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Breast Cancer Research: BCR

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https://www.readbyqxmd.com/read/28810913/selinexor-kpt-330-demonstrates-anti-tumor-efficacy-in-preclinical-models-of-triple-negative-breast-cancer
#1
Natalia Paez Arango, Erkan Yuca, Ming Zhao, Kurt W Evans, Stephen Scott, Charissa Kim, Ana Maria Gonzalez-Angulo, Filip Janku, Naoto T Ueno, Debu Tripathy, Argun Akcakanat, Aung Naing, Funda Meric-Bernstam
BACKGROUND: Selinexor (KPT-330) is an oral agent that has been shown to inhibit the nuclear exporter XPO1. Given the pressing need for novel therapies for triple-negative breast cancer (TNBC), we sought to determine the antitumor effects of selinexor in vitro and in vivo. METHODS: Twenty-six breast cancer cell lines of different breast cancer subtypes were treated with selinexor in vitro. Cell proliferation assays were used to measure the half-maximal inhibitory concentration (IC50) and to test the effects in combination with chemotherapy...
August 15, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28793923/concurrent-antitumor-and-bone-protective-effects-of-everolimus-in-osteotropic-breast-cancer
#2
Andrew J Browne, Marie L Kubasch, Andy Göbel, Peyman Hadji, David Chen, Martina Rauner, Friedrich Stölzel, Lorenz C Hofbauer, Tilman D Rachner
BACKGROUND: The mammalian target of rapamycin inhibitor everolimus is approved as an antitumor agent in advanced estrogen receptor-positive breast cancer. Surrogate bone marker data from clinical trials suggest effects on bone metabolism, but the mode of action of everolimus in bone biology remains unclear. In this study, we assessed potential bone-protective effects of everolimus in the context of osteotropic tumors. METHODS: The effects of everolimus on cancer cell viability in vitro and on tumor growth in vivo were assessed...
August 9, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28784153/effect-of-neoadjuvant-chemotherapy-on-tumor-infiltrating-lymphocytes-and-pd-l1-expression-in-breast-cancer-and-its-clinical-significance
#3
Vasiliki Pelekanou, Daniel E Carvajal-Hausdorf, Mehmet Altan, Brad Wasserman, Cristobal Carvajal-Hausdorf, Hallie Wimberly, Jason Brown, Donald Lannin, Lajos Pusztai, David L Rimm
BACKGROUND: The effects of neoadjuvant chemotherapy on immune markers remain largely unknown. The specific aim of this study was to assess stromal tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) protein expression in a cohort of breast cancer patients treated with neoadjuvant chemotherapy. METHODS: Using quantitative immunofluorescence, we investigated stromal TILs and PD-L1 protein expression in pre-treatment and residual breast cancer tissue from a Yale Cancer Center patient cohort of 58 patients diagnosed with breast cancer from 2003 to 2009 and treated with neoadjuvant chemotherapy...
August 7, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28778177/inhibition-of-basal-like-breast-cancer-growth-by-fty720-in-combination-with-epidermal-growth-factor-receptor-kinase-blockade
#4
Janet L Martin, Sohel M Julovi, Mike Z Lin, Hasanthi C de Silva, Frances M Boyle, Robert C Baxter
BACKGROUND: New molecular targets are needed for women with triple-negative breast cancer (TNBC). This pre-clinical study investigated the combination of the EGFR inhibitor gefitinib with the sphingosine kinase (SphK) inhibitor FTY720 (Fingolimod), aiming to block tumorigenic signaling downstream of IGFBP-3, which is abundantly expressed in basal-like TNBC. METHODS: In studies of breast cancer cell growth in culture, proliferation was monitored by IncuCyte live-cell imaging, and protein abundance was determined by western blotting...
August 4, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28764748/a-phase-i-trial-of-ganetespib-in-combination-with-paclitaxel-and-trastuzumab-in-patients-with-human-epidermal-growth-factor-receptor-2-her2-positive-metastatic-breast-cancer
#5
Komal Jhaveri, Rui Wang, Eleonora Teplinsky, Sarat Chandarlapaty, David Solit, Karen Cadoo, James Speyer, Gabriella D'Andrea, Sylvia Adams, Sujata Patil, Sofia Haque, Tara O'Neill, Kent Friedman, Francisco J Esteva, Clifford Hudis, Shanu Modi
BACKGROUND: Targeted therapies in HER2-positive metastatic breast cancer significantly improve outcomes but efficacy is limited by therapeutic resistance. HER2 is an acutely sensitive Heat Shock Protein 90 (HSP90) client and HSP90 inhibition can overcome trastuzumab resistance. Preclinical data suggest that HSP90 inhibition is synergistic with taxanes with the potential for significant clinical activity. We therefore tested ganetespib, a HSP90 inhibitor, in combination with paclitaxel and trastuzumab in patients with trastuzumab-refractory HER2-positive metastatic breast cancer...
August 2, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28764807/akt1-low-quiescent-cancer-cells-persist-after-neoadjuvant-chemotherapy-in-triple-negative-breast-cancer
#6
Sheheryar Kabraji, Xavier Solé, Ying Huang, Clyde Bango, Michaela Bowden, Aditya Bardia, Dennis Sgroi, Massimo Loda, Sridhar Ramaswamy
BACKGROUND: Absence of pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) correlates with poor long-term survival in patients with triple negative breast cancer (TNBC). These incomplete treatment responses are likely determined by mechanisms that enable cancer cells to resist being killed. However, the detailed characterization of a drug-resistant cancer cell state in residual TNBC tissue after NACT has remained elusive. AKT1(low) quiescent cancer cells (QCCs) are a quiescent, epigenetically plastic, and chemotherapy-resistant subpopulation initially identified in experimental cancer models...
August 1, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28750640/impact-of-somatic-pi3k-pathway-and-erbb-family-mutations-on-pathological-complete-response-pcr-in-her2-positive-breast-cancer-patients-who-received-neoadjuvant-her2-targeted-therapies
#7
Sinead Toomey, Alexander J Eustace, Joanna Fay, Katherine M Sheehan, Aoife Carr, Malgorzata Milewska, Stephen F Madden, Ausra Teiserskiene, Elaine W Kay, Norma O'Donovan, William Gallagher, Liam Grogan, Oscar Breathnach, Janice Walshe, Catherine Kelly, Brian Moulton, M John Kennedy, Guiseppe Gullo, Arnold D Hill, Colm Power, Deirdre Duke, Niamh Hambly, John Crown, Bryan T Hennessy
BACKGROUND: The Cancer Genome Atlas analysis revealed that somatic EGFR, receptor tyrosine-protein kinase erbB-2 (ERBB2), Erb-B2 receptor tyrosine kinase 3 (ERBB3) and Erb-B2 receptor tyrosine kinase 4 (ERBB4) gene mutations (ERBB family mutations) occur alone or co-occur with somatic mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) in 19% of human epidermal growth factor receptor 2 (HER2)-positive breast cancers. Because ERBB family mutations can activate the PI3K/AKT pathway and likely have similar canonical signalling effects to PI3K pathway mutations, we investigated their combined impact on response to neoadjuvant HER2-targeted therapies...
July 27, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28750639/epithelial-requirement-for-in-vitro-proliferation-and-xenograft-growth-and-metastasis-of-mda-mb-468-human-breast-cancer-cells-oncogenic-rather-than-tumor-suppressive-role-of-e-cadherin
#8
H J Hugo, N P A D Gunasinghe, B G Hollier, T Tanaka, T Blick, A Toh, P Hill, C Gilles, M Waltham, E W Thompson
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is associated with downregulated E-cadherin and frequently with decreased proliferation. Proliferation may be restored in secondary metastases by mesenchymal-to-epithelial transition (MET). We tested whether E-cadherin maintains epithelial proliferation in MDA-MB-468 breast cancer cells, facilitating metastatic colonization in severe combined immunodeficiency (SCID) mice. METHODS: EMT/MET markers were assessed in xenograft tumors by immunohistochemistry...
July 27, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28732538/consistency-now-what
#9
EDITORIAL
Mary Beth Terry
No abstract text is available yet for this article.
July 21, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28732505/body-size-in-early-life-and-risk-of-breast-cancer
#10
Md Shajedur Rahman Shawon, Mikael Eriksson, Jingmei Li
BACKGROUND: Body size in early life is inversely associated with adult breast cancer (BC) risk, but it is unclear whether the associations differ by tumor characteristics. METHODS: In a pooled analysis of two Swedish population-based studies consisting of 6731 invasive BC cases and 28,705 age-matched cancer-free controls, we examined the associations between body size in early life and BC risk. Self-reported body sizes at ages 7 and 18 years were collected by a validated nine-level pictogram (aggregated into three categories: small, medium and large)...
July 21, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28724391/hormone-receptor-status-of-a-first-primary-breast-cancer-predicts-contralateral-breast-cancer-risk-in-the-wecare-study-population
#11
Anne S Reiner, Charles F Lynch, Julia S Sisti, Esther M John, Jennifer D Brooks, Leslie Bernstein, Julia A Knight, Li Hsu, Patrick Concannon, Lene Mellemkjær, Marc Tischkowitz, Robert W Haile, Ronglai Shen, Kathleen E Malone, Meghan Woods, Xiaolin Liang, Monica Morrow, Jonine L Bernstein
BACKGROUND: Previous population-based studies have described first primary breast cancer tumor characteristics and their association with contralateral breast cancer (CBC) risk. However, information on influential covariates such as treatment, family history of breast cancer, and BRCA1/2 mutation carrier status was not available. In a large, population-based, case-control study, we evaluated whether tumor characteristics of the first primary breast cancer are associated with risk of developing second primary asynchronous CBC, overall and in subgroups of interest, including among BRCA1/2 mutation non-carriers, women who are not treated with tamoxifen, and women without a breast cancer family history...
July 19, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28720108/early-pregnancy-sex-steroids-during-primiparous-pregnancies-and-maternal-breast-cancer-a-nested-case-control-study-in-the-northern-sweden-maternity-cohort
#12
Renée T Fortner, Eglé Tolockiene, Helena Schock, Husam Oda, Hans-Åke Lakso, Göran Hallmans, Rudolf Kaaks, Paolo Toniolo, Anne Zeleniuch-Jacquotte, Kjell Grankvist, Eva Lundin
BACKGROUND: Pregnancy and parity are associated with subsequent breast cancer risk. Experimental and epidemiologic data suggest a role for pregnancy sex steroid hormones. METHODS: We conducted a nested case-control study in the Northern Sweden Maternity Cohort (1975-2007). Eligible women had provided a blood sample in the first 20 weeks of gestation during a primiparous pregnancy leading to a term delivery. The current study includes 223 cases and 417 matched controls (matching factors: age at and date of blood collection)...
July 18, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28693600/normal-breast-tissue-dna-methylation-differences-at-regulatory-elements-are-associated-with-the-cancer-risk-factor-age
#13
Kevin C Johnson, E Andres Houseman, Jessica E King, Brock C Christensen
BACKGROUND: The underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies. METHODS: Here we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450 K array) in cancer-free women from the Susan G...
July 10, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28693537/erratum-to-intratumoral-and-peritumoral-radiomics-for-the-pretreatment-prediction-of-pathological-complete-response-to-neoadjuvant-chemotherapy-based-on-breast-dce-mri
#14
Nathaniel M Braman, Maryam Etesami, Prateek Prasanna, Christina Dubchuk, Hannah Gilmore, Pallavi Tiwari, Donna Plecha, Anant Madabhushi
No abstract text is available yet for this article.
July 10, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28673354/the-footprint-of-the-ageing-stroma-in-older-patients-with-breast-cancer
#15
Barbara Brouwers, Debora Fumagalli, Sylvain Brohee, Sigrid Hatse, Olivier Govaere, Giuseppe Floris, Kathleen Van den Eynde, Yacine Bareche, Patrick Schöffski, Ann Smeets, Patrick Neven, Diether Lambrechts, Christos Sotiriou, Hans Wildiers
BACKGROUND: Tumours are not only composed of malignant cells but also consist of a stromal micro-environment, which has been shown to influence cancer cell behaviour. Because the ageing process induces accumulation of senescent cells in the body, this micro-environment is thought to be different in cancers occurring in old patients compared with younger patients. More specifically, senescence-related fibroblastic features, such as the senescence-associated secretory profile (SASP) and the induction of autophagy, are suspected to stimulate tumour growth and progression...
July 3, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28673325/maternal-intake-of-high-n-6-polyunsaturated-fatty-acid-diet-during-pregnancy-causes-transgenerational-increase-in-mammary-cancer-risk-in-mice
#16
Nguyen M Nguyen, Fabia de Oliveira Andrade, Lu Jin, Xiyuan Zhang, Madisa Macon, M Idalia Cruz, Carlos Benitez, Bryan Wehrenberg, Chao Yin, Xiao Wang, Jianhua Xuan, Sonia de Assis, Leena Hilakivi-Clarke
BACKGROUND: Maternal and paternal high-fat (HF) diet intake before and/or during pregnancy increases mammary cancer risk in several preclinical models. We studied if maternal consumption of a HF diet that began at a time when the fetal primordial germ cells travel to the genital ridge and start differentiating into germ cells would result in a transgenerational inheritance of increased mammary cancer risk. METHODS: Pregnant C57BL/6NTac mouse dams were fed either a control AIN93G or isocaloric HF diet composed of corn oil high in n-6 polyunsaturated fatty acids between gestational days 10 and 20...
July 3, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28673316/somatic-loss-of-estrogen-receptor-beta-and-p53-synergize-to-induce-breast-tumorigenesis
#17
Igor Bado, Fotis Nikolos, Gayani Rajapaksa, Wanfu Wu, Jessica Castaneda, Savitri Krishnamurthy, Paul Webb, Jan-Åke Gustafsson, Christoforos Thomas
BACKGROUND: Upregulation of estrogen receptor beta (ERβ) in breast cancer cells is associated with epithelial maintenance, decreased proliferation and invasion, and a reduction in the expression of the receptor has been observed in invasive breast tumors. However, proof of an association between loss of ERβ and breast carcinogenesis is still missing. METHODS: To study the role of ERβ in breast oncogenesis, we generated mouse conditional mutants with specific inactivation of ERβ and p53 in the mammary gland epithelium...
July 3, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28668076/ex-vivo-expanded-natural-killer-cells-from-breast-cancer-patients-and-healthy-donors-are-highly-cytotoxic-against-breast-cancer-cell-lines-and-patient-derived-tumours
#18
Mira M Shenouda, Amy Gillgrass, Tina Nham, Richard Hogg, Amanda J Lee, Marianne V Chew, Mahsa Shafaei, Craig Aarts, Dean A Lee, John Hassell, Anita Bane, Sukhbinder Dhesy-Thind, Ali A Ashkar
BACKGROUND: Natural killer (NK) cells play a critical role in cancer immunosurveillance. Recent developments in NK cell ex-vivo expansion makes it possible to generate millions of activated NK cells from a small volume of peripheral blood. We tested the functionality of ex vivo expanded NK cells in vitro against breast cancer cell lines and in vivo using a xenograft mouse model. The study aim was to assess functionality and phenotype of expanded NK cells from breast cancer patients against breast cancer cell lines and autologous primary tumours...
July 1, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28666462/two-distinct-mtorc2-dependent-pathways-converge-on-rac1-to-drive-breast-cancer-metastasis
#19
Meghan Morrison Joly, Michelle M Williams, Donna J Hicks, Bayley Jones, Violeta Sanchez, Christian D Young, Dos D Sarbassov, William J Muller, Dana Brantley-Sieders, Rebecca S Cook
BACKGROUND: The importance of the mTOR complex 2 (mTORC2) signaling complex in tumor progression is becoming increasingly recognized. HER2-amplified breast cancers use Rictor/mTORC2 signaling to drive tumor formation, tumor cell survival and resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapy. Cell motility, a key step in the metastatic process, can be activated by mTORC2 in luminal and triple negative breast cancer cell lines, but its role in promoting metastases from HER2-amplified breast cancers is not yet clear...
June 30, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28666457/neoadjuvant-radiotherapy-of-early-stage-breast-cancer-and-long-term-disease-free-survival
#20
Jan Poleszczuk, Kimberly Luddy, Lu Chen, Jae K Lee, Louis B Harrison, Brian J Czerniecki, Hatem Soliman, Heiko Enderling
BACKGROUND: Compared with surgery alone, postoperative adjuvant radiotherapy (RT) improves relapse-free survival of patients with early-stage breast cancer. We evaluated the long-term overall and disease-free survival rates of neoadjuvant (presurgical) versus adjuvant RT in early-stage breast cancer patients. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database provided by the National Institutes of Health to derive an analytic dataset of 250,195 female patients with early-stage breast cancer who received RT before (n = 2554; 1...
June 30, 2017: Breast Cancer Research: BCR
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