Leukocyte telomere length and its association with mammographic density and proliferative diagnosis among women undergoing diagnostic image-guided breast biopsy

Clara Bodelon, Christopher M. Heaphy, Alan K. Meeker, Berta Geller, Pamela M. Vacek, Donald L. Weaver, Rachael E. Chicoine, John A. Shepherd, Amir Pasha Mahmoudzadeh, Deesha A. Patel, Louise A. Brinton, Mark E. Sherman, Gretchen L. Gierach

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Abstract

Background: Elevated mammographic density (MD) is a strong breast cancer risk factor but the mechanisms underlying the association are poorly understood. High MD and breast cancer risk may reflect cumulative exposures to factors that promote epithelial cell division. One marker of cellular replicative history is telomere length, but its association with MD is unknown. We investigated the relation of telomere length, a marker of cellular replicative history, with MD and biopsy diagnosis. Methods: One hundred and ninety-five women, ages 40-65, were clinically referred for image-guided breast biopsies at an academic facility in Vermont. Relative peripheral blood leukocyte telomere length (LTL) was measured using quantitative polymerase chain reaction. MD volume was quantified in cranio-caudal views of the breast contralateral to the primary diagnosis in digital mammograms using a breast density phantom, while MD area (cm2) was measured using thresholding software. Associations between log-transformed LTL and continuous MD measurements (volume and area) were evaluated using linear regression models adjusted for age and body mass index. Analyses were stratified by biopsy diagnosis: proliferative (hyperplasia, in-situ or invasive carcinoma) or non-proliferative (benign or other non-proliferative benign diagnoses). Results: Mean relative LTL in women with proliferative disease (n = 141) was 1.6 (SD = 0.9) vs. 1.2 (SD = 0.6) in those with non-proliferative diagnoses (n = 54) (P = 0.002). Mean percent MD volume did not differ by diagnosis (P = 0.69). LTL was not associated with MD in women with proliferative (P = 0.89) or non-proliferative (P = 0.48) diagnoses. However, LTL was associated with a significant increased risk of proliferative diagnosis (adjusted OR = 2.46, 95 % CI: 1.47, 4.42). Conclusions: Our analysis of LTL did not find an association with MD. However, our findings suggest that LTL may be a marker of risk for proliferative pathology among women referred for biopsy based on breast imaging.

Original languageEnglish (US)
Article number823
JournalBMC Cancer
Volume15
Issue number1
DOIs
StatePublished - Oct 30 2015

Fingerprint

Image-Guided Biopsy
Telomere
Breast
Leukocytes
Biopsy
Linear Models
Breast Density
History
Breast Neoplasms
Cell Division
Hyperplasia

Keywords

  • Breast diseases
  • Breast neoplasms
  • Breast pathology
  • Hyperplasia
  • Mammographic density
  • Telomere

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Leukocyte telomere length and its association with mammographic density and proliferative diagnosis among women undergoing diagnostic image-guided breast biopsy. / Bodelon, Clara; Heaphy, Christopher M.; Meeker, Alan K.; Geller, Berta; Vacek, Pamela M.; Weaver, Donald L.; Chicoine, Rachael E.; Shepherd, John A.; Mahmoudzadeh, Amir Pasha; Patel, Deesha A.; Brinton, Louise A.; Sherman, Mark E.; Gierach, Gretchen L.

In: BMC Cancer, Vol. 15, No. 1, 823, 30.10.2015.

Research output: Contribution to journalArticle

Bodelon, C, Heaphy, CM, Meeker, AK, Geller, B, Vacek, PM, Weaver, DL, Chicoine, RE, Shepherd, JA, Mahmoudzadeh, AP, Patel, DA, Brinton, LA, Sherman, ME & Gierach, GL 2015, 'Leukocyte telomere length and its association with mammographic density and proliferative diagnosis among women undergoing diagnostic image-guided breast biopsy', BMC Cancer, vol. 15, no. 1, 823. https://doi.org/10.1186/s12885-015-1860-2
Bodelon, Clara ; Heaphy, Christopher M. ; Meeker, Alan K. ; Geller, Berta ; Vacek, Pamela M. ; Weaver, Donald L. ; Chicoine, Rachael E. ; Shepherd, John A. ; Mahmoudzadeh, Amir Pasha ; Patel, Deesha A. ; Brinton, Louise A. ; Sherman, Mark E. ; Gierach, Gretchen L. / Leukocyte telomere length and its association with mammographic density and proliferative diagnosis among women undergoing diagnostic image-guided breast biopsy. In: BMC Cancer. 2015 ; Vol. 15, No. 1.
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abstract = "Background: Elevated mammographic density (MD) is a strong breast cancer risk factor but the mechanisms underlying the association are poorly understood. High MD and breast cancer risk may reflect cumulative exposures to factors that promote epithelial cell division. One marker of cellular replicative history is telomere length, but its association with MD is unknown. We investigated the relation of telomere length, a marker of cellular replicative history, with MD and biopsy diagnosis. Methods: One hundred and ninety-five women, ages 40-65, were clinically referred for image-guided breast biopsies at an academic facility in Vermont. Relative peripheral blood leukocyte telomere length (LTL) was measured using quantitative polymerase chain reaction. MD volume was quantified in cranio-caudal views of the breast contralateral to the primary diagnosis in digital mammograms using a breast density phantom, while MD area (cm2) was measured using thresholding software. Associations between log-transformed LTL and continuous MD measurements (volume and area) were evaluated using linear regression models adjusted for age and body mass index. Analyses were stratified by biopsy diagnosis: proliferative (hyperplasia, in-situ or invasive carcinoma) or non-proliferative (benign or other non-proliferative benign diagnoses). Results: Mean relative LTL in women with proliferative disease (n = 141) was 1.6 (SD = 0.9) vs. 1.2 (SD = 0.6) in those with non-proliferative diagnoses (n = 54) (P = 0.002). Mean percent MD volume did not differ by diagnosis (P = 0.69). LTL was not associated with MD in women with proliferative (P = 0.89) or non-proliferative (P = 0.48) diagnoses. However, LTL was associated with a significant increased risk of proliferative diagnosis (adjusted OR = 2.46, 95 {\%} CI: 1.47, 4.42). Conclusions: Our analysis of LTL did not find an association with MD. However, our findings suggest that LTL may be a marker of risk for proliferative pathology among women referred for biopsy based on breast imaging.",
keywords = "Breast diseases, Breast neoplasms, Breast pathology, Hyperplasia, Mammographic density, Telomere",
author = "Clara Bodelon and Heaphy, {Christopher M.} and Meeker, {Alan K.} and Berta Geller and Vacek, {Pamela M.} and Weaver, {Donald L.} and Chicoine, {Rachael E.} and Shepherd, {John A.} and Mahmoudzadeh, {Amir Pasha} and Patel, {Deesha A.} and Brinton, {Louise A.} and Sherman, {Mark E.} and Gierach, {Gretchen L.}",
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T1 - Leukocyte telomere length and its association with mammographic density and proliferative diagnosis among women undergoing diagnostic image-guided breast biopsy

AU - Bodelon, Clara

AU - Heaphy, Christopher M.

AU - Meeker, Alan K.

AU - Geller, Berta

AU - Vacek, Pamela M.

AU - Weaver, Donald L.

AU - Chicoine, Rachael E.

AU - Shepherd, John A.

AU - Mahmoudzadeh, Amir Pasha

AU - Patel, Deesha A.

AU - Brinton, Louise A.

AU - Sherman, Mark E.

AU - Gierach, Gretchen L.

PY - 2015/10/30

Y1 - 2015/10/30

N2 - Background: Elevated mammographic density (MD) is a strong breast cancer risk factor but the mechanisms underlying the association are poorly understood. High MD and breast cancer risk may reflect cumulative exposures to factors that promote epithelial cell division. One marker of cellular replicative history is telomere length, but its association with MD is unknown. We investigated the relation of telomere length, a marker of cellular replicative history, with MD and biopsy diagnosis. Methods: One hundred and ninety-five women, ages 40-65, were clinically referred for image-guided breast biopsies at an academic facility in Vermont. Relative peripheral blood leukocyte telomere length (LTL) was measured using quantitative polymerase chain reaction. MD volume was quantified in cranio-caudal views of the breast contralateral to the primary diagnosis in digital mammograms using a breast density phantom, while MD area (cm2) was measured using thresholding software. Associations between log-transformed LTL and continuous MD measurements (volume and area) were evaluated using linear regression models adjusted for age and body mass index. Analyses were stratified by biopsy diagnosis: proliferative (hyperplasia, in-situ or invasive carcinoma) or non-proliferative (benign or other non-proliferative benign diagnoses). Results: Mean relative LTL in women with proliferative disease (n = 141) was 1.6 (SD = 0.9) vs. 1.2 (SD = 0.6) in those with non-proliferative diagnoses (n = 54) (P = 0.002). Mean percent MD volume did not differ by diagnosis (P = 0.69). LTL was not associated with MD in women with proliferative (P = 0.89) or non-proliferative (P = 0.48) diagnoses. However, LTL was associated with a significant increased risk of proliferative diagnosis (adjusted OR = 2.46, 95 % CI: 1.47, 4.42). Conclusions: Our analysis of LTL did not find an association with MD. However, our findings suggest that LTL may be a marker of risk for proliferative pathology among women referred for biopsy based on breast imaging.

AB - Background: Elevated mammographic density (MD) is a strong breast cancer risk factor but the mechanisms underlying the association are poorly understood. High MD and breast cancer risk may reflect cumulative exposures to factors that promote epithelial cell division. One marker of cellular replicative history is telomere length, but its association with MD is unknown. We investigated the relation of telomere length, a marker of cellular replicative history, with MD and biopsy diagnosis. Methods: One hundred and ninety-five women, ages 40-65, were clinically referred for image-guided breast biopsies at an academic facility in Vermont. Relative peripheral blood leukocyte telomere length (LTL) was measured using quantitative polymerase chain reaction. MD volume was quantified in cranio-caudal views of the breast contralateral to the primary diagnosis in digital mammograms using a breast density phantom, while MD area (cm2) was measured using thresholding software. Associations between log-transformed LTL and continuous MD measurements (volume and area) were evaluated using linear regression models adjusted for age and body mass index. Analyses were stratified by biopsy diagnosis: proliferative (hyperplasia, in-situ or invasive carcinoma) or non-proliferative (benign or other non-proliferative benign diagnoses). Results: Mean relative LTL in women with proliferative disease (n = 141) was 1.6 (SD = 0.9) vs. 1.2 (SD = 0.6) in those with non-proliferative diagnoses (n = 54) (P = 0.002). Mean percent MD volume did not differ by diagnosis (P = 0.69). LTL was not associated with MD in women with proliferative (P = 0.89) or non-proliferative (P = 0.48) diagnoses. However, LTL was associated with a significant increased risk of proliferative diagnosis (adjusted OR = 2.46, 95 % CI: 1.47, 4.42). Conclusions: Our analysis of LTL did not find an association with MD. However, our findings suggest that LTL may be a marker of risk for proliferative pathology among women referred for biopsy based on breast imaging.

KW - Breast diseases

KW - Breast neoplasms

KW - Breast pathology

KW - Hyperplasia

KW - Mammographic density

KW - Telomere

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