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NPJ Breast Cancer

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https://www.readbyqxmd.com/read/29761158/phase-ii-study-of-ruxolitinib-a-selective-jak1-2-inhibitor-in-patients-with-metastatic-triple-negative-breast-cancer
#1
Daniel G Stover, Carlos R Gil Del Alcazar, Jane Brock, Hao Guo, Beth Overmoyer, Justin Balko, Qiong Xu, Aditya Bardia, Sara M Tolaney, Rebecca Gelman, Maxwell Lloyd, Yu Wang, Yaomin Xu, Franziska Michor, Vivian Wang, Eric P Winer, Kornelia Polyak, Nancy U Lin
Preclinical data support a role for the IL-6/JAK2/STAT3 signaling pathway in breast cancer. Ruxolitinib is an orally bioavailable receptor tyrosine inhibitor targeting JAK1 and JAK2. We evaluated the safety and efficacy of ruxolitinib in patients with metastatic breast cancer. This was a non-randomized phase II study enrolling patients with refractory, metastatic triple-negative breast cancer. The primary endpoint was objective response by RECIST 1.1. The study was designed to enroll patients whose archival tumor tissue was pSTAT3-positive ( T -score >5) by central immunohistochemistry...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29736411/a-functional-genomic-screen-in-vivo-identifies-ceacam5-as-a-clinically-relevant-driver-of-breast-cancer-metastasis
#2
Emily Powell, Jiansu Shao, Hector M Picon, Christopher Bristow, Zhongqi Ge, Michael Peoples, Frederick Robinson, Sabrina L Jeter-Jones, Christopher Schlosberg, Caitlin L Grzeskowiak, Fei Yang, Yun Wu, Ignacio Wistuba, Stacy L Moulder, William F Symmans, Kenneth L Scott, John R Edwards, Han Liang, Timothy P Heffernan, Helen Piwnica-Worms
Tumor cells disseminate early in tumor development making metastasis-prevention strategies difficult. Identifying proteins that promote the outgrowth of disseminated tumor cells may provide opportunities for novel therapeutic strategies. Despite multiple studies demonstrating that the mesenchymal-to-epithelial transition (MET) is critical for metastatic colonization, key regulators that initiate this transition remain unknown. We serially passaged lung metastases from a primary triple negative breast cancer xenograft to the mammary fat pads of recipient mice to enrich for gene expression changes that drive metastasis...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29644338/hypothesis-can-the-abscopal-effect-explain-the-impact-of-adjuvant-radiotherapy-on-breast-cancer-mortality
#3
REVIEW
Ismail Jatoi, John R Benson, Ian Kunkler
Radiotherapy is an integral component of loco-regional therapy for breast cancer. Randomized controlled trials indicate that increasing the extent of extirpative surgery primarily reduces the risk of local recurrences, while the addition of radiotherapy to surgery can also reduce the risk of distant recurrences, thereby lowering breast cancer-specific mortality. This may suggest an "abscopal" effect beyond the immediate zone of loco-regional irradiation that favorably perturbs the natural history of distant micrometastases...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29582015/disparities-in-breast-cancer-tumor-characteristics-treatment-time-to-treatment-and-survival-probability-among-african-american-and-white-women
#4
Kevin Chu Foy, James L Fisher, Maryam B Lustberg, Darrell M Gray, Cecilia R DeGraffinreid, Electra D Paskett
African American (AA) women have a 42% higher breast cancer death rate compared to white women despite recent advancements in management of the disease. We examined racial differences in clinical and tumor characteristics, treatment and survival in patients diagnosed with breast cancer between 2005 and 2014 at a single institution, the James Cancer Hospital, and who were included in the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Cancer Registry in Columbus OH. Statistical analyses included likelihood ratio chi-square tests for differences in proportions, as well as univariate and multivariate Cox proportional hazards regressions to examine associations between race and overall and progression-free survival probabilities...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29560416/an-assessment-of-neuronal-calcium-sensor-1-and-response-to-neoadjuvant-chemotherapy-in-breast-cancer-patients
#5
Lauren M Moore, Rachel Wilkinson, Mehmet Altan, Maria Toki, Daniel E Carvajal-Hausdorf, John McGuire, Barbara E Ehrlich, David L Rimm
Neuronal calcium sensor-1 (NCS-1) has been identified as a binding partner of the taxane, paclitaxel. Our previous study showed that overexpression of NCS-1 increased the efficacy of paclitaxel in vitro, but was associated with poor clinical outcome. Here, we determine if NCS-1 expression is associated with pathological complete response (pCR) to taxane-based neoadjuvant chemotherapy in 105 pre-treatment breast cancer biopsies. Elevated expression of NCS-1 was found to be positively associated with pCR. These results suggest that NCS-1 may be a predictive biomarker for response to taxane-based neoadjuvant chemotherapy in breast cancer...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29532008/associations-between-genomic-stratification-of-breast-cancer-and-centrally-reviewed-tumour-pathology-in-the-metabric-cohort
#6
A Mukherjee, R Russell, Suet-Feung Chin, B Liu, O M Rueda, H R Ali, G Turashvili, B Mahler-Araujo, I O Ellis, S Aparicio, C Caldas, E Provenzano
The integration of genomic and transcriptomic profiles of 2000 breast tumours from the METABRIC [Molecular Taxonomy of Breast Cancer International Consortium] cohort revealed ten subtypes, termed integrative clusters (IntClust/s), characterised by distinct genomic drivers. Central histopathology ( N  = 1643) review was undertaken to explore the relationship between these ten molecular subtypes and traditional clinicopathological features. IntClust subtypes were significantly associated with histological type, tumour grade, receptor status, and lymphocytic infiltration ( p  < 0...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29532007/biomarkers-of-aging-associated-with-past-treatments-in-breast-cancer-survivors-when-therapy-induced-pathways-turn-out-to-be-potential-therapeutic-targets
#7
https://www.readbyqxmd.com/read/29423438/breast-cancer-risk-factors-and-mammographic-density-among-high-risk-women-in-urban-china
#8
Hyuna Sung, Jiansong Ren, Jing Li, Ruth M Pfeiffer, Yong Wang, Jennifer L Guida, Yi Fang, Jufang Shi, Kai Zhang, Ni Li, Shen Wang, Luopei Wei, Nan Hu, Gretchen L Gierach, Min Dai, Xiaohong R Yang, Jie He
Elevated mammographic density (MD) is an established breast cancer risk factor. Studies examining relationships between MD and breast cancer risk factors are limited in China, where established breast cancer risk factors are less prevalent but dense breasts are more prevalent than Western countries. This study included 11,478 women (45-69 years; 36% premenopausal) participating in an ongoing national cancer screening program in 11 urban provinces in China and predicted as having high-risk for breast cancer...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29387785/characterization-of-bone-only-metastasis-patients-with-respect-to-tumor-subtypes
#9
Amanda Parkes, Katherine Clifton, Aydah Al-Awadhi, Oluchi Oke, Carla L Warneke, Jennifer K Litton, Gabriel N Hortobagyi
Metastatic breast cancer (MBC) patients with bone only metastasis (BOM) are a unique population with limited characterization. We identified patients followed at MD Anderson Cancer Center from 01/01/1997 to 12/31/2015 for at least 6 months with a BOM diagnosis as first site of metastasis. Tumor subtype (TS) was assessed by initial breast biopsy immunohistochemistry using hormonal receptor (HR) and HER2 status, with four subtypes identified: HR+/HER2-, HR+/HER2+, HR-/HER2-, HR-/HER2+. HR+ was defined as estrogen receptor or progesterone receptor ≥1%...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29354686/e2112-randomized-phase-iii-trial-of-endocrine-therapy-plus-entinostat-placebo-in-patients-with-hormone-receptor-positive-advanced-breast-cancer
#10
REVIEW
Sri Lakshmi Hyndavi Yeruva, Fengmin Zhao, Kathy D Miller, Amye J Tevaarwerk, Lynne I Wagner, Robert J Gray, Joseph A Sparano, Roisin M Connolly
Endocrine therapies are effective in the treatment of hormone receptor (HR)-positive breast cancer, however, de novo or acquired treatment resistance is a significant clinical problem. A potential mechanism of resistance involves changes in gene expression secondary to epigenetic modifications, which might be reversed with the use of histone deacetylase (HDAC) inhibitors such as entinostat. The ENCORE 301 phase II randomized, placebo-controlled study demonstrated a significant improvement in progression-free survival (PFS) and overall survival (OS), with the addition of entinostat to exemestane in patients with HR-positive advanced breast cancer with disease progression after prior non-steroidal aromatase inhibitor (AI)...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29238750/biomarkers-of-aging-associated-with-past-treatments-in-breast-cancer-survivors
#11
Zorica Scuric, Judith E Carroll, Julienne E Bower, Sam Ramos-Perlberg, Laura Petersen, Stephanie Esquivel, Matt Hogan, Aaron M Chapman, Michael R Irwin, Elizabeth C Breen, Patricia A Ganz, Robert Schiestl
Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3-6 years after completion of primary treatments in breast cancer survivors (stage 0-IIIA breast cancer at diagnosis)...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29238749/a-feasibility-study-of-neoadjuvant-talazoparib-for-operable-breast-cancer-patients-with-a-germline-brca-mutation-demonstrates-marked-activity
#12
J K Litton, M Scoggins, D L Ramirez, R K Murthy, G J Whitman, K R Hess, B E Adrada, S L Moulder, C H Barcenas, V Valero, J Schwartz Gomez, E A Mittendorf, A Thompson, T Helgason, G B Mills, H Piwnica-Worms, B K Arun
This study was undertaken to determine the feasibility of enrolling breast cancer patients on a single-agent-targeted therapy trial before neoadjuvant chemotherapy. Specifically, we evaluated talazoparib in patients harboring a deleterious BRCA mutation (BRCA+). Patients with a germline BRCA mutation and ≥1 cm, HER2-negative primary tumors were eligible. Study participants underwent a pretreatment biopsy, 2 months of talazoparib, off-study core biopsy, anthracycline, and taxane-based chemotherapy ± carboplatin, followed by surgery...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29214215/genomic-and-transcriptomic-heterogeneity-in-metaplastic-carcinomas-of-the-breast
#13
Salvatore Piscuoglio, Charlotte K Y Ng, Felipe C Geyer, Kathleen A Burke, Catherine F Cowell, Luciano G Martelotto, Rachael Natrajan, Tatiana Popova, Christopher A Maher, Raymond S Lim, Ino de Bruijn, Odette Mariani, Larry Norton, Anne Vincent-Salomon, Britta Weigelt, Jorge S Reis-Filho
Metaplastic breast cancer (MBC) is a rare special histologic type of triple-negative breast cancer, characterized by the presence of neoplastic cells showing differentiation towards squamous epithelium and/or mesenchymal elements. Here we sought to define whether histologically distinct subgroups of MBCs would be underpinned by distinct genomic and/or transcriptomic alterations. Microarray-based copy number profiling identified limited but significant differences between the distinct MBC subtypes studied here, despite the limited sample size ( n  = 17)...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29214214/molecular-changes-in-premenopausal-oestrogen-receptor-positive-primary-breast-cancer-in-vietnamese-women-after-oophorectomy
#14
Ben P Haynes, Ophira Ginsburg, Qiong Gao, Elizabeth Folkerd, Maria Afentakis, Le Hong Quang, Pham Thi Han, Pham Hong Khoa, Nguyen Van Dinh, Ta Van To, Mark Clemons, Ian E Smith, Mitch Dowsett
For premenopausal women with primary ER + breast cancer, oophorectomy (OvX) is an evidence-based cost-effective option and is standard treatment in many countries. However, there is virtually no data describing the effects of OvX on breast tumour biology. We therefore, characterised the endocrine and genome-wide transcriptional impact of OvX in 56 premenopausal women with ER + breast cancer for 2 weeks prior to mastectomy. Plasma estradiol concentrations decreased from 406 ± 41 to 20.7 ± 2...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29177190/functional-germline-variants-as-potential-co-oncogenes
#15
REVIEW
Divyansh Agarwal, Christoph Nowak, Nancy R Zhang, Lajos Pusztai, Christos Hatzis
Germline variants that affect the expression or function of proteins contribute to phenotypic variation in humans and likely determine individual characteristics and susceptibility to diseases including cancer. A number of high penetrance germline variants that increase cancer risk have been identified and studied, but germline functional polymorphisms are not typically considered in the context of cancer biology, where the focus is primarily on somatic mutations. Yet, there is evidence from familial cancers indicating that specific cancer subtypes tend to arise in carriers of high-risk germline variants (e...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29167821/ptk6-regulates-growth-and-survival-of-endocrine-therapy-resistant-er-breast-cancer-cells
#16
Koichi Ito, Sun Hee Park, Igor Katsyv, Weijia Zhang, Carmine De Angelis, Rachel Schiff, Hanna Y Irie
The non-receptor tyrosine kinase, PTK6/BRK, is highly expressed in multiple tumor types, including prostate, ovarian, and breast cancers, and regulates oncogenic phenotypes such as proliferation, migration, and survival. PTK6 inhibition also overcomes targeted therapy resistance of HER2+ breast cancer. Although PTK6 is highly expressed in ER+ Luminal breast cancers, the role of PTK6 in this subtype has not been elucidated. In this study, we investigated the functions of PTK6 in ER+ Luminal breast cancer cells, including those that are relatively resistant to estrogen deprivation or targeted endocrine therapies used in the treatment of ER+ cancers...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29152563/integrated-radiomic-framework-for-breast-cancer-and-tumor-biology-using-advanced-machine-learning-and-multiparametric-mri
#17
Vishwa S Parekh, Michael A Jacobs
Radiomics deals with the high throughput extraction of quantitative textural information from radiological images that not visually perceivable by radiologists. However, the biological correlation between radiomic features and different tissues of interest has not been established. To that end, we present the radiomic feature mapping framework to generate radiomic MRI texture image representations called the radiomic feature maps (RFM) and correlate the RFMs with quantitative texture values, breast tissue biology using quantitative MRI and classify benign from malignant tumors...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29138761/a-metastasis-biomarker-metasite-breast-%C3%A2-score-is-associated-with-distant-recurrence-in-hormone-receptor-positive-her2-negative-early-stage-breast-cancer
#18
Joseph A Sparano, Robert Gray, Maja H Oktay, David Entenberg, Thomas Rohan, Xiaonan Xue, Michael Donovan, Michael Peterson, Anthony Shuber, Douglas A Hamilton, Timothy D'Alfonso, Lori J Goldstein, Frank Gertler, Nancy E Davidson, John Condeelis, Joan Jones
Metastasis is the primary cause of death in early-stage breast cancer. We evaluated the association between a metastasis biomarker, which we call "Tumor Microenviroment of Metastasis" (TMEM), and risk of recurrence. TMEM are microanatomic structures where invasive tumor cells are in direct contact with endothelial cells and macrophages, and which serve as intravasation sites for tumor cells into the circulation. We evaluated primary tumors from 600 patients with Stage I-III breast cancer treated with adjuvant chemotherapy in trial E2197 (NCT00003519), plus endocrine therapy for hormone receptor (HR)+ disease...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29119134/erratum-author-correction-the-contribution-of-pathogenic-variants-in-breast-cancer-susceptibility-genes-to-familial-breast-cancer-risk
#19
Thomas P Slavin, Kara N Maxwell, Jenna Lilyquist, Joseph Vijai, Susan L Neuhausen, Steve N Hart, Vignesh Ravichandran, Tinu Thomas, Ann Maria, Danylo Villano, Kasmintan A Schrader, Raymond Moore, Chunling Hu, Bradley Wubbenhorst, Brandon M Wenz, Kurt D'Andrea, Mark E Robson, Paolo Peterlongo, Bernardo Bonanni, James M Ford, Judy E Garber, Susan M Domchek, Csilla Szabo, Kenneth Offit, Katherine L Nathanson, Jeffrey N Weitzel, Fergus J Couch
[This corrects the article DOI: 10.1038/s41523-017-0024-8.].
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29067357/use-of-21-gene-recurrence-score-assay-to-individualize-adjuvant-chemotherapy-recommendations-in-er-her2-node-positive-breast-cancer-a-national-cancer-database-study
#20
Prema P Peethambaram, Tanya L Hoskin, Courtney N Day, Matthew P Goetz, Elizabeth B Habermann, Judy C Boughey
The 21-gene Recurrence Score (RS) assay is prognostic and predictive of adjuvant chemotherapy benefit in node positive (N+) breast cancer (BC). We sought to evaluate use patterns of RS assay in N+, ER+/HER2- BC and the impact of RS on recommendations for adjuvant chemotherapy. Patients with T1-T4c,N1mi-N3, ER+/HER2- BC diagnosed 2010-2013 in the National Cancer Database were analyzed. Multivariable logistic regression assessed factors influencing RS testing and chemotherapy recommendations based on RS. Among 72,897 patients, RS was obtained in 20...
2017: NPJ Breast Cancer
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