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https://www.readbyqxmd.com/read/28923573/neoadjuvant-buparlisib-plus-trastuzumab-and-paclitaxel-for-women-with-her2-primary-breast-cancer-a-randomised-double-blind-placebo-controlled-phase-ii-trial-neophoebe
#1
Sibylle Loibl, Lorena de la Pena, Valentina Nekljudova, Dimitrios Zardavas, Stefan Michiels, Carsten Denkert, Mahdi Rezai, Begoña Bermejo, Michael Untch, Soo Chin Lee, Sabine Turri, Patrick Urban, Sherko Kümmel, Guenther Steger, Andrea Gombos, Michael Lux, Martine J Piccart, Gunter Von Minckwitz, José Baselga, Sherene Loi
AIM: The Neoadjuvant PI3K inhibition in HER2 OverExpressing Breast cancEr (NeoPHOEBE) trial evaluated the efficacy and safety of buparlisib, a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, plus trastuzumab and paclitaxel as neoadjuvant treatment for human epidermal growth factor receptor-2 positive (HER2+) breast cancer. METHODS: NeoPHOEBE was a neoadjuvant, phase II, randomised, double-blind study. Women with HER2+ breast cancer were randomised within two independent cohorts by PIK3CA mutation status and, in each cohort stratified by oestrogen receptor (ER) status to receive buparlisib or placebo plus trastuzumab (first 6 weeks) followed by buparlisib or placebo with trastuzumab and paclitaxel...
September 15, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28923419/tumor-associated-macrophages-are-strongly-related-to-vascular-invasion-non-luminal-subtypes-and-interval-breast-cancer
#2
Tor A Klingen, Ying Chen, Hans Aas, Elisabeth Wik, Lars A Akslen
Tumor associated macrophages (TAM) resemble M2 macrophages, promote tumor invasion and show strong expression of CD163 in breast cancer. We here investigated the association between CD163 positive macrophages and vascular invasion, molecular subgroups, mode of detection, and patient outcome. We performed a population-based, retrospective study of invasive breast cancer from the Norwegian Breast Cancer Screening Programme in Vestfold County (2004-2009), including 200 screen-detected and 82 interval cancers. Immunohistochemically CD163 positive macrophages were counted in the most active areas (hot-spots) and dichotomized as high (upper quartile) and low counts...
September 15, 2017: Human Pathology
https://www.readbyqxmd.com/read/28923217/current-challenges-in-the-management-of-breast-cancer-brain-metastases
#3
REVIEW
Ciara C O'Sullivan, Nicole N Davarpanah, Jame Abraham, Susan E Bates
Approximately 50% of patients with advanced human epidermal growth factor 2 (HER2)-positive breast cancer and triple-negative breast cancer (TNBC) ultimately develop breast cancer brain metastases (BCBM), which are associated with significant morbidity and mortality. The advent of HER2-directed therapy resulted in greatly improved survival outcomes, but unfortunately at the price of an increased cumulative incidence of BCBM. We review challenges in the management of BCBM, and potential treatment strategies, including novel agents such as poly-adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors (olaparib, veliparib), cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (palbociclib, abemaciclib), and taxane derivatives (eg, ANG1005 and TPI-287)...
April 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28922685/neoadjuvant-systemic-therapy-for-breast-cancer-the-westmead-experience
#4
Annelise M Cocco, David Messer, Alexander Brown, Nina Sriram, Jenny Gilchrist, Loma Al-Mansouri, Richard Kefford, Farid Meybodi, James French, Jeremy Hsu, Elisabeth Elder
BACKGROUND: Neoadjuvant systemic therapy (NAST) can be used to treat breast cancer. Pathologic complete response (pCR) is a surrogate marker for improved survival. This study examined response in the breast and axilla to NAST and identified features associated with pCR. METHODS: Patients undergoing NAST and surgery between January 2012 and June 2016 by surgeons at Westmead Breast Cancer Institute were identified. Patients with inflammatory or metastatic disease were excluded...
September 18, 2017: ANZ Journal of Surgery
https://www.readbyqxmd.com/read/28922402/new-insights-into-the-metastatic-behavior-after-breast-cancer-surgery-according-to-well-established-clinicopathological-variables-and-molecular-subtypes
#5
Oreste Claudio Buonomo, Emanuele Caredda, Ilaria Portarena, Gianluca Vanni, Augusto Orlandi, Claudia Bagni, Giuseppe Petrella, Leonardo Palombi, Paolo Orsaria
Despite advances in treatment, up to 30% of patients with early breast cancer (BC) experience distant disease relapse. However, a comprehensive understanding of tumor spread and site-specific recurrence patterns remains lacking. This retrospective case-control study included 103 consecutive patients with metastatic BC admitted to our institution (2000-2013). Cases were matched according to age, tumor biology, and clinicopathological features to 221 patients with non-metastatic BC (control group). The median follow-up period among the 324 eligible patients was 7...
2017: PloS One
https://www.readbyqxmd.com/read/28919786/genetic-variants-in-long-noncoding-rna-h19-contribute-to-the-risk-of-breast-cancer-in-a-southeast-china-han-population
#6
Yuxiang Lin, Fangmeng Fu, Yazhen Chen, Wei Qiu, Songping Lin, Peidong Yang, Meng Huang, Chuan Wang
The long noncoding RNA (lncRNA) H19 is a maternally expressed imprinted gene that plays important roles in tumorigenesis, progression, and metastasis. However, the association between polymorphisms on H19 and breast cancer (BC) susceptibility has remained obscure. In this case-control study, we assessed the interaction between two lncRNA H19 single-nucleotide polymorphisms (SNPs) (rs217727 C>T, rs2839698 C>T) and the risk of BC in a Chinese Han population. In total, 1,005 BC cases and 1,020 healthy controls were enrolled in this study...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28919579/mri-and-prediction-of-pathologic-complete-response-in-the-breast-and-axilla-after-neoadjuvant-chemotherapy-for-breast-cancer-mri-and-pathologic-complete-response
#7
Joseph J Weber, Maxine S Jochelson, Anne Eaton, Emily C Zabor, Andrea V Barrio, Mary L Gemignani, Melissa Pilewskie, Kimberly J Van Zee, Monica Morrow, Mahmoud El-Tamer
BACKGROUND: In the setting where determining extent of residual disease is key for surgical planning after neoadjuvant chemotherapy (NAC), herein we evaluate reliability of MRI in predicting pathologic complete response (pCR) of the breast primary and axillary nodes following NAC. STUDY DESIGN: Patients who had MRI before and after NAC between 06/2014-08/2015 were identified in a prospective database following IRB approval. Post NAC-MRI of the breast and axillary nodes was correlated with residual disease on final pathology...
September 14, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28918565/forward-genetic-screens-identify-a-role-for-the-mitochondrial-her2-in-e-2-hexenal-responsiveness
#8
Alessandra Scala, Rossana Mirabella, Joachim Goedhart, Michel de Vries, Michel A Haring, Robert C Schuurink
This work adds a new player, HER2, downstream of the perception of E-2-hexenal, a green leaf volatile, and shows that E-2-hexenal specifically changes the redox status of the mitochondria. It is widely accepted that plants produce and respond to green leaf volatiles (GLVs), but the molecular components involved in transducing their perception are largely unknown. The GLV E-2-hexenal inhibits root elongation in seedlings and, using this phenotype, we isolated E-2-hexenal response (her) Arabidopsis thaliana mutants...
September 16, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28918115/the-interplay-of-endocrine-therapy-steroid-pathways-and-therapeutic-resistance-importance-of-androgen-in-breast-carcinoma
#9
REVIEW
Kiyoshi Takagi, Yasuhiro Miki, Takanori Ishida, Hironobu Sasano, Takashi Suzuki
A great majority of breast carcinomas expresses estrogen receptor (ER) and estrogens have crucial roles in the progress of breast carcinomas. Endocrine therapy targeting ER and/or intratumoral estrogen production significantly improved clinical outcomes of the patients with ER-positive breast carcinomas. However, resistance to endocrine therapy is often observed and significant number of patients will recur after the treatment. In addition, treatment for the patients with triple-negative breast carcinomas (negative for all ER, progesterone receptor (PR) and HER2) are limited to cytotoxic chemotherapy and novel therapeutic targets need to be identified...
September 13, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28916978/tumor-biology-predicts-pathologic-complete-response-to-neoadjuvant-chemotherapy-in-patients-presenting-with-locally-advanced-breast-cancer
#10
Lori F Gentile, George Plitas, Emily C Zabor, Michelle Stempel, Monica Morrow, Andrea V Barrio
BACKGROUND: Neoadjuvant chemotherapy (NAC) is used to convert patients with inoperable locally advanced breast cancer (LABC) to operability, but has not traditionally been used to avoid mastectomy or axillary dissection in this subset. OBJECTIVE: The purpose of this study was to determine the rates of pathologic complete response (pCR) in LABC patients, and identify factors predictive of pCR to determine if responding patients might be suitable for limited surgery...
September 15, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28916815/programmed-death-ligand-1-pd-l1-expression-in-tumour-cell-and-tumour-infiltrating-lymphocytes-of-her2-positive-breast-cancer-and-its-prognostic-value
#11
Ahrong Kim, So Jeong Lee, Young Keum Kim, Won Young Park, Do Youn Park, Jee Yeon Kim, Chang Hun Lee, Gyungyub Gong, Gi Yeong Huh, Kyung Un Choi
Immunotherapy targeting PD-1/PD-L1 axis showed benefits in cancer. Prognostic significance of tumour infiltrating lymphocytes (TILs) has been determined. We evaluated PD-L1 protein expression in tumour cells and TILs, PD-L1 mRNA level and various histopathologic factors including TILs using 167 formalin-fixed paraffin embedded tissues and 39 fresh tissue of HER2-positive breast cancer. TILs level and PD-L1 expression in tumour cells and TILs were significantly correlated one another. PD-L1 positivity in tumour cells was associated with high histologic grade and high TILs level (p < 0...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28915642/a-retrospective-multicentric-observational-study-of-trastuzumab-emtansine-in-her2-positive-metastatic-breast-cancer-a-real-world-experience
#12
Patrizia Vici, Laura Pizzuti, Andrea Michelotti, Isabella Sperduti, Clara Natoli, Lucia Mentuccia, Luigi Di Lauro, Domenico Sergi, Paolo Marchetti, Daniele Santini, Emanuela Magnolfi, Laura Iezzi, Luca Moscetti, Agnese Fabbri, Alessandra Cassano, Antonino Grassadonia, Claudia Omarini, Federico Piacentini, Andrea Botticelli, Ilaria Bertolini, Angelo Fedele Scinto, Germano Zampa, Maria Mauri, Loretta D'Onofrio, Valentina Sini, Maddalena Barba, Marcello Maugeri-Saccà, Ernesto Rossi, Elisabetta Landucci, Silverio Tomao, Antonio Maria Alberti, Francesco Giotta, Corrado Ficorella, Vincenzo Adamo, Antonio Russo, Vito Lorusso, Katia Cannita, Sandro Barni, Lucio Laudadio, Filippo Greco, Ornella Garrone, Marina Della Giulia, Paolo Marolla, Giuseppe Sanguineti, Barbara Di Cocco, Gennaro Ciliberto, Ruggero De Maria, Teresa Gamucci
We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915617/predictive-factors-of-pathologic-complete-response-in-her2-positive-and-axillary-lymph-node-positive-breast-cancer-after-neoadjuvant-paclitaxel-carboplatin-plus-with-trastuzumab
#13
Jinhua Ding, Yinlong Yang, Li Jiang, Weizhu Wu, Zhiming Shao
OBJECTIVE: This study was performed to investigate the proportion as well as the predictive factors of pathologic complete response in HER2-positive and axillary lymph node positive breast cancer after neoadjuvant paclitaxel, carboplatin plus with trastuzumab (PCH). RESULTS: The pCR rate in the breast, axilla and both was 44.3% (39/88), 47.7% (42/88) and 34.1% (30/88), respectively. Patients with and without pCR were similar in term of age, BMI, menstrual status, family history, treatment cycles and tumor characteristics (laterality and size of tumor)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915606/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#14
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915591/eugenol-alleviated-breast-precancerous-lesions-through-her2-pi3k-akt-pathway-induced-cell-apoptosis-and-s-phase-arrest
#15
Min Ma, Yi Ma, Gui-Juan Zhang, Rui Liao, Xue-Feng Jiang, Xian-Xin Yan, Feng-Jie Bie, Xiao-Bo Li, Yan-Hong Lv
Eugenol can be separated from the oil extract of clove bud, and has many pharmacological functions such as anticancer and transdermal absorption. HER2/PI3K-AKT is a key signaling pathway in the development of breast cancer. In this study, 80 μM eugenol could significantly inhibit the proliferation of HER-2 positive MCF-10AT cells and the inhibition rate was up to 32.8%, but had no obvious inhibitory effect on MCF-7 and MCF-10A cells with HER2 weak expression. Eugenol also significantly induced human breast precancerous lesion MCF-10AT cell apoptosis and cell cycle S-phase arrest, but the biological effects nearly disappeared after HER2 over-expression through transfecting pcDNA3...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915583/n-acetylcysteine-breaks-resistance-to-trastuzumab-caused-by-muc4-overexpression-in-human-her2-positive-bc-bearing-nude-mice-monitored-by-89-zr-trastuzumab-and-18-f-fdg-pet-imaging
#16
Zéna Wimana, Geraldine Gebhart, Thomas Guiot, Bruno Vanderlinden, Denis Larsimont, Gilles Doumont, Gaetan Van Simaeys, Serge Goldman, Patrick Flamen, Ghanem Ghanem
Trastuzumab remains an important drug in the management of human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer (BC). Several studies reported resistance mechanisms to trastuzumab, including impaired HER2-accessibility caused by mucin 4 (MUC4). Previously, we demonstrated an increase of Zirconium-89-radiolabeled-trastuzumab ((89)Zr-Trastuzumab) accumulation when MUC4-overexpressing BC-cells were challenged with the mucolytic drug N-Acetylcysteine (NAC). Hereby, using the same approach we investigated whether tumor exposure to NAC would also enhance trastuzumab-efficacy...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915525/infiltrating-mammary-duct-adenocarcinoma-in-the-right-labia-majora-along-the-milk-line
#17
Haitham Atef Torky, Anwar Elshenawy, Ahmed Eesa
Introduction Breast tissue rarely arises from the vulva and malignancy might develop in it. Case Thirty-eight-year-old woman presented with a suspicious ulcer in the right labia majora discovered accidently and removed by wide local excision. Histopathology revealed infiltrating mammary duct adenocarcinoma along the milk line. Immunohistochemistry was positive for estrogen and progesterone receptors and equivocal overexpression for HER2 protein with a score of 2+. Metastatic work-up was clear. Inguinal lymph nodes were enlarged and lymphadenectomy done which showed positive lymph nodes on the right side and none on the left...
September 15, 2017: Zeitschrift Für Geburtshilfe und Neonatologie
https://www.readbyqxmd.com/read/28914398/characteristics-and-prognosis-of-breast-cancer-after-liver-or-kidney-transplantation
#18
I-Ji Jeong, Sung-Gyu Lee, Young Hoon Kim, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Se-Hyun Ahn, Hee Jeong Kim
PURPOSE: Immunoediting is crucial in cancer development and progression. This study compared the characteristics and prognosis of post-transplant breast cancer (PTBC) patients receiving immunosuppressants and general breast cancer patients. METHODS: Data from the Asan Medical Center Breast Cancer (AMCBC), kidney transplantation, and liver transplantation databases recorded during 1989-2013 were retrospectively analyzed. Four controls of AMCBC cohort per one case of PTBC cohort were selected based on tumor size, lymph node metastasis, and age...
September 15, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28912877/fen1-knockdown-improves-trastuzumab-sensitivity-in-human-epidermal-growth-factor-2-positive-breast-cancer-cells
#19
Xue Zeng, Xiaofang Che, Yun-Peng Liu, Xiu-Juan Qu, Lu Xu, Chen-Yang Zhao, Chun-Lei Zheng, Ke-Zuo Hou, Yuee Teng
Trastuzumab has been widely applied as a treatment for human epidermal growth factor 2 (HER2)-overexpressing breast cancer. However, the therapeutic efficacy of trastuzumab is limited. Flap endonuclease 1 (FEN1) is a multifunctional endonuclease that has a crucial role in DNA recombination and repair. Inhibition of FEN1 is associated with the reversal of anticancer drug resistance. However, it is unclear whether FEN1 is involved in trastuzumab resistance. In the present study, it was demonstrated that trastuzumab increases the expression of FEN1, and FEN1 knockdown significantly enhanced the sensitivity of BT474 cells to trastuzumab (P<0...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28912526/mpzl1-forms-a-signalling-complex-with-grb2-adaptor-and-ptpn11-phosphatase-in-her2-positive-breast-cancer-cells
#20
Alice Beigbeder, François J M Chartier, Nicolas Bisson
HER2/ErbB2 is overexpressed in a significant fraction of breast tumours and is associated with a poor prognosis. The adaptor protein GRB2 interacts directly with activated HER2 and is sufficient to transmit oncogenic signals. However, the consequence of HER2 activation on global GRB2 signalling networks is poorly characterized. We performed GRB2 affinity purification combined with mass spectrometry analysis of associated proteins in a HER2+ breast cancer model to delineate GRB2-nucleated protein interaction networks...
September 14, 2017: Scientific Reports
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