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

  • Epidemiology
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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, P trend = 0.0006). Compared with premenopausal women, TDLUs of postmenopausal women showed lower levels of PR (OR = 0.90, 95 % CI = 0.83–0.97, P trend = 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.

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Acknowledgments

This research was supported in part by the Intramural Research Program of the NIH, NCI, and DCEG (an Intramural Research Award to Dr. X.R. Yang). We thank Dr. David Rimm and Yale Pathology Tissue Service for their help in making tissue microarrays.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

The study was approved by the National Cancer Institute and local Institutional Review Boards in Poland. All experiments comply with the current US laws.

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Authors and Affiliations

  1. Genetic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd., Bethesda, MD, USA

    Xiaohong R. Yang

  2. Applied Molecular Pathology Laboratory, Division of Cancer Epidemiology & Genetics and Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA

    Stephen M. Hewitt & Mark E. Sherman

  3. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA

    Stephen M. Hewitt

  4. Department of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, 02-781, Warsaw, Poland

    Jolanta Lissowska

  5. Nofer Institute of Occupational Medicine, 91-348, Lodz, Poland

    Beata Peplonska

  6. Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK

    Montserrat Garcia-Closas

  7. Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd., Bethesda, MD, USA

    Jonine D. Figueroa, Roni T. Falk, Louise A. Brinton, Montserrat Garcia-Closas & Mark E. Sherman

  8. Biostatistics Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd., Bethesda, MD, USA

    Ruth M. Pfeiffer

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  1. Xiaohong R. Yang
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Correspondence to Xiaohong R. Yang.

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Yang, X.R., Figueroa, J.D., Hewitt, S.M. et al. Estrogen receptor and progesterone receptor expression in normal terminal duct lobular units surrounding invasive breast cancer. Breast Cancer Res Treat 137, 837–847 (2013). https://doi.org/10.1007/s10549-012-2380-2

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  • DOI: https://doi.org/10.1007/s10549-012-2380-2

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