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NPJ Breast Cancer

Valentina I Petkov, Dave P Miller, Nadia Howlader, Nathan Gliner, Will Howe, Nicola Schussler, Kathleen Cronin, Frederick L Baehner, Rosemary Cress, Dennis Deapen, Sally L Glaser, Brenda Y Hernandez, Charles F Lynch, Lloyd Mueller, Ann G Schwartz, Stephen M Schwartz, Antoinette Stroup, Carol Sweeney, Thomas C Tucker, Kevin C Ward, Charles Wiggins, Xiao-Cheng Wu, Lynne Penberthy, Steven Shak
[This corrects the article DOI: 10.1038/npjbcancer.2016.17.].
2018: NPJ Breast Cancer
Zsofia Sztupinszki, Miklos Diossy, Marcin Krzystanek, Lilla Reiniger, István Csabai, Francesco Favero, Nicolai J Birkbak, Aron C Eklund, Ali Syed, Zoltan Szallasi
The first genomic scar-based homologous recombination deficiency (HRD) measures were produced using SNP arrays. As array-based technology has been largely replaced by next generation sequencing approaches, it has become important to develop algorithms that derive the same type of genomic scar scores from next generation sequencing (whole exome "WXS", whole genome "WGS") data. In order to perform this analysis, we introduce here the scarHRD R package and show that using this method the SNP array-based and next generation sequencing-based derivation of HRD scores show good correlation (Pearson correlation between 0...
2018: NPJ Breast Cancer
Chloe M Beverly, Michelle J Naughton, Michael L Pennell, Randi E Foraker, Gregory Young, Lauren Hale, Elizabeth M Cespedes Feliciano, Kathy Pan, Tracy E Crane, Suzanne C Danhauer, Electra D Paskett
Breast cancer survivors frequently report sleep problems, but little research has studied sleep patterns longitudinally. We examined trends in sleep quality and duration up to 15 years before and 20 years after a diagnosis of breast cancer, over time among postmenopausal women participating in the Women's Health Initiative (WHI). We included 12,098 participants who developed invasive breast cancer after study enrollment. A linear mixed-effects model was used to determine whether the time trend in sleep quality, as measured by the WHI Insomnia Rating Scale (WHIIRS), a measure of perceived insomnia symptoms from the past 4 weeks, changed following a cancer diagnosis...
2018: NPJ Breast Cancer
Marie-Laure Tanguy, Luc Cabel, Fréderique Berger, Jean-Yves Pierga, Alexia Savignoni, Francois-Clement Bidard
Palbociclib, ribociclib, and abemaciclib have been investigated in combination with aromatase inhibitors as first-line therapy for metastatic hormone receptor-positive breast cancer (PALOMA-2, MONALEESA-2 and MONALEESA-7, MONARCH-3 trials, respectively); pivotal trials led to absolute median progression-free survival (PFS) gain of about 15 months. We aimed to estimate, for each trial, the statistical power to demonstrate a significant gain in overall survival (OS). Power was calculated with Freedman's formula...
2018: NPJ Breast Cancer
Lindsay A Williams, Ebonee N Butler, Xuezheng Sun, Emma H Allott, Stephanie M Cohen, Ashley M Fuller, Katherine A Hoadley, Charles M Perou, Joseph Geradts, Andrew F Olshan, Melissa A Troester
Mutations in tumor suppressor TP53 have been inconsistently linked to breast cancer risk factors and survival. Immunohistochemistry (IHC) staining, a primary clinical means of TP53 mutation determination, only detects mutations that facilitate protein accumulation (e.g., missense mutations). RNA-based pathway methods capture functional status and may aid in understanding the role of TP53 function in racial disparities of breast cancer. TP53 status was assessed among invasive breast cancer cases from the Carolina Breast Cancer Study (CBCS) (2008-2013) using IHC and an established RNA-based TP53 signature (CBCS and The Cancer Genome Atlas (TCGA))...
2018: NPJ Breast Cancer
Fatima Cardoso, Giuseppe Curigliano
No abstract text is available yet for this article.
2018: NPJ Breast Cancer
Joseph A Sparano
No abstract text is available yet for this article.
2018: NPJ Breast Cancer
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
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
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
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
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
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
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
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
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
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
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
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
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