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Clinical Cancer Research 13, 5474-5479, September 15, 2007. doi: 10.1158/1078-0432.CCR-07-0928
© 2007 American Association for Cancer Research

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Cancer Susceptibility and Prevention

Multiplicity of Benign Breast Lesions Is a Risk Factor for Progression to Breast Cancer

Maria J. Worsham1, Usha Raju2, Mei Lu3, Alissa Kapke3, Jingfang Cheng1 and Sandra R. Wolman4

Authors' Affiliations: Departments of 1 Otolaryngology/Head and Neck Surgery, 2 Pathology, and 3 Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, Michigan; and 4 Department of Pathology, George Washington University, Washington, District of Columbia

Requests for reprints: Maria J. Worsham, Henry Ford Health System, 1 Ford Place, 1D, Detroit, MI 48202. Phone: 313-874-3350; Fax: 313-874-1079; E-mail: mworsha1{at}hfhs.org.

Purpose: Benign breast disease (BBD) in women encompasses a broad spectrum of histopathologic lesions. Studies on BBD have focused on the risks for subsequent breast cancer associated with three broad categories of lesions, classified as nonproliferative, proliferative, or proliferative with atypia, without addressing the issue of the contribution of concurrent multiple BBD lesions. There is very limited information with regard to the issue of BBD lesion multiplicity and breast cancer risk.

Experimental Design: We evaluated a detailed microscopic spectrum of 18 BBD lesions from fibrosis to atypical hyperplasia in a BBD cohort of 4,544 subjects, within which 4.5% (n = 201) developed breast cancer during an average follow-up period of 10.3 years. Lesions were defined as nonproliferative (8 diagnoses; risk level 1 = no risk or low risk), proliferative without atypical hyperplasia (8 diagnoses; risk level 2 = intermediate risk), and proliferative with atypical hyperplasia (2 diagnoses; risk level 3 = highest risk level). Twenty variables including age (≥50 or <50 years) at the time of BBD diagnosis and race (African American or non–African American) were assessed. A categorical variable, surrogate for lesion type and number, was represented initially by four levels: 1, nonproliferative = 1 (reference); 2, nonproliferative > 1; 3, proliferative = 1; and 4, proliferative > 1.

Results: The majority of BBD subjects in our cohort (almost 70%) had more than one BBD lesion. Concurrent multiple nonproliferative or proliferative BBD lesions with or without atypia in a BBD biopsy and age are significant predictors of risk for progression of BBD to breast cancer. The presence of atypical hyperplasia in a BBD biopsy alone or in conjunction with other lesions without atypia conferred higher risks. Women with fibrosis had a reduced risk for progression to breast cancer. Race was not a significant predictor of progression to breast cancer. The effect of age, fibrosis, and multiple lesions (whether nonproliferative, proliferative, or atypia) on breast cancer progression was not influenced by race.

Conclusion: BBD lesion multiplicity is frequent, and teasing out the heterogeneity of multiple concurrent BBD lesions is warranted to refine and improve risk estimates for progression of breast cancer from BBD.







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Copyright © 2007 by the American Association for Cancer Research.