Evidence map›Paper›PMID 27090210›Full record

ArticleBMC cancer2016

Identification of stromal ColXα1 and tumor-infiltrating lymphocytes as putative predictive markers of neoadjuvant therapy in estrogen receptor-positive/HER2-positive breast cancer.

Alexander S Brodsky, Jinjun Xiong, Dongfang Yang, Christoph Schorl, Mary Anne Fenton, Theresa A Graves, William M Sikov, Murray B Resnick, Yihong Wang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.

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  5. COL10A1Journal of experimental & clinical cancer research : CR · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Alexander S BrodskyDepartment of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, Providence, USA. alex_brodsky@brown.edu.
Jinjun XiongDepartment of Pathology, Women and Infants Hospital, Warren Alpert Medical School of Brown University, Providence, USA.
Dongfang YangDepartment of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, Providence, USA.
Christoph SchorlMolecular Biology, Cell Biology, & Biochemistry, Brown University, Providence, USA.
Mary Anne FentonDepartment of Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, Providence, USA.
Theresa A GravesDepartment of Surgery, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, Providence, USA.
William M SikovProgram in Women's Oncology, Women and Infants Hospital, Warren Alpert Medical School of Brown University, Providence, USA.
Murray B ResnickDepartment of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, Providence, USA.
Yihong WangDepartment of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, Providence, USA. ywang6@lifespan.org.
Brown University · USLifespan · USRhode Island Hospital · US

Funding

UTERINE NK CELL HOMING FROM THE PERIPHERAL CIRCULATIONP20RR018728 · NCRR · WOMEN AND INFANTS HOSPITAL-RHODE ISLAND · PI MARSIT, CARMEN JOSEPH · 2003 to 2011
$16.7M
COBRE Center for Cancer Research DevelopmentP20GM103421 · NIGMS · RHODE ISLAND HOSPITAL · PI RAMRATNAM, BHARAT · 2012 to 2013
$4.5M
Center for Cancer Signaling NetworksP30GM103410 · NIGMS · BROWN UNIVERSITY · PI ATWOOD, WALTER J · 2012 to 2015
$4.3M
CENTER FOR CANCER SIGNALING NETWORKSP30RR031153 · NCRR · BROWN UNIVERSITY · PI ATWOOD, WALTER J · 2011 to 2011
$1.1M
NCRR NIH HHS P20 RR018728NCRR NIH HHS P20RR018728NCRR NIH HHS P30 RR031153NCRR NIH HHS P30RR031153NCRR NIH HHS S10RR02763NIGMS NIH HHS P20 GM103421NIGMS NIH HHS P20GM103421NIGMS NIH HHS P30 GM103410NIGMS NIH HHS P30GM103410
6 · The paper itself

Abstract

backgroundThe influence of the tumor microenvironment and tumor-stromal interactions on the heterogeneity of response within breast cancer subtypes have just begun to be explored. This study focuses on patients with estrogen receptor-positive/human epidermal growth factor receptor 2-positive (ER+/HER2+) breast cancer receiving neoadjuvant chemotherapy and HER2-targeted therapy (NAC+H), and was designed to identify novel predictive biomarkers by combining gene expression analysis and immunohistochemistry with pathologic response.

methodsWe performed gene expression profiling on pre-NAC+H tumor samples from responding (no or minimal residual disease at surgery) and non-responding patients. Gene set enrichment analysis identified potentially relevant pathways, and immunohistochemical staining of pre-treatment biopsies was used to measure protein levels of those pathways, which were correlated with pathologic response in both univariate and multivariate analysis.

resultsIncreased expression of genes encoding for stromal collagens, including Col10A1, and reduced expression of immune-associated genes, reflecting lower levels of total tumor-infiltrating lymphocytes (TILs), were strongly associated with poor pathologic response. Lower TILs in tumor biopsies correlated with reduced likelihood of achieving an optimal pathologic response, but increased expression of the Col10A1 gene product, colXα1, had greater predictive value than stromal abundance for poor response (OR = 18.9, p = 0.003), and the combination of increased colXα1 expression and low TILs was significantly associated with poor response in multivariate analysis. ROC analysis suggests strong specificity and sensitivity for this combination in predicting treatment response.

conclusionsIncreased expression of stromal colXα1 and low TILs correlate with poor pathologic response in ER+/HER2+ breast tumors. Further studies are needed to confirm their predictive value and impact on long-term outcomes, and to determine whether this collagen exerts a protective effect on the cancer cells or simply reflects other factors within the tumor microenvironment.

Indexed as

AdultAgedBiomarkers, TumorBreast NeoplasmsCollagen Type XErb-b2 Receptor Tyrosine KinasesFemaleGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingMiddle AgedPrognosisReceptors, EstrogenTreatment OutcomeTumor MicroenvironmentBiomarkers, TumorCollagen Type XERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesReceptors, EstrogenCollagenHER2-positive breast cancerNeoadjuvant chemotherapyTumor infiltrating lymphocytesTumor microenvironment

Identifiers

PMID27090210
PMCPMC4835834
OpenAlexW2340064377

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.