Relationship of serum progesterone and progesterone metabolites with mammographic breast density and terminal ductal lobular unit involution among women undergoing diagnostic breast biopsy

Manila Hada, Hannah Oh, Shaoqi Fan, Roni T. Falk, Berta Geller, Pamela Vacek, Donald Weaver, John Shepherd, Jeff Wang, Bo Fan, Sally Herschorn, Louise A. Brinton, Xia Xu, Mark E. Sherman, Britton Trabert, Gretchen L. Gierach

Research output: Contribution to journalArticlepeer-review

Abstract

The association of progesterone/progesterone metabolites with elevated mammographic breast density (MBD) and delayed age-related terminal duct lobular unit (TDLU) involution, strong breast cancer risk factors, has received limited attention. Using a reliable liquid chromatography-tandem mass-spectrometry assay, we quantified serum progesterone/progesterone metabolites and explored cross-sectional relationships with MBD and TDLU involution among women, ages 40–65, undergoing diagnostic breast biopsy. Quantitative MBD measures were estimated in pre-biopsy digital mammograms. TDLU involution was quantified in diagnostic biopsies. Adjusted partial correlations and trends across MBD/TDLU categories were calculated. Pregnenolone was positively associated with percent MBD-area (MBD-A, rho: 0.30; p-trend = 0.01) among premenopausal luteal phase women. Progesterone tended to be positively associated with percent MBD-A among luteal phase (rho: 0.26; p-trend = 0.07) and postmenopausal (rho: 0.17; p-trend = 0.04) women. Consistent with experimental data, implicating an elevated 5α-pregnanes/3α-dihydroprogesterone (5αP/3αHP) metabolite ratio in breast cancer, higher 5αP/3αHP was associated with elevated percent MBD-A among luteal phase (rho: 0.29; p-trend = 0.08), but not postmenopausal women. This exploratory analysis provided some evidence that endogenous progesterone and progesterone metabolites might be correlated with MBD, a strong breast cancer risk factor, in both pre- and postmenopausal women undergoing breast biopsy. Additional studies are needed to understand the role of progesterone/progesterone metabolites in breast tissue composition and breast cancer risk.

Original languageEnglish (US)
Article number245
JournalJournal of Clinical Medicine
Volume9
Issue number1
DOIs
StatePublished - Jan 2020

Keywords

  • Breast cancer
  • Breast density
  • Liquid chromatography-tandem mass spectrometry
  • Mammographic density
  • Progesterone
  • Serum progesterone assay

ASJC Scopus subject areas

  • General Medicine

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