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https://www.readbyqxmd.com/read/28912426/deconvolution-of-dna-methylation-identifies-differentially-methylated-gene-regions-on-1p36-across-breast-cancer-subtypes
#1
Alexander J Titus, Gregory P Way, Kevin C Johnson, Brock C Christensen
Breast cancer is a complex disease consisting of four distinct molecular subtypes. DNA methylation-based (DNAm) studies in tumors are complicated further by disease heterogeneity. In the present study, we compared DNAm in breast tumors with normal-adjacent breast samples from The Cancer Genome Atlas (TCGA). We constructed models stratified by tumor stage and PAM50 molecular subtype and performed cell-type reference-free deconvolution to control for cellular heterogeneity. We identified nineteen differentially methylated gene regions (DMGRs) in early stage tumors across eleven genes (AGRN, C1orf170, FAM41C, FLJ39609, HES4, ISG15, KLHL17, NOC2L, PLEKHN1, SAMD11, WASH5P)...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28878133/exome-capture-rna-sequencing-of-decade-old-breast-cancers-and-matched-decalcified-bone-metastases
#2
Nolan Priedigkeit, Rebecca J Watters, Peter C Lucas, Ahmed Basudan, Rohit Bhargava, William Horne, Jay K Kolls, Zhou Fang, Margaret Q Rosenzweig, Adam M Brufsky, Kurt R Weiss, Steffi Oesterreich, Adrian V Lee
Bone metastases (BoM) are a significant cause of morbidity in patients with estrogen receptor-positive (ER-positive) breast cancer; yet, characterizations of human specimens are limited. In this study, exome-capture RNA sequencing (ecRNA-seq) on aged (8-12 years), formalin-fixed, paraffin-embedded (FFPE), and decalcified cancer specimens was evaluated. Gene expression values and ecRNA-seq quality metrics from FFPE or decalcified tumor RNA showed minimal differences when compared with matched flash-frozen or nondecalcified tumors...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28859291/relevance-of-spatial-heterogeneity-of-immune-infiltration-for-predicting-risk-of-recurrence-after-endocrine-therapy-of-er-breast-cancer
#3
Andreas Heindl, Ivana Sestak, Kalnisha Naidoo, Jack Cuzick, Mitchell Dowsett, Yinyin Yuan
Background: Despite increasing evidence supporting the clinical utility of immune infiltration in the estrogen receptor-negative (ER-) subtype, the prognostic value of immune infiltration for ER+ disease is not well defined. Methods: Quantitative immune scores of cell abundance and spatial heterogeneity were computed using a fully automated hematoxylin and eosin-stained image analysis algorithm and spatial statistics for 1178 postmenopausal patients with ER+ breast cancer treated with five years' tamoxifen or anastrozole...
February 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28859290/racial-differences-in-pam50-subtypes-in-the-carolina-breast-cancer-study
#4
Melissa A Troester, Xuezheng Sun, Emma H Allott, Joseph Geradts, Stephanie M Cohen, Chiu-Kit Tse, Erin L Kirk, Leigh B Thorne, Michelle Mathews, Yan Li, Zhiyuan Hu, Whitney R Robinson, Katherine A Hoadley, Olufunmilayo I Olopade, Katherine E Reeder-Hayes, H Shelton Earp, Andrew F Olshan, Lisa A Carey, Charles M Perou
Background: African American breast cancer patients have lower frequency of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative disease and higher subtype-specific mortality. Racial differences in molecular subtype within clinically defined subgroups are not well understood. Methods: Using data and biospecimens from the population-based Carolina Breast Cancer Study (CBCS) Phase 3 (2008-2013), we classified 980 invasive breast cancers using RNA expression-based PAM50 subtype and recurrence (ROR) score that reflects proliferation and tumor size...
February 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28629479/evaluation-of-invasive-breast-cancer-samples-using-a-12-chemokine-gene-expression-score-correlation-with-clinical-outcomes
#5
Sangeetha Prabhakaran, Victoria T Rizk, Zhenjun Ma, Chia-Ho Cheng, Anders E Berglund, Dominico Coppola, Farah Khalil, James J Mulé, Hatem H Soliman
BACKGROUND: A unique 12-chemokine gene expression score (CS) accurately predicted the presence of tumor-localized, ectopic lymph node-like structures (TL-ELNs) and improved overall survival (OS) in primary colorectal cancer and metastatic melanoma. We analyzed the correlation between CS, clinicopathological variables, molecular data, and 366 survival in Moffitt Cancer Center's Total Cancer Care (TCC) patients with non-metastatic breast cancer. METHODS: Affymetrix gene expression profiles were used to interrogate the CS by the principal component method...
June 19, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28512241/assessment-of-breast-cancer-risk-factors-reveals-subtype-heterogeneity
#6
Johanna Holm, Louise Eriksson, Alexander Ploner, Mikael Eriksson, Mattias Rantalainen, Jingmei Li, Per Hall, Kamila Czene
Subtype heterogeneity for breast cancer risk factors has been suspected, potentially reflecting etiologic differences and implicating risk prediction. However, reports are conflicting regarding the presence of heterogeneity for many exposures. To examine subtype heterogeneity across known breast cancer risk factors, we conducted a case-control analysis of 2,632 breast cancers and 15,945 controls in Sweden. Molecular subtype was predicted from pathology record-derived IHC markers by a classifier trained on PAM50 subtyping...
July 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28510570/bag-1-as-a-biomarker-in-early-breast-cancer-prognosis-a-systematic-review-with-meta-analyses
#7
REVIEW
E S Papadakis, T Reeves, N H Robson, T Maishman, G Packham, R I Cutress
BACKGROUND: The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is overexpressed in breast cancer and has been incorporated in the oncotype DX and PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as multiple protein isoforms that interact with diverse partners, including chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell survival. The BAG-1L isoform specifically binds to and increases the transcriptional activity of oestrogen receptor in cells, and in some, but not all studies, BAG-1 expression is predictive of clinical outcome in breast cancer...
June 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28494073/associations-of-luminal-and-basal-subtyping-of-prostate-cancer-with-prognosis-and-response-to-androgen-deprivation-therapy
#8
Shuang G Zhao, S Laura Chang, Nicholas Erho, Menggang Yu, Jonathan Lehrer, Mohammed Alshalalfa, Corey Speers, Matthew R Cooperberg, Won Kim, Charles J Ryan, Robert B Den, Stephen J Freedland, Edwin Posadas, Howard Sandler, Eric A Klein, Peter Black, Roland Seiler, Scott A Tomlins, Arul M Chinnaiyan, Robert B Jenkins, Elai Davicioni, Ashley E Ross, Edward M Schaeffer, Paul L Nguyen, Peter R Carroll, R Jeffrey Karnes, Daniel E Spratt, Felix Y Feng
Importance: There is a clear need for a molecular subtyping approach in prostate cancer to identify clinically distinct subgroups that benefit from specific therapies. Objectives: To identify prostate cancer subtypes based on luminal and basal lineage and to determine associations with clinical outcomes and response to treatment. Design, Setting, and Participants: The PAM50 classifier was used to subtype 1567 retrospectively collected (median follow-up, 10 years) and 2215 prospectively collected prostate cancer samples into luminal- and basal-like subtypes...
May 11, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28423537/limitations-in-predicting-pam50-intrinsic-subtype-and-risk-of-relapse-score-with-ki67-in-estrogen-receptor-positive-her2-negative-breast-cancer
#9
Aranzazu Fernandez-Martinez, Tomás Pascual, Giuseppe Perrone, Serafin Morales, Juan de la Haba, Milagros González-Rivera, Patricia Galván, Francesca Zalfa, Michela Amato, Lucia Gonzalez, Miquel Prats, Federico Rojo, Luis Manso, Laia Paré, Immaculada Alonso, Joan Albanell, Ana Vivancos, Antonio González, Judit Matito, Sonia González, Pedro Fernandez, Barbara Adamo, Montserrat Muñoz, Margarita Viladot, Carme Font, Francisco Aya, Maria Vidal, Rosalía Caballero, Eva Carrasco, Vittorio Altomare, Giuseppe Tonini, Aleix Prat, Miguel Martin
PAM50/Prosigna gene expression-based assay identifies three categorical risk of relapse groups (ROR-low, ROR-intermediate and ROR-high) in post-menopausal patients with estrogen receptor estrogen receptor-positive (ER+)/ HER2-negative (HER2-) early breast cancer. Low risk patients might not need adjuvant chemotherapy since their risk of distant relapse at 10-years is below 10% with endocrine therapy only. In this study, 517 consecutive patients with ER+/HER2- and node-negative disease were evaluated for Ki67 and Prosigna...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28376177/progesterone-receptor-isoform-ratio-a-breast-cancer-prognostic-and-predictive-factor-for-antiprogestin-responsiveness
#10
Paola A Rojas, María May, Gonzalo R Sequeira, Andrés Elia, Michelle Alvarez, Paula Martínez, Pedro Gonzalez, Stephen Hewitt, Xiaping He, Charles M Perou, Alfredo Molinolo, Luz Gibbons, Martin C Abba, Hugo Gass, Claudia Lanari
Background: Compelling evidence shows that progestins regulate breast cancer growth. Using preclinical models, we demonstrated that antiprogestins are inhibitory when the level of progesterone receptor isoform A (PR-A) is higher than that of isoform B (PR-B) and that they might stimulate growth when PR-B is predominant. The aims of this study were to investigate ex vivo responses to mifepristone (MFP) in breast carcinomas with different PR isoform ratios and to examine their clinical and molecular characteristics...
July 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28365335/competing-risks-of-mortality-by-pam50-intrinsic-subtype-of-british-columbia-tamoxifen-treated-cohort-of-postmenopausal-patients-with-breast-cancer
#11
Judith-Anne W Chapman, Shuzhen Liu, Samuel Leung, Torsten O Nielsen
BACKGROUND: PAM50 intrinsic subtypes have been shown to affect breast cancer prognosis. METHODS: A British Columbia cohort of 718 postmenopausal women treated with tamoxifen, without chemotherapy, had tumors intrinsically subtyped (luminal A, luminal B, basal, HER2) and centrally reviewed by immunohistochemistry (IHC) for estrogen and progesterone receptor (ER and PgR). We tested whether intrinsic subtype and other patient and tumor characteristics were associated with type of death...
January 20, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28356166/integrative-clustering-reveals-a-novel-split-in-the-luminal-a-subtype-of-breast-cancer-with-impact-on-outcome
#12
MULTICENTER STUDY
Miriam Ragle Aure, Valeria Vitelli, Sandra Jernström, Surendra Kumar, Marit Krohn, Eldri U Due, Tonje Husby Haukaas, Suvi-Katri Leivonen, Hans Kristian Moen Vollan, Torben Lüders, Einar Rødland, Charles J Vaske, Wei Zhao, Elen K Møller, Silje Nord, Guro F Giskeødegård, Tone Frost Bathen, Carlos Caldas, Trine Tramm, Jan Alsner, Jens Overgaard, Jürgen Geisler, Ida R K Bukholm, Bjørn Naume, Ellen Schlichting, Torill Sauer, Gordon B Mills, Rolf Kåresen, Gunhild M Mælandsmo, Ole Christian Lingjærde, Arnoldo Frigessi, Vessela N Kristensen, Anne-Lise Børresen-Dale, Kristine K Sahlberg
BACKGROUND: Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. METHODS: Tumor tissue from 425 patients with primary breast cancer from the Oslo2 study was cut and blended, and divided into fractions for DNA, RNA and protein isolation and metabolomics, allowing the acquisition of representative and comparable molecular data...
March 29, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28295245/body-mass-index-pam50-subtype-recurrence-and-survival-among-patients-with-nonmetastatic-breast-cancer
#13
Elizabeth M Cespedes Feliciano, Marilyn L Kwan, Lawrence H Kushi, Wendy Y Chen, Erin K Weltzien, Adrienne L Castillo, Carol Sweeney, Philip S Bernard, Bette J Caan
BACKGROUND: Studies of obesity and survival among patients with breast cancer produce conflicting results, possibly because of heterogeneity by molecular subtype. METHODS: This study examined whether the association of body mass index (BMI) at diagnosis with breast cancer recurrence and survival varied across subtypes defined by PAM50 (Prediction Analysis of Microarray 50) gene expression. Included were 1559 Kaiser Permanente Northern California members ages 18 to 79 years who had PAM50 assays and were diagnosed with American Joint Committee on Cancer stage I through III breast cancer from 1996 to 2013...
July 1, 2017: Cancer
https://www.readbyqxmd.com/read/28259011/clinical-use-of-biomarkers-in-breast-cancer-updated-guidelines-from-the-european-group-on-tumor-markers-egtm
#14
REVIEW
M J Duffy, N Harbeck, M Nap, R Molina, A Nicolini, E Senkus, F Cardoso
Biomarkers play an essential role in the management of patients with invasive breast cancer. For selecting patients likely to respond to endocrine therapy, both oestrogen receptors (ERs) and progesterone receptors (PRs) should be measured on all newly diagnosed invasive breast cancers. On the other hand, for selecting likely response to all forms of anti-HER2 therapy (trastuzumab, pertuzumab, lapatinib or ado-trastuzumab emtansine), determination of HER2 expression or gene copy number is mandatory. Where feasible, measurement of ER, PR and HER2 should be performed on recurrent lesions and the primary invasive tumour...
April 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28249905/intrinsic-subtypes-and-gene-expression-profiles-in-primary-and-metastatic-breast-cancer
#15
Juan M Cejalvo, Eduardo Martínez de Dueñas, Patricia Galván, Susana García-Recio, Octavio Burgués Gasión, Laia Paré, Silvia Antolín, Rosella Martinello, Isabel Blancas, Barbara Adamo, Ángel Guerrero-Zotano, Montserrat Muñoz, Paolo Nucíforo, María Vidal, Ramón M Pérez, José I Chacón López-Muniz, Rosalía Caballero, Vicente Peg, Eva Carrasco, Federico Rojo, Charles M Perou, Javier Cortés, Vincenzo Adamo, Joan Albanell, Roger R Gomis, Ana Lluch, Aleix Prat
Biological changes that occur during metastatic progression of breast cancer are still incompletely characterized. In this study, we compared intrinsic molecular subtypes and gene expression in 123 paired primary and metastatic tissues from breast cancer patients. Intrinsic subtype was identified using a PAM50 classifier and χ(2) tests determined the differences in variable distribution. The rate of subtype conversion was 0% in basal-like tumors, 23.1% in HER2-enriched (HER2-E) tumors, 30.0% in luminal B tumors, and 55...
May 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28249895/individualized-breast-cancer-characterization-through-single-cell-analysis-of-tumor-and-adjacent-normal-cells
#16
Manjushree Anjanappa, Angelo Cardoso, Lijun Cheng, Safa Mohamad, Andrea Gunawan, Susan Rice, Yan Dong, Lang Li, George E Sandusky, Edward F Srour, Harikrishna Nakshatri
There is a need to individualize assays for tumor molecular phenotyping, given variations in the differentiation status of tumor and normal tissues in different patients. To address this, we performed single-cell genomics of breast tumors and adjacent normal cells propagated for a short duration under growth conditions that enable epithelial reprogramming. Cells analyzed were either unselected for a specific subpopulation or phenotypically defined as undifferentiated and highly clonogenic ALDH(+)/CD49f(+)/EpCAM(+) luminal progenitors, which express both basal cell and luminal cell-enriched genes...
May 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28238593/her2-enriched-subtype-as-a-predictor-of-pathological-complete-response-following-trastuzumab-and-lapatinib-without-chemotherapy-in-early-stage-her2-positive-breast-cancer-pamela-an-open-label-single-group-multicentre-phase-2-trial
#17
MULTICENTER STUDY
Antonio Llombart-Cussac, Javier Cortés, Laia Paré, Patricia Galván, Begoña Bermejo, Noelia Martínez, Maria Vidal, Sònia Pernas, Rafael López, Montserrat Muñoz, Paolo Nuciforo, Serafín Morales, Mafalda Oliveira, Lorena de la Peña, Alexandra Peláez, Aleix Prat
BACKGROUND: HER2-positive breast cancer consists of four intrinsic molecular subtypes-luminal A, luminal B, HER2-enriched, and basal-like-and a normal-like subtype, with the HER2-enriched subtype having the highest activation of the EGFR-HER2 pathway. We aimed to test the hypothesis that patients with the HER2-enriched subtype benefit the most from dual HER2 blockade. METHODS: PAMELA is an open-label, single-group, phase 2 trial done in 19 hospitals in Spain. We recruited female patients aged at least 18 years with previously untreated, centrally confirmed HER2-positive, stage I-IIIA invasive breast cancer regardless of hormone receptor status...
April 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28062443/a-novel-non-parametric-method-for-uncertainty-evaluation-of-correlation-based-molecular-signatures-its-application-on-pam50-algorithm
#18
Cristóbal Fresno, Germán Alexis González, Gabriela Alejandra Merino, Ana Georgina Flesia, Osvaldo Luis Podhajcer, Andrea Sabina Llera, Elmer Andrés Fernández
Motivation: The PAM50 classifier is used to assign patients to the highest correlated breast cancer subtype irrespectively of the obtained value. Nonetheless, all subtype correlations are required to build the risk of recurrence (ROR) score, currently used in therapeutic decisions. Present subtype uncertainty estimations are not accurate, seldom considered or require a population-based approach for this context. Results: Here we present a novel single-subject non-parametric uncertainty estimation based on PAM50's gene label permutations...
March 1, 2017: Bioinformatics
https://www.readbyqxmd.com/read/27926948/intrinsic-subtype-switching-and-acquired-erbb2-her2-amplifications-and-mutations-in-breast-cancer-brain-metastases
#19
MULTICENTER STUDY
Nolan Priedigkeit, Ryan J Hartmaier, Yijing Chen, Damir Vareslija, Ahmed Basudan, Rebecca J Watters, Roby Thomas, Jose P Leone, Peter C Lucas, Rohit Bhargava, Ronald L Hamilton, Juliann Chmielecki, Shannon L Puhalla, Nancy E Davidson, Steffi Oesterreich, Adam M Brufsky, Leonie Young, Adrian V Lee
Importance: Patients with breast cancer (BrCa) brain metastases (BrM) have limited therapeutic options. A better understanding of molecular alterations acquired in BrM could identify clinically actionable metastatic dependencies. Objective: To determine whether there are intrinsic subtype differences between primary tumors and matched BrM and to uncover BrM-acquired alterations that are clinically actionable. Design, Setting, and Participants: In total, 20 cases of primary breast cancer tissue and resected BrM (10 estrogen receptor [ER]-negative and 10 ER-positive) from 2 academic institutions were included...
May 1, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/27925203/the-genetic-landscape-of-breast-carcinomas-with-neuroendocrine-differentiation
#20
Caterina Marchiò, Felipe C Geyer, Charlotte Ky Ng, Salvatore Piscuoglio, Maria R De Filippo, Marco Cupo, Anne M Schultheis, Raymond S Lim, Kathleen A Burke, Elena Guerini-Rocco, Mauro Papotti, Larry Norton, Anna Sapino, Britta Weigelt, Jorge S Reis-Filho
Neuroendocrine breast carcinomas (NBCs) account for 2-5% of all invasive breast cancers, and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), and are HER2-negative and of luminal 'intrinsic' subtype. Here, we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER(+) /HER2(-) ) breast carcinoma show distinct repertoires of somatic mutations. Eighteen ER(+) /HER2(-) NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissues were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast carcinomas and/or related to DNA repair...
February 2017: Journal of Pathology
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