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J Clin Med. 2019 Nov 4;8(11). pii: E1868. doi: 10.3390/jcm8111868.

Involution of Breast Lobules, Mammographic Breast Density and Prognosis Among Tamoxifen-Treated Estrogen Receptor-Positive Breast Cancer Patients.

Author information

1
Division of Population Health Sciences, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland. maevemullooly@rcsi.ie.
2
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. maevemullooly@rcsi.ie.
3
Department of Radiology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. sarah_nyante@med.unc.edu.
4
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. pfeiffer@mail.nih.gov.
5
Independent Contractor, CT(ASCP), MB(ASCP), Stamford, CT 06901, USA. renata.cora@nih.gov.
6
Pathology-Histotechnology Laboratory, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD 21702, USA. butcherdo@mail.nih.gov.
7
Pathology-Histotechnology Laboratory, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD 21702, USA. sternberglr@mail.nih.gov.
8
Kaiser Permanente Washington Health Research Institute, Seattle, WA 98101, USA. Erin.A.Bowles@kp.org.
9
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. shaoqi.fan@nih.gov.
10
Usher Institute of Population Health Sciences and Informatics, CRUK Edinburgh Centre, Medical School, The University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. jonine.figueroa@ed.ac.uk.
11
Kaiser Permanente Northwest Center for Health Research, Portland, OR 97227, USA. Sheila.Weinmann@kpchr.org.
12
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. hooverr@exchange.nih.gov.
13
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. brintonl@exchange.nih.gov.
14
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. berringtona@mail.nih.gov.
15
Kaiser Permanente Northwest Center for Health Research, Portland, OR 97227, USA. andy_5241@msn.com.
16
Mayo Clinic, Jacksonville, FL 32224, USA. Sherman.Mark@mayo.edu.
17
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. gierachg@mail.nih.gov.

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.

KEYWORDS:

breast cancer; involution; mammographic breast density; terminal duct lobular unit

PMID:
31689948
DOI:
10.3390/jcm8111868
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