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27-01-2015 | Breast cancer | Article

Current management of lesions associated with an increased risk of breast cancer

Monica Morrow, Stuart J. Schnitt, Larry Norton


High-risk breast lesions, which comprise benign lesions and in situ carcinomas (lobular carcinoma in situ and ductal carcinoma in situ), are clinically, morphologically, and biologically heterogeneous and are associated with an increased risk of invasive breast cancer development, albeit to varying degrees. Recognition and proactive management of such lesions can help to prevent progression to invasive disease, and might, therefore, reduce breast cancer incidence, morbidity, and mortality. However, this opportunity comes with the possibility of overdiagnosis and overtreatment, necessitating risk-based intervention. Notably, despite the progress in defining the molecular changes associated with carcinogenesis, alterations identifying the individuals with high-risk lesions that will progress to invasive carcinoma remain to be identified. Thus, until reproducible clinicopathological or molecular features predicting an individual's risk of breast cancer are found, management strategies must be defined by population-level risks as determined by models such as the Gail or IBIS models, as well as patient attitudes toward the risks and benefits of interventions. Herein, we review the contemporary approaches to diagnosis and management of high-risk breast lesions. Progress in this area will ultimately be dependent on the ability to individualize risk prediction through better definition of the key drivers in the carcinogenic process.

Nat Rev Clin Oncol 2015; 12: 227–238. doi: 0.1038/nrclinonc.2015.8

Subject terms: Breast cancer • Cancer prevention • Chemoprevention • Preventive medicine

High-risk lesions of the breast represent a clinically, morphologically, and biologically heterogeneous group of lesions associated with an elevated risk of breast cancer, albeit to varying levels. In a seminal study, Dupont and Page1 reviewed over 3,000 benign breast biopsies and categorized lesions as nonproliferative, proliferative without atypia, or atypical hyperplasia; atypical hyperplasias were the only benign lesions associated with a substantially elevated risk of breast cancer development (5.3-fold increased risk).1 By contrast, nonproliferative disease was associated with no increase in the risk of breast cancer, and proliferative disease without atypia with a small, 1.9-fold increase in risk of this disease.1 This classification scheme was endorsed by a 1985 consensus conference of the College of American Pathologists, and subsequently updated in 1998.2

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