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Breast Cancer HER2+

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https://www.readbyqxmd.com/read/27926948/intrinsic-subtype-switching-and-acquired-erbb2-her2-amplifications-and-mutations-in-breast-cancer-brain-metastases
#1
Nolan Priedigkeit, Ryan J Hartmaier, Yijing Chen, Damir Vareslija, Ahmed Basudan, Rebecca J Watters, Roby Thomas, Jose P Leone, Peter C Lucas, Rohit Bhargava, Ronald L Hamilton, Juliann Chmielecki, Shannon L Puhalla, Nancy E Davidson, Steffi Oesterreich, Adam M Brufsky, Leonie Young, Adrian V Lee
Importance: Patients with breast cancer (BrCa) brain metastases (BrM) have limited therapeutic options. A better understanding of molecular alterations acquired in BrM could identify clinically actionable metastatic dependencies. Objective: To determine whether there are intrinsic subtype differences between primary tumors and matched BrM and to uncover BrM-acquired alterations that are clinically actionable. Design, Setting, and Participants: In total, 20 cases of primary breast cancer tissue and resected BrM (10 estrogen receptor [ER]-negative and 10 ER-positive) from 2 academic institutions were included...
December 7, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27926493/developmental-therapeutics-for-inflammatory-breast-cancer-biology-and-translational-directions
#2
REVIEW
Ricardo Costa, Cesar A Santa-Maria, Giovanna Rossi, Benedito A Carneiro, Young Kwang Chae, William J Gradishar, Francis J Giles, Massimo Cristofanilli
Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer, which accounts for approximately 3% of cases of breast malignancies. Diagnosis relies largely on its clinical presentation, and despite a characteristic phenotype, underlying molecular mechanisms are poorly understood. Unique clinical presentation indicates that IBC is a distinct clinical and biological entity when compared to non-IBC. Biological understanding of non-IBC has been extrapolated into IBC and targeted therapies for HER2 positive (HER2+) and hormonal receptor positive non-IBC led to improved patient outcomes in the recent years...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925203/the-genetic-landscape-of-breast-carcinomas-with-neuroendocrine-differentiation
#3
Caterina Marchiò, Felipe C Geyer, Charlotte Ky Ng, Salvatore Piscuoglio, Maria R De Filippo, Marco Cupo, Anne M Schultheis, Raymond S Lim, Kathleen A Burke, Elena Guerini-Rocco, Mauro Papotti, Larry Norton, Anna Sapino, Britta Weigelt, Jorge S Reis-Filho
Neuroendocrine breast carcinomas (NBCs) account for 2-5% of all invasive breast cancers and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), are HER2-negative and of luminal subtype. Here we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER+/HER2-) breast cancer display distinct repertoires of somatic mutations. Eighteen ER+/HER2- NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissue were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast cancer and/or related to DNA repair...
December 7, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27923043/clonal-evolutionary-analysis-during-her2-blockade-in-her2-positive-inflammatory-breast-cancer-a-phase-ii-open-label-clinical-trial-of-afatinib-vinorelbine
#4
Gerald Goh, Ramona Schmid, Kelly Guiver, Wichit Arpornwirat, Imjai Chitapanarux, Vinod Ganju, Seock-Ah Im, Sung-Bae Kim, Arunee Dechaphunkul, Jedzada Maneechavakajorn, Neil Spector, Thomas Yau, Mehdi Afrit, Slim Ben Ahmed, Stephen R Johnston, Neil Gibson, Martina Uttenreuther-Fischer, Javier Herrero, Charles Swanton
BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923036/cotargeting-of-cyp-19-aromatase-and-emerging-pivotal-signalling-pathways-in-metastatic-breast-cancer
#5
REVIEW
Stine Daldorff, Randi Margit Ruud Mathiesen, Olav Erich Yri, Hilde Presterud Ødegård, Jürgen Geisler
Aromatase inhibition is one of the cornerstones of modern endocrine therapy of oestrogen receptor-positive (ER+) metastatic breast cancer (MBC). The nonsteroidal aromatase inhibitors anastrozole and letrozole, as well as the steroidal aromatase inactivator exemestane, are the preferred drugs and established worldwide in all clinical phases of the disease. However, although many patients suffering from MBC experience an initial stabilisation of their metastatic burden, drug resistance and disease progression occur frequently, following in general only a few months on treatment...
December 6, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27920729/transcriptional-network-architecture-of-breast-cancer-molecular-subtypes
#6
Guillermo de Anda-Jáuregui, Tadeo E Velázquez-Caldelas, Jesús Espinal-Enríquez, Enrique Hernández-Lemus
Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27920688/complete-and-sustained-response-with-a-doublet-chemotherapy-protocol-in-an-81-year-old-patient-with-metastatic-breast-cancer
#7
Taynah Cascaes Puty, Gabriel S A Brito, Mariana S Dias, Henrique C Miranda, Juliana R Chaves, Heryvelton L Freitas, Luís E W Carvalho
Metastatic breast cancer (MBC) entails an overall 5-year survival of approximately 25%. The choice of therapy is influenced by expression of the HER2 gene and hormone receptors, by a disease-free interval, and by age. The use of paclitaxel combined with gemcitabine (doublet protocol) has shown efficacy as first-line treatment for MBC in either initial or maintenance therapy when compared to monotherapy with paclitaxel. There is evidence showing that the doublet protocol is a good alternative to maintenance therapy in women under 50 years old...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27920624/neoadjuvant-chemotherapy-with-docetaxel-carboplatin-and-weekly-trastuzumab-is-active-in-her2-positive-early-breast-cancer-results-after-a-median-follow-up-of-over-4-years
#8
Hans-Christian Kolberg, Leyla Akpolat-Basci, Miltiades Stephanou, Bahriye Aktas, Carla Verena Hannig, Cornelia Liedtke
INTRODUCTION: Most patients with HER2-positive breast cancer receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline-containing regimes. Previous investigations on neoadjuvant treatment with taxanes, platinum salts and trastuzumab showed pathological complete remission (pCR) rates between 43.3 and 76%. To date, the longest published follow-up in this indication is 3 years...
October 2016: Breast Care
https://www.readbyqxmd.com/read/27920432/discovery-of-an-enzyme-and-substrate-selective-inhibitor-of-adam10-using-an-exosite-binding-glycosylated-substrate
#9
Franck Madoux, Daniela Dreymuller, Jean-Phillipe Pettiloud, Radleigh Santos, Christoph Becker-Pauly, Andreas Ludwig, Gregg B Fields, Thomas Bannister, Timothy P Spicer, Mare Cudic, Louis D Scampavia, Dmitriy Minond
ADAM10 and ADAM17 have been shown to contribute to the acquired drug resistance of HER2-positive breast cancer in response to trastuzumab. The majority of ADAM10 and ADAM17 inhibitor development has been focused on the discovery of compounds that bind the active site zinc, however, in recent years, there has been a shift from active site to secondary substrate binding site (exosite) inhibitor discovery in order to identify non-zinc-binding molecules. In the present work a glycosylated, exosite-binding substrate of ADAM10 and ADAM17 was utilized to screen 370,276 compounds from the MLPCN collection...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919976/phase-i-study-of-triweekly-nab-paclitaxel-combined-with-s-1-in-patients-with-her2-negative-metastatic-breast-cancer
#10
Koichi Sakaguchi, Katsuhiko Nakatsukasa, Tetsuya Taguchi
AIM: We conducted a phase I study to determine the maximum tolerated dose (MTD) and recommended dose (RD) of triweekly nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and S-1 combination therapy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). PATIENTS AND METHODS: This study was carried out with a 3+3 dose escalation design; patients with HER2-negative MBC received nab-paclitaxel at 180-260 mg/m(2) on day 1 and S-1 at 65-80 mg/m(2) daily on days 1-14, repeated every 3 weeks...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919974/a-phase-ii-study-of-adjuvant-chemotherapy-of-tegafur-uracil-for-patients-with-breast-cancer-with-her2-negative-pathologic-residual-invasive-disease-after-neoadjuvant-chemotherapy
#11
Satoru Tanaka, Mitsuhiko Iwamoto, Kosei Kimura, Yuko Takahashi, Hiyoya Fujioka, Nayuko Sato, Risa Terasawa, Kanako Kawaguchi, Ayana Ikari, Tomo Tominaga, Saki Maezawa, Nodoka Umezaki, Junna Matsuda, Kazuhisa Uchiyama
BACKGROUND: There is no consensus on the need for adjuvant chemotherapy for patients with pathological residual invasive breast cancer (non-pCR) after neoadjuvant chemotherapy (NAC). We evaluated the tolerability and safety of tegafur-uracil (UFT) as adjuvant chemotherapy for patients with human epidermal growth factor receptor 2-negative breast cancer that resulted in non-pCR after NAC. PATIENTS AND METHODS: We treated patients with 270 mg/m(2) UFT per day for 2 years after definitive surgery and radiotherapy, if necessary...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919965/bevacizumab-combined-with-docetaxel-or-paclitaxel-as-first-line-treatment-of-her2-negative-metastatic-breast-cancer
#12
Leena Tiainen, Minna Tanner, Outi Lahdenperä, Pia Vihinen, Arja Jukkola, Peeter Karihtala, Niina Paunu, Teppo Huttunen, Pirkko-Liisa Kellokumpu-Lehtinen
AIM: The study evaluated the efficacy of bevacizumab combined with a taxane-based treatment for advanced breast cancer. PATIENTS AND METHODS: In this non-randomized phase II study 65 patients received 10 mg/kg bevacizumab i.v. (days 1 and 15, q4w) plus either 50 mg/m(2) docetaxel (days 1 and 15, q4w) or 90 mg/m(2) paclitaxel (days 1,8 and 15, q4w) i.v. until disease progression, maximal response, unacceptable toxicity or the withdrawal of consent. Patients without progression continued bevacizumab at 15 mg/kg i...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919946/in-vivo-selection-of-intermediately-and-highly-malignant-variants-of-triple-negative-breast-cancer-in-orthotopic-nude-mouse-models
#13
Shuya Yano, Kiyoto Takehara, Hiroyuki Kishimoto, Hiroshi Tazawa, Yasuo Urata, Shunsuke Kagawa, Michael Bouvet, Toshiyoshi Fujiwara, Robert M Hoffman
AIM: Triple-negative breast cancer (TNBC), defined by the absence of receptors for estrogen, progesterone and human epithelial receptor 2 (HER2), is a recalcitrant disease in need of effective therapy. We previously isolated very-highly metastatic variants of the TNBC cell line MDA-MB-231 using serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. MATERIALS AND METHODS: MDA-MB-231 cells expressing red fluorescent protein (MDA-MB-231-RFP) (1×10(7) cells/site) were initially injected subcutaneously in the flank of nude mice...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27918782/biosimilar-therapy-for-erbb2-her2-positive-breast-cancer-close-enough
#14
Harold J Burstein, Deborah Schrag
No abstract text is available yet for this article.
December 1, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27918780/effect-of-a-proposed-trastuzumab-biosimilar-compared-with-trastuzumab-on-overall-response-rate-in-patients-with-erbb2-her2-positive-metastatic-breast-cancer-a-randomized-clinical-trial
#15
Hope S Rugo, Abhijit Barve, Cornelius F Waller, Miguel Hernandez-Bronchud, Jay Herson, Jinyu Yuan, Rajiv Sharma, Mark Baczkowski, Mudgal Kothekar, Subramanian Loganathan, Alexey Manikhas, Igor Bondarenko, Guzel Mukhametshina, Gia Nemsadze, Joseph D Parra, Maria Luisa T Abesamis-Tiambeng, Kakhaber Baramidze, Charuwan Akewanlop, Ihor Vynnychenko, Virote Sriuranpong, Gopichand Mamillapalli, Sirshendu Ray, Eduardo P Yanez Ruiz, Eduardo Pennella
Importance: Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab and chemotherapy significantly improves outcome in patients with ERBB2 (HER2)-positive metastatic breast cancer; a clinically effective biosimilar may help increase access to this therapy. Objective: To compare the overall response rate and assess the safety of a proposed trastuzumab biosimilar plus a taxane or trastuzumab plus a taxane in patients without prior treatment for ERBB2-positive metastatic breast cancer...
December 1, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27918430/androgen-receptor-a-complex-therapeutic-target-for-breast-cancer
#16
REVIEW
Ramesh Narayanan, James T Dalton
Molecular and histopathological profiling have classified breast cancer into multiple sub-types empowering precision treatment. Although estrogen receptor (ER) and human epidermal growth factor receptor (HER2) are the mainstay therapeutic targets in breast cancer, the androgen receptor (AR) is evolving as a molecular target for cancers that have developed resistance to conventional treatments. The high expression of AR in breast cancer and recent discovery and development of new nonsteroidal drugs targeting the AR provide a strong rationale for exploring it again as a therapeutic target in this disease...
December 2, 2016: Cancers
https://www.readbyqxmd.com/read/27918429/correction-budiarto-bugi-ratno-and-desriani-detection-of-her2-gene-polymorphism-in-breast-cancer-pcr-optimization-study-sci-pharm-2016-84-103-111
#17
Bugi Ratno Budiarto, Desriani
The authors wish to make the following corrections to their paper [1]:[...].
December 2, 2016: Scientia Pharmaceutica
https://www.readbyqxmd.com/read/27917007/roles-of-ras-homolog-a-in-invasive-ductal-breast-carcinoma
#18
Eriko Murakami, Yoko Nakanishi, Yukari Hirotani, Sumie Ohni, Xiaoyan Tang, Shinobu Masuda, Katsuhisa Enomoto, Kenichi Sakurai, Sadao Amano, Tsutomu Yamada, Norimichi Nemoto
Breast cancer has a poor prognosis owing to tumor cell invasion and metastasis. Although Ras homolog (Rho) A is involved in tumor cell invasion, its role in breast carcinoma is unclear. Here, RhoA expression was examined in invasive ductal carcinoma (IDC), with a focus on its relationships with epidermal-mesenchymal transition (EMT) and collective cell invasion. Forty-four surgical IDC tissue samples and two normal breast tissue samples were obtained. RhoA, E-cadherin, vimentin, and F-actin protein expression were analyzed by immunohistochemistry...
November 1, 2016: Acta Histochemica et Cytochemica
https://www.readbyqxmd.com/read/27916281/intratumoral-heterogeneity-of-macrophages-and-fibroblasts-in-breast-cancer-is-associated-with-the-morphological-diversity-of-tumor-cells-and-contributes-to-lymph-node-metastasis
#19
Lubov A Tashireva, Evgeny V Denisov, Tatiana S Gerashchenko, Daria N Pautova, Mikhail A Buldakov, Marina V Zavyalova, Julia Kzhyshkowska, Nadezhda V Cherdyntseva, Vladimir M Perelmuter
Recent studies have highlighted the heterogeneity of the tumor microenvironment (ME) and the importance of its analysis to the understanding of its impact on clinical outcomes. In this study, we aimed to analyze the intratumoral distribution of macrophages and fibroblasts in breast cancer (BC) based on the morphological diversity of tumor cells (tubular, alveolar, solid, trabecular and discrete structures) and the clinicopathological parameters of the disease. Thirty-six patients with invasive breast carcinoma of no special type were included in the study...
November 27, 2016: Immunobiology
https://www.readbyqxmd.com/read/27915204/powerpiinc-preoperative-window-of-endocrine-therapy-provides-information-to-increase-compliance-trial-changes-in-tumor-proliferation-index-and-quality-of-life-with-7-days-of-preoperative-tamoxifen
#20
Adam L Cohen, Rachel E Factor, Kathi Mooney, Mohamed E Salama, Mark Wade, Victoria Serpico, Emily Ostrander, Edward Nelson, Jane Porretta, Cindy Matsen, Philip Bernard, Ken Boucher, Leigh Neumayer
OBJECTIVES: A decrease in Ki67 during neoadjuvant therapy predicts response to tamoxifen. Previous trials have shown a decreased Ki67 in breast tumors with as little as two or more weeks of preoperative tamoxifen. Shortening the preoperative treatment time in window of opportunity clinical trials makes these trials more attractive to women. POWERPIINC examined the effect of 7 days of preoperative tamoxifen on breast tumor proliferation and patient symptoms. METHODS: Women with untreated stage I/II, ER-positive, invasive breast cancer with no contraindications to tamoxifen were enrolled...
December 1, 2016: Breast: Official Journal of the European Society of Mastology
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