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Serum hormone levels and normal breast histology among premenopausal women

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Breast terminal duct lobular units (TDLUs) are the main source of breast cancer (BC) precursors. Higher serum concentrations of hormones and growth factors have been linked to increased TDLU numbers and to elevated BC risk, with variable effects by menopausal status. We assessed associations of circulating factors with breast histology among premenopausal women using artificial intelligence (AI) and preliminarily tested whether parity modifies associations.

Methods

Pathology AI analysis was performed on 316 digital images of H&E-stained sections of normal breast tissues from Komen Tissue Bank donors ages ≤ 45 years to assess 11 quantitative metrics. Associations of circulating factors with AI metrics were assessed using regression analyses, with inclusion of interaction terms to assess effect modification.

Results

Higher prolactin levels were related to larger TDLU area (p < 0.001) and increased presence of adipose tissue proximate to TDLUs (p < 0.001), with less significant positive associations for acini counts (p = 0.012), dilated acini (p = 0.043), capillary area (p = 0.014), epithelial area (p = 0.007), and mononuclear cell counts (p = 0.017). Testosterone levels were associated with increased TDLU counts (p < 0.001), irrespective of parity, but associations differed by adipose tissue content. AI data for TDLU counts generally agreed with prior visual assessments.

Conclusion

Among premenopausal women, serum hormone levels linked to BC risk were also associated with quantitative features of normal breast tissue. These relationships were suggestively modified by parity status and tissue composition. We conclude that the microanatomic features of normal breast tissue may represent a marker of BC risk.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request or from the Komen Tissue Bank and Indiana University.

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Funding

The authors thank donors to the Komen Tissue Bank. This work is supported in part by the Mayo Clinic Cancer Center P30CA15083-45.

Author information

Author notes

  1. Mark E. Sherman and Thomas de Bel equally contributed to this study.

Authors and Affiliations

  1. Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, 32224, USA

    Mark E. Sherman, Michael G. Heckman, Launia J. White, Joshua Ogony, Tracy Hilton & Laura Pacheco-Spann

  2. Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands

    Thomas de Bel & Jeroen van der Laak

  3. Radboud Institute of Health Sciences, Nijmegen, The Netherlands

    Thomas de Bel & Jeroen van der Laak

  4. Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, 32224, USA

    Melody Stallings-Mann & Derek C. Radisky

  5. Department of Surgery, Mayo Clinic, Rochester, MN, USA

    Amy C. Degnim

  6. Quantitative Health Sciences, Mayo Clinic, Rochester, MN, 55905, USA

    Robert A. Vierkant, Tanya Hoskin, Matthew R. Jensen & Stacey J. Winham

  7. Susan G. Komen Tissue Bank at the IU Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Jill E. Henry & Anna Maria Storniolo

  8. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA

    Jodi M. Carter

  9. Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden

    Jeroen van der Laak

Authors
  1. Mark E. Sherman
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  2. Thomas de Bel
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Correspondence to Mark E. Sherman.

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Sherman, M.E., de Bel, T., Heckman, M.G. et al. Serum hormone levels and normal breast histology among premenopausal women. Breast Cancer Res Treat 194, 149–158 (2022). https://doi.org/10.1007/s10549-022-06600-9

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