Breast Cancer Research and Treatment

, Volume 133, Issue 1, pp 169–177 | Cite as

Histologic findings in normal breast tissues: comparison to reduction mammaplasty and benign breast disease tissues

  • Amy C. Degnim
  • Daniel W. Visscher
  • Tanya L. Hoskin
  • Marlene H. Frost
  • Robert A. Vierkant
  • Celine M. Vachon
  • V. Shane Pankratz
  • Derek C. Radisky
  • Lynn C. Hartmann
Preclinical Study


Investigations of breast carcinogenesis often rely upon comparisons between cancer tissue and nonmalignant breast tissue. It is unclear how well common reference sources of nonmalignant breast tissues reflect normal breast tissue. Breast tissue samples were evaluated from three sources: (1) normal donor tissues in the Susan G. Komen for the Cure® Tissue Bank at Indiana University Simon Cancer Center (KTB), (2) women who underwent reduction mammaplasty (RM) at Mayo Clinic Rochester, and (3) the Mayo Clinic Benign Breast Disease Cohort Study (BBD). Samples were examined histologically and assessed for proliferative disease and degree of lobular involution. Univariate comparisons were performed among the study groups, and multivariate analyses were performed with logistic regression to assess the association between study group and the presence of epithelial proliferative disease and complete lobular involution. Histologic data were collected for 455 KTB samples, 259 RM samples, and 319 BBD samples. Histologic findings and the frequency of epithelial proliferation were significantly different among the groups. Histologic abnormalities were seen in a minority of the KTB samples (35%), whereas an abnormality was present in 88% of RM tissues and 97.5% of BBD samples. The presence of proliferative disease (with or without atypical hyperplasia) was present in 3.3% of normal donors (3.3%), 17% of RM samples, and 34.9% of BBD samples (P < 0.0001 for each comparison). Multivariate analyses confirmed that these differences remained significant and also showed higher likelihood of complete lobular involution in the normal donor samples compared to RM and BBD tissues. Compared to benign breast disease tissues and reduction mammaplasty tissues, breast tissue samples from normal donors have significantly fewer histologic abnormalities and a higher frequency of more complete lobular involution. Breast tissue samples from normal donors represent a unique tissue resource with histologic features consistent with lower breast cancer risk.


Normal breast tissue Benign breast disease Reduction mammoplasty 



Amy C. Degnim is supported by the CA90628 Paul Calabresi Award for Clinical-Translational Research (K12) via the Mayo Clinic Cancer Center. Lynn C. Hartmann, V. Shane Pankratz, Derek C. Radisky, Marlene H. Frost, Celine M. Vachon, and Daniel W. Visscher are supported in part by CA132879 and by the Mayo Clinic Breast SPORE CA116201 (JN Ingle, PI). Special thanks to Teresa Allers for assistance with study materials, Shaun Maloney for database development; and Marilyn Churchward for assistance with manuscript preparation. Samples from the Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center were used in this study. We thank contributors, including Indiana University who collected samples used in this study, as well as donors and their families, whose help and participation made this work possible. This project was also supported by NIH/NCRR CTSA Grant Number UL1 RR024150. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.


  1. 1.
    Jin L, Fuchs A, Schnitt SJ et al (1997) Expression of scatter factor and c-met receptor in benign and malignant breast tissue. Cancer 79:749–760PubMedCrossRefGoogle Scholar
  2. 2.
    Bernardes JR Jr, Nonogaki S, Seixas MT et al (1999) Effect of a half dose of tamoxifen on proliferative activity in normal breast tissue. Int J Gynaecol Obstet 67:33–38PubMedCrossRefGoogle Scholar
  3. 3.
    Ma XJ, Salunga R, Tuggle JT et al (2003) Gene expression profiles of human breast cancer progression. Proc Natl Acad Sci USA 100:5974–5979PubMedCrossRefGoogle Scholar
  4. 4.
    Ciris IM, Bozkurt KK, Baspinar S, Kapucuoglu FN (2011) Immunohistochemical COX-2 overexpression correlates with HER-2/neu overexpression in invasive breast carcinomas: a pilot study. Pathol Res Pract 207:182–187PubMedCrossRefGoogle Scholar
  5. 5.
    Dedes KJ, Natrajan R, Lambros MB et al (2011) Down-regulation of the miRNA master regulators Drosha and Dicer is associated with specific subgroups of breast cancer. Eur J Cancer 47:138–150PubMedCrossRefGoogle Scholar
  6. 6.
    Hartmann LC, Sellers TA, Frost MH et al (2005) Benign breast disease and the risk of breast cancer. N Engl J Med 353:229–237PubMedCrossRefGoogle Scholar
  7. 7.
    Degnim AC, Visscher DW, Berman HK et al (2007) Stratification of breast cancer risk in women with atypia: a Mayo cohort study. J Clin Oncol 25:2671–2677PubMedCrossRefGoogle Scholar
  8. 8.
    McKian KP, Reynolds CA, Visscher DW et al (2009) Novel breast tissue feature strongly associated with risk of breast cancer. J Clin Oncol 27:5893–5898PubMedCrossRefGoogle Scholar
  9. 9.
    Visscher DW, Pankratz VS, Santisteban M et al (2008) Association between cyclooxygenase-2 expression in atypical hyperplasia and risk of breast cancer. J Natl Cancer Inst 100:421–427PubMedCrossRefGoogle Scholar
  10. 10.
    Santisteban M, Reynolds C, Barr Fritcher EG et al (2010) Ki67: a time-varying biomarker of risk of breast cancer in atypical hyperplasia. Breast Cancer Res Treat 121:431–437PubMedCrossRefGoogle Scholar
  11. 11.
    Madigan MP, Ziegler RG, Benichou J, Byrne C, Hoover RN (1995) Proportion of breast cancer cases in the United States explained by well-established risk factors. J Natl Cancer Inst 87:1681–1685PubMedCrossRefGoogle Scholar
  12. 12.
    Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center. Accessed 23 Aug 2011
  13. 13.
    Dupont WD, Page DL (1985) Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 312:146–151PubMedCrossRefGoogle Scholar
  14. 14.
    Carter CL, Corle DK, Micozzi MS, Schatzkin A, Taylor PR (1988) A prospective study of the development of breast cancer in 16,692 women with benign breast disease. Am J Epidemiol 128:467–477PubMedGoogle Scholar
  15. 15.
    London SJ, Connolly JL, Schnitt SJ, Colditz GA (1992) A prospective study of benign breast disease and the risk of breast cancer. JAMA 267:941–944PubMedCrossRefGoogle Scholar
  16. 16.
    Milanese TR, Hartmann LC, Sellers TA et al (2006) Age-related lobular involution and risk of breast cancer. J Natl Cancer Inst 98:1600–1607PubMedCrossRefGoogle Scholar
  17. 17.
    Pitanguy I, Torres E, Salgado F, Pires Viana GA (2005) Breast pathology and reduction mammaplasty. Plast Reconstr Surg 115:729–734 discussion 735PubMedCrossRefGoogle Scholar
  18. 18.
    Boice JD Jr, Persson I, Brinton LA et al (2000) Breast cancer following breast reduction surgery in Sweden. Plast Reconstr Surg 106:755–762PubMedCrossRefGoogle Scholar
  19. 19.
    Brown MH, Weinberg M, Chong N, Levine R, Holowaty E (1999) A cohort study of breast cancer risk in breast reduction patients. Plast Reconstr Surg 103:1674–1681PubMedCrossRefGoogle Scholar
  20. 20.
    Gail MH, Brinton LA, Byar DP et al (1989) Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 81:1879–1886PubMedCrossRefGoogle Scholar
  21. 21.
    Rosen PP, Senie R, Schottenfeld D, Ashikari R (1979) Noninvasive breast carcinoma: frequency of unsuspected invasion and implications for treatment. Ann Surg 189:377–382PubMedCrossRefGoogle Scholar
  22. 22.
    Chuba PJ, Hamre MR, Yap J et al (2005) Bilateral risk for subsequent breast cancer after lobular carcinoma-in situ: analysis of surveillance, epidemiology, and end results data. J Clin Oncol 23:5534–5541PubMedCrossRefGoogle Scholar
  23. 23.
    Fabian CJ, Kimler BF, Zalles CM et al (2000) Short-term breast cancer prediction by random periareolar fine-needle aspiration cytology and the Gail risk model. J Natl Cancer Inst 92:1217–1227PubMedCrossRefGoogle Scholar
  24. 24.
    Vierkant RA, Hartmann LC, Pankratz VS et al (2009) Lobular involution: localized phenomenon or field effect? Breast Cancer Res Treat 117:193–196PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Amy C. Degnim
    • 1
  • Daniel W. Visscher
    • 2
  • Tanya L. Hoskin
    • 3
  • Marlene H. Frost
    • 4
  • Robert A. Vierkant
    • 3
  • Celine M. Vachon
    • 5
  • V. Shane Pankratz
    • 3
  • Derek C. Radisky
    • 6
  • Lynn C. Hartmann
    • 7
  1. 1.Department of SurgeryMayo ClinicRochesterUSA
  2. 2.Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA
  3. 3.Department of Biomedical Statistics and InformaticsMayo ClinicRochesterUSA
  4. 4.Women’s Cancer ProgramMayo ClinicRochesterUSA
  5. 5.Department of Health Sciences Research, EpidemiologyMayo ClinicRochesterUSA
  6. 6.Department of Biochemistry and Molecular BiologyMayo ClinicJacksonvilleUSA
  7. 7.Department of OncologyMayo ClinicRochesterUSA

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