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Breast Cancer HER2+

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https://www.readbyqxmd.com/read/28918577/microarray-based-snp-genotyping-to-identify-genetic-risk-factors-of-triple-negative-breast-cancer-tnbc-in-south-indian-population
#1
M Aravind Kumar, Vineeta Singh, Shaik Mohammad Naushad, Uday Shanker, M Lakshmi Narasu
In the view of aggressive nature of Triple-Negative Breast cancer (TNBC) due to the lack of receptors (ER, PR, HER2) and high incidence of drug resistance associated with it, a case-control association study was conducted to identify the contributing genetic risk factors for Triple-negative breast cancer (TNBC). A total of 30 TNBC patients and 50 age and gender-matched controls of Indian origin were screened for 9,00,000 SNP markers using microarray-based SNP genotyping approach. The initial PLINK association analysis (p < 0...
September 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28918548/tumor-and-serum-dna-methylation-in-women-receiving-preoperative-chemotherapy-with-or-without-vorinostat-in-tbcrc008
#2
Roisin M Connolly, Mary Jo Fackler, Zhe Zhang, Xian C Zhou, Matthew P Goetz, Judy C Boughey, Bridget Walsh, John T Carpenter, Anna Maria Storniolo, Stanley P Watkins, Edward W Gabrielson, Vered Stearns, Saraswati Sukumar
BACKGROUND: Methylated gene markers have shown promise in predicting breast cancer outcomes and treatment response. We evaluated whether baseline and changes in tissue and serum methylation levels would predict pathological complete response (pCR) in patients with HER2-negative early breast cancer undergoing preoperative chemotherapy. METHODS: The TBCRC008 trial investigated pCR following 12 weeks of preoperative carboplatin and albumin-bound paclitaxel + vorinostat/placebo (n = 62)...
September 16, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28916978/tumor-biology-predicts-pathologic-complete-response-to-neoadjuvant-chemotherapy-in-patients-presenting-with-locally-advanced-breast-cancer
#3
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
#4
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/28916248/breast-cancer-vaccines-delivered-by-dendritic-cell-targeted-lentivectors-induce-potent-antitumor-immune-responses-and-protect-mice-from-mammary-tumor-growth
#5
Paul D Bryson, Xiaolu Han, Norman Truong, Pin Wang
Breast cancer immunotherapy is a potent treatment option, with antibody therapies such as trastuzumab increasing 2-year survival rates by 50%. However, active immunotherapy through vaccination has generally been clinically ineffective. One potential means of improving vaccine therapy is by delivering breast cancer antigens to dendritic cells (DCs) for enhanced antigen presentation. To accomplish this in vivo, we pseudotyped lentiviral vector (LV) vaccines with a modified Sindbis Virus glycoprotein so that they could deliver genes encoding the breast cancer antigen alpha-lactalbumin (Lalba) or erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) directly to resident DCs...
September 12, 2017: Vaccine
https://www.readbyqxmd.com/read/28915642/a-retrospective-multicentric-observational-study-of-trastuzumab-emtansine-in-her2-positive-metastatic-breast-cancer-a-real-world-experience
#6
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
#7
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
#8
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
#9
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
#10
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/28914398/characteristics-and-prognosis-of-breast-cancer-after-liver-or-kidney-transplantation
#11
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/28913760/impact-of-histopathology-tumor-infiltrating-lymphocytes-and-adjuvant-chemotherapy-on-prognosis-of-triple-negative-breast-cancer
#12
Roberto A Leon-Ferre, Mei-Yin Polley, Heshan Liu, Judith A Gilbert, Victoria Cafourek, David W Hillman, Ahmed Elkhanany, Margaret Akinhanmi, Jenna Lilyquist, Abigail Thomas, Vivian Negron, Judy C Boughey, Minetta C Liu, James N Ingle, Krishna R Kalari, Fergus J Couch, Daniel W Visscher, Matthew P Goetz
BACKGROUND: Given its high recurrence risk, guidelines recommend systemic therapy for most patients with early-stage triple-negative breast cancer (TNBC). While some clinicopathologic factors and tumor-infiltrating lymphocytes (TILs) are known to be prognostic in patients receiving chemotherapy, their prognostic implications in systemically untreated patients remain unknown. METHODS: From a cohort of 9982 women with surgically treated non-metastatic breast cancer, all patients with clinically reported ER-negative/borderline (≤10%) disease were selected for central assessment of ER/PR/HER2, histopathology, Ki-67, and TILs...
September 14, 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
#13
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/28912626/clinical-impact-of-sphingosine-1-phosphate-in-breast-cancer
#14
REVIEW
Junko Tsuchida, Masayuki Nagahashi, Kazuaki Takabe, Toshifumi Wakai
Breast cancer metastasizes to lymph nodes or other organs, which determine the prognosis of patients. It is difficult to cure the breast cancer patients with distant metastasis due to resistance to drug therapies. Elucidating the underlying mechanisms of breast cancer metastasis and drug resistance is expected to provide new therapeutic targets. Sphingosine-1-phosphate (S1P) is a pleiotropic, bioactive lipid mediator that regulates many cellular functions, including proliferation, migration, survival, angiogenesis/lymphangiogenesis, and immune responses...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28912526/mpzl1-forms-a-signalling-complex-with-grb2-adaptor-and-ptpn11-phosphatase-in-her2-positive-breast-cancer-cells
#15
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
https://www.readbyqxmd.com/read/28912475/the-impact-of-young-age-for-prognosis-by-subtype-in-women-with-early-breast-cancer
#16
Weibin Lian, Fangmeng Fu, Yuxiang Lin, Minjun Lu, Boyang Chen, Peidong Yang, Bangwei Zeng, Meng Huang, Chuan Wang
Young age (≤40 years) use to be considered an independent risk factor for the prognosis of women with early-stage breast cancer. We conducted a retrospective analysis to investigate this claim in a population of young patients who were stratified by molecular subtype. We identified 2,125 women with stage I to III breast cancer from the Fujian Medical University Union Hospital. Multivariable Cox proportional hazards models were used to analyze the relationship between age groups stratified by molecular subtype and 5-year disease-free survival (DFS), 5-year distant metastasis-free survival (DMFS), and 5-year breast cancer-specific survival (BCSS)...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912144/androgen-and-estrogen-receptor-imaging-in-metastatic-breast-cancer-patients-as-a-surrogate-for-tissue-biopsies
#17
Clasina M Venema, Lemonitsa H Mammatas, Carolina P Schröder, Michel van Kruchten, Giulia Apollonio, Andor W J M Glaudemans, A H H Bongaerts, Otto S Hoekstra, Henk M W Verheul, Epie Boven, Bert van der Vegt, Erik F de Vries, Elisabeth G E de Vries, Ronald Boellaard, Catharina Willemien Menke-van der Houven van Oordt, Geke Ap Hospers
In addition to the well-known estrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER2), the androgen receptor (AR) is also a potential drug target in breast cancer treatment. Whole body imaging can provide information across lesions within a patient. ER expression in tumor lesions can be visualized by (18)F-fluoroestradiol (FES) PET, and AR expression has been visualized in prostate cancer patients with (18)F-fluorodihydrotestosterone (FDHT) PET. Our aim was to assess the concordance between FDHT- and FES-PET and tumor AR- and ER-expression measured immunohistochemically (IHC) in patients with metastatic breast cancer...
September 14, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28911092/concurrent-and-sequential-initiation-of-ovarian-function-suppression-with-chemotherapy-in-premenopausal-women-with-endocrine-responsive-early-breast-cancer-an-exploratory-analysis-of-text-and-soft
#18
M M Regan, B A Walley, P A Francis, G F Fleming, I Láng, H L Gómez, M Colleoni, C Tondini, G Pinotti, M Salim, S Spazzapan, V Parmar, T Ruhstaller, E A Abdi, R D Gelber, A S Coates, A Goldhirsch, O Pagani
Background: Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression (OFS) as part of adjuvant endocrine therapy. If chemotherapy is also given, it is uncertain whether to select concurrent or sequential OFS initiation. Design and methods: We analyzed 1872 patients enrolled in the randomized phase III TEXT and SOFT trials who received adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer and upon randomization to an OFS-containing adjuvant endocrine therapy, initiated gonadotropin-releasing-hormone-agonist triptorelin...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28911063/stromal-lymphocyte-infiltration-after-neoadjuvant-chemotherapy-is-associated-with-aggressive-residual-disease-and-lower-disease-free-survival-in-her2-positive-breast-cancer
#19
A-S Hamy, J-Y Pierga, A Sabaila, E Laas, H Bonsang-Kitzis, C Laurent, A Vincent-Salomon, P Cottu, F Lerebours, R Rouzier, M Lae, F Reyal
Background: The role of tumor-infiltrating lymphocytes (TILs) in breast cancer has been extensively studied over the last decade. High TILs levels have been associated with pathological response rate in the neoadjuvant setting and with better outcomes in the adjuvant setting. However, little attention has been paid to changes in TILs and residual TIL levels after neoadjuvant chemotherapy (NAC). We investigated TIL levels before, after chemotherapy, and their dynamics during treatment; and we assessed the correlation of these levels with response to NAC and prognosis...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28905250/tumour-infiltrating-lymphocytes-tils-related-genomic-signature-predicts-chemotherapy-response-in-breast-cancer
#20
Mariko Kochi, Takayuki Iwamoto, Naoki Niikura, Giampaolo Bianchini, Shinobu Masuda, Taeko Mizoo, Tomohiro Nogami, Tadahiko Shien, Takayuki Motoki, Naruto Taira, Yutaka Tokuda, Hiroyoshi Doihara, Junji Matsuoka, Toshiyoshi Fujiwara
PURPOSE: The present study evaluated whether morphological-measured stromal and intra-tumour tumour-infiltrating lymphocytes (TILs) levels were associated with gene expression profiles, and whether TILs-associated genomic signature (GS) could be used to predict clinical outcomes and response to therapies in several breast cancer subtypes. METHODS: We retrospectively evaluated haematoxylin eosin (HE)-TILs levels and gene expression profiling data from 40 patients with primary breast cancer and extracted the 22 overexpressed genes in cases with high TILs scores as the TILs-GS...
September 13, 2017: Breast Cancer Research and Treatment
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