Breast Cancer Research and Treatment

, Volume 137, Issue 3, pp 837–847

Estrogen receptor and progesterone receptor expression in normal terminal duct lobular units surrounding invasive breast cancer

  • Xiaohong R. Yang
  • Jonine D. Figueroa
  • Stephen M. Hewitt
  • Roni T. Falk
  • Ruth M. Pfeiffer
  • Jolanta Lissowska
  • Beata Peplonska
  • Louise A. Brinton
  • Montserrat Garcia-Closas
  • Mark E. Sherman
Epidemiology

Abstract

Molecular and morphological alterations related to carcinogenesis have been found in terminal duct lobular units (TDLUs), the microscopic structures from which most breast cancer precursors and cancers develop, and therefore, analysis of these structures may reveal early changes in breast carcinogenesis and etiologic heterogeneity. Accordingly, we evaluated relationships of breast cancer risk factors and tumor pathology to estrogen receptor (ER) and progesterone receptor (PR) expression in TDLUs surrounding breast cancers. We analyzed 270 breast cancer cases included in a population-based breast cancer case–control study conducted in Poland. TDLUs were mapped in relation to breast cancer: within the same block as the tumor (TDLU-T), proximal to tumor (TDLU-PT), or distant from (TDLU-DT). ER/PR was quantitated using image analysis of immunohistochemically stained TDLUs prepared as tissue microarrays. In surgical specimens containing ER-positive breast cancers, ER and PR levels were significantly higher in breast cancer cells than in normal TDLUs, and higher in TDLU-T than in TDLU-DT or TDLU-PT, which showed similar results. Analyses combining DT−/PT TDLUs within subjects demonstrated that ER levels were significantly lower in premenopausal women versus postmenopausal women (odds ratio [OR] = 0.38, 95 % confidence interval [CI] = 0.19, 0.76, P = 0.0064) and among recent or current menopausal hormone therapy users compared with never users (OR = 0.14, 95 % CI = 0.046–0.43, Ptrend = 0.0006). Compared with premenopausal women, TDLUs of postmenopausal women showed lower levels of PR (OR = 0.90, 95 % CI = 0.83–0.97, Ptrend = 0.007). ER and PR expression in TDLUs was associated with epidermal growth factor receptor (EGFR) expression in invasive tumors (P = 0.019 for ER and P = 0.03 for PR), but not with other tumor features. Our data suggest that TDLUs near breast cancers reflect field effects, whereas those at a distance demonstrate influences of breast cancer risk factors on at-risk breast tissue. Analyses of mapped TDLUs may provide information about the sequence of molecular changes occurring in breast carcinogenesis.

Keywords

Terminal duct lobular units (TDLUs) Estrogen receptor Progesterone receptor Breast cancer Risk factors Tumor characteristics 

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Copyright information

© Springer Science+Business Media New York 2012 (outside the USA) 2012

Authors and Affiliations

  • Xiaohong R. Yang
    • 1
  • Jonine D. Figueroa
    • 8
  • Stephen M. Hewitt
    • 3
    • 4
  • Roni T. Falk
    • 8
  • Ruth M. Pfeiffer
    • 9
  • Jolanta Lissowska
    • 5
  • Beata Peplonska
    • 6
  • Louise A. Brinton
    • 8
  • Montserrat Garcia-Closas
    • 7
    • 8
  • Mark E. Sherman
    • 3
    • 8
  1. 1.Genetic Epidemiology Branch, Division of Cancer Epidemiology & GeneticsNational Cancer Institute, NIH, DHHSBethesdaUSA
  2. 2.Department of PathologyYale University School of MedicineNew HavenUSA
  3. 3.Applied Molecular Pathology Laboratory, Division of Cancer Epidemiology & Genetics and Center for Cancer ResearchNational Cancer Institute, NIHBethesdaUSA
  4. 4.Laboratory of Pathology, Center for Cancer ResearchNational Cancer Institute, NIHBethesdaUSA
  5. 5.Department of Cancer Epidemiology and PreventionCancer Center and M. Sklodowska-Curie Institute of OncologyWarsawPoland
  6. 6.Nofer Institute of Occupational MedicineLodzPoland
  7. 7.Division of Genetics and EpidemiologyInstitute of Cancer ResearchLondonUK
  8. 8.Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology & GeneticsNational Cancer Institute, NIH, DHHSBethesdaUSA
  9. 9.Biostatistics Branch, Division of Cancer Epidemiology & GeneticsNational Cancer Institute, NIH, DHHSBethesdaUSA

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