Breast Cancer Research and Treatment

, Volume 151, Issue 1, pp 89–97 | Cite as

Ki-67 expression in sclerosing adenosis and adjacent normal breast terminal ductal lobular units: a nested case–control study from the Mayo Benign Breast Disease Cohort

  • Aziza Nassar
  • Tanya L. Hoskin
  • Melody L. Stallings-Mann
  • Amy C. Degnim
  • Derek C. Radisky
  • Marlene H. Frost
  • Robert A. Vierkant
  • Lynn C. Hartmann
  • Daniel W. Visscher
Preclinical study


Sclerosing adenosis (SA) increases risk for invasive breast cancer (BC) 2.1 times relative to that in the general population. Here, we sought to evaluate whether the proliferation marker Ki-67 stratifies risk among women with SA. A nested case–control sample of patients with SA was obtained from the Mayo Clinic Benign Breast Disease Cohort. Ki-67 expression was evaluated in SA lesions and in the adjacent normal terminal duct lobular units (TDLU) in women who did (cases, n = 133) or did not (controls, n = 239) develop BC. Ki-67 was scored by intensity and number of positively stained cells per one high-power field (magnification, ×40) (40× HPF) for both SA and normal TDLU. Associations of Ki-67 expression with case–control status were assessed using conditional logistic regression. Higher Ki-67 expression was significantly associated with case–control status in both SA (P = 0.03) and normal background TDLU (P = 0.006). For the SA lesion, >2 average positively stained cells/40× HPF showed an adjusted odds ratio (OR) of 1.9 (95 % CI, 1.1–3.4) compared to samples with an average of ≤2 positively stained cells. For background TDLU, lobules with >2 but ≤6 average positively stained cells showed an adjusted OR of 1.3–1.5, whereas those with an average of >6 positively stained cells had an OR of 2.4 (95 % CI, 1.1–5.3) compared to those with an average of <2 positively stained cells. Among women with SA, increased Ki-67 expression in either the SA lesion or the normal background TDLU carried an approximately twofold increased odds of subsequent BC as compared to lower Ki-67 expression.


Benign breast disease Breast cancer Ki-67 Sclerosing adenosis Terminal duct lobular unit 



Benign breast disease


Breast cancer


Diaminobenzidine substrate


Ductal carcinoma in situ


High-power field

40× HPF

High-power field (magnification, ×40)


Image analysis


Intraclass correlation coefficient


Interquartile range


Odds ratio


Sclerosing adenosis


Standardized incidence ratio


Terminal duct lobular unit



The research reported in this publication was supported by the National Cancer Institute of the NIH, US Department of Health and Human Services, under the Award Number P50CA116201, and by the Mayo Clinic Breast Cancer SPORE Grant Number CA116201 (PI, James N. Ingle, MD). This publication was supported by CTSA Grant Number UL1 TR000135 from the National Center for Advancing Translational Science (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical standard

This article does not contain any studies with human participants or animals performed by any of the authors. This research has been approved by the institutional review board of the Mayo Clinic for conducting research under ethical standards.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Aziza Nassar
    • 1
  • Tanya L. Hoskin
    • 3
  • Melody L. Stallings-Mann
    • 2
  • Amy C. Degnim
    • 4
  • Derek C. Radisky
    • 2
  • Marlene H. Frost
    • 5
  • Robert A. Vierkant
    • 3
  • Lynn C. Hartmann
    • 5
  • Daniel W. Visscher
    • 6
  1. 1.Department of Laboratory Medicine and PathologyMayo ClinicJacksonvilleUSA
  2. 2.Department of Cancer BiologyMayo ClinicJacksonvilleUSA
  3. 3.Division of Biomedical Statistics and InformaticsMayo ClinicRochesterUSA
  4. 4.Department of SurgeryMayo ClinicRochesterUSA
  5. 5.Division of Medical OncologyMayo ClinicRochesterUSA
  6. 6.Division of Anatomic PathologyMayo ClinicRochesterUSA

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