Circulating sex hormones and terminal duct lobular unit involution of the normal breast

Zeina G. Khodr, Mark E. Sherman, Ruth M. Pfeiffer, Gretchen L. Gierach, Louise A. Brinton, Roni T. Falk, Deesha A. Patel, Laura M. Linville, Daphne Papathomas, Susan E. Clare, Daniel W. Visscher, Carolyn Mies, Stephen M. Hewitt, Anna Maria Storniolo, Adrian Rosebrock, Jesus J. Caban, Jonine D. Figueroa

Research output: Contribution to journalArticle

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Abstract

Background: Terminal duct lobular units (TDLU) are the predominant source of breast cancers. Lesser degrees of age-related TDLU involution have been associated with increased breast cancer risk, but factors that influence involution are largely unknown. We assessed whether circulating hormones, implicated in breast cancer risk, are associated with levels of TDLU involution using data from the Susan G. Komen Tissue Bank (KTB) at the Indiana University Simon Cancer Center (2009-2011).

Methods: We evaluated three highly reproducible measures of TDLU involution, using normal breast tissue samples from the KTB (n = 390): TDLU counts, median TDLU span, and median acini counts per TDLU. RRs (for continuous measures), ORs (for categorical measures), 95% confidence intervals (95% CI), and Prends were calculated to assess the association between tertiles of estradiol, testosterone, sex hormone-binding globulin (SHBG), progesterone, and prolactin with TDLU measures. All models were stratified by menopausal status and adjusted for confounders.

Results: Among premenopausal women, higher prolactin levels were associated with higher TDLU counts (RRT3vsT1:1.18; 95% CI: 1.07-1.31; Ptrend = 0.0005), but higher progesterone was associated with lower TDLU counts (RRT3vsT1: 0.80; 95% CI: 0.72-0.89; Ptrend <0.0001). Among postmenopausal women, higher levels of estradiol (RRT3vsT1:1.61; 95% CI: 1.32-1.97; Ptrend <0.0001) and testosterone (RRT3vsT1: 1.32; 95% CI: 1.09-1.59; Ptrend = 0.0043) were associated with higher TDLU counts.

Conclusions: These data suggest that select hormones may influence breast cancer risk potentially through delaying TDLU involution.

Impact: Increased understanding of the relationship between circulating markers and TDLU involution may offer new insights into breast carcinogenesis.

Original languageEnglish (US)
Pages (from-to)2765-2773
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume23
Issue number12
DOIs
StatePublished - Dec 1 2014

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Gonadal Steroid Hormones
Breast
Confidence Intervals
Tissue Banks
Breast Neoplasms
Prolactin
Progesterone
Testosterone
Estradiol
Hormones
Sex Hormone-Binding Globulin
Carcinogenesis
Neoplasms

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Khodr, Z. G., Sherman, M. E., Pfeiffer, R. M., Gierach, G. L., Brinton, L. A., Falk, R. T., ... Figueroa, J. D. (2014). Circulating sex hormones and terminal duct lobular unit involution of the normal breast. Cancer Epidemiology Biomarkers and Prevention, 23(12), 2765-2773. https://doi.org/10.1158/1055-9965.EPI-14-0667

Circulating sex hormones and terminal duct lobular unit involution of the normal breast. / Khodr, Zeina G.; Sherman, Mark E.; Pfeiffer, Ruth M.; Gierach, Gretchen L.; Brinton, Louise A.; Falk, Roni T.; Patel, Deesha A.; Linville, Laura M.; Papathomas, Daphne; Clare, Susan E.; Visscher, Daniel W.; Mies, Carolyn; Hewitt, Stephen M.; Storniolo, Anna Maria; Rosebrock, Adrian; Caban, Jesus J.; Figueroa, Jonine D.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 23, No. 12, 01.12.2014, p. 2765-2773.

Research output: Contribution to journalArticle

Khodr, ZG, Sherman, ME, Pfeiffer, RM, Gierach, GL, Brinton, LA, Falk, RT, Patel, DA, Linville, LM, Papathomas, D, Clare, SE, Visscher, DW, Mies, C, Hewitt, SM, Storniolo, AM, Rosebrock, A, Caban, JJ & Figueroa, JD 2014, 'Circulating sex hormones and terminal duct lobular unit involution of the normal breast', Cancer Epidemiology Biomarkers and Prevention, vol. 23, no. 12, pp. 2765-2773. https://doi.org/10.1158/1055-9965.EPI-14-0667
Khodr, Zeina G. ; Sherman, Mark E. ; Pfeiffer, Ruth M. ; Gierach, Gretchen L. ; Brinton, Louise A. ; Falk, Roni T. ; Patel, Deesha A. ; Linville, Laura M. ; Papathomas, Daphne ; Clare, Susan E. ; Visscher, Daniel W. ; Mies, Carolyn ; Hewitt, Stephen M. ; Storniolo, Anna Maria ; Rosebrock, Adrian ; Caban, Jesus J. ; Figueroa, Jonine D. / Circulating sex hormones and terminal duct lobular unit involution of the normal breast. In: Cancer Epidemiology Biomarkers and Prevention. 2014 ; Vol. 23, No. 12. pp. 2765-2773.
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abstract = "Background: Terminal duct lobular units (TDLU) are the predominant source of breast cancers. Lesser degrees of age-related TDLU involution have been associated with increased breast cancer risk, but factors that influence involution are largely unknown. We assessed whether circulating hormones, implicated in breast cancer risk, are associated with levels of TDLU involution using data from the Susan G. Komen Tissue Bank (KTB) at the Indiana University Simon Cancer Center (2009-2011).Methods: We evaluated three highly reproducible measures of TDLU involution, using normal breast tissue samples from the KTB (n = 390): TDLU counts, median TDLU span, and median acini counts per TDLU. RRs (for continuous measures), ORs (for categorical measures), 95{\%} confidence intervals (95{\%} CI), and Prends were calculated to assess the association between tertiles of estradiol, testosterone, sex hormone-binding globulin (SHBG), progesterone, and prolactin with TDLU measures. All models were stratified by menopausal status and adjusted for confounders.Results: Among premenopausal women, higher prolactin levels were associated with higher TDLU counts (RRT3vsT1:1.18; 95{\%} CI: 1.07-1.31; Ptrend = 0.0005), but higher progesterone was associated with lower TDLU counts (RRT3vsT1: 0.80; 95{\%} CI: 0.72-0.89; Ptrend <0.0001). Among postmenopausal women, higher levels of estradiol (RRT3vsT1:1.61; 95{\%} CI: 1.32-1.97; Ptrend <0.0001) and testosterone (RRT3vsT1: 1.32; 95{\%} CI: 1.09-1.59; Ptrend = 0.0043) were associated with higher TDLU counts.Conclusions: These data suggest that select hormones may influence breast cancer risk potentially through delaying TDLU involution.Impact: Increased understanding of the relationship between circulating markers and TDLU involution may offer new insights into breast carcinogenesis.",
author = "Khodr, {Zeina G.} and Sherman, {Mark E.} and Pfeiffer, {Ruth M.} and Gierach, {Gretchen L.} and Brinton, {Louise A.} and Falk, {Roni T.} and Patel, {Deesha A.} and Linville, {Laura M.} and Daphne Papathomas and Clare, {Susan E.} and Visscher, {Daniel W.} and Carolyn Mies and Hewitt, {Stephen M.} and Storniolo, {Anna Maria} and Adrian Rosebrock and Caban, {Jesus J.} and Figueroa, {Jonine D.}",
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T1 - Circulating sex hormones and terminal duct lobular unit involution of the normal breast

AU - Khodr, Zeina G.

AU - Sherman, Mark E.

AU - Pfeiffer, Ruth M.

AU - Gierach, Gretchen L.

AU - Brinton, Louise A.

AU - Falk, Roni T.

AU - Patel, Deesha A.

AU - Linville, Laura M.

AU - Papathomas, Daphne

AU - Clare, Susan E.

AU - Visscher, Daniel W.

AU - Mies, Carolyn

AU - Hewitt, Stephen M.

AU - Storniolo, Anna Maria

AU - Rosebrock, Adrian

AU - Caban, Jesus J.

AU - Figueroa, Jonine D.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Background: Terminal duct lobular units (TDLU) are the predominant source of breast cancers. Lesser degrees of age-related TDLU involution have been associated with increased breast cancer risk, but factors that influence involution are largely unknown. We assessed whether circulating hormones, implicated in breast cancer risk, are associated with levels of TDLU involution using data from the Susan G. Komen Tissue Bank (KTB) at the Indiana University Simon Cancer Center (2009-2011).Methods: We evaluated three highly reproducible measures of TDLU involution, using normal breast tissue samples from the KTB (n = 390): TDLU counts, median TDLU span, and median acini counts per TDLU. RRs (for continuous measures), ORs (for categorical measures), 95% confidence intervals (95% CI), and Prends were calculated to assess the association between tertiles of estradiol, testosterone, sex hormone-binding globulin (SHBG), progesterone, and prolactin with TDLU measures. All models were stratified by menopausal status and adjusted for confounders.Results: Among premenopausal women, higher prolactin levels were associated with higher TDLU counts (RRT3vsT1:1.18; 95% CI: 1.07-1.31; Ptrend = 0.0005), but higher progesterone was associated with lower TDLU counts (RRT3vsT1: 0.80; 95% CI: 0.72-0.89; Ptrend <0.0001). Among postmenopausal women, higher levels of estradiol (RRT3vsT1:1.61; 95% CI: 1.32-1.97; Ptrend <0.0001) and testosterone (RRT3vsT1: 1.32; 95% CI: 1.09-1.59; Ptrend = 0.0043) were associated with higher TDLU counts.Conclusions: These data suggest that select hormones may influence breast cancer risk potentially through delaying TDLU involution.Impact: Increased understanding of the relationship between circulating markers and TDLU involution may offer new insights into breast carcinogenesis.

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