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

Maeve Mullooly^{1

2}, Sarah J Nyante³, Ruth M Pfeiffer⁴, Renata Cora⁵, Donna Butcher⁶, Lawrence Sternberg⁷, Erin J Aiello Bowles⁸, Shaoqi Fan⁹, Jonine D Figueroa¹⁰, Sheila Weinmann¹¹, Robert N Hoover¹², Louise A Brinton¹³, Amy Berrington de Gonzalez¹⁴, Andrew Glass¹⁵, Mark E Sherman¹⁶, Gretchen L Gierach¹⁷

Affiliations

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.

PMID: 31689948
PMCID: PMC6912285
DOI: 10.3390/jcm8111868

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

Maeve Mullooly et al. J Clin Med. 2019.

. 2019 Nov 4;8(11):1868.

doi: 10.3390/jcm8111868.

Authors

Affiliations

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.

PMID: 31689948
PMCID: PMC6912285
DOI: 10.3390/jcm8111868

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Overview of the study population of breast cancer cases and controls with benign breast tissue suitable for terminal duct lobular unit (TDLU) assessment in this study and representative examples of TDLU measures.

See this image and copyright information in PMC

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources