Involution of breast lobules, mammographic breast density and prognosis among tamoxifen-treated estrogen receptor-positive breast cancer patients

Maeve Mullooly, Sarah J. Nyante, Ruth M. Pfeiffer, Renata Cora, Donna Butcher, Lawrence Sternberg, Erin J. Aiello Bowles, Shaoqi Fan, Jonine D. Figueroa, Sheila Weinmann, Robert N. Hoover, Louise A. Brinton, Amy Berrington de Gonzalez, Andrew Glass, Mark E. Sherman, Gretchen L. Gierach

Research output: Contribution to journalArticlepeer-review

Abstract

Mammographic breast density (MD) reflects breast fibroglandular content. Its decline following adjuvant tamoxifen treated, estrogen receptor (ER)-positive breast cancer has been associated with improved outcomes. Breast cancers arise from structures termed lobules, and lower MD is associated with increased age-related lobule involution. We assessed whether pre-treatment involution influenced associations between MD decline and risk of breast cancer-specific death. ER-positive tamoxifen treated patients diagnosed at Kaiser Permanente Northwest (1990–2008) were defined as cases who died of breast cancer (n = 54) and matched controls (remained alive over similar follow-up; n = 180). Lobule involution was assessed by examining terminal duct lobular units (TDLUs) in benign tissues surrounding cancers as TDLU count/mm2, median span and acini count/TDLU. MD (%) was measured in the unaffected breast at baseline (median 6-months before) and follow-up (median 12-months after tamoxifen initiation). TDLU measures and baseline MD were positively associated among controls (p < 0.05). In multivariable regression models, MD decline (≥10%) was associated with reduced risk of breast cancer-specific death before (odds ratio (OR): 0.41, 95% CI: 0.18–0.92) and after (OR: 0.41, 95% CI: 0.18–0.94) adjustment for TDLU count/mm2, TDLU span (OR: 0.34, 95% CI: 0.14–0.84), and acini count/TDLU (OR: 0.33, 95% CI: 0.13–0.81). MD decline following adjuvant tamoxifen is associated with reduced risk of breast cancer-specific death, irrespective of pre-treatment lobule involution.

Original languageEnglish (US)
Article number1868
JournalJournal of Clinical Medicine
Volume8
Issue number11
DOIs
StatePublished - Nov 2019

Keywords

  • Breast cancer
  • Involution
  • Mammographic breast density
  • Terminal duct lobular unit

ASJC Scopus subject areas

  • Medicine(all)

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