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

Research output: Contribution to journalArticle

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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, 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.

Original languageEnglish (US)
Pages (from-to)837-847
Number of pages11
JournalBreast Cancer Research and Treatment
Volume137
Issue number3
DOIs
StatePublished - Feb 2013

Fingerprint

Progesterone Receptors
Estrogen Receptors
Breast Neoplasms
Neoplasms
Carcinogenesis
Breast
Odds Ratio
Confidence Intervals
Poland
Epidermal Growth Factor Receptor
Case-Control Studies
Hormones
Pathology

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Estrogen receptor and progesterone receptor expression in normal terminal duct lobular units surrounding invasive breast cancer. / Yang, Xiaohong R.; Figueroa, Jonine D.; Hewitt, Stephen M.; Falk, Roni T.; Pfeiffer, Ruth M.; Lissowska, Jolanta; Peplonska, Beata; Brinton, Louise A.; Garcia-Closas, Montserrat; Sherman, Mark E.

In: Breast Cancer Research and Treatment, Vol. 137, No. 3, 02.2013, p. 837-847.

Research output: Contribution to journalArticle

Yang, XR, Figueroa, JD, Hewitt, SM, Falk, RT, Pfeiffer, RM, Lissowska, J, Peplonska, B, Brinton, LA, Garcia-Closas, M & Sherman, ME 2013, 'Estrogen receptor and progesterone receptor expression in normal terminal duct lobular units surrounding invasive breast cancer', Breast Cancer Research and Treatment, vol. 137, no. 3, pp. 837-847. https://doi.org/10.1007/s10549-012-2380-2
Yang, Xiaohong R. ; Figueroa, Jonine D. ; Hewitt, Stephen M. ; Falk, Roni T. ; Pfeiffer, Ruth M. ; Lissowska, Jolanta ; Peplonska, Beata ; Brinton, Louise A. ; Garcia-Closas, Montserrat ; Sherman, Mark E. / Estrogen receptor and progesterone receptor expression in normal terminal duct lobular units surrounding invasive breast cancer. In: Breast Cancer Research and Treatment. 2013 ; Vol. 137, No. 3. pp. 837-847.
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