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

• Published in: Clinical cancer research 2007-09, Vol.13 (18), p.5474-5479
• Main Authors: WORSHAM, Maria J, RAJU, Usha, MEI LU, KAPKE, Alissa, JINGFANG CHENG, WOLMAN, Sandra R
• Format: Article
• Language: English
• Subjects: Adult; Antineoplastic agents; benign breast disease; Biological and medical sciences; Breast Diseases - complications; Breast Diseases - epidemiology; Breast Diseases - pathology; Breast Neoplasms - etiology; Breast Neoplasms - pathology; Disease Progression; Female; Fibrosis; Gynecology. Andrology. Obstetrics; Humans; Hyperplasia - pathology; Mammary gland diseases; Medical sciences; Middle Aged; multiple lesions; nonproliferative; Pharmacology. Drug treatments; Precancerous Conditions - epidemiology; Precancerous Conditions - pathology; progression; proliferative; Risk Factors; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-0928

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 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.