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

1
Division of Population Health Sciences, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland
2
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
3
Department of Radiology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
4
Independent Contractor, CT(ASCP), MB(ASCP), Stamford, CT 06901, USA
5
Pathology-Histotechnology Laboratory, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD 21702, USA
6
Kaiser Permanente Washington Health Research Institute, Seattle, WA 98101, USA
7
Usher Institute of Population Health Sciences and Informatics, CRUK Edinburgh Centre, Medical School, The University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK
8
Kaiser Permanente Northwest Center for Health Research, Portland, OR 97227, USA
9
Mayo Clinic, Jacksonville, FL 32224, USA
*
Author to whom correspondence should be addressed.
Contributed equally as senior authors.
Deceased.
J. Clin. Med. 2019, 8(11), 1868; https://doi.org/10.3390/jcm8111868
Received: 30 September 2019 / Revised: 17 October 2019 / Accepted: 22 October 2019 / Published: 4 November 2019
(This article belongs to the Special Issue Mammographic Density: Biology and Clinical Applications)
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. View Full-Text
Keywords: breast cancer; mammographic breast density; involution; terminal duct lobular unit breast cancer; mammographic breast density; involution; terminal duct lobular unit
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Mullooly, M.; Nyante, S.J.; Pfeiffer, R.M.; Cora, R.; Butcher, D.; Sternberg, L.; Aiello Bowles, E.J.; Fan, S.; Figueroa, J.D.; Weinmann, S.; Hoover, R.N.; Brinton, L.A.; Berrington de Gonzalez, A.; Glass, A.; Sherman, M.E.; Gierach, G.L. Involution of Breast Lobules, Mammographic Breast Density and Prognosis Among Tamoxifen-Treated Estrogen Receptor-Positive Breast Cancer Patients. J. Clin. Med. 2019, 8, 1868.

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