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Breast Cancer HER2+

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https://www.readbyqxmd.com/read/28445946/dose-invasive-apocrine-adenocarcinoma-has-worse-prognosis-than-invasive-ductal-carcinoma-of-breast-evidence-from-seer-database
#1
Ning Zhang, Hanwen Zhang, Tong Chen, Qifeng Yang
BACKGROUND: Invasive apocrine adenocarcinoma (AAC) of breast is a rare histopathological subtype of breast carcinomas. We aim to investigate the different characteristics and prognostic outcomes between AAC and invasive ductal carcinoma (IDC) of breast cancer. RESULTS: AAC patients presented with older ages, more aggressive behaviors, lower ER and PR proportions, higher HER2 amplification rates and less application of breast-conserving therapy and adjuvant chemotherapy compared to IDC patients...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445439/her2-in-breast-cancer-stemness-a-negative-feedback-loop-towards-trastuzumab-resistance
#2
REVIEW
Babak Nami, Zhixiang Wang
HER2 receptor tyrosine kinase that is overexpressed in approximately 20% of all breast cancers (BCs) is a poor prognosis factor and a precious target for BC therapy. Trastuzumab is approved by FDA to specifically target HER2 for treating HER2+ BC. However, about 60% of patients with HER2+ breast tumor develop de novo resistance to trastuzumab, partially due to the loss of expression of HER2 extracellular domain on their tumor cells. This is due to shedding/cleavage of HER2 by metalloproteinases (ADAMs and MMPs)...
April 26, 2017: Cancers
https://www.readbyqxmd.com/read/28445153/increased-risk-of-brain-metastases-in-women-with-breast-cancer-and-p16-expression-in-metastatic-lymph-nodes
#3
Elise Furet, Morad El Bouchtaoui, Jean-Paul Feugeas, Catherine Miquel, Christophe Leboeuf, Clémentine Beytout, Philippe Bertheau, Emilie Le Rhun, Jacques Bonneterre, Anne Janin, Guilhem Bousquet
PURPOSE: Metastatic breast cancer is a leading cause of mortality in women, partly on account of brain metastases. However, the mechanisms by which cancer cells cross the blood-brain barrier remain undeciphered. Most molecular studies predicting metastatic risk have been performed on primary breast cancer samples. Here we studied metastatic lymph-nodes from patients with breast cancers to identify markers associated with the occurrence of brain metastases. RESULTS: Transcriptomic analyses identified CDKN2A/p16 as a gene potentially associated with brain metastases...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445098/comparative-analysis-of-human-epidermal-growth-factor-receptor-2-testing-in-breast-cancer-according-to-2007-and-2013-american-society-of-clinical-oncology-college-of-american-pathologists-guideline-recommendations
#4
Wedad M Hanna, Elzbieta Slodkowska, Fang-I Lu, Houman Nafisi, Sharon Nofech-Mozes
Purpose To study the effect of the 2013 updates to the 2007 American Society of Clinical Oncology/College of American Pathologists recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer on testing patterns and interpretation in a large regional reference laboratory. Patients and Methods Patient cases with HER2 testing scores for breast biomarker evaluation were selected from our laboratory information system during two 12-month periods (2012 and 2014). The number of tests performed, type of specimens, proportion of HER2-positive and equivocal patient cases, and number of repeat tests on subsequent excisional specimens were examined and compared...
April 26, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28443700/role-of-everolimus-in-the-treatment-of-metastatic-her2-negative-hr-positive-breast-cancer
#5
Pronzato Paolo
Metastatic breast cancer (mBC) is a leading cause of mortality for women around the world. The response to hormonotherapy of the patients with HER2-negative/HR-positive mBC is usually limited, and many strategies are in place to contrast the hormonotherapy resistance. Since efficacy and effectiveness of everolimus have been established by many trials, this review is aimed to give a structured synthesis to define the everolimus clinical role among the treatment options for mBC. Key aspects of everolimus dosing and safety profile, drawn up by relevant findings, are included, as well as the role of biomarkers to identify subgroups of mBC patients who may best benefit from everolimus treatment...
April 26, 2017: Future Oncology
https://www.readbyqxmd.com/read/28442763/impact-of-hormone-receptor-status-and-distant-recurrence-free-interval-on-survival-benefits-from-trastuzumab-in-her2-positive-metastatic-breast-cancer
#6
Hai-Yuan Yang, Ding Ma, Yi-Rong Liu, Xin Hu, Jian Zhang, Zhong-Hua Wang, Gen-Hong Di, Xi-Chun Hu, Zhi-Ming Shao
We sought to investigate the impact of hormone receptor (HR) status and distant recurrence-free interval (DRFI) on the degree of overall survival (OS) benefit from palliative trastuzumab-containing treatment in HER2-positive metastatic breast cancer (MBC). Here, we retrospectively identified 588 eligible HER2-positive patients with postoperative distant recurrence. DRFI of HR+HER2+ MBC patients (median: 30.7 months, IQR: 18.5-45.9, P < 0.001) was significant longer compared with HR-HER2+ patients. Patients were categorized into four subgroups based on HR status and palliative trastuzumab (trast+) received...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442704/discovery-of-an-enzyme-and-substrate-selective-inhibitor-of-adam10-using-an-exosite-binding-glycosylated-substrate
#7
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 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28441617/the-magic-survey-in-hormone-receptor-positive-hr-her2-negative-her2-breast-cancer-when-might-multigene-assays-be-of-value
#8
Matti Aapro, Michelino De Laurentiis, Dan Rea, Juan Enrique Bargallo Rocha, Roberto Elizalde, László Landherr, Barbro Linderholm, Eleftherios Mamounas, Christos Markopoulos, Patrick Neven, Alexander Petrovsky, Roman Rouzier, Vincent Smit, Christer Svedman, Daniel Schneider, Christoph Thomssen, Miguel Martin
BACKGROUND: A modest proportion of patients with early stage hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer benefit from adjuvant chemotherapy. Traditionally, treatment recommendations are based on clinical/pathologic criteria that are not predictive of chemotherapy benefit. Multigene assays provide prognostic and predictive information that can help to make more informed treatment decisions. The MAGIC survey evaluated international differences in treatment recommendations, how traditional parameters are used for making treatment choices, and for which patients treating physicians feel most uncertain about their decisions...
April 22, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28440514/silibinin-downregulates-mmp2-expression-via-jak2-stat3-pathway-and-inhibits-the-migration-and-invasive-potential-in-mda-mb-231-cells
#9
Hyo Joo Byun, Pramod Darvin, Dong Young Kang, Nipin Sp, Youn Hee Joung, Jong Hwan Park, Sun Jin Kim, Young Mok Yang
Worldwide, breast cancer (BCa) is the most common cancer in women. Among its subtypes, triple-negative breast cancer (TNBC) is an aggressive form associated with diminished survival. TNBCs are characterized by their absence, or minimal expression, of the estrogen and progesterone receptors, as well as the human epidermal growth factor receptor 2 (i.e. ER-/-, PR-/-, Her2-/Low). Consequently, treatment for this subtype of BCa remains problematic. Silibinin, a derivative of the flavonoid silymarin, is reported to have anticancer activities against hepatic and non-small cell lung cancers...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440460/triple-negative-breast-cancer-new-therapeutic-options-via-signalling-transduction-cascades
#10
Ulrich Andergassen, Alexandra C Kölbl, Jan-Niclas Mumm, Sven Mahner, Udo Jeschke
Triple-negative breast cancer is a highly aggressive type of mammalian carcinoma. It is defined by a rather weak expression of estrogen-, progesterone- and Her2-receptor, and is thus difficult to treat, resulting in low disease-free and overall survival rates of the affected patients. Hence it is important to find new therapeutic options. To this aim we analysed the incidence of some molecules from different signal transduction cascades by immunohistochemistry, which are known to correlate with triple-negative breast cancer, and correlated the expression of these molecules to different tumour traits, such as size, grading, menopausal stage, histology, lymph node affection, remote metastasis formation, and to the incidence of local and lymph node recurrence and metastasis by statistical analysis...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28438884/safety-evaluation-of-trastuzumab-emtansine-in-japanese-patients-with-her2-positive-advanced-breast-cancer
#11
Junichiro Watanabe, Yoshinori Ito, Toshiaki Saeki, Norikazu Masuda, Toshimi Takano, Shintaro Takao, Kazuhiko Nakagami, Koichiro Tsugawa, Shintaro Nakagawa, Kazumitsu Kanatani, Takahiro Nakayama
BACKGROUND/AIM: Tolerability and safety of trastuzumab emtansine (T-DM1) was investigated in Japanese patients with HER2-positive advanced breast cancer who were previously treated with chemotherapy and trastuzumab. PATIENTS AND METHODS: Patients with inoperable or recurrent breast cancer who were previously treated with chemotherapy and trastuzumab in adjuvant and/or metastatic disease were included. T-DM1 3.6 mg/kg was administered intravenously every 21 days...
May 2017: In Vivo
https://www.readbyqxmd.com/read/28438385/small-molecules-inhibit-stat3-activation-autophagy-and-cancer-cell-anchorage-independent-growth
#12
Donghui Zhou, Maya Z Springer, David Xu, Degang Liu, Andy Hudmon, Kay F Macleod, Samy O Meroueh
Triple-negative breast cancers (TNBCs) lack the signature targets of other breast tumors, such as HER2, estrogen receptor, and progesterone receptor. These aggressive basal-like tumors are driven by a complex array of signaling pathways that are activated by multiple driver mutations. Here we report the discovery of 6 (KIN-281), a small molecule that inhibits multiple kinases including maternal leucine zipper kinase (MELK) and the non-receptor tyrosine kinase bone marrow X-linked (BMX) with single-digit micromolar IC50s...
March 23, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28435291/role-of-postmastectomy-radiotherapy-in-early-stage-t1-2n0-1m0-triple-negative-breast-cancer-a-systematic-review
#13
REVIEW
Fengxia Chen, Feifei Pu
Triple-negative breast cancer (TNBC), which represents 15%-20% of all breast cancers, is defined by the absence of estrogen receptor (ER) and progesterone receptor (PR) and overexpression of human epidermal growth factor receptor 2 (HER2). Owing to the absence of specific therapeutic targets and its aggressive biologic characteristics, TNBC patients often experience a high risk of disease progression and poor overall survival. Furthermore, TNBC exhibits an early pattern of recurrence with a peak recurrence risk at 2-3 years after surgery...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28433541/the-impact-of-2013-updated-asco-cap-her2-guidelines-on-the-diagnosis-and-management-of-invasive-breast-cancer-a-single-center-study-of-1739-cases
#14
Xiaofei Zhang, Ira Bleiweiss, Shabnam Jaffer, Anupma Nayak
BACKGROUND: The purpose of this study was to determine the impact of revised ASCO/CAP 2013 HER2 guidelines on the clinical practice of pathologists and oncologists. MATERIALS AND METHODS: Retrospective analysis of 1739 patients with invasive breast carcinoma who underwent reflex HER2 (fluorescence in situ hybridization [FISH]) testing, using both 2007 and 2013 guidelines (2007-2014). RESULTS: Using 2013 guidelines, 255 (15%; 95% confidence interval [CI], 13%-16%) cases were classified as HER2(+) as opposed to 186 (11%; 95% CI, 9%-12%) by 2007 guidelines (odds ratio [OR] 1...
March 29, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28432515/mri-predicts-pathologic-complete-response-in-her2-positive-breast-cancer-after-neoadjuvant-chemotherapy
#15
Mette S van Ramshorst, Claudette E Loo, Emilie J Groen, Gonneke H Winter-Warnars, Jelle Wesseling, Frederieke van Duijnhoven, Marie-Jeanne T Vrancken Peeters, Gabe S Sonke
BACKGROUND: Neoadjuvant treatment of HER2-positive breast cancer frequently leads to a pathologic complete response (pCR), which is associated with favourable long-term outcome. Treatment regimens typically consist of 6-9 cycles of trastuzumab-based chemotherapy, although many patients achieve early radiologic complete response (rCR). If rCR accurately predicts pCR, the number of chemotherapy cycles can possibly be reduced. METHODS: We performed a diagnostic accuracy study to determine the association between rCR and pCR in patients with stage II-III HER2-positive breast cancer treated with neoadjuvant trastuzumab-based chemotherapy at the Netherlands Cancer Institute...
April 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28432480/predictive-value-of-18-f-fdg-pet-ct-for-axillary-lymph-node-metastasis-in-invasive-ductal-breast-cancer
#16
Bong-Il Song, Hae Won Kim, Kyoung Sook Won
BACKGROUND: This study assessed whether primary tumor maximum standardized uptake value (pSUVmax) measured by (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) could improve the prediction of axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC). METHODS: In this study, 128 IDC patients who underwent pretreatment (18)F-FDG PET/CT and surgical resection of primary tumor with sentinel lymph node biopsy, ALN dissection, or both were analyzed...
April 21, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28432397/downregulation-of-neuropilin-1-on-macrophages-modulates-antibody-mediated-tumoricidal-activity
#17
Kosuke Kawaguchi, Eiji Suzuki, Mariko Nishie, Isao Kii, Tatsuki R Kataoka, Masahiro Hirata, Masashi Inoue, Fengling Pu, Keiko Iwaisako, Moe Tsuda, Ayane Yamaguchi, Hironori Haga, Masatoshi Hagiwara, Masakazu Toi
Neuropilin-1 (NRP-1)-expressing macrophages are engaged in antitumor immune functions via various mechanisms. In this study, we investigated the role of NRP-1 on macrophages in antibody-mediated tumoricidal activity. Treatment of macrophages with NRP-1 knockdown or an anti-NRP-1-neutralizing antibody significantly suppressed antibody-dependent cellular cytotoxicity and modulated cytokine secretion from macrophages in vitro. Furthermore, in vivo studies using a humanized mouse model bearing human epidermal growth factor receptor-2 (HER2)-positive breast cancer xenografts showed that antibody-mediated antitumor activity and tumor infiltration of CD4(+) T lymphocytes were significantly downregulated when peripheral blood mononuclear cells in which NRP-1 was knocked down were co-administered with an anti-HER2 antibody...
April 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28430808/quantification-of-hypoxia-related-gene-expression-as-a-potential-approach-for-clinical-outcome-prediction-in-breast-cancer
#18
Abderrahim El Guerrab, Anne Cayre, Fabrice Kwiatkowski, Maud Privat, Jean-Marc Rossignol, Fabrice Rossignol, Frédérique Penault-Llorca, Yves-Jean Bignon
Breast cancers are solid tumors frequently characterized by regions with low oxygen concentrations. Cellular adaptations to hypoxia are mainly determined by "hypoxia inducible factors" that mediate transcriptional modifications involved in drug resistance and tumor progression leading to metastasis and relapse occurrence. In this study, we investigated the prognostic value of hypoxia-related gene expression in breast cancer. A systematic review was conducted to select a set of 45 genes involved in hypoxia signaling pathways and breast tumor progression...
2017: PloS One
https://www.readbyqxmd.com/read/28430631/loss-of-steroid-hormone-receptors-is-common-in-malignant-pleural-and-peritoneal-effusions-of-breast-cancer-patients-treated-with-endocrine-therapy
#19
Willemijne A M E Schrijver, Karianne Schuurman, Annelot van Rossum, Ton Peeters, Natalie Ter Hoeve, Wilbert Zwart, Paul J van Diest, Cathy B Moelans
Discordance in estrogen receptor alpha (ERα), progesterone receptor (PR), androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancers and solid distant metastases ("conversion") has been reported previously. Even though metastatic spread to the peritoneal and pleural cavities occurs frequently and is associated with high mortality, the rate of receptor conversion and the prognostic implications thereof remain elusive.We therefore determined receptor conversion in 91 effusion metastases (78 pleural, 13 peritoneal effusions) of 69 patients by immunohistochemistry (IHC) and in situ hybridization...
February 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429898/subclassification-of-the-molecular-types-of-breast-cancer-based-on-the-expression-of-immunohistochemical-markers-and-evolution
#20
Aldo Reigosa, David Hardisson, Francisco Sanzi, Eduardo Caleiras, Felipe Saldivia, Angel Fernández
Breast carcinomas have been classified from the molecular point of view into four major groups (Luminal A, Luminal B, HER2 and triple negative). However, these groups are not homogeneous and there is a need to establish subcategories that can be identified by immunohistochemistry (IHC), to better predict prognosis and carry out treatments that are more effective. This study was conducted in 354 patients diagnosed with invasive ductal breast carci- noma. The expression of 22 molecules was analyzed by tissue matrices and the results obtained were compared with molecular classes defined by IHC, according to the expression of estrogen receptor (ER), progesterone receptor (PR) and HER2, and the overall survival...
June 2016: Investigación Clínica
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