Morphologic and immunophenotypic markers as surrogate endpoints of tamoxifen effect for prevention of breast cancer

Syed K. Mohsin, D. Craig Allred, C. Kent Osborne, Anatolio Cruz, Pamela Otto, Helen K Chew, Gary M. Clark, Richard M. Elledge

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Prevention trials using incidence or mortality as endpoints require a large number of participants and long follow-up. Trials using biomarkers as endpoints would potentially require fewer participants, less time, and significantly less resources to test promising new agents for breast cancer prevention. To test this idea, a randomized trial of tamoxifen for 1 year versus observation for 1 year was conducted to determine whether tamoxifen can cause regression of hyperplastic breast tissue, whether it changes the biomarker phenotype of premalignant disease or normal breast epithelium, and if biomarkers can be used as early surrogate indicators of response to tamoxifen. Women were identified by having an abnormal mammogram and ductal hyperplasia diagnosed by core needle biopsy. Image-directed needle biopsy was repeated in the same site of the breast after 1 year. Approximately 3000 women were screened, and 265 were eligible. Sixty-three women were randomized and paired biopsies from 45 subjects were available for analysis. There was no evidence of substantial regression of hyperplasia - fewer samples showed hyperplasia at 1 year follow-up, but this was seen in both untreated and tamoxifen-treated women. There were trends for reductions in ER and PgR and trends for increases in bcl-2 in normal and hyperplastic tissue in the tamoxifen-treated arm, though these changes did not reach statistical significance. Proliferation, determined by Ki67 staining, was not significantly changed. Clinical trials of this type are difficult to carry out and modifications in trial design are needed to make this process more efficient.

Original languageEnglish (US)
Pages (from-to)205-211
Number of pages7
JournalBreast Cancer Research and Treatment
Volume94
Issue number3
DOIs
StatePublished - Dec 2005

Fingerprint

Tamoxifen
Biomarkers
Breast Neoplasms
Hyperplasia
Breast
Large-Core Needle Biopsy
Needle Biopsy
Arm
Epithelium
Observation
Clinical Trials
Staining and Labeling
Phenotype
Biopsy
Mortality
Incidence

Keywords

  • Breast cancer
  • Estrogen receptor
  • Molecular markers
  • Prevention
  • Tamoxifen

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Morphologic and immunophenotypic markers as surrogate endpoints of tamoxifen effect for prevention of breast cancer. / Mohsin, Syed K.; Allred, D. Craig; Osborne, C. Kent; Cruz, Anatolio; Otto, Pamela; Chew, Helen K; Clark, Gary M.; Elledge, Richard M.

In: Breast Cancer Research and Treatment, Vol. 94, No. 3, 12.2005, p. 205-211.

Research output: Contribution to journalArticle

Mohsin, Syed K. ; Allred, D. Craig ; Osborne, C. Kent ; Cruz, Anatolio ; Otto, Pamela ; Chew, Helen K ; Clark, Gary M. ; Elledge, Richard M. / Morphologic and immunophenotypic markers as surrogate endpoints of tamoxifen effect for prevention of breast cancer. In: Breast Cancer Research and Treatment. 2005 ; Vol. 94, No. 3. pp. 205-211.
@article{760029b572404f28bbf3b908b5e5af21,
title = "Morphologic and immunophenotypic markers as surrogate endpoints of tamoxifen effect for prevention of breast cancer",
abstract = "Prevention trials using incidence or mortality as endpoints require a large number of participants and long follow-up. Trials using biomarkers as endpoints would potentially require fewer participants, less time, and significantly less resources to test promising new agents for breast cancer prevention. To test this idea, a randomized trial of tamoxifen for 1 year versus observation for 1 year was conducted to determine whether tamoxifen can cause regression of hyperplastic breast tissue, whether it changes the biomarker phenotype of premalignant disease or normal breast epithelium, and if biomarkers can be used as early surrogate indicators of response to tamoxifen. Women were identified by having an abnormal mammogram and ductal hyperplasia diagnosed by core needle biopsy. Image-directed needle biopsy was repeated in the same site of the breast after 1 year. Approximately 3000 women were screened, and 265 were eligible. Sixty-three women were randomized and paired biopsies from 45 subjects were available for analysis. There was no evidence of substantial regression of hyperplasia - fewer samples showed hyperplasia at 1 year follow-up, but this was seen in both untreated and tamoxifen-treated women. There were trends for reductions in ER and PgR and trends for increases in bcl-2 in normal and hyperplastic tissue in the tamoxifen-treated arm, though these changes did not reach statistical significance. Proliferation, determined by Ki67 staining, was not significantly changed. Clinical trials of this type are difficult to carry out and modifications in trial design are needed to make this process more efficient.",
keywords = "Breast cancer, Estrogen receptor, Molecular markers, Prevention, Tamoxifen",
author = "Mohsin, {Syed K.} and Allred, {D. Craig} and Osborne, {C. Kent} and Anatolio Cruz and Pamela Otto and Chew, {Helen K} and Clark, {Gary M.} and Elledge, {Richard M.}",
year = "2005",
month = "12",
doi = "10.1007/s10549-005-4896-1",
language = "English (US)",
volume = "94",
pages = "205--211",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

T1 - Morphologic and immunophenotypic markers as surrogate endpoints of tamoxifen effect for prevention of breast cancer

AU - Mohsin, Syed K.

AU - Allred, D. Craig

AU - Osborne, C. Kent

AU - Cruz, Anatolio

AU - Otto, Pamela

AU - Chew, Helen K

AU - Clark, Gary M.

AU - Elledge, Richard M.

PY - 2005/12

Y1 - 2005/12

N2 - Prevention trials using incidence or mortality as endpoints require a large number of participants and long follow-up. Trials using biomarkers as endpoints would potentially require fewer participants, less time, and significantly less resources to test promising new agents for breast cancer prevention. To test this idea, a randomized trial of tamoxifen for 1 year versus observation for 1 year was conducted to determine whether tamoxifen can cause regression of hyperplastic breast tissue, whether it changes the biomarker phenotype of premalignant disease or normal breast epithelium, and if biomarkers can be used as early surrogate indicators of response to tamoxifen. Women were identified by having an abnormal mammogram and ductal hyperplasia diagnosed by core needle biopsy. Image-directed needle biopsy was repeated in the same site of the breast after 1 year. Approximately 3000 women were screened, and 265 were eligible. Sixty-three women were randomized and paired biopsies from 45 subjects were available for analysis. There was no evidence of substantial regression of hyperplasia - fewer samples showed hyperplasia at 1 year follow-up, but this was seen in both untreated and tamoxifen-treated women. There were trends for reductions in ER and PgR and trends for increases in bcl-2 in normal and hyperplastic tissue in the tamoxifen-treated arm, though these changes did not reach statistical significance. Proliferation, determined by Ki67 staining, was not significantly changed. Clinical trials of this type are difficult to carry out and modifications in trial design are needed to make this process more efficient.

AB - Prevention trials using incidence or mortality as endpoints require a large number of participants and long follow-up. Trials using biomarkers as endpoints would potentially require fewer participants, less time, and significantly less resources to test promising new agents for breast cancer prevention. To test this idea, a randomized trial of tamoxifen for 1 year versus observation for 1 year was conducted to determine whether tamoxifen can cause regression of hyperplastic breast tissue, whether it changes the biomarker phenotype of premalignant disease or normal breast epithelium, and if biomarkers can be used as early surrogate indicators of response to tamoxifen. Women were identified by having an abnormal mammogram and ductal hyperplasia diagnosed by core needle biopsy. Image-directed needle biopsy was repeated in the same site of the breast after 1 year. Approximately 3000 women were screened, and 265 were eligible. Sixty-three women were randomized and paired biopsies from 45 subjects were available for analysis. There was no evidence of substantial regression of hyperplasia - fewer samples showed hyperplasia at 1 year follow-up, but this was seen in both untreated and tamoxifen-treated women. There were trends for reductions in ER and PgR and trends for increases in bcl-2 in normal and hyperplastic tissue in the tamoxifen-treated arm, though these changes did not reach statistical significance. Proliferation, determined by Ki67 staining, was not significantly changed. Clinical trials of this type are difficult to carry out and modifications in trial design are needed to make this process more efficient.

KW - Breast cancer

KW - Estrogen receptor

KW - Molecular markers

KW - Prevention

KW - Tamoxifen

UR - http://www.scopus.com/inward/record.url?scp=27944486767&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27944486767&partnerID=8YFLogxK

U2 - 10.1007/s10549-005-4896-1

DO - 10.1007/s10549-005-4896-1

M3 - Article

VL - 94

SP - 205

EP - 211

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 3

ER -