Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort: Differences by age, race, and tumor characteristics

Carol Sweeney, Philip S. Bernard, Rachel E. Factor, Marilyn L. Kwan, Laurel A. Habel, Charles P. Quesenberry, Kaylynn Shakespear, Erin K. Weltzien, Inge J. Stijleman, Carole A. Davis, Mark T W Ebbert, Adrienne Castillo, Lawrence H. Kushi, Bette J. Caan

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Background: Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups. Methods:Westudied a diverse cohort ofwomenwith breast cancer from the Life After Cancer Epidemiology and Pathways studies. RNA was extracted from 1mmpunches from fixed tumor tissue. Quantitative reversetranscriptase PCR was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier. Results: In a subcohort of 1,319 women, the overall subtype distribution based onPAM50 was 53.1% luminal A, 20.5% luminal B, 13.0% HER2-enriched, 9.8% basal-like, and 3.6% normal-like. Among low-risk endocrinepositive tumors (i.e., estrogen and progesterone receptor positive by immunohistochemistry, HER2 negative, and low histologic grade), only 76.5% were categorized as luminal A by PAM50. Continuous-scale luminal A, luminal B, HER2-enriched, and normal-like scores fromPAM50were mutually positively correlated. Basal-like score was inversely correlated with other subtypes. The proportion with non-luminal A subtype decreased with older age at diagnosis, PTrend < 0.0001. Compared with non-Hispanic Whites, African American women were more likely to have basal-like tumors, age-adjusted OR = 4.4 [95% confidence intervals (CI), 2.3-8.4], whereas Asian and Pacific Islander women had reduced odds of basal-like subtype, OR=0.5 (95% CI, 0.3-0.9). Conclusions: Our data indicate that over 50% of breast cancers treated in the community have luminal A subtype. Gene expression-based classification shifted some tumors categorized as low risk by surrogate clinicopathologic criteria to higher-risk subtypes. Impact: Subtyping in a population-based cohort revealed distinct profiles by age and race.

Original languageEnglish (US)
Pages (from-to)714-724
Number of pages11
JournalCancer Epidemiology Biomarkers and Prevention
Volume23
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Breast Neoplasms
Gene Expression
Population
Neoplasms
Confidence Intervals
Progesterone Receptors
Estrogen Receptors
African Americans
Epidemiology
Immunohistochemistry
RNA
Polymerase Chain Reaction
Genes

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Medicine(all)

Cite this

Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort : Differences by age, race, and tumor characteristics. / Sweeney, Carol; Bernard, Philip S.; Factor, Rachel E.; Kwan, Marilyn L.; Habel, Laurel A.; Quesenberry, Charles P.; Shakespear, Kaylynn; Weltzien, Erin K.; Stijleman, Inge J.; Davis, Carole A.; Ebbert, Mark T W; Castillo, Adrienne; Kushi, Lawrence H.; Caan, Bette J.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 23, No. 5, 2014, p. 714-724.

Research output: Contribution to journalArticle

Sweeney, C, Bernard, PS, Factor, RE, Kwan, ML, Habel, LA, Quesenberry, CP, Shakespear, K, Weltzien, EK, Stijleman, IJ, Davis, CA, Ebbert, MTW, Castillo, A, Kushi, LH & Caan, BJ 2014, 'Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort: Differences by age, race, and tumor characteristics', Cancer Epidemiology Biomarkers and Prevention, vol. 23, no. 5, pp. 714-724. https://doi.org/10.1158/1055-9965.EPI-13-1023
Sweeney, Carol ; Bernard, Philip S. ; Factor, Rachel E. ; Kwan, Marilyn L. ; Habel, Laurel A. ; Quesenberry, Charles P. ; Shakespear, Kaylynn ; Weltzien, Erin K. ; Stijleman, Inge J. ; Davis, Carole A. ; Ebbert, Mark T W ; Castillo, Adrienne ; Kushi, Lawrence H. ; Caan, Bette J. / Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort : Differences by age, race, and tumor characteristics. In: Cancer Epidemiology Biomarkers and Prevention. 2014 ; Vol. 23, No. 5. pp. 714-724.
@article{83385aa64942412ba82a2df782e30a4c,
title = "Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort: Differences by age, race, and tumor characteristics",
abstract = "Background: Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups. Methods:Westudied a diverse cohort ofwomenwith breast cancer from the Life After Cancer Epidemiology and Pathways studies. RNA was extracted from 1mmpunches from fixed tumor tissue. Quantitative reversetranscriptase PCR was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier. Results: In a subcohort of 1,319 women, the overall subtype distribution based onPAM50 was 53.1{\%} luminal A, 20.5{\%} luminal B, 13.0{\%} HER2-enriched, 9.8{\%} basal-like, and 3.6{\%} normal-like. Among low-risk endocrinepositive tumors (i.e., estrogen and progesterone receptor positive by immunohistochemistry, HER2 negative, and low histologic grade), only 76.5{\%} were categorized as luminal A by PAM50. Continuous-scale luminal A, luminal B, HER2-enriched, and normal-like scores fromPAM50were mutually positively correlated. Basal-like score was inversely correlated with other subtypes. The proportion with non-luminal A subtype decreased with older age at diagnosis, PTrend < 0.0001. Compared with non-Hispanic Whites, African American women were more likely to have basal-like tumors, age-adjusted OR = 4.4 [95{\%} confidence intervals (CI), 2.3-8.4], whereas Asian and Pacific Islander women had reduced odds of basal-like subtype, OR=0.5 (95{\%} CI, 0.3-0.9). Conclusions: Our data indicate that over 50{\%} of breast cancers treated in the community have luminal A subtype. Gene expression-based classification shifted some tumors categorized as low risk by surrogate clinicopathologic criteria to higher-risk subtypes. Impact: Subtyping in a population-based cohort revealed distinct profiles by age and race.",
author = "Carol Sweeney and Bernard, {Philip S.} and Factor, {Rachel E.} and Kwan, {Marilyn L.} and Habel, {Laurel A.} and Quesenberry, {Charles P.} and Kaylynn Shakespear and Weltzien, {Erin K.} and Stijleman, {Inge J.} and Davis, {Carole A.} and Ebbert, {Mark T W} and Adrienne Castillo and Kushi, {Lawrence H.} and Caan, {Bette J.}",
year = "2014",
doi = "10.1158/1055-9965.EPI-13-1023",
language = "English (US)",
volume = "23",
pages = "714--724",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

TY - JOUR

T1 - Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort

T2 - Differences by age, race, and tumor characteristics

AU - Sweeney, Carol

AU - Bernard, Philip S.

AU - Factor, Rachel E.

AU - Kwan, Marilyn L.

AU - Habel, Laurel A.

AU - Quesenberry, Charles P.

AU - Shakespear, Kaylynn

AU - Weltzien, Erin K.

AU - Stijleman, Inge J.

AU - Davis, Carole A.

AU - Ebbert, Mark T W

AU - Castillo, Adrienne

AU - Kushi, Lawrence H.

AU - Caan, Bette J.

PY - 2014

Y1 - 2014

N2 - Background: Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups. Methods:Westudied a diverse cohort ofwomenwith breast cancer from the Life After Cancer Epidemiology and Pathways studies. RNA was extracted from 1mmpunches from fixed tumor tissue. Quantitative reversetranscriptase PCR was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier. Results: In a subcohort of 1,319 women, the overall subtype distribution based onPAM50 was 53.1% luminal A, 20.5% luminal B, 13.0% HER2-enriched, 9.8% basal-like, and 3.6% normal-like. Among low-risk endocrinepositive tumors (i.e., estrogen and progesterone receptor positive by immunohistochemistry, HER2 negative, and low histologic grade), only 76.5% were categorized as luminal A by PAM50. Continuous-scale luminal A, luminal B, HER2-enriched, and normal-like scores fromPAM50were mutually positively correlated. Basal-like score was inversely correlated with other subtypes. The proportion with non-luminal A subtype decreased with older age at diagnosis, PTrend < 0.0001. Compared with non-Hispanic Whites, African American women were more likely to have basal-like tumors, age-adjusted OR = 4.4 [95% confidence intervals (CI), 2.3-8.4], whereas Asian and Pacific Islander women had reduced odds of basal-like subtype, OR=0.5 (95% CI, 0.3-0.9). Conclusions: Our data indicate that over 50% of breast cancers treated in the community have luminal A subtype. Gene expression-based classification shifted some tumors categorized as low risk by surrogate clinicopathologic criteria to higher-risk subtypes. Impact: Subtyping in a population-based cohort revealed distinct profiles by age and race.

AB - Background: Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups. Methods:Westudied a diverse cohort ofwomenwith breast cancer from the Life After Cancer Epidemiology and Pathways studies. RNA was extracted from 1mmpunches from fixed tumor tissue. Quantitative reversetranscriptase PCR was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier. Results: In a subcohort of 1,319 women, the overall subtype distribution based onPAM50 was 53.1% luminal A, 20.5% luminal B, 13.0% HER2-enriched, 9.8% basal-like, and 3.6% normal-like. Among low-risk endocrinepositive tumors (i.e., estrogen and progesterone receptor positive by immunohistochemistry, HER2 negative, and low histologic grade), only 76.5% were categorized as luminal A by PAM50. Continuous-scale luminal A, luminal B, HER2-enriched, and normal-like scores fromPAM50were mutually positively correlated. Basal-like score was inversely correlated with other subtypes. The proportion with non-luminal A subtype decreased with older age at diagnosis, PTrend < 0.0001. Compared with non-Hispanic Whites, African American women were more likely to have basal-like tumors, age-adjusted OR = 4.4 [95% confidence intervals (CI), 2.3-8.4], whereas Asian and Pacific Islander women had reduced odds of basal-like subtype, OR=0.5 (95% CI, 0.3-0.9). Conclusions: Our data indicate that over 50% of breast cancers treated in the community have luminal A subtype. Gene expression-based classification shifted some tumors categorized as low risk by surrogate clinicopathologic criteria to higher-risk subtypes. Impact: Subtyping in a population-based cohort revealed distinct profiles by age and race.

UR - http://www.scopus.com/inward/record.url?scp=84899473980&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899473980&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-13-1023

DO - 10.1158/1055-9965.EPI-13-1023

M3 - Article

C2 - 24521995

AN - SCOPUS:84899473980

VL - 23

SP - 714

EP - 724

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 5

ER -