Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Computer Resources
      • Highly Cited Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Early Career Award
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citations
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Research
Cancer Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Computer Resources
      • Highly Cited Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Early Career Award
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citations
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Poster Session Abstracts

Abstract P6-09-07: Mutation characteristics and tumor infiltrating lymphocytes in early and metastatic HER2-positive breast cancer

V Kotoula, E Giannoulatou, G Kouvatseas, I Tikas, G Lazaridis, E Charalambous, I Efstratiou, M Bobos, E Tsolaki, F Zagouri, C Christodoulou, G Pentheroudakis, A Koutras, P Papakostas, PA Kosmidis, D Pectasides and G Fountzilas
V Kotoula
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E Giannoulatou
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G Kouvatseas
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
I Tikas
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G Lazaridis
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E Charalambous
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
I Efstratiou
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M Bobos
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E Tsolaki
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
F Zagouri
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C Christodoulou
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G Pentheroudakis
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A Koutras
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P Papakostas
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
PA Kosmidis
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
D Pectasides
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G Fountzilas
Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; Health Data Specialists Ltd, Athens, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1538-7445.SABCS16-P6-09-07 Published February 2017
  • Article
  • Info & Metrics
Loading
Abstracts: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, Texas

Abstract

Background-aim: HER2-positive breast cancer (BC) features high rates of tumor infiltrating lymphocytes (TILs) and mutations (mut) in various genes, more frequently in TP53. We investigated associations between TILs and mutations in HER2-positive BC and their impact on patient outcome in early and metastatic BC (EBC and MBC, respectively), which remain largely unexplored.

Methods:In 352 primary paraffin tumors from patients with HER2-positive disease, we examined amino acid changing mutations (<0.1% minor allele frequency) in 58 genes for type and possible clonality (>20% variant frequency). Study groups were: (A) 218 EBC, including 117 patients treated with adjuvant chemotherapy only (CT) and 101 patients treated with CT and trastuzumab (CTT); (B) 134 MBC, including 95 patients who relapsed upon adjuvant CT without trastuzumab (R-MBC) and 39 patients who were first diagnosed with metastatic disease (de novo MBC). TILs were assessed as percentage of stromal tumor area. Clinical endpoints were disease-free survival in 5 years (5yr DFS) for EBC, and time-to-progression (TTP) from 1st line CTT treatment start for MBC.

Results: 243/352 tumors (69%) carried at least one mut; 27/352 (8%) of tumors >10 up to 150 mut (hypermut); 192/352 (54%) at least one possibly clonal mut. Mean mut number and TP53 mut in particular were highest in R-MBC and lowest in EBC; mean TILs density followed the opposite pattern (all p<0.001). TILs density was lower in all settings in hypermut tumors and in tumors with multiple clonal mut (p values 0.043 – 0.050). Upon multivariate analysis in EBC, higher risk for relapse in 5yrs was noticed for CT patients compared to CTT (odds ratio [OR] 2.39, 95%CI [CI] 1.13-5.04, p=0.023) and for >3 compared to 0-3 positive nodes (OR 3.83, CI 1.76-8.34, p=0.001); lower risk for relapse was observed for higher TILs irrespectively of treatment (OR 0.93, CI 0.90-0.97, p=0.001), for TP53 mut (OR 0.39, CI 0.18-0.87, p=0.022) and for clonal TP53 mut in CTT-treated patients (OR 0.10, CI 0.02-0.58) but not in CT-treated patients (interaction p=0.084). The presence of any clonal mut (hazard ratio [HR] 2.77, CI 1.42-5.38) and of clonal TP53 mut (HR 2.24, CI 1.20-4.17) conferred worse TTP in de novo but not in R-MBC; these interactions remained significant upon multivariate analysis (interaction p=0.007 and p=0.061, respectively). Higher TILs in the absence of clonal mut conferred longer TTP (HR 0.75, CI 0.56-0.99) but no such effect was observed for tumors with clonal mut (multivariate interaction p=0.052). Classic independent predictors of unfavorable TTP in MBC were younger age (p=0.002), absence of hormone receptors (p=0.001) and poor performance status (p=0.044). PIK3CA mut did not remain significant in any of the examined settings.

Conclusions: The expected pattern of higher TILs associated with mutation number and clonality was not observed in HER2-positive BC; the favorable effect of TILs only in the absence of clonal mut in MBC may imply exhausted immune response. Clonal TP53 mut may serve as a predictor for trastuzumab benefit in EBC but as an adverse prognosticator in trastuzumab-treated de novo MBC, which, if further validated, is of potential clinical relevance.Background-aim: HER2-positive breast cancer (BC) features high rates of tumor infiltrating lymphocytes (TILs) and mutations (mut) in various genes, more frequently in TP53. We investigated associations between TILs and mutations in HER2-positive BC and their impact on patient outcome in early and metastatic BC (EBC and MBC, respectively), which remain largely unexplored.

Methods:In 352 primary paraffin tumors from patients with HER2-positive disease, we examined amino acid changing mutations (<0.1% minor allele frequency) in 58 genes for type and possible clonality (>20% variant frequency). Study groups were: (A) 218 EBC, including 117 patients treated with adjuvant chemotherapy only (CT) and 101 patients treated with CT and trastuzumab (CTT); (B) 134 MBC, including 95 patients who relapsed upon adjuvant CT without trastuzumab (R-MBC) and 39 patients who were first diagnosed with metastatic disease (de novo MBC). TILs were assessed as percentage of stromal tumor area. Clinical endpoints were disease-free survival in 5 years (5yr DFS) for EBC, and time-to-progression (TTP) from 1st line CTT treatment start for MBC.

Results: 243/352 tumors (69%) carried at least one mut; 27/352 (8%) of tumors >10 up to 150 mut (hypermut); 192/352 (54%) at least one possibly clonal mut. Mean mut number and TP53 mut in particular were highest in R-MBC and lowest in EBC; mean TILs density followed the opposite pattern (all p<0.001). TILs density was lower in all settings in hypermut tumors and in tumors with multiple clonal mut (p values 0.043 – 0.050). Upon multivariate analysis in EBC, higher risk for relapse in 5yrs was noticed for CT patients compared to CTT (odds ratio [OR] 2.39, 95%CI [CI] 1.13-5.04, p=0.023) and for >3 compared to 0-3 positive nodes (OR 3.83, CI 1.76-8.34, p=0.001); lower risk for relapse was observed for higher TILs irrespectively of treatment (OR 0.93, CI 0.90-0.97, p=0.001), for TP53 mut (OR 0.39, CI 0.18-0.87, p=0.022) and for clonal TP53 mut in CTT-treated patients (OR 0.10, CI 0.02-0.58) but not in CT-treated patients (interaction p=0.084). The presence of any clonal mut (hazard ratio [HR] 2.77, CI 1.42-5.38) and of clonal TP53 mut (HR 2.24, CI 1.20-4.17) conferred worse TTP in de novo but not in R-MBC; these interactions remained significant upon multivariate analysis (interaction p=0.007 and p=0.061, respectively). Higher TILs in the absence of clonal mut conferred longer TTP (HR 0.75, CI 0.56-0.99) but no such effect was observed for tumors with clonal mut (multivariate interaction p=0.052). Classic independent predictors of unfavorable TTP in MBC were younger age (p=0.002), absence of hormone receptors (p=0.001) and poor performance status (p=0.044). PIK3CA mut did not remain significant in any of the examined settings.

Conclusions: The expected pattern of higher TILs associated with mutation number and clonality was not observed in HER2-positive BC; the favorable effect of TILs only in the absence of clonal mut in MBC may imply exhausted immune response. Clonal TP53 mut may serve as a predictor for trastuzumab benefit in EBC but as an adverse prognosticator in trastuzumab-treated de novo MBC, which, if further validated, is of potential clinical relevance.

Citation Format: Kotoula V, Giannoulatou E, Kouvatseas G, Tikas I, Lazaridis G, Charalambous E, Efstratiou I, Bobos M, Tsolaki E, Zagouri F, Christodoulou C, Pentheroudakis G, Koutras A, Papakostas P, Kosmidis PA, Pectasides D, Fountzilas G. Mutation characteristics and tumor infiltrating lymphocytes in early and metastatic HER2-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-07.

Previous
Back to top
Cancer Research: 77 (4 Supplement)
February 2017
Volume 77, Issue 4 Supplement
  • Table of Contents

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Abstract P6-09-07: Mutation characteristics and tumor infiltrating lymphocytes in early and metastatic HER2-positive breast cancer
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Abstract P6-09-07: Mutation characteristics and tumor infiltrating lymphocytes in early and metastatic HER2-positive breast cancer
V Kotoula, E Giannoulatou, G Kouvatseas, I Tikas, G Lazaridis, E Charalambous, I Efstratiou, M Bobos, E Tsolaki, F Zagouri, C Christodoulou, G Pentheroudakis, A Koutras, P Papakostas, PA Kosmidis, D Pectasides and G Fountzilas
Cancer Res February 15 2017 (77) (4 Supplement) P6-09-07; DOI: 10.1158/1538-7445.SABCS16-P6-09-07

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract P6-09-07: Mutation characteristics and tumor infiltrating lymphocytes in early and metastatic HER2-positive breast cancer
V Kotoula, E Giannoulatou, G Kouvatseas, I Tikas, G Lazaridis, E Charalambous, I Efstratiou, M Bobos, E Tsolaki, F Zagouri, C Christodoulou, G Pentheroudakis, A Koutras, P Papakostas, PA Kosmidis, D Pectasides and G Fountzilas
Cancer Res February 15 2017 (77) (4 Supplement) P6-09-07; DOI: 10.1158/1538-7445.SABCS16-P6-09-07
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Poster Session Abstracts

  • Abstract PS17-31: Investigating the estrogen receptor Y537S mutation in transgenic models of luminal B breast cancer
  • Abstract PS18-24: Impact of protein corona formation on Fn14-targeted DART nanoparticle selectivity, uptake, and cytotoxicity on TNBC cells
  • Abstract PS19-07: Plasma exosomal miRNAs: A minimally invasive diagnostic biomarker for inflammatory breast carcinoma
Show more Poster Session Abstracts

Prognostic and Predictive Factors: Prognostic and Predictive Factors - Other

  • Abstract P6-09-37: Ductal carcinoma in situ: Patient outcomes and association with hormone receptors
  • Abstract P6-09-11: Genetic variation in CYP3A affects steady-state exemestane concentrations but does not explain inter-race difference
  • Abstract P6-09-10: Results of multigene assay (MammaPrint®) and molecular subtyping (BluePrint®) substantially impact treatment decision making in early breast cancer: Final analysis of the WSG PRIME decision impact study
Show more Prognostic and Predictive Factors: Prognostic and Predictive Factors - Other
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement