline scaffold of EGFR/HER2 inhibitors were designed and synthesized as multi-target-directed ligands against tumor cells. In vitro assays showed that tumor cell lines with high HER2 level were more sensitive to the compounds than tumor cells with low HER2 level. Compound 10d (EMB-3) was one of the most potent inhibitors with IC50 of 7.4 nM and 82 nM against EGFR and HER2, respectively. The mechanism studies were also supported by the effect of 10d-induced DNA damage in MDA-MB-468 cells...
January 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28092723/pertuzumab-and-breast-cancer-another-piece-in-the-anti-her2-puzzle
#2
Dr Lorenzo Gerratana, Dr Marta Bonotto, Dr Claudia Bozza, Dr Elena Ongaro, Dr Valentina Fanotto, Dr Giacomo Pelizzari, Prof Fabio Puglisi
The mechanism of action of pertuzumab, a recombinant anti-HER2 humanized monoclonal antibody, is complementary to trastuzumab's. On June 8, 2012, the Food and Drug Administration approved the combination of pertuzumab with trastuzumab and docetaxel as first-line treatment of HER2-positive metastatic breast cancer. Furthermore, pertuzumab is the first drug to be approved in the neoadjuvant setting using a pathological complete response as an endpoint. Areas covered: The review provides insights into the main mechanisms of action of pertuzumab...
January 16, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28090417/pattern-of-local-recurrence-and-distant-metastasis-in-breast-cancer-by-molecular-subtype
#3
Xingrao Wu, Ayesha Baig, Goulnar Kasymjanova, Kamran Kafi, Christina Holcroft, Hind Mekouar, Annie Carbonneau, Boris Bahoric, Khalil Sultanem, Thierry Muanza
BACKGROUND AND PURPOSE:  No longer considered a single disease entity, breast cancer is being classified into several distinct molecular subtypes based on gene expression profiling. These subtypes appear to carry prognostic implications and have the potential to be incorporated into treatment decisions. In this study, we evaluated patterns of local recurrence (LR), distant metastasis (DM), and association of survival with molecular subtype in breast cancer patients in the post-adjuvant radiotherapy setting...
December 9, 2016: Curēus
https://www.readbyqxmd.com/read/28089784/axillary-management-of-stage-ii-iii-breast-cancer-patients-treated-with-neoadjuvant-systemic-therapy-results-of-calgb-40601-her2-positive-and-calgb-40603-triple-negative
#4
David W Ollila, Constance T Cirrincione, Donald A Berry, Lisa A Carey, William M Sikov, Clifford A Hudis, Eric P Winer, Mehra Golshan
OBJECTIVES: Management of the axilla in stage II/III breast cancer undergoing neoadjuvant systemic therapy (NST) is controversial. To understand current patterns of care, we collected axillary data from two NST trials: HER2-positive (CALGB40601) and triple-negative (CALGB40603). METHODS: Axillary evaluation pre-/post-NST was per the treating surgeon and could include sentinel node biopsy (SNB). Post-NST, node-positive patients were recommended to undergo axillary lymph node dissection (ALND)...
January 12, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28089283/myc-amplification-as-a-predictive-factor-of-complete-pathologic-response-to-docetaxel-based-neoadjuvant-chemotherapy-for-breast-cancer
#5
Cynthia Brito Lins Pereira, Mariana Ferreira Leal, Eliana Saul Furquim Werneck Abdelhay, Sâmia Demachki, Paulo Pimentel Assumpção, Mirian Carvalho de Souza, Caroline Aquino Moreira-Nunes, Adriana Michiko da Silva Tanaka, Marília Cardoso Smith, Rommel Rodríguez Burbano
BACKGROUND: Neoadjuvant chemotherapy is a standard treatment for stage II and III breast cancer. The identification of biomarkers that may help in the prediction of response to neoadjuvant therapies is necessary for a more precise definition of the best drug or drug combination to induce a better response. MATERIAL AND METHODS: We assessed the role of Ki67, hormone receptors expression, HER2, MYC genes and their protein status, and KRAS codon 12 mutations as predictor factors of pathologic response to anthracycline-cyclophosphamide (AC) followed by taxane docetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer...
December 24, 2016: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28087106/charge-variant-analysis-of-proposed-biosimilar-to-trastuzumab
#6
Pravinkumar Dakshinamurthy, Pavithra Mukunda, Bhargav Prasad Kodaganti, Bharath Ravindra Shenoy, Bairavabalakumar Natarajan, Amol Maliwalave, Vivek Halan, Sathyabalan Murugesan, Sunit Maity
Trastuzumab is a humanized monoclonal antibody (mAb) employed for the treatment of HER2 Positive Breast Cancer. A HER2 overexpressing tumor cell binds to Trastuzumab and attracts immune cells which lead to induction of Antibody Dependent Cellular Cytotoxicity (ADCC) by binding to Fc receptors (CD16a or FcγRIIIa) on an effector cell, such as natural killer (NK) cells. The most commonly expressed receptor on NK cell is CD16a which binds to the Fc portion of Trastuzumab. The ligand-independent HER2-HER3 dimerization is the most potent stimulator of downstream pathways for regulation of cell growth and survival...
January 10, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28081544/nomogram-to-predict-pathologic-complete-response-in-her2-positive-breast-cancer-treated-with-neoadjuvant-systemic-therapy
#7
Takeo Fujii, Takahiro Kogawa, Jimin Wu, Aysegul A Sahin, Dian D Liu, Mariana Chavez-MacGregor, Sharon H Giordano, Akshara Raghavendra, Rushmy K Murthy, Debu Tripathy, Yu Shen, Jose-Miguel Yamal, Naoto T Ueno
BACKGROUND: Pathologic complete response (pCR) is associated with improved survival outcomes in patients with HER2-positive primary breast cancer. We developed a nomogram to predict the probability of pCR rates by using oestrogen receptor (ER) expression, progesterone receptor (PR) expression and HER2/CEP17 ratio as continuous variables. METHODS: We retrospectively reviewed patients with stages I-III HER2-positive invasive breast cancer who had definitive surgery in 1999-2015 and received neoadjuvant systemic therapy (NST)...
January 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28079792/amplification-of-her2-and-top2a-and-deletion-of-top2a-genes-in-a-series-of-taiwanese-breast-cancer
#8
Jim-Ray Chen, Hui-Ping Chien, Kuo-Su Chen, Cheng-Cheng Hwang, Huang-Yang Chen, Kun-Yan Yeh, Tsan-Yu Hsieh, Liang-Che Chang, Yuan-Chun Hsu, Ren-Jie Lu, Chung-Ching Hua
BACKGROUND: The prognostic relevance of topoisomerase II alpha (TOP2A) copy number change remains not well established. This study is aimed to investigate the frequency and pattern of TOP2A aberrations; to correlate TOP2A alterations with human epidermal growth factor receptor 2 (HER2) status and clinicopathological parameters, and further to explore prognostic value of TOP2A and HER2 status in breast cancer in Taiwan. METHODS: We analyzed tissue samples from 311 invasive carcinomas in tissue microarrays for TOP2A and HER2 status by fluorescent in situ hybridization...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28079291/prognostic-value-of-pd-l1-in-breast-cancer-a-meta-analysis
#9
Changjun Wang, Hanjiang Zhu, Yidong Zhou, Feng Mao, Yan Lin, Bo Pan, Xiaohui Zhang, Qianqian Xu, Xin Huang, Qiang Sun
Programmed cell death 1 ligand 1 (PD-L1) is a promising therapeutic target for cancer immunotherapy. However, the correlation between PD-L1 and breast cancer survival remains unclear. Here, we present the first meta-analysis to investigate the prognostic value of PD-L1 in breast cancer. We searched Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies evaluating PD-L1 expression and breast cancer survival. Fixed- and random-effect meta-analyses were conducted based on heterogeneity of included studies...
January 12, 2017: Breast Journal
https://www.readbyqxmd.com/read/28078108/egfr-family-and-cmet-expression-profiles-and-prognostic-significance-in-esophagogastric-adenocarcinoma
#10
Ellie Chan, Ahmad Alkhasawneh, Lizette Vila Duckworth, Tabish Aijaz, Tania Zuluaga Toro, Xiaomin Lu, Steven J Hughes, Amy Collinsworth, Thomas J George
BACKGROUND: Targeted therapy with anti-human epidermal growth factor receptor-2 (HER2) monoclonal antibody in patients with HER2 overexpressed esophagogastric adenocarcinoma (EGA) improves survival; however, the effect is transient due to the development of resistance. Some studies suggest that cMet overexpression provides cross talk for epidermal growth factor receptor (EGFR) and HER2 inhibition. We sought to characterize the expression profile of the EGFR family and cMet receptors in untreated, resected EGA...
December 2016: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28077399/her2-testing-and-clinical-decision-making-in-gastroesophageal-adenocarcinoma-guideline-from-the-college-of-american-pathologists-american-society-for-clinical-pathology-and-american-society-of-clinical-oncology
#11
REVIEW
Angela N Bartley, Mary Kay Washington, Christina B Ventura, Nofisat Ismaila, Carol Colasacco, Al B Benson, Alfredo Carrato, Margaret L Gulley, Dhanpat Jain, Sanjay Kakar, Helen J Mackay, Catherine Streutker, Laura Tang, Megan Troxell, Jaffer A Ajani
CONTEXT: ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA. OBJECTIVES: To establish an evidence-based guideline for HER2 testing in patients with GEA, to formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making...
December 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28076434/diabetes-and-breast-cancer-subtypes
#12
Heleen K Bronsveld, Vibeke Jensen, Pernille Vahl, Marie L De Bruin, Sten Cornelissen, Joyce Sanders, Anssi Auvinen, Jari Haukka, Morten Andersen, Peter Vestergaard, Marjanka K Schmidt
BACKGROUND: Women with diabetes have a worse survival after breast cancer diagnosis compared to women without diabetes. This may be due to a different etiological profile, leading to the development of more aggressive breast cancer subtypes. Our aim was to investigate whether insulin and non-insulin treated women with diabetes develop specific clinicopathological breast cancer subtypes compared to women without diabetes. METHODS AND FINDINGS: This cross-sectional study included randomly selected patients with invasive breast cancer diagnosed in 2000-2010...
2017: PloS One
https://www.readbyqxmd.com/read/28075166/the-predictive-value-of-ki-67-before-neoadjuvant-chemotherapy-for-breast-cancer-a-systematic-review-and-meta-analysis
#13
Xianyu Chen, Chao He, Dongdong Han, Meirong Zhou, Quan Wang, Jinhui Tian, Lun Li, Feng Xu, Enxiang Zhou, Kehu Yang
AIM: To review the predictive values of Ki-67 before neoadjuvant chemotherapy (NAC) for breast cancer patients. METHODS: PubMed and EMBASE were searched. Random-effect model meta-analysis was conducted using Revman software. RESULTS: High Ki-67 was associated with more pathological complete responses (pCRs) events (odds ratio: 3.10; 95% CI: 2.52-3.81; 53 studies, 10,848 patients) regardless of HR(+), HER2(+) and triple-negative breast cancer types, the definitions of pCR and cut-off points for Ki-67...
January 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/28074330/comparison-of-core-needle-biopsy-and-excision-specimens-for-the-accurate-evaluation-of-breast-cancer-molecular-markers-a-report-of-1003-cases
#14
Jie Chen, Zu Wang, Qing Lv, Zhenggui Du, Qiuwen Tan, Di Zhang, Bingjun Xiong, Helin Zeng, Juxiang Gou
In this study, we compared the accuracy of marker evaluation in core needle biopsy (CNB) specimens versus excision specimens (ESs) from breast cancer patients. This retrospective study used data collected from the breast cancer database at the West China Hospital, China. Immunohistochemistry (IHC) results from CNB specimens and ESs were compared, using estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 as markers. Molecular subtyping and endocrine therapy usage correlations based on CNB samples and ESs were evaluated...
January 10, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28074265/pharmacokinetic-and-exposure-response-analyses-of-pertuzumab-in-combination-with-trastuzumab-and-docetaxel-during-neoadjuvant-treatment-of-her2-%C3%A2-early-breast-cancer
#15
Angelica L Quartino, Hanbin Li, Jin Y Jin, D Russell Wada, Mark C Benyunes, Virginia McNally, Lucia Viganò, Ihsan Nijem, Bert L Lum, Amit Garg
PURPOSE: The NeoSphere trial evaluated pertuzumab in the neoadjuvant setting [early breast cancer (EBC)] with pathological complete response (pCR) as the primary efficacy end point. This analysis of pertuzumab aimed to (1) compare its pharmacokinetics (PK) in patients with EBC versus advanced cancers, (2) to further evaluate PK drug-drug interactions (DDIs) when given in combination with trastuzumab, and (3) to assess the relationship between exposure and efficacy to assess the clinical dosing regimen in the EBC patients...
January 10, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28073608/design-synthesis-and-biological-evaluation-of-7-aryl-2-3-dihydro-1-4-dioxino-2-3-g-quinoline-derivatives-as-potential-hsp90-inhibitors-and-anticancer-agents
#16
Sina Omid Malayeri, Khalil Abnous, Atefeh Arab, Maryam Akaberi, Soghra Mehri, Afshin Zarghi, Razieh Ghodsi
A new series of quinoline analogues was designed and synthesized as Hsp90 inhibitors. The cytotoxic activity of the synthesized compounds was evaluated against three human cancer cell lines including MCF-7 (human breast cancer cells), DU145 (human prostate cancer cell lines), and A549 (adenocarcinomic human alveolar basal epithelial cells). Some of our compounds (13a-13f) showed significant cytotoxic activity on MCF-7 cells. The most potent anti-proliferative compounds were also tested against Her2, a client protein of Hsp90...
January 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28072973/-expression-of-foxm1-and-bcrp-in-invasive-breast-carcinoma-of-no-special-type-and-its-prognosis-significance
#17
Y Liu, Y P Liu, J Y Liu, H C Yang, Z D Wang
Objective: To investigate the relationship between expression of FoxM1 and BCRP in invasive breast carcinoma of no special type (IBC-NST) tissues and the clinical pathological characteristics and prognosis of the patients. Methods: Seventy-eight cases of IBC-NST with excision were included. The expression of FoxM1 and BCRP was assessed by immunohistochemistry and its relationship with the clinical pathological characteristics and prognosis was evaluated. Results: FoxM1 was expressed in 71.8%(56/78) of IBC-NST, and the expression was related to tumor diameter, TNM staging, ER, PR and HER2...
January 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28071616/presenting-features-treatment-patterns-and-outcomes-of-patients-with-breast-cancer-in-pakistan-experience-at-a-university-hospital
#18
S Kumar, A J Shaikh, Y A Rashid, N Masood, Atv Mohammed, U Z Malik, G Haider, N Niamutullah, S Khan
BACKGROUND: Breast cancer is the most common cancer in Pakistani women. We report the presenting features, treatment patterns and survival of breast cancer from a University Hospital in Southern Pakistan and compare the data with international population based studies. MATERIALS AND METHODS: Medical records of patients diagnosed to have breast cancer between January 1999 and November 2008 were reviewed retrospectively. RESULTS: A total of 845 patients were identified...
April 2016: Indian Journal of Cancer
https://www.readbyqxmd.com/read/28070095/two-cases-of-unresectable-advanced-her2-positive-gastric-cancer-perforation-during-chemotherapy-with-trastuzumab
#19
Katsunori Matsueda, Tatsuya Toyokawa, Yuya Ueda, Shinya Endo, Masahiro Sakata, Isao Fujita, Jouichiro Horii, Takako Murakami
Case 1 was a 70-year-old man, and case 2 was a 65-year-old woman. Both were diagnosed with type 2 advanced HER2-positive gastric cancer. Capecitabine, cisplatin, and trastuzumab (HXP therapy) were administered to both patients. However, both patients developed peritonitis caused by gastric cancer perforation during HXP therapy on day 38 for case 1 and day 8 for case 2. Emergency omentum filling and gastric segmental resection were performed for both patients. The same chemotherapy regimen was continued after the surgery, and partial response was observed in both patients...
2017: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
https://www.readbyqxmd.com/read/28069112/-immunohistochemical-assessment-of-her2-expression-in-gastric-cancer-a-clinicopathologic-study-of-93-cases
#20
Isabel Alvarado-Cabrero, Sara Gil-Hernández, Ana Ruelas-Perea, Diego Villaverde-Rodríguez, José Roberto Montes-Ochoa, Rafael Medrano-Guzmán
BACKGROUND: Gastric cancer in Mexico is ranked third in both males and females. Most patients present clinically with advanced disease and treatment options are sparse. HER2 overexpression in gastric cancer is related to poor outcome. Immunohistochemical testing for HER2 is becoming the standard of care for guiding adjuvant treatment of gastric cancer with trastuzumab. OBJECTIVES: To determine the frequency of HER2 overexpression in patients with gastric cancer in the Hospital de Oncología del Centro Médico Nacional, Siglo XXI and its association with other histopathological findings...
January 6, 2017: Cirugia y Cirujanos
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