Evidence map›Paper›PMID 30560461›Full record

ArticleBreast cancer research and treatment2019

The estrogen receptor-alpha S118P variant does not affect breast cancer incidence or response to endocrine therapies.

Berry Button, Sarah Croessmann, David Chu, D Marc Rosen, Daniel J Zabransky, W Brian Dalton, Karen Cravero, Kelly Kyker-Snowman, Ian Waters, Swathi Karthikeyan and 11 more

Abstract read
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In one paragraph

Article in Breast cancer research and treatment, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Genetic regulation of the estrogen receptor and inherited predisposition to breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  2. Review
  3. Review
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

21 authors.

Berry ButtonThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sarah CroessmannVanderbilt Ingram Cancer Center, Vanderbilt Universtiy Medical Center, 2220 Pierce Avenue, PRB 777, Nashville, TN, 37232, USA.
David ChuThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
D Marc RosenThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Daniel J ZabranskyThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
W Brian DaltonThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Karen CraveroThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kelly Kyker-SnowmanThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ian WatersThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Swathi KarthikeyanThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Eric S ChristensonThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Josh DonaldsonThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tasha HunterThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lauren DennisonThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cody RaminThe Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Betty MayThe Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Richard RodenThe Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Dana PetryThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Deborah K ArmstrongThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kala VisvanathanThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ben Ho ParkThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. ben.h.park@vumc.org.ORCID http://orcid.org/0000-0001-8119-2291

Funding

VACCINES--A NEW PARADIGM FOR BREAST CANCERP50CA088843 · NCI · JOHNS HOPKINS UNIVERSITY · PI DAVIDSON, NANCY ELLEN · 2000 to 2010
$27.8M
Vanderbilt Clinical Oncology Research Career Development ProgramK12CA090625 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Debra L. Friedman, Paula Jill Hurley · 2001 to 2026
$16.9M
University of California Launching Future Leaders in Global Health Research Training ProgramD43TW009343 · FIC · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRAIG R COHEN, Sung-Jae Lee · 2017 to 2026
$14.7M
Comprehensive Sequencing and Analysis of Variation in NHLBI CohortsUC2HL102925 · NHLBI · BROAD INSTITUTE, INC. · PI ALTSHULER, DAVID, GABRIEL, STACEY · 2010 to 2010
$14.7M
Northwest Genomics CenterUC2HL102926 · NHLBI · UNIVERSITY OF WASHINGTON · PI GREEN, PHILIP P, NICKERSON, DEBORAH A · 2010 to 2010
$14.0M
ONCOLOGY: CHEMOTHERAPY, IMMUNOLOGY, BIOLOGYT32CA009071 · NCI · JOHNS HOPKINS UNIVERSITY · PI Mary Y Armanios, Nilofer S. Azad · 1985 to 2026
$12.8M
Training Program in Cellular and Molecular MedicineT32GM008752 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI RAO, RAJINI · 2000 to 2019
$11.7M
INSTITUTIONAL RESEARCH CANCER EPIDEMIOLOGY FELLOWSHIPT32CA009314 · NCI · JOHNS HOPKINS UNIVERSITY · PI Corinne E. Joshu, Meghan Bridgid Moran · 1985 to 2026
$11.2M
Northwest Genomics CenterRC2HL102926 · NHLBI · UNIVERSITY OF WASHINGTON · PI GREEN, PHILIP P, NICKERSON, DEBORAH A · 2009 to 2009
$11.0M
Studies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5M
Comprehensive Sequencing and Analysis of Variation in NHLBI CohortsRC2HL102925 · NHLBI · BROAD INSTITUTE, INC. · PI ALTSHULER, DAVID, GABRIEL, STACEY · 2009 to 2009
$10.2M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
FIC NIH HHS D43 TW009343NCI NIH HHS CA009071NCI NIH HHS CA009314NCI NIH HHS CA088843NCI NIH HHS CA194024NCI NIH HHS CA214494NCI NIH HHS K12 CA090625NCI NIH HHS K24 CA198315NCI NIH HHS P50 CA088843NCI NIH HHS R01 CA194024NCI NIH HHS R01 CA214494NCI NIH HHS T32 CA009071NCI NIH HHS T32 CA009314NHLBI NIH HHS HHSN268201700001CNHLBI NIH HHS HHSN268201700001INHLBI NIH HHS HHSN268201700002CNHLBI NIH HHS HHSN268201700002INHLBI NIH HHS HHSN268201700003CNHLBI NIH HHS HHSN268201700003INHLBI NIH HHS HHSN268201700004CNHLBI NIH HHS HHSN268201700004INHLBI NIH HHS HHSN268201700005CNHLBI NIH HHS HHSN268201700005INHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS RC2 HL102923NHLBI NIH HHS RC2 HL102924NHLBI NIH HHS RC2 HL102925NHLBI NIH HHS RC2 HL102926NHLBI NIH HHS RC2 HL103010NHLBI NIH HHS UC2 HL102923NHLBI NIH HHS UC2 HL102924NHLBI NIH HHS UC2 HL102925NHLBI NIH HHS UC2 HL102926NHLBI NIH HHS UC2 HL103010NIGMS NIH HHS T32 GM008752NIH HHS GM008752Susan G. Komen SAC170079
6 · The paper itself

Abstract

purposeEstrogen receptor-alpha (ER) is a therapeutic target of ER-positive (ER+) breast cancers. Although ER signaling is complex, many mediators of this pathway have been identified. Specifically, phosphorylation of ER at serine 118 affects responses to estrogen and therapeutic ligands and has been correlated with clinical outcomes in ER+ breast cancer patients. We hypothesized that a newly described germline variant (S118P) at this residue would drive cellular changes consistent with breast cancer development and/or hormone resistance.

methodsIsogenic human breast epithelial cell line models harboring ER S118P were developed via genome editing and characterized to determine the functional effects of this variant. We also examined the frequency of ER S118P in a case-control study (N = 536) of women with and without breast cancer with a familial risk.

resultsIn heterozygous knock-in models, the S118P variant demonstrated no significant change in proliferation, migration, MAP Kinase pathway signaling, or response to the endocrine therapies tamoxifen and fulvestrant. Further, there was no difference in the prevalence of S118P between women with and without cancer relative to population registry databases.

conclusionsThis study suggests that the ER S118P variant does not affect risk for breast cancer or hormone therapy resistance. Germline screening and modification of treatments for patients harboring this variant are likely not warranted.

Indexed as

Germ-Line MutationAdultAgedAntineoplastic Agents, HormonalBreast NeoplasmsCase-Control StudiesCell Line, TumorCell MovementCell ProliferationEstrogen Receptor alphaFemaleFulvestrantGenetic VariationHumansIncidenceMCF-7 CellsAntineoplastic Agents, HormonalESR1 protein, humanEstrogen Receptor alphaFulvestrantTamoxifenBreast cancerEndocrine resistanceESR1

Identifiers

PMID30560461
PMCPMC6447053

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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.