Macrophagic "crown-like structures" are associated with an increased risk of breast cancer in Benign Breast Disease

Jodi Carter, Tanya L. Hoskin, M. Alvaro Pena, Rushin Brahmbhatt, Stacey J Winham, Marlene H. Frost, Melody Stallings-Mann, Derek C Radisky, Keith L Knutson, Daniel W Visscher, Amy C Degnim

Research output: Contribution to journalArticle

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Abstract

In breast adipose tissue, macrophages that encircle damaged adipocytes form "crown-like structures of breast" (CLS-B). Although CLS-B have been associated with breast cancer, their role in benign breast disease (BBD) and early carcinogenesis is not understood. We evaluated breast biopsies from three age-matched groups (n = 86 each, mean age 55 years), including normal tissue donors of the Susan G. Komen for the Cure Tissue Bank (KTB), and subjects in the Mayo Clinic Benign Breast Disease Cohort who developed cancer (BBD cases) or did not develop cancer (BBD controls, median follow-up 14 years). Biopsies were classified into histologic categories, and CD68-immunostained tissue sections were evaluated for the frequency and density of CLS-B. Our data demonstrate that CLS-B are associated with BBD: CLS-B-positive samples were significantly less frequent among KTB biopsies (3/86, 3.5%) than BBD controls (16/86 = 18.6%, P = 0.01) and BBD cases (21/86 = 24%, P = 0.002). CLS-B were strongly associated with body mass index (BMI); BMI < 25: 7% CLS-B positive, BMI 25-29: 13%, and BMI ≥ 30: 29% (P = 0.0005). Among BBD biopsies, a high CLS-B count [>5 CLS-B/sample: 10.5% (BBD cases) vs 4.7% (BBD controls), P = 0.007] conferred a breast cancer OR of 6.8 (95% CI, 1.4-32.4), P = 0.02, after adjusting for adipose tissue area (cm2 ), histologic impression, and BMI. As high CLS-B densities are independently associated with an increased breast cancer risk, they may be a promising histologic marker of breast cancer risk in BBD. Cancer Prev Res; 11(2); 113-9.

Original languageEnglish (US)
Pages (from-to)113-119
Number of pages7
JournalCancer Prevention Research
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2018

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Breast Diseases
Crowns
Breast Neoplasms
Breast
Tissue Banks
Body Mass Index
Biopsy
Adipose Tissue
Adipocytes
Carcinogenesis
Research Design
Age Groups
Macrophages
Tissue Donors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Macrophagic "crown-like structures" are associated with an increased risk of breast cancer in Benign Breast Disease. / Carter, Jodi; Hoskin, Tanya L.; Pena, M. Alvaro; Brahmbhatt, Rushin; Winham, Stacey J; Frost, Marlene H.; Stallings-Mann, Melody; Radisky, Derek C; Knutson, Keith L; Visscher, Daniel W; Degnim, Amy C.

In: Cancer Prevention Research, Vol. 11, No. 2, 01.02.2018, p. 113-119.

Research output: Contribution to journalArticle

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abstract = "In breast adipose tissue, macrophages that encircle damaged adipocytes form {"}crown-like structures of breast{"} (CLS-B). Although CLS-B have been associated with breast cancer, their role in benign breast disease (BBD) and early carcinogenesis is not understood. We evaluated breast biopsies from three age-matched groups (n = 86 each, mean age 55 years), including normal tissue donors of the Susan G. Komen for the Cure Tissue Bank (KTB), and subjects in the Mayo Clinic Benign Breast Disease Cohort who developed cancer (BBD cases) or did not develop cancer (BBD controls, median follow-up 14 years). Biopsies were classified into histologic categories, and CD68-immunostained tissue sections were evaluated for the frequency and density of CLS-B. Our data demonstrate that CLS-B are associated with BBD: CLS-B-positive samples were significantly less frequent among KTB biopsies (3/86, 3.5{\%}) than BBD controls (16/86 = 18.6{\%}, P = 0.01) and BBD cases (21/86 = 24{\%}, P = 0.002). CLS-B were strongly associated with body mass index (BMI); BMI < 25: 7{\%} CLS-B positive, BMI 25-29: 13{\%}, and BMI ≥ 30: 29{\%} (P = 0.0005). Among BBD biopsies, a high CLS-B count [>5 CLS-B/sample: 10.5{\%} (BBD cases) vs 4.7{\%} (BBD controls), P = 0.007] conferred a breast cancer OR of 6.8 (95{\%} CI, 1.4-32.4), P = 0.02, after adjusting for adipose tissue area (cm2 ), histologic impression, and BMI. As high CLS-B densities are independently associated with an increased breast cancer risk, they may be a promising histologic marker of breast cancer risk in BBD. Cancer Prev Res; 11(2); 113-9.",
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AU - Carter, Jodi

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AU - Brahmbhatt, Rushin

AU - Winham, Stacey J

AU - Frost, Marlene H.

AU - Stallings-Mann, Melody

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